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Clinical and Applied... Nov 2012The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE)... (Comparative Study)
Comparative Study Meta-Analysis Review
The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery. Electronic databases were interrogated to identify relevant randomized controlled trials. A series of direct/indirect comparisons and a network meta-analysis were conducted. Indirect comparisons found that the odds ratio of "all VTE and all-cause death" were significantly higher for dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42). Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR, 0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No significant differences were observed in bleeding outcomes between treatments. The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated similar or improved efficacy and similar safety compared with current therapies in this indication.
Topics: Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; beta-Alanine
PubMed: 22387582
DOI: 10.1177/1076029612437579 -
Blood Cancer Journal Jul 2021Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors have been used for the treatment of myelofibrosis for several years, but there is a lack of comparative information between those treatments. A systematic review and network meta-analysis was performed on randomized controlled trials in patients with myelofibrosis receiving JAK inhibitor or placebo or control. Primary outcomes were efficacy on spleen volume reduction and total symptom score reduction. Additional analyses were conducted on anemia and thrombopenia events. Seven studies were included in the network meta-analysis including 1953 patients randomly assigned to four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, momelotinib-or control. In first-line therapy, momelotinib and fedratinib were associated with comparable efficacy to ruxolitinib, and with less toxicity on erythrocytes and platelets, respectively. Pacritinib was less effective on splenomegaly than ruxolitinib as a first-line treatment but seemed effective in second line, after ruxolitinib exposure. Fedratinib and ruxolitinib that are FDA approved in myelofibrosis have both confirmed being valuable option to treat splenomegaly and constitutional symptoms, and their slightly different tolerance-profiles can guide therapeutic choice for first-line treatment, according to patient profile. Momelotinib could be another option especially due to its positive effect on anemia.
Topics: Bridged-Ring Compounds; Humans; Janus Kinase Inhibitors; Nitriles; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Pyrrolidines; Splenomegaly; Sulfonamides; Treatment Outcome
PubMed: 34315858
DOI: 10.1038/s41408-021-00526-z -
Journal of Thrombosis and Haemostasis :... 2014New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.
INTRODUCTION
New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models.
RESULTS
Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban.
CONCLUSIONS
NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.
Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 24330006
DOI: 10.1111/jth.12485 -
Psychopharmacology Jul 2024Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression. (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression.
OBJECTIVES
Our aim is to evaluate Zuranolone's efficacy and safety in treating depression.
METHODS
Five databases were searched until September 2023 for relevant randomized clinical trials evaluating the efficacy and safety of zuranolone. The potential risk of bias in the included trials was evaluated by the Cochrane Risk of Bias II guideline Data were extracted and pooled using Review Manager Software (RevMan 5.3).
RESULTS
An analysis of eight studies highlights Zuranolone's efficacy in treating depression compared to placebo across most of the outcomes. Notably, the 30mg and 50mg doses demonstrated significant improvements in reducing HAM-D scores by over 50% within a 15-day follow-up (RR) of 1.46 (95% CI [1.27, 1.68], p < 0.0001) and 1.14 (95% CI [1.01, 1.3], p = 0.04). Additionally, the HAM-D ≤ 7% score analysis revealed significant enhancements with the 30mg dose over both 15-day (RR = 1.82, 95% CI [1.44, 2.31], p < 0.0001) and 45-day (RR = 1.43, 95% CI [1.16, 1.77], p = 0.0008) durations. Adverse Events Drug Discontinuation demonstrated no overall significant difference (OR = 1.33, 95% CI: [0.79, 2.23], p = 0.282). Further, specific adverse events, such as headache, showed no significant overall difference between Zuranolone and placebo (OR = 1.11, 95% CI: [0.84, 1.47], p = 0.47), with dose-dependent analysis revealing less headache in the 30 mg group.
CONCLUSION
Zuranolone demonstrates favorable tolerability and safety, particularly at 30mg and 50mg doses after 15 days, suggesting its potential and effective treatment for depression.
Topics: Humans; Randomized Controlled Trials as Topic; Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Treatment Outcome; Pregnanolone; Pyrazoles
PubMed: 38802705
DOI: 10.1007/s00213-024-06611-y -
The Cochrane Database of Systematic... Jul 2018Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality... (Review)
Review
BACKGROUND
Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality of life (QoL) and function. The underlying pathophysiological mechanism remains unclear for this condition, which makes establishing effective treatments challenging.
