-
Journal of the Neurological Sciences Nov 2021Parkinson's disease (PD) ranks the second most common neurodegenerative disease. Aside from genetic predisposition, many external factors such as traumatic brain injury... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Parkinson's disease (PD) ranks the second most common neurodegenerative disease. Aside from genetic predisposition, many external factors such as traumatic brain injury and exposure of substances including pesticides also contribute to PD's pathogenesis. Many previous studies observed the association between the use of β-adrenoceptor acting agents and risk of PD.
OBJECTIVE
To conduct systematic review and meta-analysis to summarize whether the use of β-agonist and β-antagonist agents were associated with risk of PD.
METHOD
We independently searched for published studies from EMBASE and MEDLINE databases from inception to February 2021. This meta-analysis includes 9 case-control studies and 1 cohort study meeting the eligibility criteria, with a total of 380,105 participants.
RESULTS
Overall β-antagonists use appeared to associate with increase PD risk with an odd ratio (OR) of 1.2 (95% CI 1.07-1.34). Propranolol and metoprolol had a statistically significant association with higher risk of PD: pooled OR was 1.67 (95% CI 1.22-2.29) and 1.07 (95% CI 1.03-1.1), respectively. On the other hand, β-agonists significantly inverse association with PD risk with OR of 0.88 (95% CI 0.85-0.92). Salbutamol unexpectedly showed no statistical significance in reduced risk of PD with a pooled risk ratio of 1.0 (95% CI 0.87-1.16).
CONCLUSION
Overall β-antagonists, including propranolol and metoprolol, were associated with an increased risk of PD, in contrast to β-agonists, which were associated with decreased the risk.
Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Cohort Studies; Humans; Neurodegenerative Diseases; Parkinson Disease; Propranolol; Receptors, Adrenergic
PubMed: 34598055
DOI: 10.1016/j.jns.2021.120009 -
Minerva Pediatrics Oct 2021A systematic review and meta-analysis was performed to investigate the effect of fluticasone + salmeterol and fluticasone alone in the treatment of pediatric asthma. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic review and meta-analysis was performed to investigate the effect of fluticasone + salmeterol and fluticasone alone in the treatment of pediatric asthma.
EVIDENCE ACQUISITION
Studies meeting specific selection criteria were selected from online databases, including Pubmed, Embase, and the Cochrane Library. The quality of randomized controlled trials was assessed using the Cochrane Library. Weighted mean difference (WMD) and 95% CI were used to evaluate the effect size of continuous variables, while rate ratio (RR) and 95% CI were used for dichotomous variables.
EVIDENCE SYNTHESIS
A total of 11 studies, including 8272 pediatric asthma patients, were included in this meta-analysis. Among these, 4133 patients were in the salmeterol + fluticasone group. The changes in forced expiratory volume in 1 second in children with asthma in the salmeterol + fluticasone and fluticasone alone groups were significantly different (fixed effects model, WMD=3.26, 95% CI: 1.52-5.00, P=0.0002). Asthma exacerbation between two groups were significantly different (fixed effects model, RR=0.85, 95% CI: 0.73-0.98, Z=2.18, P=0.03). There was no difference in the incidence of adverse events between salmeterol + fluticasone and fluticasone alone in the treatment of pediatric asthma (P>0.05). When the control group was treated with double dose fluticasone, the difference of changes in FEV1 and asthma exacerbation in children with asthma between the two groups was not significant.
CONCLUSIONS
The efficacy of salmeterol + fluticasone is better than fluticasone alone, and the efficacy of salmeterol + fluticasone is equal to doubling the dose of fluticasone in the treatment of pediatric asthma.
Topics: Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Salmeterol Xinafoate
PubMed: 33988019
DOI: 10.23736/S2724-5276.21.05939-5 -
Pediatrics May 2021Uncertainty exists as to which treatments are most effective for bronchiolitis, with considerable practice variation within and across health care sites. (Comparative Study)
Comparative Study Meta-Analysis
CONTEXT
Uncertainty exists as to which treatments are most effective for bronchiolitis, with considerable practice variation within and across health care sites.
OBJECTIVE
A network meta-analysis to compare the effectiveness of common treatments for bronchiolitis in children aged ≤2 years.
DATA SOURCES
Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to September 1, 2019.
STUDY SELECTION
A total 150 randomized controlled trials comparing a placebo or active comparator with any bronchodilator, glucocorticoid steroid, hypertonic saline solution, antibiotic, helium-oxygen therapy, or high-flow oxygen therapy were included.
DATA EXTRACTION
Data were extracted by 1 reviewer and independently verified. Primary outcomes were admission rate on day 1 and by day 7 and hospital length of stay. Strength of evidence was assessed by using Confidence in Network Meta-Analysis .
