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International Journal of Chronic... 2023Inhaled corticosteroids (ICSs) combined with bronchodilators have been identified to improve outcomes in COPD but also to be associated with certain adverse effects. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhaled corticosteroids (ICSs) combined with bronchodilators have been identified to improve outcomes in COPD but also to be associated with certain adverse effects.
OBJECTIVE
We performed a systematic review and meta-analysis to compile and summarize data on the efficacy and safety of dosing levels (high versus medium/low) of ICS alongside ancillary bronchodilators following PRISMA guidelines.
DATA SOURCES
Medline and Embase were systematically searched until December 2021. Randomized, clinical trials (RCTs) that met predefined inclusion criteria were included.
DATA EXTRACTION
Risk ratios (RRs) with 95% confidence intervals (CI) were extracted. Any acute exacerbation of COPD (AECOPD) risk was chosen as the primary efficacy outcome, mortality rate as the primary safety outcome, moderate/severe AECOPD risk as the secondary efficacy outcome and pneumonia risk as the secondary safety outcome. Subgroup analyses of individual ICS agents, of patients with baseline moderate/severe/very severe COPD and of patients with recent COPD exacerbation history were also performed. A random-effects model was used.
RESULTS
We included 13 RCTs in our study. No data on low doses were included in the analysis. High dose ICS was not associated with a statistically significant difference in any AECOPD risk (RR: 0.98, 95% CI: 0.91-1.05, I: 41.3%), mortality rate (RR: 0.99, 95% CI: 0.75-1.32, I: 0.0%), moderate/severe AECOPD risk (RR: 1.01, 95% CI: 0.96-1.06, I: 0.0%) or pneumonia risk (RR: 1.07, 95% CI: 0.86 -1.33, I: 9.3%) compared to medium dose ICS. The same trend was identified with the several subgroup analyses.
CONCLUSION
Our study collected RCTs investigating the optimal dosing level of ICS prescribed alongside ancillary bronchodilators to patients with COPD. We identified that the high ICS dose neither reduces AECOPD risk and mortality rates nor increases pneumonia risk relative to the medium dose.
Topics: Humans; Bronchodilator Agents; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Pneumonia; Administration, Inhalation
PubMed: 37056683
DOI: 10.2147/COPD.S401736 -
The Cochrane Database of Systematic... Apr 2023Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥... (Review)
Review
BACKGROUND
Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017.
OBJECTIVES
To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 13 January 2022. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 13 January 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department (ED) trials was rate of hospitalisation.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics.
MAIN RESULTS
We included six new trials (N = 1010) in this update, bringing the total number of included trials to 34, involving 5205 infants with acute bronchiolitis, of whom 2727 infants received hypertonic saline. Eleven trials await classification due to insufficient data for eligibility assessment. All included trials were randomised, parallel-group, controlled trials, of which 30 were double-blinded. Twelve trials were conducted in Asia, five in North America, one in South America, seven in Europe, and nine in Mediterranean and Middle East regions. The concentration of hypertonic saline was defined as 3% in all but six trials, in which 5% to 7% saline was used. Nine trials had no funding, and five trials were funded by sources from government or academic agencies. The remaining 20 trials did not provide funding sources. Hospitalised infants treated with nebulised hypertonic saline may have a shorter mean length of hospital stay compared to those treated with nebulised normal (0.9%) saline or standard care (mean difference (MD) -0.40 days, 95% confidence interval (CI) -0.69 to -0.11; 21 trials, 2479 infants; low-certainty evidence). Infants who received hypertonic saline may also have lower postinhalation clinical scores than infants who received normal saline in the first three days of treatment (day 1: MD -0.64, 95% CI -1.08 to -0.21; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 893 infants; day 2: MD -1.07, 95% CI -1.60 to -0.53; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 907 infants; day 3: MD -0.89, 95% CI -1.44 to -0.34; 10 trials (1 outpatient, 9 inpatient trials), 785 infants; low-certainty evidence). Nebulised hypertonic saline may reduce the risk of hospitalisation by 13% compared with nebulised normal saline amongst infants who were outpatients and those treated in the ED (risk ratio (RR) 0.87, 95% CI 0.78 to 0.97; 8 trials, 1760 infants; low-certainty evidence). However, hypertonic saline may not reduce the risk of readmission to hospital up to 28 days after discharge (RR 0.83, 95% CI 0.55 to 1.25; 6 trials, 1084 infants; low-certainty evidence). We are uncertain whether infants who received hypertonic saline have a lower number of days to resolution of wheezing compared to those who received normal saline (MD -1.16 days, 95% CI -1.43 to -0.89; 2 trials, 205 infants; very low-certainty evidence), cough (MD -0.87 days, 95% CI -1.31 to -0.44; 3 trials, 363 infants; very low-certainty evidence), and pulmonary moist crackles (MD -1.30 days, 95% CI -2.28 to -0.32; 2 trials, 205 infants; very low-certainty evidence). Twenty-seven trials presented safety data: 14 trials (1624 infants; 767 treated with hypertonic saline, of which 735 (96%) co-administered with bronchodilators) did not report any adverse events, and 13 trials (2792 infants; 1479 treated with hypertonic saline, of which 416 (28%) co-administered with bronchodilators and 1063 (72%) hypertonic saline alone) reported at least one adverse event such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea, most of which were mild and resolved spontaneously (low-certainty evidence).
