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Frontiers in Medicine 2024This network meta-analysis was to analyze and rank the efficacy and safety of different systemic drugs in the treatment of uremic pruritus (UP) among hemodialysis...
Efficacy and safety of different systemic drugs in the treatment of uremic pruritus among hemodialysis patients: a network meta-analysis based on randomized clinical trials.
AIM
This network meta-analysis was to analyze and rank the efficacy and safety of different systemic drugs in the treatment of uremic pruritus (UP) among hemodialysis patients.
METHOD
PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to 10 July 2023 for randomized controlled trials (RCTs) investigating different drugs in the treatment of UP among hemodialysis patients. Drugs including cromolyn sodium, dexchlorpheniramine, difelikefalin, gabapentin, hydroxyzine, ketotifen, melatonin, montelukast, nalbuphine, nalfurafine, nemolizumab, nicotinamide, pregabalin, sertraline, thalidomide, and placebo were assessed. Outcome measures, including pruritus relief, response, and adverse events, were analyzed. Network plots, forest plots, league tables, and the surface under the cumulative ranking (SUCRA) probabilities were depicted for each outcome.
RESULTS
The network meta-analysis retrieved 22 RCTs. Gabapentin (69.74%) had the highest likelihood to be the most effective drug for pruritus relief in UP patients receiving hemodialysis, followed by cromolyn sodium and hydroxyzine. Thalidomide (60.69%) and gabapentin (58.99%) were associated with significantly more drug responses for treating UP among patients receiving hemodialysis. Patients who were treated with gabapentin (40.01%) were likely to have risks of adverse events and dizziness. Lower risks of adverse events, nausea, and diarrhea were found in patients who received cromolyn sodium and lower risks of somnolence.
CONCLUSION
This study suggests considering gabapentin treatment when facing a patient suffering from UP. This study provides a reference for the selection of drug therapy for UP patients receiving hemodialysis.
PubMed: 38646551
DOI: 10.3389/fmed.2024.1334944 -
The Cochrane Database of Systematic... Mar 2015Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV). Management of bronchiolitis varies between clinicians, reflecting the lack of evidence for a specific treatment approach. The leukotriene pathway has been reported to be involved in the pathogenesis of bronchiolitis. Leukotriene inhibitors such as montelukast have been used in infants and young children with bronchiolitis. However, the results from limited randomised controlled trials (RCTs) are controversial and necessitate a thorough evaluation of their efficacy for bronchiolitis in infants and young children.
OBJECTIVES
To assess the efficacy and safety of leukotriene inhibitors for bronchiolitis in infants and young children.
SEARCH METHODS
We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to April week 4, 2014), EMBASE (1974 to May 2014), CINAHL (1981 to May 2014), LILACS (1982 to May 2014), Web of Science (1985 to May 2014), WHO ICTRP and ClinicalTrials.gov (6 May 2014).
SELECTION CRITERIA
RCTs comparing leukotriene inhibitors versus placebo or another intervention in infants and young children under two years of age diagnosed with bronchiolitis. Our primary outcomes were length of hospital stay and all-cause mortality. Secondary outcomes included clinical severity score, percentage of symptom-free days, percentage of children requiring ventilation, oxygen saturation, recurrent wheezing, respiratory rate and clinical adverse effects.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Collaboration methodological practices. Two authors independently assessed trial eligibility and extracted data, such as general information, participant characteristics, interventions and outcomes. We assessed risk of bias and graded the quality of the evidence. We used Review Manager software to pool results and chose random-effects models for meta-analysis.
