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COPD Aug 2017The β-adrenergic receptor (ADRB) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB... (Meta-Analysis)
Meta-Analysis Review
The β-adrenergic receptor (ADRB) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in the ADRB gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β-agonists in COPD. We searched the medical literature from 1966 to 2017 and found 16 relevant studies comprising 85381 study subjects. The meta-analyses found no significant association between ADRB genotype and COPD risk. The summary odds ratios (ORs) for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence interval (CI): 0.54-12.4) and 1.17 (95% CI: 0.96-1.44), respectively. Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were 0.97 (95% CI: 0.76-1.22) and 1.01 (95% CI: 0.81-1.26), while summary ORs for COPD in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80-1.25) and 0.94 (95% CI: 0.69-1.24), respectively. When stratified by ethnicity, the summary ORs for COPD did not differ from 1.0 for any of the ADRB variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB genotype and treatment response to inhaled β-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB genotypes are required.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asian People; Black People; Bronchodilator Agents; Genetic Predisposition to Disease; Genotype; Humans; Pulmonary Disease, Chronic Obstructive; Receptors, Adrenergic, beta-2; Risk Factors; Treatment Outcome; White People
PubMed: 28506092
DOI: 10.1080/15412555.2017.1320370 -
Journal of Cardiac Failure Jul 2023Traditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in patients with heart... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in patients with heart failure. This study sought to characterize alternative models of care involving nonphysician provider-led GDMT interventions and their associations with therapy use and clinical outcomes.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing nonphysician provider-led GDMT initiation and/or uptitration interventions vs usual physician care (PROSPERO ID: CRD42022334661). We queried PubMed, Embase, the Cochrane Library, and the World Health Organization International Clinical Trial Registry Platform for peer-reviewed studies from database inception to July 31, 2022. In the meta-analysis, we used RCT data only and leveraged random-effects models to estimate pooled outcomes. Primary outcomes were GDMT initiation and titration to target dosages by therapeutic class. Secondary outcomes included all-cause mortality and HF hospitalizations.
RESULTS
We reviewed 33 studies, of which 17 (52%) were randomized controlled trials with median follow-ups of 6 months; 14 (82%) trials evaluated nurse interventions, and the remainder assessed pharmacists' interventions. The primary analysis pooled data from 16 RCTs, which enrolled 5268 patients. Pooled risk ratios (RR) for renin-angiotensin system inhibitor (RASI) and beta-blocker initiation were 2.09 (95% CI 1.05-4.16; I = 68%) and 1.91 (95% CI1.35-2.70; I = 37%), respectively. Outcomes were similar for uptitration of RASI (RR 1.99, 95% CI 1.24-3.20; I = 77%) and beta-blocker (RR 2.22, 95% CI 1.29-3.83; I = 66%). No association was found with mineralocorticoid receptor antagonist initiation (RR 1.01, 95% CI 0.47-2.19). There were lower rates of mortality (RR 0.82, 95% CI 0.67-1.04; I = 12%) and hospitalization due to HF (RR 0.80, 95% CI 0.63-1.01; I = 25%) across intervention arms, but these differences were small and not statistically significant. Prediction intervals were wide due to moderate-to-high heterogeneity across trial populations and interventions. Subgroup analyses by provider type did not show significant effect modification.
CONCLUSIONS
Pharmacist- and nurse-led interventions for GDMT initiation and/or uptitration improved guideline concordance. Further research evaluating newer therapies and titration strategies integrated with pharmacist- and/or nurse-based care may be valuable.
Topics: Humans; Heart Failure; Pharmacists; Nurse's Role; Antihypertensive Agents; Adrenergic beta-Antagonists
PubMed: 37004867
DOI: 10.1016/j.cardfail.2023.03.012 -
Hellenic Journal of Cardiology : HJC =... 2023Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is... (Review)
Review
Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is an essential protein for maintaining muscle integrity. The lack of dystrophin plays a pathophysiological role in the development of dilated cardiomyopathy in Duchenne muscular dystrophy. Currently, no consensus exists on specific pharmacological therapy guidelines for these patients; however, it centers around the guidelines for heart failure management. This systematic review investigated 12 randomized control trials dating back to 2005 in the pharmacotherapy of patients with dilated cardiomyopathy Duchenne muscular dystrophy. This review specifically included angiotensin-converting enzyme inhibitors, aldosterone receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Despite their limitations, these studies have shown promising effects in improving the overall heart function and prognosis in patients with this condition. However, to attain higher statistical significance, future studies should investigate larger populations and for longer periods.