AUTHORS' CONCLUSIONS
Nebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.
Topics: Child; Humans; Infant; Bronchiolitis; Bronchodilator Agents; Cough; Saline Solution; Saline Solution, Hypertonic
PubMed: 37014057
DOI: 10.1002/14651858.CD006458.pub5 -
The Cochrane Database of Systematic... Apr 2023Acute bronchiolitis is the leading cause of medical emergencies during winter months in infants younger than 24 months old. Chest physiotherapy is sometimes used to... (Review)
Review
BACKGROUND
Acute bronchiolitis is the leading cause of medical emergencies during winter months in infants younger than 24 months old. Chest physiotherapy is sometimes used to assist infants in the clearance of secretions in order to decrease ventilatory effort. This is an update of a Cochrane Review first published in 2005 and updated in 2006, 2012, and 2016.
OBJECTIVES
To determine the efficacy of chest physiotherapy in infants younger than 24 months old with acute bronchiolitis. A secondary objective was to determine the efficacy of different techniques of chest physiotherapy (vibration and percussion, passive exhalation, or instrumental).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, PEDro (October 2011 to 20 April 2022), and two trials registers (5 April 2022).
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which chest physiotherapy was compared to control (conventional medical care with no physiotherapy intervention) or other respiratory physiotherapy techniques in infants younger than 24 months old with bronchiolitis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Our update of the searches dated 20 April 2022 identified five new RCTs with 430 participants. We included a total of 17 RCTs (1679 participants) comparing chest physiotherapy with no intervention or comparing different types of physiotherapy. Five trials (246 participants) assessed percussion and vibration techniques plus postural drainage (conventional chest physiotherapy), and 12 trials (1433 participants) assessed different passive flow-oriented expiratory techniques, of which three trials (628 participants) assessed forced expiratory techniques, and nine trials (805 participants) assessed slow expiratory techniques. In the slow expiratory subgroup, two trials (78 participants) compared the technique with instrumental physiotherapy techniques, and two recent trials (116 participants) combined slow expiratory techniques with rhinopharyngeal retrograde technique (RRT). One trial used RRT alone as the main component of the physiotherapy intervention. Clinical severity was mild in one trial, severe in four trials, moderate in six trials, and mild to moderate in five trials. One study did not report clinical severity. Two trials were performed on non-hospitalised participants. Overall risk of bias was high in six trials, unclear in five, and low in six trials. The analyses showed no effects of conventional techniques on change in bronchiolitis severity status, respiratory parameters, hours with oxygen supplementation, or length of hospital stay (5 trials, 246 participants). Regarding instrumental techniques (2 trials, 80 participants), one trial observed similar results in bronchiolitis severity status when comparing slow expiration to instrumental techniques (mean difference 0.10, 95% confidence interval (C) -0.17 to 0.37). Forced passive expiratory techniques failed to show an effect on bronchiolitis severity in time to recovery (2 trials, 509 participants; high-certainty evidence) and time to clinical stability (1 trial, 99 participants; high-certainty evidence) in infants with severe bronchiolitis. Important adverse effects were reported with the use of forced expiratory techniques. Regarding slow expiratory techniques, a mild to moderate improvement was observed in bronchiolitis severity score (standardised mean difference -0.43, 95% CI -0.73 to -0.13; I = 55%; 7 trials, 434 participants; low-certainty evidence). Also, in one trial an improvement in time to recovery was observed with the use of slow expiratory techniques. No benefit was observed in length of hospital stay, except for one trial which showed a one-day reduction. No effects were shown or reported for other clinical outcomes such as duration on oxygen supplementation, use of bronchodilators, or parents' impression of physiotherapy benefit.