MAIN RESULTS
We included five studies with a total of 1296 participants under two years of age hospitalised with bronchiolitis. Two studies with low risk of bias compared 4 mg montelukast (a leukotriene inhibitor) daily use from admission until discharge with a matching placebo. Both selected length of hospital stay as a primary outcome and clinical severity score as a secondary outcome. However, the effects of leukotriene inhibitors on length of hospital stay and clinical severity score were uncertain due to considerable heterogeneity between the study results and wide confidence intervals around the estimated effects (hospital stay: mean difference (MD) -0.95 days, 95% confidence interval (CI) -3.08 to 1.19, P value = 0.38, low quality evidence; clinical severity score on day two: MD -0.57, 95% CI -2.37 to 1.23, P value = 0.53, low quality evidence; clinical severity score on day three: MD 0.17, 95% CI -1.93 to 2.28, P value = 0.87, low quality evidence). The other three studies compared montelukast for several weeks for preventing post-bronchiolitis symptoms with placebo. We assessed one study as low risk of bias, whereas we assessed the other two studies as having a high risk of attrition bias. Due to the significant clinical heterogeneity in severity of disease, duration of treatment, outcome measurements and timing of assessment, we did not pool the results. Individual analyses of these studies did not show significant differences between the leukotriene inhibitors group and the control group in symptom-free days and incidence of recurrent wheezing. One study of 952 children reported two deaths in the leukotriene inhibitors group: neither was determined to be drug-related. No data were available on the percentage of children requiring ventilation, oxygen saturation and respiratory rate. Finally, three studies reported adverse events including diarrhoea, wheezing shortly after administration and rash. No differences were reported between the study groups.
AUTHORS' CONCLUSIONS
The current evidence does not allow definitive conclusions to be made about the effects of leukotriene inhibitors on length of hospital stay and clinical severity score in infants and young children with bronchiolitis. The quality of the evidence was low due to inconsistency (unexplained high levels of statistical heterogeneity) and imprecision arising from small sample sizes and wide confidence intervals, which did not rule out a null effect or harm. Data on symptom-free days and incidence of recurrent wheezing were from single studies only. Further large studies are required. We identified one registered ongoing study, which may make a contribution in the updates of this review.
Topics: Acetates; Bronchiolitis; Cyclopropanes; Humans; Infant; Length of Stay; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides
PubMed: 25773054
DOI: 10.1002/14651858.CD010636.pub2 -
The Cochrane Database of Systematic... Oct 2018Eczema is a common, chronic, inflammatory skin condition that is frequently associated with atopic conditions, including asthma. Leukotriene receptor antagonists (LTRAs)...
BACKGROUND
Eczema is a common, chronic, inflammatory skin condition that is frequently associated with atopic conditions, including asthma. Leukotriene receptor antagonists (LTRAs) have a corticosteroid-sparing role in asthma, but their role in eczema remains controversial. Currently available topical therapies for eczema are often poorly tolerated, and use of systemic agents is restricted by their adverse effect profile. A review of alternative treatments was therefore warranted.
OBJECTIVES
To assess the possible benefits and harms of leukotriene receptor antagonists for eczema.
SEARCH METHODS
We searched the following databases to September 2017: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and the GREAT database. We also searched five trial registries, and handsearched the bibliographies of all extracted studies for further relevant trials.
SELECTION CRITERIA
Randomised controlled trials of LTRAs alone or in combination with other (topical or systemic) treatments compared with other treatments alone such as topical corticosteroids or placebo for eczema in the acute or chronic (maintenance) phase of eczema in adults and children.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. The primary outcome measures were change in disease severity, long-term symptom control, and adverse effects of treatment. Secondary outcomes were change in corticosteroid requirement, reduction of pruritis, quality of life, and emollient requirement. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
Only five studies (including a total of 202 participants) met the inclusion criteria, all of which assessed oral montelukast; hence, we found no studies assessing other LTRAs. Treatment ranged from four to eight weeks, and outcomes were assessed at the end of treatment; therefore, we could only report short-term measurements (defined as less than three months follow-up from baseline). Montelukast dosing was 10 mg for adults (age 14 years and above) and 5 mg for children (age 6 years to 14 years). One study included children (aged 6 years and above) among their participants, while the remaining studies only included adults (participant age ranged from 16 to 70 years). The participants were diagnosed with moderate-to-severe eczema in four studies and moderate eczema in one study. The study setting was unclear in two studies, multicentre in two studies, and single centre in one study; the studies were conducted in Europe and Bangladesh. Two studies were industry funded. The comparator was placebo in three studies and conventional treatment in two studies. The conventional treatment comparator was a combination