Topics: Humans; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Dystrophin; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists
PubMed: 37406964
DOI: 10.1016/j.hjc.2023.06.007 -
European Journal of Clinical... Mar 2024Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic receptor (β3-AR) agonists have also gained attention as potential agents for BAT activation and metabolic regulation. Mirabegron, a selective β3-AR-agonist used clinically for overactive bladder syndrome, has been explored for its utility in metabolic disorders. However, the controversy surrounding the ability of mirabegron to activate BAT to accelerate metabolism requires further investigation. The aim of this systematic review is to characterize comprehensively the impact of mirabegron on human BAT and its metabolism.
METHODS
We searched PubMed Central, Web of Science, Embase, and Cochrane Library databases for relevant papers published from the date of database inception to March 2023 for systematic reviews and meta-analyses. We extracted data on primary outcome indicators such as BAT volume, BAT activity, body temperature, and resting energy expenditure (REE), as well as secondary outcome indicators such as heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), non-esterified fatty acids (NEFA), blood glucose, and blood insulin from relevant studies. For studies that did not provide suitable data for meta-analysis, we used narrative data synthesis. For studies that provided suitable data for meta-analysis, we conducted meta-analysis using RevMan 5.4 software.
RESULTS
We reviewed 10 papers and included 6 in our meta-analysis. Our findings revealed no significant changes in BAT volume (p = 0.72) or blood glucose (p = 0.52) with mirabegron when compared to the placebo or pre-dose population. However, patients showed significant increases in BAT activity (p < 0.01), blood NEFA (p < 0.01), body temperature (p < 0.01), REE (p < 0.01), HR (p < 0.01), DBP (p < 0.01), SBP (p = 0.25), and blood insulin (p < 0.01).
CONCLUSION
Through our meta-analysis of 6 papers, we found that mirabegron has the potential to increase human BAT activity, REE, NEFA content, body temperature, HR, blood pressure, and blood insulin content. These effects may lead to reductions in blood glucose levels in obese/overweight and diabetic patients. Additionally, the activation of BAT by mirabegron could represent a novel approach for treating obesity, diabetes, and cardiovascular disease.
TRIAL REGISTRATION NUMBER AND DATE
CRD42023413446, 04/11/2023.
Topics: Humans; Acetanilides; Adipose Tissue, Brown; Blood Glucose; Diabetes Mellitus; Fatty Acids, Nonesterified; Insulins; Obesity; Thiazoles
PubMed: 38159219
DOI: 10.1007/s00228-023-03614-0 -
International Journal of Surgery... May 2023Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of... (Meta-Analysis)
Meta-Analysis
The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.
BACKGROUND
Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy.
OBJECTIVE
The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO.
METHODS
The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual.
RESULTS
A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and β3-adrenoceptor-agonists possessed good effectiveness and safety.
CONCLUSION
OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and β3-adrenoceptor-agonists have good effectiveness and safety.
Topics: Humans; Adult; Female; Botulinum Toxins, Type A; Quality of Life; Network Meta-Analysis; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Treatment Outcome; Receptors, Adrenergic; Tibial Nerve
PubMed: 36974676
DOI: 10.1097/JS9.0000000000000338 -
American Journal of Obstetrics and... Dec 2013The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor.
STUDY DESIGN
We conducted a systematic review and metaanalysis of randomized controlled trials.
RESULTS
Thirteen studies were included (1302 women) comparing transdermal nitroglycerin vs placebo (2 studies; n = 186); β2-adrenergic receptor agonists (9 studies; n = 1024); nifedipine (1 study; n = 50); and magnesium sulfate (1 study; n = 42). There were no significant differences between transdermal nitroglycerin and placebo for delivery within 48 hours of the initiation of treatment or at <28, <34, or <37 weeks of gestation, adverse neonatal outcomes, and neurodevelopmental status at 24 months of life. Nevertheless, 1 study found a marginally significant reduction in the risk of a composite outcome of major neonatal morbidity and perinatal death (3/74 [4.1%] vs 11/79 [13.9%]; relative risk, 0.29; 95% confidence interval, 0.08-1.00). When compared with β2-adrenergic receptor agonists, transdermal nitroglycerin was associated with a significant reduction in the risk of preterm birth at <34 and <37 weeks of gestation, admission to the neonatal intensive care unit, use of mechanical ventilation, and maternal side effects. There were no significant differences between transdermal nitroglycerin and nifedipine and magnesium sulfate in delivery within 48 hours of treatment and pregnancy prolongation, respectively. Overall, women who received transdermal nitroglycerin had a higher risk of headache.
CONCLUSION
Although transdermal nitroglycerin appears to be more effective than β2-adrenergic receptor agonists, the current evidence does not support its routine use as a tocolytic agent for the treatment of preterm labor. Further double-blind placebo-controlled trials are needed.