AUTHORS' CONCLUSIONS
We found low-certainty evidence that passive slow expiratory technique may result in a mild to moderate improvement in bronchiolitis severity when compared to control. This evidence comes mostly from infants with moderately acute bronchiolitis treated in hospital. The evidence was limited with regard to infants with severe bronchiolitis and those with moderately severe bronchiolitis treated in ambulatory settings. We found high-certainty evidence that conventional techniques and forced expiratory techniques result in no difference in bronchiolitis severity or any other outcome. We found high-certainty evidence that forced expiratory techniques in infants with severe bronchiolitis do not improve their health status and can lead to severe adverse effects. Currently, the evidence regarding new physiotherapy techniques such as RRT or instrumental physiotherapy is scarce, and further trials are needed to determine their effects and potential for use in infants with moderate bronchiolitis, as well as the potential additional effect of RRT when combined with slow passive expiratory techniques. Finally, the effectiveness of combining chest physiotherapy with hypertonic saline should also be investigated.
Topics: Child; Child, Preschool; Humans; Infant; Infant, Newborn; Bronchiolitis; Bronchodilator Agents; Drainage, Postural; Oxygen; Physical Therapy Modalities; Respiratory Therapy
PubMed: 37010196
DOI: 10.1002/14651858.CD004873.pub6 -
Journal of Infection and Public Health May 2023The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear.
METHODS
We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3.
RESULTS
Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664-1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693-2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533-2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415-1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970-1.206; p = 0.160).
CONCLUSIONS
The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection.
Topics: Humans; Bronchodilator Agents; Cross-Sectional Studies; COVID-19; SARS-CoV-2; Adrenal Cortex Hormones; Observational Studies as Topic
PubMed: 37003028
DOI: 10.1016/j.jiph.2023.03.019 -
The Cochrane Database of Systematic... Mar 2023The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much uncertainty. COPD clinical guidelines currently... (Review)
Review
BACKGROUND
The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much uncertainty. COPD clinical guidelines currently recommend selective use of ICS. ICS are not recommended as monotherapy for people with COPD, and are only given in combination with long-acting bronchodilators due to greater efficacy of combination therapy. Incorporating and critiquing newly published placebo-controlled trials into the monotherapy evidence base may help to resolve ongoing uncertainties and conflicting findings about their role in this population.
OBJECTIVES
To evaluate the benefits and harms of inhaled corticosteroids, used as monotherapy versus placebo, in people with stable COPD, in terms of objective and subjective outcomes.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was October 2022.
SELECTION CRITERIA
We included randomised trials comparing any dose of any type of ICS, given as monotherapy, with a placebo control in people with stable COPD. We excluded studies of less than 12 weeks' duration and studies of populations with known bronchial hyper-responsiveness (BHR) or bronchodilator reversibility.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our a priori primary outcomes were 1. exacerbations of COPD and 2. quality of life. Our secondary outcomes were 3. all-cause mortality, 4. lung function (rate of decline of forced expiratory volume in one second (FEV)), 5. rescue bronchodilator use, 6. exercise capacity, 7. pneumonia and 8. adverse events including pneumonia. ]. We used GRADE to assess certainty of evidence.
MAIN RESULTS
Thirty-six primary studies with 23,139 participants met the inclusion criteria. Mean age ranged from 52 to 67 years, and females were 0% to 46% of participants. Studies recruited across the severities of COPD. Seventeen studies were of duration longer than three months and up to six months and 19 studies were of duration longer than six months. We judged the overall risk of bias as low. Long-term (more than six months) use of ICS as monotherapy reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: rate ratio 0.88 exacerbations per participant per year, 95% confidence interval (CI) 0.82 to 0.94; I = 48%, 5 studies, 10,097 participants; moderate-certainty evidence; pooled means analysis: mean difference (MD) -0.05 exacerbations per participant per year, 95% CI -0.07 to -0.02; I = 78%, 5 studies, 10,316 participants; moderate-certainty evidence). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60; I = 0%; 5 studies, 2507 participants; moderate-certainty evidence; minimal clinically importance difference 4 points). There was no evidence of a difference in all-cause mortality in people with COPD (odds ratio (OR) 0.94, 95% CI 0.84 to 1.07; I = 0%; 10 studies, 16,636 participants; moderate-certainty evidence). Long-term use of ICS reduced the rate of decline in FEV in people with COPD (generic inverse variance analysis: MD 6.31 mL/year benefit, 95% CI 1.76 to 10.85; I = 0%; 6 studies, 9829 participants; moderate-certainty evidence; pooled means analysis: 7.28 mL/year, 95% CI 3.21 to 11.35; I = 0%; 6 studies, 12,502 participants; moderate-certainty evidence).