of antihistamines and topical corticosteroids (plus oral antibiotics in one study).Four of the studies did not adequately describe their randomisation or allocation concealment method and were considered as at unclear risk of selection bias. Only one study was at low risk of performance and detection bias. However, we judged all studies to be at low risk of attrition and reporting bias.We found no evidence of a difference in disease severity of moderate-to-severe eczema after short-term use of montelukast (10 mg) when compared with placebo. The outcome was assessed using the modified EASI (Eczema Area and Severity Index) score and SASSAD (Six Area, Six Sign Atopic Dermatitis) severity score (standardised mean difference 0.29, with a positive score showing montelukast is favoured, 95% confidence interval (CI) -0.23 to 0.81; 3 studies; n = 131; low-quality evidence).When short-term montelukast (10 mg) treatment was compared with conventional treatment in one study, the mean improvement in severity of moderate-to-severe eczema was greater in the intervention group (measured using SCORAD (SCORing of Atopic Dermatitis) severity index) (mean difference 10.57, 95% CI 4.58 to 16.56; n = 31); however, another study of 32 participants found no significant difference between groups using the same measure (mean improvement was 25.2 points with montelukast versus 23.9 points with conventional treatment; no further numerical data provided). We judged the quality of the evidence as very low for this outcome, meaning the results are uncertain.All studies reported their adverse event rate during treatment. Four studies (136 participants) reported no adverse events. In one study of 58 participants with moderate eczema who received montelukast 10 mg (compared with placebo), there was one case of septicaemia and one case of dizziness reported in the intervention group, both resulting in study withdrawal, although whether these effects were related to the medication is unclear. Mild side effects (e.g. headache and mild gastrointestinal disturbances) were also noted, but these were fairly evenly distributed between the montelukast and placebo groups. The quality of evidence for this outcome was low.No studies specifically evaluated emollient requirement or quality of life. One study that administered treatment for eight weeks specifically evaluated pruritus improvement at the end treatment and topical corticosteroid use during treatment. We found no evidence of a difference between montelukast (10 mg) and placebo for both outcomes (low-quality evidence, n = 58). No other study assessed these outcomes.
AUTHORS' CONCLUSIONS
The findings of this review are limited to montelukast. There was a lack of evidence addressing the review question, and the quality of the available evidence for most of the measured outcomes was low. Some primary and secondary outcomes were not addressed at all, including long-term control.We found no evidence of a difference between montelukast (10 mg) and placebo on disease severity, pruritus improvement, and topical corticosteroid use. Very low-quality evidence means we are uncertain of the effect of montelukast (10 mg) compared with conventional treatment on disease severity. Participants in only one study reported adverse events, which were mainly mild (low-quality evidence).There is no evidence that LTRA is an effective treatment for eczema. Serious limitations were that all studies focused on montelukast and only included people with moderate-to-severe eczema, who were mainly adults; and that each outcome was evaluated with a small sample size, if at all.Further large randomised controlled trials, with a longer treatment duration, of adults and children who have eczema of all severities may help to evaluate the effect of all types of LTRA, especially on eczema maintenance.
Topics: Acetates; Administration, Oral; Cyclopropanes; Eczema; Humans; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides
PubMed: 30343498
DOI: 10.1002/14651858.CD011224.pub2 -
The Cochrane Database of Systematic... Mar 2018Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere.
OBJECTIVES
To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period.
SEARCH METHODS
We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers' trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication.
SELECTION CRITERIA
We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period.
MAIN RESULTS
Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment.A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December.Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses.
AUTHORS' CONCLUSIONS
Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender.
Topics: Acetates; Adrenal Cortex Hormones; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Behavior Therapy; Child; Chromones; Cyclopropanes; Disease Progression; Humans; Leukotriene Antagonists; Omalizumab; Quinolines; Randomized Controlled Trials as Topic; Seasons; Sulfides
PubMed: 29518252
DOI: 10.1002/14651858.CD012393.pub2 -
Herbal Medicine for Adult Patients with Cough Variant Asthma: A Systematic Review and Meta-Analysis.Evidence-based Complementary and... 2021Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the... (Review)
Review
INTRODUCTION
Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the first time, we performed a meta-analysis to integrate the current evidence of randomized controlled trials (RCTs) on this topic and assess the efficacy of herbal medicine in adults with CVA.
METHODS
A comprehensive search was conducted in electronic databases to identify RCTs of herbal medicine for adult CVA. Cochrane systematic review methods were followed, and the Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence.