OBJECTIVES
To assess the effectiveness of interventions used for the treatment of brain radionecrosis in adults over 18 years old.
SEARCH METHODS
In October 2017, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for eligible studies. We also searched unpublished data through Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials for ongoing trials and handsearched relevant conference material.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any intervention directed to treat brain radionecrosis in adults over 18 years old previously treated with radiation therapy to the brain. We anticipated a limited number of RCTs, so we also planned to include all comparative prospective intervention trials and quasi-randomised trials of interventions for brain radionecrosis in adults as long as these studies had a comparison group that reflects the standard of care (i.e. placebo or corticosteroids). Selection bias was likely to be an issue in all the included non-randomised studies therefore results are interpreted with caution.
DATA COLLECTION AND ANALYSIS
Two review authors (CC, PB) independently extracted data from selected studies and completed a 'Risk of bias' assessment. For dichotomous outcomes, the odds ratio (OR) for the outcome of interest was reported. For continuous outcomes, treatment effect was reported as mean difference (MD) between treatment arms with 95% confidence intervals (CIs).
MAIN RESULTS
Two RCTs and one prospective non-randomised study evaluating pharmacological interventions met the inclusion criteria for this review. As each study evaluated a different drug or intervention using different endpoints, a meta-analysis was not possible. There were no trials of non-pharmacological interventions that met the inclusion criteria.A very small randomised, double-blind, placebo-controlled trial of bevacizumab versus placebo reported that 100% (7/7) of participants on bevacizumab had reduction in brain oedema by at least 25% and reduction in post-gadolinium enhancement, whereas all those receiving placebo had clinical or radiological worsening or both. This was an encouraging finding but due to the small sample size we did not report a relative effect. The authors also failed to provide adequate details regarding the randomisation and blinding procedures Therefore, the certainty of this evidence is low and a larger RCT adhering to reporting standards is needed.An open-label RCT demonstrated a greater reduction in brain oedema (T2 hyperintensity) in the edaravone plus corticosteroid group than in the corticosteroid alone group (MD was 3.03 (95% CI 0.14 to 5.92; low-certainty evidence due to high risk of bias and imprecision); although the result approached borderline significance, there was no evidence of any important difference in the reduction in post-gadolinium enhancement between arms (MD = 0.47, 95% CI - 0.80 to 1.74; low-certainty evidence due to high risk of bias and imprecision).In the RCT of bevacizumab versus placebo, all seven participants receiving bevacizumab were reported to have neurological improvement, whereas five of seven participants on placebo had neurological worsening (very low-certainty evidence due to small sample size and concerns over validity of analyses). While no adverse events were noted with placebo, three severe adverse events were noted with bevacizumab, which included aspiration pneumonia, pulmonary embolus and superior sagittal sinus thrombosis. In the RCT of corticosteroids with or without edaravone, the participants who received the combination treatment were noted to have significantly greater clinical improvement than corticosteroids alone based on LENT/SOMA scale (OR = 2.51, 95% CI 1.26 to 5.01; low-certainty evidence due to open-label design). No differences in treatment toxicities were observed between arms.One included prospective non-randomised study of alpha-tocopherol (vitamin E) versus no active treatment was found but it did not include any radiological assessment. As only one included study was a double-blinded randomised controlled trial, the other studies were prone to selection and detection biases.None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements.A limited number of prospective studies were identified but subsequently excluded as these studies had a limited number of participants evaluating different pharmacological interventions using variable endpoints.
AUTHORS' CONCLUSIONS
There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.