Topics: Administration, Cutaneous; Adrenergic beta-2 Receptor Agonists; Female; Humans; Magnesium Sulfate; Nifedipine; Nitroglycerin; Obstetric Labor, Premature; Pregnancy; Tocolytic Agents
PubMed: 23891631
DOI: 10.1016/j.ajog.2013.07.022 -
The Journal of International Medical... Oct 2013A meta-analysis of published studies was performed to determine whether administration of any of five antihypertensive drug classes (thiazide diuretics,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A meta-analysis of published studies was performed to determine whether administration of any of five antihypertensive drug classes (thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers and β-blockers) affected the risk of fall injuries in the elderly (aged ≥60 years).
METHODS
Articles reporting the risk of fall injury in elderly people being treated with the five main classes of antihypertensive drugs were retrieved using MEDLINE®, EMBASE, SCOPUS® and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction and analysed using odds ratios with 95% confidence intervals.
RESULTS
Sixty-two articles, included in two meta-analyses, were identified. These meta-analyses drew opposite conclusions about the role of antihypertensive drugs in fall injuries in the elderly. However, the present analysis did not reveal a clear association (or the lack of one) between antihypertensive drugs and risk of fall injuries.
CONCLUSIONS
There is no clear, statistically significant clinical precedent indicating that the use of any of the antihypertensive drugs considered here increases the risk of fall injuries in the elderly. Nonetheless, in following standard clinical guidelines for hypertension management, physicians need to be aware of the impact of drug therapies on fall injuries.
Topics: Accidental Falls; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Analysis of Variance; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Databases, Bibliographic; Diuretics; Humans; Hypertension; Middle Aged; Risk Factors; Root Cause Analysis
PubMed: 24051019
DOI: 10.1177/0300060513497562 -
Hellenic Journal of Cardiology : HJC =... 2022The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients... (Meta-Analysis)
Meta-Analysis Review
The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients receiving guideline-directed treatment to identify the proportion of under-treatment patients and those who are treated with optimal doses, to evaluate the correlation of under-treatment patients' characteristics with the prescribed therapy, and finally, to evaluate the combined effect of the above on incidental mortality and rehospitalization. We conducted a systematic review of the literature indexed in Medline. We screened 1224 papers and excluded 1166 as they did not meet the inclusion criteria. Of the remaining 58 papers, which were evaluated by studying the full text, 11 papers that referred to 45866 patients were finally studied in this work. Angiotensin-Converting-Enzyme Inhibitor (ACEI) and Angiotensin II-Receptor Blocker (ARB) use was estimated to be 80.9% (95% CI: 73.9%, 86.4%), β-blockers' use was 78% (95% CI: 70.4%, 84.1%), Mineralocorticoid Receptor Antagonists' use was 47.4% (95% Cl 41.6%, 53.4%), and cardiac resynchronization therapy's use was 5.8% (95% Cl 3.4%, 9.6%). Meta-regression analysis showed that prescription of more than the half of target dose of ACEI/ARBs was found to be associated with reduced all-cause mortality (Z = -3.61, P = 0.0003), while the relationship with β-blockers was borderline (Z = -1.56, P = 0.11). A satisfactory adherence to the prescription of guideline-recommended treatment in patients with HF was observed. However, the under titration of the life-saving HF drugs need to be improved as only ultimate adherence to guideline-directed treatments may lead to the reduction of HF burden.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Stroke Volume
PubMed: 35508296
DOI: 10.1016/j.hjc.2022.04.006 -
The Cochrane Database of Systematic... Oct 2014Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of... (Review)
Review
BACKGROUND
Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke.
OBJECTIVES
To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2014, Issue 5), the Database of Abstracts of Reviews of Effects (DARE) (May 2014), MEDLINE (1966 to May 2014), EMBASE (1980 to May 2014), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to May 2014). We also searched ongoing trials registers and reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism. The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the trials identified, appraised quality, and extracted data.
MAIN RESULTS
We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo and were of a high methodological quality. We noted no statistical differences among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.76 to 1.18). For other outcomes analysed (major vascular events, death from all causes, death from cardiovascular causes) , we observed no significant differences between the groups. There were minor blood pressure reductions in the intervention group. Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life. Adverse events were significantly more frequent in participants taking atenolol than in those given placebo, and were the most common reason given for discontinuing treatment (RR 1.85, 95% CI 1.45 to 2.35).
AUTHORS' CONCLUSIONS
To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.
Topics: Adrenergic beta-1 Receptor Antagonists; Atenolol; Humans; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Stroke
PubMed: 25317988
DOI: 10.1002/14651858.CD007890.pub3 -
Clinical Breast Cancer Dec 2015The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine.... (Meta-Analysis)
Meta-Analysis Review
The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer.
Topics: Adrenergic beta-Antagonists; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local
PubMed: 26516037
DOI: 10.1016/j.clbc.2015.07.001