RESULTS
Twenty-eight RCTs were included. Compared with placebo, moderate-quality evidence from two studies showed that herbal medicine was associated with reduced cough symptom score (CSS) (MD -1.15 points; 95% CI, -1.67 to -0.63) and visual analogue scale (VAS) (MD -1.76 points; 95% CI, -2.66 to -0.86). Compared with montelukast, low- to moderate-quality evidence from 11 studies indicated that herbal medicine was associated with improved Leicester Cough Questionnaire (LCQ) (MD 2.38 points; 95% CI, 1.32 to 3.44), reduced CSS (SMD -0.81 points; 95% CI, -1.09 to -0.53), and VAS (MD -1.34 points; 95% CI, -1.82 to -0.86). There were no significant differences between herbal medicine and ICS plus bronchodilator.
CONCLUSIONS
In adults with CVA, herbal medicine may result in improved quality of life and reduced cough frequency and severity scores compared with placebo or montelukast. Herbal medicine was not better than ICS plus a bronchodilator but the evidence is very uncertain.
PubMed: 33747103
DOI: 10.1155/2021/5853137 -
Frontiers in Pediatrics 2022The global prevalence of allergic diseases has led to a negative and extensive impact on the health and lives of a large population of children. This study investigates...
OBJECTIVE
The global prevalence of allergic diseases has led to a negative and extensive impact on the health and lives of a large population of children. This study investigates the efficacy, acceptability, and safety of cetirizine (CTZ) for treating allergic diseases in children and provides evidence-based assertions for decision-making.
METHODS
PubMed, Embase, the Cochrane Library, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and the European Union Clinical Trials Register were systematically searched from inception to April 21, 2022. Randomized controlled trials (RCTs) or quasi-RCTs of children with allergic diseases receiving CTZ compared with those receiving placebo or other drugs were included without language limitations. Two investigators independently identified articles, extracted data, conducted meta-analyses, assessed the Cochrane risk of bias of individual studies, and evaluated the evidence certainty using the Grading of Recommendations Assessment, Development, and Evaluation approach; any discrepancies were resolved by consulting with a third investigator. Primary outcomes included scales that evaluated the recovery of allergic conditions in AR, such as the total symptom score (TSS). Secondary outcomes included laboratory test changes, safety (adverse events, AEs), and quality of life (QOL). Data were pooled using the Cochrane Review Manager 5.4, and a fixed-effects model was used if heterogeneity was evaluated as low ( < 50%); otherwise, a random-effects model was adopted.
RESULTS
A total of 22 studies (5,867 patients) were ultimately included [eight with perennial AR, six with seasonal AR, four with atopic dermatitis (AD), and four with other allergic diseases], most of which had a low or unclear risk of bias. Moderate certainty evidence showed that CTZ was found to benefit allergic symptom control [mean difference (MD) of TSS at 1 week: MD, -0.32 (-0.52, -0.12); at 2 weeks: MD, -0.25 (-0.35, -0.14); at 4 weeks: MD, -4.07 (-4.71, -3.43); at 8 weeks: MD, -4.22 (-4.73, -3.72); at 12 weeks: MD, -5.63 (-6.14, -5.13); all -values were less than 0.05] and QOL [at 12 weeks: MD, -23.16 (-26.92, -19.39); < 0.00001] in children with AR. It had similar efficacy compared with other antihistamines (AHs) or montelukast, without showing better control of AD severity in children. Moderate-to-low certainty evidence demonstrated that CTZ was well tolerated and did not increase the risk of severe and overall AEs, cardiotoxicity, damage to the central nervous and digestive systems, or other systems in children, except for the risk of somnolence [risk ratio, 1.62 (1.02, 2.57); = 0.04, compared with placebo].
CONCLUSION
Moderate-to-low certainty evidence revealed that CTZ could improve clinical improvement and QOL in children with AR and have comparable efficacy with other AHs. CTZ is well tolerated in the pediatric population, except for an increased risk of somnolence.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021262767].
PubMed: 36090559
DOI: 10.3389/fped.2022.940213 -
Respiratory Research Jul 2021Very preterm infants are at high risk of developing chronic lung disease, which requires respiratory support and might have long-term sequelae. As lung inflammation...