RESULTS
Nebulized epinephrine (odds ratio: 0.64, 95% confidence interval [CI]: 0.44 to 0.93, low confidence) and nebulized hypertonic saline plus salbutamol (odds ratio: 0.44, 95% CI: 0.23 to 0.84, low confidence) reduced the admission rate on day 1. No treatment significantly reduced the admission rate on day 7. Nebulized hypertonic saline (mean difference: -0.64 days, 95% CI: -1.01 to -0.26, low confidence) and nebulized hypertonic saline plus epinephrine (mean difference: -0.91 days, 95% CI: -1.14 to -0.40, low confidence) reduced hospital length of stay.
LIMITATIONS
Because we did not report adverse events in this analysis, we cannot make inferences about the safety of these treatments.
CONCLUSIONS
Although hypertonic saline alone, or combined with epinephrine, may reduce an infant's stay in the hospital, poor strength of evidence necessitates additional rigorous trials.
Topics: Bronchiolitis; Child, Preschool; Critical Care; Humans; Infant; Network Meta-Analysis; Treatment Outcome
PubMed: 33893229
DOI: 10.1542/peds.2020-040816 -
The Cochrane Database of Systematic... Apr 2021Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and... (Meta-Analysis)
Meta-Analysis
Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.
BACKGROUND
Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.
OBJECTIVES
To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.
SEARCH METHODS
We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was 24 February 2021.
SELECTION CRITERIA
We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.
MAIN RESULTS
Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.
Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate
PubMed: 33852162
DOI: 10.1002/14651858.CD007694.pub3 -
The Journal of Asthma : Official... Jun 2022An inhaled corticosteroid (ICS)-long-acting beta-2 agonist (LABA) combination has become the standard of care in asthma. Various ICS-LABAs are commercially available...
OBJECTIVES
An inhaled corticosteroid (ICS)-long-acting beta-2 agonist (LABA) combination has become the standard of care in asthma. Various ICS-LABAs are commercially available providing the clinician with many choices. A thorough understanding of the clinical efficacy and safety of various formulations will immensely benefit the prescribing doctor to decide the choice of agent. The present systematic review was undertaken to compare the clinical efficacy and safety of formoterol fluticasone (FF) to other ICS/LABA combinations in asthmatics.
METHODS
The review adhered to the general principles mentioned in the CRD guidance and the PRISMA statement. We searched Medline, Embase, and Cochrane Controlled Trials Register databases on the efficacy of FF in treating asthma compared with other ICS-LABAs. A total of 138 trials identified initially. Only trials comparing the efficacy and safety of FF in comparision with Salmeterol/fluticasone (SF) or Budesonide/Formoterol (BF) were selected. The outcomes compared were onset of bronchodilator action, improvement in lung function, asthma control, asthma-related quality of life and risk of pneumonia.
RESULTS
Sixteen studies were included in the final analysis. FF therapy provided faster onset of bronchodilatation than SF. A better improvement in lung function was seen with FF inhaler use as compared with comparators in two studies. Patients using the FF inhaler had a non-inferior asthma control and asthma-related quality of life. Pneumonia risk was least with FF usage.
CONCLUSION
FF provides faster onset of action, numerically superior improvement in lung function and comparable asthma control than other ICS-LABA formulations. FF has better safety evidenced by lower occurrence of pneumonia.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Androstadienes; Asthma; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Pneumonia; Quality of Life
PubMed: 33685323
DOI: 10.1080/02770903.2021.1900864 -
The Cochrane Database of Systematic... Feb 2021Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Although transient tachypnea of the newborn is usually a self-limited condition, it is associated with wheezing syndromes in late childhood. The rationale for the use of salbutamol (albuterol) for transient tachypnea of the newborn is based on studies showing that β-agonists can accelerate the rate of alveolar fluid clearance. This review was originally published in 2016 and updated in 2020.
OBJECTIVES
To assess whether salbutamol compared to placebo, no treatment or any other drugs administered to treat transient tachypnea of the newborn, is effective and safe for infants born at 34 weeks' gestational age with this diagnosis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2020, Issue 4) in the Cochrane Library; PubMed (1996 to April 2020), Embase (1980 to April 2020); and CINAHL (1982 to April 2020). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia New Zealand and Pediatric Academic Societies) from 2000 to 2020 and clinical trial registries.