ADVERSE EVENTS
in the long-term studies, the rate of pneumonia was increased in the ICS group, compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.38, 95% CI 1.02 to 1.88; I = 55%; 9 studies, 14,831 participants; low-certainty evidence). There was an increased risk of oropharyngeal candidiasis (OR 2.66, 95% CI 1.91 to 3.68; 5547 participants) and hoarseness (OR 1.98, 95% CI 1.44 to 2.74; 3523 participants). The long-term studies that measured bone effects generally showed no major effect on fractures or bone mineral density over three years. We downgraded the certainty of evidence to moderate for imprecision and low for imprecision and inconsistency.
AUTHORS' CONCLUSIONS
This systematic review updates the evidence base for ICS monotherapy with newly published trials to aid the ongoing assessment of their role for people with COPD. Use of ICS alone for COPD likely results in a reduction of exacerbation rates of clinical relevance, probably results in a reduction in the rate of decline of FEV of uncertain clinical relevance and likely results in a small improvement in health-related quality of life not meeting the threshold for a minimally clinically important difference. These potential benefits should be weighed up against adverse events (likely to increase local oropharyngeal adverse effects and may increase the risk of pneumonia) and probably no reduction in mortality. Though not recommended as monotherapy, the probable benefits of ICS highlighted in this review support their continued consideration in combination with long-acting bronchodilators. Future research and evidence syntheses should be focused in that area.
Topics: Female; Humans; Middle Aged; Aged; Bronchodilator Agents; Quality of Life; Adrenal Cortex Hormones; Pulmonary Disease, Chronic Obstructive; Pneumonia; Disease Progression
PubMed: 36971693
DOI: 10.1002/14651858.CD002991.pub4 -
Frontiers in Public Health 2023Complementary and alternative medicine (CAM) therapies are widely used for nausea and vomiting during pregnancy (NVP) due to the limitations of conventional medicine.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Complementary and alternative medicine (CAM) therapies are widely used for nausea and vomiting during pregnancy (NVP) due to the limitations of conventional medicine. However, their efficacy and safety remain controversial. Therefore, this meta-analysis was performed to assess the improvement of CAM therapy on NVP.
METHODS
Randomized controlled trials (RCTs) were searched for where the trial group was CAM and the control group was a conventional medicine or a placebo for NVP. This was done 8 databases, including PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP, from inception to October 25, 2022. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) was used to assess the quality of evidence. The Stata 15.0 software was used to perform the meta-analysis.
RESULTS
Thirty-three RCTs were included in this study. The acupuncture treatment was superior to conventional medicine at the effective rate [RR = 1.71, 95% CI (1.02, 2.86), = 0.042; Low-quality evidence]. Ginger had more significant effects than conventional medicine at the Rhodes index [WMD = -0.52, 95% CI (-0.79, -0.24), ≤ 0.001; Moderate-quality evidence] and it had the same effect as drugs to relieve vomiting [SMD = 0.30, 95% CI (-0.12, 0.73), = 0.160; Low-quality evidence]. Compared with placebo, ginger had a higher effective rate [RR = 1.68, 95% CI (1.09, 2.57), = 0.018; Low-quality evidence], and lower Visual analog scale (VAS) of Nausea [WMD = -1.21, 95% CI (-2.34, -0.08), = 0.036; Low-quality evidence]. Ginger had the same antiemetic effect as placebo [WMD = 0.05, 95% CI (-0.23, 0.32), = 0.743; Low-quality evidence]. Acupressure was superior to conventional medicine at the reduction of antiemetic drugs [SMD = -0.44, 95% CI (-0.77, -0.11), = 0.008; Low-quality evidence], and at the effective rate [RR = 1.55, 95% CI (1.30, 1.86), ≤ 0.001; Low-quality evidence]. Acupressure had the same effect as placebo at the effective rate [RR = 1.25, 95% CI (0.94, 1.65), = 0.124; Low-quality evidence]. Overall, CAM therapy was safer than conventional medicine or a placebo.