BACKGROUND
Very preterm infants are at high risk of developing chronic lung disease, which requires respiratory support and might have long-term sequelae. As lung inflammation plays an important role in pathogenesis, antileukotrienes have been explored in both clinical and animal studies. We aimed to assess the benefits and harms of antileukotrienes for the prevention and treatment of respiratory morbidity and mortality in very preterm newborns.
METHODS
In this systematic review, we included randomized trials and non-randomized studies in humans and animals reporting the effects of antileukotrienes in very preterm infants or other mammals within 10 days of birth. Our pre-specified primary outcomes were all-cause mortality and any harm, and, for the clinical studies, incidence of chronic lung disease. Included studies underwent risk of bias-assessment and data extraction performed by two authors independently. There were no language restrictions.
RESULTS
Fifteen studies totally met our inclusion criteria: one randomized trial and four non-randomized studies in humans and 10 animal studies (five in rodents, two in lambs and one in either guinea pigs, rabbits or caprinae). All five clinical studies used montelukast and had a small sample size, ranging from 4 to 77 infants. The randomized trial (n = 60) found no difference in the incidence of chronic lung disease between the groups. Only one clinical study, which enrolled four very preterm infants and had a critical overall risk of bias, reported long-term outcomes. All other studies had unclear or greater overall risk of bias and meta-analyses were therefore deemed unfeasible. Eight of ten animal studies used leukotriene receptor antagonists as antileukotriene (montelukast in three of ten studies) and seven had an experimental study design (i.e. some animals were not exposed to antileukotrienes but no randomization). Three of the ten animal studies assessed different doses. Animal studies found no effect on the outcomes mortality, growth, or lung function related surrogate outcomes.
CONCLUSIONS
Use of antileukotrienes in very preterm infants to prevent or treat chronic lung disease is not supported by the available evidence. Large randomized trials focusing on outcomes relevant to patients, including long-term outcomes, are needed. Studies should also minimize risk of bias.
Topics: Animals; Animals, Newborn; Chronic Disease; Disease Models, Animal; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Leukotriene Antagonists; Lung Diseases; Randomized Controlled Trials as Topic
PubMed: 34273977
DOI: 10.1186/s12931-021-01800-1 -
Gastroenterology May 2020Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert...
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.
Topics: Administration, Topical; Adult; Advisory Committees; Age Factors; Allergy and Immunology; Child; Dilatation; Eosinophilic Esophagitis; Eosinophils; Esophagoscopy; Evidence-Based Medicine; Food Hypersensitivity; Food, Formulated; Gastroenterology; Glucocorticoids; Humans; Proton Pump Inhibitors; Societies, Medical; Treatment Outcome; United States
PubMed: 32359563
DOI: 10.1053/j.gastro.2020.02.039 -
The Cochrane Database of Systematic... Jan 2020Obstructive sleep apnoea (OSA) is characterised by partial or complete upper airway obstruction during sleep. Approximately 1% to 4% of children are affected by OSA,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnoea (OSA) is characterised by partial or complete upper airway obstruction during sleep. Approximately 1% to 4% of children are affected by OSA, with adenotonsillar hypertrophy being the most common underlying risk factor. Surgical removal of enlarged adenoids or tonsils is the currently recommended first-line treatment for OSA due to adenotonsillar hypertrophy. Given the perioperative risk and an estimated recurrence rate of up to 20% following surgery, there has recently been an increased interest in less invasive alternatives to adenotonsillectomy. As the enlarged adenoids and tonsils consist of hypertrophied lymphoid tissue, anti-inflammatory drugs have been proposed as a potential non-surgical treatment option in children with OSA.
OBJECTIVES
To assess the efficacy and safety of anti-inflammatory drugs for the treatment of OSA in children.
SEARCH METHODS
We identified trials from searches of the Cochrane Airways Group Specialised Register, CENTRAL and MEDLINE (1950 to 2019). For identification of ongoing clinical trials, we searched ClinicalTrials.gov and the World Health Organization (WHO) trials portal.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing anti-inflammatory drugs against placebo in children between one and 16 years with objectively diagnosed OSA (apnoea/hypopnoea index (AHI) ≥ 1 per hour).