Topics: Adrenal Cortex Hormones; Adult; Antipyrine; Bevacizumab; Brain; Brain Edema; Drug Therapy, Combination; Edaravone; Gadolinium; Humans; Non-Randomized Controlled Trials as Topic; Radiation Injuries; Radiosurgery; Radiotherapy; Randomized Controlled Trials as Topic
PubMed: 29987845
DOI: 10.1002/14651858.CD011492.pub2 -
The Cochrane Database of Systematic... Apr 2015Myelofibrosis is a bone marrow disorder characterized by excessive production of reticulin and collagen fiber deposition caused by hematological and non-hematological... (Review)
Review
BACKGROUND
Myelofibrosis is a bone marrow disorder characterized by excessive production of reticulin and collagen fiber deposition caused by hematological and non-hematological disorders. The prognosis of myelofibrosis is poor and treatment is mainly palliative. Janus kinase inhibitors are a novel strategy to treat people with myelofibrosis.
OBJECTIVES
To determine the clinical benefits and harms of Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis secondary to hematological or non-hematological conditions.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2014, Issue 11), Ovid MEDLINE (from 1946 to 13 November 2014), EMBASE (from 1980 to 12 January 2013), and LILACS (from 1982 to 20 November 2014). We searched WHO International Clinical Trials Registry Platform and The metaRegister of Controlled Trials. We also searched for conference proceedings of the American Society of Hematology (from 2009 to October 2013), European Hematology Association (from 2009 to October 2013), American Society of Clinical Oncology (from 2009 to October 2013), and European Society of Medical Oncology (from 2009 to October 2013). We included searches in FDA, European Medicines Agency, and Epistemonikos. We handsearched the references of all identified included trials, and relevant review articles. We did not apply any language restrictions. Two review authors independently screened search results.
SELECTION CRITERIA
We included randomized clinical trials comparing Janus kinase-1 and Janus kinase-2 inhibitors with placebo or other treatments. Both previously treated and treatment naive patients were included.
DATA COLLECTION AND ANALYSIS
We used the hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival, progression-free survival and leukemia-free survival, risk ratio (RR) and 95% CI for reduction in spleen size and adverse events binary data, and standardized mean differences (SMD) and 95% CI for continuous data (health-related quality of life). Two review authors independently extracted data and assessed the risk of bias of included trials. Primary outcomes were overall survival, progression-free survival and adverse events.
MAIN RESULTS
We included two trials involving 528 participants, comparing ruxolitinib with placebo or best available therapy (BAT). As the two included trials had different comparators we did not pool the data. The confidence in the results estimates of these trials was low due to the bias in their design, and their limited sample sizes that resulted in imprecise results.There is low quality evidence for the effect of ruxolitinib on survival when compared with placebo at 51 weeks of follow-up (HR 0.51, 95% CI 0.27 to 0.98) and compared with BAT at 48 weeks of follow-up (HR 0.70, 95% CI 0.20 to 2.47). Similarly there was very low quality evidence for the effect of ruxolitinib on progression free survival compared with BAT (HR 0.81, 95% CI 0.47 to 1.39).There is low quality evidence for the effect of ruxolitinib in terms of quality of life. Compared with placebo, the drug achieved a greater proportion of patients with a significant reduction of symptom scores (RR 8.82, 95% CI 4.40 to 17.69), and treated patients with ruxolitinib obtained greater MFSAF scores at the end of follow-up (MD -87.90, 95% CI -139.58 to -36.22). An additional trial showed significant differences in EORTC QLQ-C30 scores when compared ruxolitinib with best available therapy (MD 7.60, 95% CI 0.35 to 14.85).The effect of ruxolitinib on reduction in the spleen size of participants compared with placebo or BAT was uncertain (versus placebo: RR 64.58, 95% CI 9.08 to 459.56, low quality evidence; versus BAT: RR 41.78, 95% CI 2.61 to 669.75, low quality evidence).There is low quality evidence for the effect of the drug compared with placebo on anemia (RR 2.35, 95% CI 1.62 to 3.41), neutropenia (RR 3.57, 95% CI 1.02 to 12.55) and thrombocytopenia (RR 9.74, 95% CI 2.32 to 40.96). Ruxolitinib did not result in differences versus BAT in the risk of anemia (RR 1.35, 95% CI 0.91 to 1.99, low quality evidence) or thrombocytopenia (RR 1.20; 95% CI 0.44 to 3.28, low quality evidence). The risk of non-hematologic grade 3 or 4 adverse events (including fatigue, arthralgia, nausea, diarrhea, extremity pain and pyrexia) was similar when ruxolitinib was compared with placebo or BAT. The rate of neutropenia comparing ruxolitinib with standard medical treatment was not reported by the trial.