CONCLUSION
The results showed that CAM therapies were able to alleviate NVP. However, due to the low quality of existing RCTs, more RCTs with large sample sizes are needed to validate this conclusion in the future.
Topics: Female; Pregnancy; Humans; Vomiting; Complementary Therapies; Antiemetics; Nausea; Acupuncture Therapy; Randomized Controlled Trials as Topic
PubMed: 36969661
DOI: 10.3389/fpubh.2023.1108756 -
Chronic Respiratory Disease 2023The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of additional treatment with short-acting muscarinic antagonist combined with long-acting beta-2 agonist in stable patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.
BACKGROUND
The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied.
METHODS
We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest.
RESULTS
We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV (mean difference (MD) 98.70 mL, < .00001), transitional dyspnea index score (MD .85, = .02), and St George's Respiratory Questionnaire score (MD -2.00, = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD ( = .20) and only a slight trend of increased severe adverse events (OR: 2.16, = .08) and cardiovascular events (OR: 2.38, = .06).
CONCLUSION
Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.
Topics: Humans; Muscarinic Antagonists; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Administration, Inhalation; Dyspnea
PubMed: 36967224
DOI: 10.1177/14799731231166008 -
The Cochrane Database of Systematic... Mar 2023Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications.
OBJECTIVES
To assess the effectiveness of various medical interventions in the management of traumatic hyphema.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022.
SELECTION CRITERIA
Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest.
AUTHORS' CONCLUSIONS
We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
Topics: Humans; Adrenal Cortex Hormones; Aminocaproic Acid; Antifibrinolytic Agents; Aspirin; Glaucoma; Hyphema; Mydriatics; Tranexamic Acid
PubMed: 36912744
DOI: 10.1002/14651858.CD005431.pub5 -
Cancer Treatment Reviews Apr 2023Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative data remain insufficient, as many new regimes lack head-to-head comparisons. In this study, through an indirect comparison, we overcome this limit by providing the most up-to-date estimate of the efficacy and safety of all combinations used for HEC-induced nausea and vomiting.
PATIENTS AND METHODS
We retrieved randomized controlled trials (RCTs) published in Pubmed, Embase, and Cochrane Library until June, 30th 2022. We included phase II-III RCTs, including adults with any cancer receiving HEC, and compared different antiemetic regimes to prevent CINV. The primary outcome was the overall complete response (defined as the absence of vomiting and of the use of rescue drugs from 0 to 120 hrs since chemotherapy); secondary outcomes were acute (absence of vomiting and use of rescue medicine 0-24 hrs after chemotherapy) and delayed (24-120 hrs) response and adverse events.
RESULTS
A total of 53 RCTs enrolling 22 228 patients were included. We classified the different antiemetic regimes into 21 different groups. Overall, 3- or 4-drug regimens containing a combination of dexamethasone, 5HT3 antagonists, mirtazapine or olanzapine with or without NK antagonists, yielded the highest probability to be the most effective regimen in terms of complete response. Regimens containing a combination of dexamethasone and 5-HT3 antagonist have the lowest probability of being the most effective regimen in terms of complete, acute, and delayed response.
CONCLUSION
In our network meta-analysis, 4-drug regimens with olanzapine displayed the highest probability of efficacy in terms of complete response. A 3-drug regimen with olanzapine represents a valid option in a limited resource context.
Topics: Adult; Humans; Antiemetics; Antineoplastic Agents; Dexamethasone; Nausea; Network Meta-Analysis; Olanzapine; Vomiting
PubMed: 36774658
DOI: 10.1016/j.ctrv.2023.102512 -
Respiratory Research Dec 2022Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes.
METHODS
A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted.
RESULTS
Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0-1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities.
CONCLUSIONS
LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.
Topics: Humans; Adrenergic beta-2 Receptor Agonists; Exercise Tolerance; Quality of Life; Administration, Inhalation; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Exercise; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36522735
DOI: 10.1186/s12931-022-02268-3