DATA COLLECTION AND ANALYSIS
Two authors independently performed screening, data extraction, and quality assessment. We separately pooled results for the comparisons 'intranasal steroids' and 'montelukast' against placebo using random-effects models. The primary outcomes for this review were AHI and serious adverse events. Secondary outcomes included the respiratory disturbance index, desaturation index, respiratory arousal index, nadir arterial oxygen saturation, mean arterial oxygen saturation, avoidance of surgical treatment for OSA, clinical symptom score, tonsillar size, and adverse events.
MAIN RESULTS
We included five trials with a total of 240 children aged one to 18 years with mild to moderate OSA (AHI 1 to 30 per hour). All trials were performed in specialised sleep medicine clinics at tertiary care centres. Follow-up time ranged from six weeks to four months. Three RCTs (n = 137) compared intranasal steroids against placebo; two RCTs compared oral montelukast against placebo (n = 103). We excluded one trial from the meta-analysis since the patients were not analysed as randomised. We also had concerns about selective reporting in another trial. We are uncertain about the difference in AHI (MD -3.18, 95% CI -8.70 to 2.35) between children receiving intranasal corticosteroids compared to placebo (2 studies, 75 participants; low-certainty evidence). In contrast, children receiving oral montelukast had a lower AHI (MD -3.41, 95% CI -5.36 to -1.45) compared to those in the placebo group (2 studies, 103 participants; moderate-certainty evidence). We are uncertain whether the secondary outcomes are different between children receiving intranasal corticosteroids compared to placebo: desaturation index (MD -2.12, 95% CI -4.27 to 0.04; 2 studies, 75 participants; moderate-certainty evidence), respiratory arousal index (MD -0.71, 95% CI -6.25 to 4.83; 2 studies, 75 participants; low-certainty evidence), and nadir oxygen saturation (MD 0.59%, 95% CI -1.09 to 2.27; 2 studies, 75 participants; moderate-certainty evidence). Children receiving oral montelukast had a lower respiratory arousal index (MD -2.89, 95% CI -4.68 to -1.10; 2 studies, 103 participants; moderate-certainty evidence) and nadir of oxygen saturation (MD 4.07, 95% CI 2.27 to 5.88; 2 studies, 103 participants; high-certainty evidence) compared to those in the placebo group. We are uncertain, however, about the difference in desaturation index (MD -2.50, 95% CI -5.53 to 0.54; 2 studies, 103 participants; low-certainty evidence) between the montelukast and placebo group. Adverse events were assessed and reported in all trials and were rare, of minor nature (e.g. nasal bleeding), and evenly distributed between study groups. No study examined the avoidance of surgical treatment for OSA as an outcome.
AUTHORS' CONCLUSIONS
There is insufficient evidence for the efficacy of intranasal corticosteroids for the treatment of OSA in children; they may have short-term beneficial effects on the desaturation index and oxygen saturation in children with mild to moderate OSA but the certainty of the benefit on the primary outcome AHI, as well as the respiratory arousal index, was low due to imprecision of the estimates and heterogeneity between studies. Montelukast has short-term beneficial treatment effects for OSA in otherwise healthy, non-obese, surgically untreated children (moderate certainty for primary outcome and moderate and high certainty, respectively, for two secondary outcomes) by significantly reducing the number of apnoeas, hypopnoeas, and respiratory arousals during sleep. In addition, montelukast was well tolerated in the children studied. The clinical relevance of the observed treatment effects remains unclear, however, because minimal clinically important differences are not yet established for polysomnography-based outcomes in children. Long-term efficacy and safety data on the use of anti-inflammatory medications for the treatment of OSA in childhood are still not available. In addition, patient-centred outcomes like concentration ability, vigilance, or school performance have not been investigated yet. There are currently no RCTs on the use of other kinds of anti-inflammatory medications for the treatment of OSA in children. Future RCTs should investigate sustainability of treatment effects, avoidance of surgical treatment for OSA, and long-term safety of anti-inflammatory medications for the treatment of OSA in children and include patient-centred outcomes.