SELECTION CRITERIA
Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing salbutamol versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology for data collection and analysis. The primary outcomes considered in this review were duration of oxygen therapy, need for continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Seven trials, which included 498 infants, met the inclusion criteria. All trials compared a nebulized dose of salbutamol with normal saline. Four studies used one single dose of salbutamol; in two studies, three to four doses were provided; in one study, additional doses were administered if needed. The certainty of the evidence was low for duration of hospital stay and very low for the other outcomes. Among the primary outcomes of this review, four trials (338 infants) reported the duration of oxygen therapy, (mean difference (MD) -19.24 hours, 95% confidence interval (CI) -23.76 to -14.72); one trial (46 infants) reported the need for continuous positive airway pressure (risk ratio (RR) 0.73, 95% CI 0.38 to 1.39; risk difference (RD) -0.15, 95% CI -0.45 to 0.16), and three trials (254 infants) reported the need for mechanical ventilation (RR 0.60, 95% CI 0.13 to 2.86; RD -0.01, 95% CI -0.05 to 0.03). Both duration of hospital stay (4 trials; 338 infants) and duration of respiratory support (2 trials, 228 infants) were shorter in the salbutamol group (MD -1.48, 95% CI -1.8 to -1.16; MD -9.24, 95% CI -14.24 to -4.23, respectively). One trial (80 infants) reported duration of mechanical ventilation and pneumothorax but data could not be extracted due to the reporting of these outcomes (type of units of effect measure and unclear number of events, respectively). Five trials are ongoing.
AUTHORS' CONCLUSIONS
There was limited evidence to establish the benefits and harms of salbutamol in the management of transient tachypnea of the newborn. We are uncertain whether salbutamol administration reduces the duration of oxygen therapy, duration of tachypnea, need for continuous positive airway pressure and for mechanical ventilation. Salbutamol may slightly reduce hospital stay. Five trials are ongoing. Given the limited and low certainty of the evidence available, we could not determine whether salbutamol was safe or effective for the treatment of transient tachypnea of the newborn.
Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Continuous Positive Airway Pressure; Humans; Infant, Newborn; Intermittent Positive-Pressure Ventilation; Length of Stay; Nebulizers and Vaporizers; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Time Factors; Transient Tachypnea of the Newborn
PubMed: 33543473
DOI: 10.1002/14651858.CD011878.pub3 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Nov 2020To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary... (Meta-Analysis)
Meta-Analysis
To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.
Topics: Administration, Inhalation; Bronchodilator Agents; Drug Combinations; Drugs, Chinese Herbal; Humans; Medicine; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate
PubMed: 33350192
DOI: 10.19540/j.cnki.cjcmm.20200720.501 -
The Cochrane Database of Systematic... Dec 2020Acute bronchiolitis is a significant burden on children, their families and healthcare facilities. It mostly affects children younger than two years of age. Treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute bronchiolitis is a significant burden on children, their families and healthcare facilities. It mostly affects children younger than two years of age. Treatment involves adequate hydration, humidified oxygen supplementation, and nebulisation of medications, such as salbutamol, epinephrine, and hypertonic saline. The effectiveness of magnesium sulphate for acute bronchiolitis is unclear.
OBJECTIVES
To assess the effects of magnesium sulphate in acute bronchiolitis in children up to two years of age.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, and two trials registries to 30 April 2020. We contacted trial authors to identify additional studies. We searched conference proceedings and reference lists of retrieved articles. Unpublished and published studies were eligible for inclusion.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs, comparing magnesium sulphate, alone or with another treatment, with placebo or another treatment, in children up to two years old with acute bronchiolitis. Primary outcomes were time to recovery, mortality, and adverse events. Secondary outcomes were duration of hospital stay, clinical severity score at 0 to 24 hours and 25 to 48 hours after treatment, pulmonary function test, hospital readmission within 30 days, duration of mechanical ventilation, and duration of intensive care unit stay.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used GRADE methods to assess the certainty of the evidence.