AUTHORS' CONCLUSIONS
Currently, there is insufficient evidence to allow any conclusions regarding the efficacy and safety of ruxolitinib for treating myelofibrosis. The findings of this Cochrane review should be interpreted with caution as they are based on trials sponsored by industry, and include a small number of patients. Unless powered randomized clinical trials provide strong evidence of a treatment effect, and the trade-off between potential benefits and harms is established, clinicians should be cautious when administering ruxolitinib for treating patients with myelofibrosis.
Topics: Humans; Janus Kinase 1; Janus Kinase 2; Nitriles; Primary Myelofibrosis; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 25860512
DOI: 10.1002/14651858.CD010298.pub2 -
BMJ (Clinical Research Ed.) Sep 2002To determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and... (Review)
Review
Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials.
OBJECTIVE
To determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis.
DESIGN
Systematic review of randomised trials that compared at least 12 weeks' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis.
PARTICIPANTS
15 187 patients with osteoarthritis or rheumatoid arthritis.
EFFICACY
Western Ontario and McMaster universities osteoarthritis index; American College of Rheumatology responder index and joint scores for rheumatoid arthritis. Tolerability: withdrawal rates for adverse effects. Gastrointestinal safety: incidence of ulcers, bleeds, perforations, and obstructions.
RESULTS
Nine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin.
CONCLUSION
Celecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Celecoxib; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Humans; Osteoarthritis; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome
PubMed: 12242171
DOI: 10.1136/bmj.325.7365.619 -
Asian Journal of Surgery Mar 2024Due to the large cost of joint replacement for surgical treatment of knee osteoarthritis, there are many complications in elderly patients, and there are many... (Meta-Analysis)
Meta-Analysis Review
Due to the large cost of joint replacement for surgical treatment of knee osteoarthritis, there are many complications in elderly patients, and there are many contraindications to surgery, and conservative treatment is still based on drugs. To further evaluate the efficacy and safety of sodium hyaluronate combined with celecoxib for the treatment of osteoarthritis of the knee. In total, 202 studies were screened, with a final selection of 9 RCTs involving 2339 participants; of these, 9 RCTs were included in the final meta-analysis. Treatment group reduces VAS (SMD = -1.61; 95 % CI [-2.25, -0.98]; I = 95 %; P < 0.00001) and adverse reactions (OR = 0.45; 95 % CI [0.22,0.94]; I = 0 %; P < 0.33); Meanwhile, improving Lysholm knee scores (SMD = 0.19; 95 % CI [-0.06, -0.44]; I = 76 %; P = 0.0004) and Clinical efficiency (OR = 0.31; 95 % CI [0.19,0.50]; I = 0 %; P < 0.00001). All indicators were superior to the control group. Our primary findings suggest that KOA treatment with celecoxib combined with sodium hyaluronate reduces VAS, while improving Lysholm scores and Clinical efficiency. In addition, we found that celecoxib combined with sodium hyaluronate treatment had fewer adverse effects than the control group, indicating that the combination is safe and effective in the treatment of KOA.
Topics: Humans; Aged; Celecoxib; Hyaluronic Acid; Osteoarthritis, Knee; Knee Joint; Pain Management; Treatment Outcome
PubMed: 38008631
DOI: 10.1016/j.asjsur.2023.11.077 -
Blood Jul 2016
Meta-Analysis Review
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Atrial Fibrillation; Humans; Incidence; Leukemia; Lymphoma; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines
PubMed: 27247135
DOI: 10.1182/blood-2016-05-712828 -
The Cochrane Database of Systematic... Jul 2018Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are among the commonest reasons for patients to present to primary care with ear trouble.Wax is part of the ear's self-cleaning mechanism and is usually naturally expelled from the ear canal without causing problems. When this mechanism fails, wax is retained in the canal and may become impacted; interventions to encourage its removal may then be needed. Application of ear drops is one of these methods. Liquids used to remove and soften wax are of several kinds: oil-based compounds (e.g. olive or almond oil); water-based compounds (e.g. sodium bicarbonate or water itself); a combination of the above or non-water, non-oil-based solutions, such as carbamide peroxide (a hydrogen peroxide-urea compound) and glycerol.