Topics: Acetates; Adenoidectomy; Adolescent; Anti-Inflammatory Agents; Child; Child, Preschool; Cyclopropanes; Female; Humans; Infant; Male; Quinolines; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Sulfides; Tonsillectomy
PubMed: 31978261
DOI: 10.1002/14651858.CD007074.pub3 -
The Cochrane Database of Systematic... Oct 2015Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers to take time away from employment. About a third of children experience a wheezing episode before the age of five years. EVW therefore represents a significant public health problem. Many pre-school children only wheeze in association with viral infections and in such cases EVW appears to be a separate entity from atopic asthma. Some trials have explored the effectiveness of leukotriene receptor antagonists (LTRAs) as regular (maintenance) or episodic (intermittent) treatment in this context.
OBJECTIVES
To evaluate the evidence for the efficacy and safety of maintenance and intermittent LTRAs in the management of EVW in children aged one to six years.
SEARCH METHODS
We searched the Cochrane Airways Group register of trials with pre-specified terms. We performed additional searches by consulting the authors of identified trials, online trial registries of manufacturers' web sites, and reference lists of identified primary papers and reviews. Search results are current to June 2015.
SELECTION CRITERIA
We included randomised controlled trials with a parallel-group or cross-over (for intermittent LTRA only) design. Maintenance was considered as treatment for more than two months and intermittent as less than 14 days. EVW was defined as a history of at least one previous episode of wheezing in association with a viral respiratory tract infection in the absence of symptoms between episodes. As far as possible, relevant specific data were obtained from authors of studies that included children of a wider age group or phenotype.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion in the review and assessed risk of bias. The primary outcome was number of children with one or more viral-induced episodes requiring one or more treatments with rescue oral corticosteroids. We analysed combined continuous data outcomes with the mean difference and dichotomous data outcomes with an odds ratio (OR).
MAIN RESULTS
We identified five studies eligible for inclusion in the review (one investigated maintenance treatment, three intermittent therapy and one had both maintenance and intermittent treatment arms) these included 3741 participants. Each study involved oral montelukast and was of good methodological quality, but differed in choice of outcome measures thus limiting our ability to aggregate data across studies. Only primary outcome and adverse event data are reported in this abstract.For maintenance treatment, specific data obtained from a single study, pertaining to children with only an EVW phenotype, showed no statistically significant group reduction in the number of episodes requiring rescue oral corticosteroids associated with daily montelukast versus placebo (OR 1.20, 95% CI 0.70 to 2.06, moderate quality evidence).For intermittent LTRA, pooled data showed no statistically significant reduction in the number of episodes requiring rescue oral steroids in children treated with LTRA versus placebo (OR 0.77, 95% CI 0.48 to 1.25, moderate quality evidence). Specific data for children with an EVW phenotype obtained from a single study of intermittent montelukast treatment showed a small, but statistically significant reduction in unscheduled medical attendances due to wheeze (RR 0.83, 95% CI 0.71 to 0.98).For maintenance compared to intermittent LTRA treatment no data relating to the primary outcome of the review were identified.There were no other significant group differences identified in other secondary efficacy outcomes for maintenance or intermittent LTRA treatment versus placebo, or maintenance versus intermittent LTRA treatment. We collected descriptive data on adverse events as reported by four of the five included studies, and rates were similar between treatment and placebo groups.Potential heterogeneity in the phenotype of participants within and across trials is a limitation of the evidence.
AUTHORS' CONCLUSIONS
In pre-school children with EVW, there is no evidence of benefit associated with maintenance or intermittent LTRA treatment, compared to placebo, for reducing the number of children with one or more viral-induced episodes requiring rescue oral corticosteroids, and little evidence of significant clinical benefit for other secondary outcomes. Therefore until further data are available, LTRA should be used with caution in individual children. When used, we suggest a therapeutic trial is undertaken, during which efficacy should be carefully monitored. It is likely that children with an apparent EVW phenotype are not a homogeneous group and that subgroups may respond to LTRA treatment depending on the exact patho-physiological mechanisms involved.
Topics: Acetates; Child, Preschool; Common Cold; Cyclopropanes; Humans; Leukotriene Antagonists; Maintenance Chemotherapy; Quinolines; Randomized Controlled Trials as Topic; Respiratory Sounds; Respiratory Tract Infections; Sulfides; Time Factors; Virus Diseases
PubMed: 26482324
DOI: 10.1002/14651858.CD008202.pub2