MAIN RESULTS
We included four RCTs (564 children). One study received funding from a hospital and one from a university; two studies did not report funding sources. Comparator interventions differed among all four trials. Studies were conducted in Qatar, Turkey, Iran, and India. We assessed two studies to be at an overall low risk of bias, and two to be at unclear risk of bias, overall. The certainty of the evidence for all outcomes and comparisons was very low except for one: hospital re-admission rate within 30 days of discharge for magnesium sulphate versus placebo. None of the studies measured time to recovery, duration of mechanical ventilation, duration of intensive care unit stay, or pulmonary function. There were no events of mortality or adverse effects for magnesium sulphate compared with placebo (1 RCT, 160 children). The effects of magnesium sulphate on clinical severity are uncertain (at 0 to 24 hours: mean difference (MD) on the Wang score 0.13, 95% confidence interval (CI) -0.28 to 0.54; and at 25 to 48 hours: MD on the Wang score -0.42, 95% CI -0.84 to -0.00). Magnesium sulphate may increase hospital re-admission rate within 30 days of discharge (risk ratio (RR) 3.16, 95% CI 1.20 to 8.27; 158 children; low-certainty evidence). None of our primary outcomes were measured for magnesium sulphate compared with hypertonic saline (1 RCT, 220 children). Effects were uncertain on the duration of hospital stay in days (MD 0.00, 95% CI -0.28 to 0.28), and on clinical severity on the Respiratory Distress Assessment Instrument (RDAI) score at 25 to 48 hours (MD 0.10, 95% CI -0.39 to 0.59). There were no events of mortality or adverse effects for magnesium sulphate, with or without salbutamol, compared with salbutamol (1 RCT, 57 children). Effects on the duration of hospital stay were uncertain (magnesium sulphate: 24 hours (95% CI 25.8 to 47.4), magnesium sulphate + salbutamol: 20 hours (95% CI 15.3 to 39.0), and salbutamol: 24 hours (95% CI 23.4 to 76.9)). None of our primary outcomes were measured for magnesium sulphate + epinephrine compared with no treatment or normal saline + epinephrine (1 RCT,120 children). Effects were uncertain for the duration of hospital stay in hours (MD -0.40, 95% CI -3.94 to 3.14), and for RDAI scores (0 to 24 hours: MD -0.20, 95% CI -1.06 to 0.66; and 25 to 48 hours: MD -0.90, 95% CI -1.75 to -0.05).
AUTHORS' CONCLUSIONS
There is insufficient evidence to establish the efficacy and safety of magnesium sulphate for treating children up to two years of age with acute bronchiolitis. No evidence was available for time to recovery, duration of mechanical ventilation and intensive care unit stay, or pulmonary function. There was no information about adverse events for some comparisons. Well-designed RCTs to assess the effects of magnesium sulphate for children with acute bronchiolitis are needed. Important outcomes, such as time to recovery and adverse events should be measured.
Topics: Acute Disease; Albuterol; Bias; Bronchiolitis; Bronchodilator Agents; Drug Therapy, Combination; Epinephrine; Humans; Infant; Infant, Newborn; Length of Stay; Magnesium Sulfate; Patient Readmission; Placebos; Randomized Controlled Trials as Topic; Saline Solution; Severity of Illness Index
PubMed: 33316083
DOI: 10.1002/14651858.CD012965.pub2 -
The Cochrane Database of Systematic... Sep 2020Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review.
OBJECTIVES
To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders.
SEARCH METHODS
We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress.
MAIN RESULTS
This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events.
AUTHORS' CONCLUSIONS
Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
Topics: Adolescent; Adult; Antioxidants; Asthma; Attention Deficit Disorder with Hyperactivity; Bias; Bone Diseases, Metabolic; Brain Injuries, Traumatic; Cardiovascular Diseases; Child; Chronic Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erectile Dysfunction; Female; Flavonoids; Humans; Hypertension; Male; Middle Aged; Osteoarthritis; Pinus; Plant Bark; Plant Extracts; Randomized Controlled Trials as Topic; Sexual Dysfunctions, Psychological; Venous Insufficiency
PubMed: 32990945
DOI: 10.1002/14651858.CD008294.pub5 -
British Journal of Clinical Pharmacology Apr 2021The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are... (Meta-Analysis)
Meta-Analysis Review
AIMS
The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are conflicting. We conducted a meta-analysis to examine the cumulative evidence of the effects of these 2 variants on percent forced expiratory volume in 1 second (FEV1.0%) after albuterol use in asthma patients.
METHODS
We conducted a comprehensive literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies examining the association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% shortly after albuterol administration. The individual study results were combined with weights based on the inverse variance method. This systematic review was registered in the PROSPERO (registration number: CRD42019074554).
RESULTS
Among 273 initial studies identified, 7 studies met the inclusion criteria for quantitative evaluation. Results of the overall meta-analysis indicated no statistically significant mean difference of FEV1.0% between genotypes of Arg16Gly and Gln27Glu. In subgroup analyses, significant associations were found for Arg16Gly GG (vs AA) among studies where no methacholine bronchoconstriction was conducted (mean difference, -3.92; 95% confidence interval, -7.29 to -0.54; I = 0%), and for Arg16Gly GG (vs GA) among studies that included patients with no comorbidities (mean difference, -1.93; 95% confidence interval, -3.77 to -0.10; I = 0%).
CONCLUSION
Synthesis of the studies to date shows weak evidence for an association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% after albuterol use, results of which underscore significant heterogeneity across studies and the need for careful design and sample size considerations.
Topics: Albuterol; Asthma; Bronchodilator Agents; Humans; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2
PubMed: 32986886
DOI: 10.1111/bcp.14570