OBJECTIVES
To assess the effects of ear drops (or sprays) to remove or aid the removal of ear wax in adults and children.
SEARCH METHODS
We searched the Cochrane ENT Trials Register; Cochrane Register of Studies; PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 23 March 2018.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which a 'cerumenolytic' was compared with no treatment, water or saline, an alternative liquid treatment (oil or almond oil) or another 'cerumenolytic' in adults or children with obstructing or impacted ear wax.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. The primary outcomes were 1) the proportion of patients (or ears) with complete clearance of ear wax and 2) adverse effects (discomfort, irritation or pain). Secondary outcomes were: extent of wax clearance; proportion of people (or ears) with relief of symptoms due to wax; proportion of people (or ears) requiring further intervention to remove wax; success of mechanical removal of residual wax following treatment; any other adverse effects recorded and cost. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included 10 studies, with 623 participants (900 ears). Interventions included: oil-based treatments (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based treatments (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), other active comparators (e.g. saline or water alone) and no treatment. Nine of the studies were more than 15 years old.The overall risk of bias across the 10 included studies was low or unclear.
PRIMARY OUTCOME
proportion of patients (or ears) with complete clearance of ear waxSix studies (360 participants; 491 ears) contributed quantitative data and were included in our meta-analyses.Active treatment versus no treatmentOnly one study addressed this comparison. The proportion of ears with complete clearance of ear wax was higher in the active treatment group (22%) compared with the no treatment group (5%) after five days of treatment (risk ratio (RR) 4.09, 95% confidence interval (CI) 1.00 to 16.80); one study; 117 ears; NNTB = 8) (low-quality evidence).Active treatment versus water or salineWe found no evidence of a difference in the proportion of patients (or ears) with complete clearance of ear wax when the active treatment group was compared to the water or saline group (RR 1.47, 95% CI 0.79 to 2.75; three studies; 213 participants; 257 ears) (low-quality evidence). Two studies applied drops for five days, but one study only applied the drops for 15 minutes. When we excluded this study in a sensitivity analysis it did not change the result.Water or saline versus no treatmentThis comparison was only addressed in the single study cited above (active versus no treatment) and there was no evidence of a difference in the proportion of ears with complete wax clearance when comparing water or saline with no treatment after five days of treatment (RR 4.00, 95% CI 0.91 to 17.62; one study; 76 ears) (low-quality evidence).Active treatment A versus active treatment BSeveral single studies evaluated 'head-to-head' comparisons between two active treatments. We found no evidence to show that one was superior to any other.Subgroup analysis of oil-based active treatments versus non-oil based active treatmentsWe found no evidence of a difference in this outcome when oil-based treatments were compared with non-oil-based active treatments.
PRIMARY OUTCOME
adverse effects: discomfort, irritation or painOnly seven studies planned to measure and did report this outcome. Only two (141 participants;176 ears) provided useable data. There was no evidence of a significant difference in the number of adverse effects between the types of ear drops in these two studies. We summarised the remaining five studies narratively. All events were mild and reported in fewer than 30 participants across the seven studies (low-quality evidence).Secondary outcomesThree studies reported 'other' adverse effects (how many studies planned to report these is unclear). The available information was limited and included occasional reports of dizziness, unpleasant smell, tinnitus and hearing loss. No significant differences between groups were reported. There were no emergencies or serious adverse effects reported in any of the 10 studies.There was very limited or no information available on our remaining secondary outcomes.
AUTHORS' CONCLUSIONS
Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain.A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments.There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.
Topics: Adult; Antipyrine; Benzocaine; Carbamide Peroxide; Carbonates; Cerumen; Child; Chlorobutanol; Choline; Dioctyl Sulfosuccinic Acid; Drug Combinations; Ear Canal; Ethanolamines; Humans; Hygiene; Peroxides; Pharmaceutical Solutions; Plant Oils; Potassium; Randomized Controlled Trials as Topic; Salicylates; Sodium Chloride; Surface-Active Agents; Urea; Water
PubMed: 30043448
DOI: 10.1002/14651858.CD012171.pub2