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Translational Psychiatry Jun 2023Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories....
Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories. Not all patients benefit, however, and there is room for improvement of efficacy. Pharmacologically augmenting trauma memory modulation in the context of tf-PT may help optimise treatment outcome. To systematically review effects of pharmacologically augmented memory modulation in the context of tf-PT for PTSD (PROSPERO preregistration ID: CRD42021230623). We conducted a systematic review of randomised controlled trials of psychotherapy treatment for PTSD. We included placebo-controlled studies that augmented at least one treatment session pharmacologically targeting memory extinction or reconsolidation. We calculated post-treatment between group (pharmacological augmentation vs placebo control) effect sizes of PTSD symptom severity. We included 13 RCTs. There was large heterogeneity in augmentation procedure and methodological quality. Four studies showed significantly greater PTSD symptom reduction in the pharmacological augmentation group (propranolol, hydrocortisone, dexamethasone, D-cycloserine) compared to placebo. Seven studies showed no significant effect of pharmacological augmentation compared to placebo (D-cycloserine, rapamycin, mifepristone, propranolol, mifepristone combined with D-cycloserine, methylene blue). Two studies showed significantly smaller PTSD symptom reduction in the pharmacological augmentation group (D-cycloserine, dexamethasone) compared to placebo. Results of pharmacological augmentation were mixed overall and heterogenous for the pharmacological agents tested in more than one study. Additional studies and replications are needed to identify which pharmacological agents work, in which combination and to identify patient groups that benefit most to tailor PTSD treatment.
Topics: Humans; Cycloserine; Dexamethasone; Mifepristone; Propranolol; Psychotherapy; Stress Disorders, Post-Traumatic; Randomized Controlled Trials as Topic
PubMed: 37321998
DOI: 10.1038/s41398-023-02495-2 -
The Cochrane Database of Systematic... Jun 2023Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic... (Meta-Analysis)
Meta-Analysis Review
Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease.
BACKGROUND
Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic obstructive pulmonary disease (COPD). When two classes of medications are required, a LAMA plus an ICS (LABA+ICS) were previously recommended within a single inhaler as the first-line treatment for managing stable COPD in people in high-risk categories. However, updated international guidance recommends a LAMA plus a LABA (LAMA+LABA). This systematic review is an update of a Cochrane Review first published in 2017.
OBJECTIVES
To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD.
SEARCH METHODS
We performed an electronic search of the Cochrane Airways Group Specialised Register, ClinicalTrials.gov, and the World Health Organization Clinical Trials Search Portal, followed by handsearches. Two review authors screened the selected articles. The most recent search was run on 10 September 2022.
SELECTION CRITERIA
We included parallel or cross-over randomised controlled trials of at least one month's duration, comparing LAMA+LABA and LABA+ICS for stable COPD. We included studies conducted in an outpatient setting and irrespective of blinding.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs), with 95% confidence intervals (CIs) using Review Manager 5. Primary outcomes were: participants with one or more exacerbations of COPD; serious adverse events; quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score change from baseline; and trough forced expiratory volume in one second (FEV). We used the GRADE framework to rate our certainty of the evidence in each meta-analysis as high, moderate, low or very low. MAIN RESULTS: This review updates the first version of the review, published in 2017, and increases the number of included studies from 11 to 19 (22,354 participants). The median number of participants per study was 700. In each study, between 54% and 91% (median 70%) of participants were males. Study participants had an average age of 64 years and percentage predicted FEV of 51.5% (medians of study means). Included studies had a generally low risk of selection, performance, detection, attrition, and reporting biases. All but two studies were sponsored by pharmaceutical companies, which had varying levels of involvement in study design, conduct, and data analysis. Primary outcomes The odds of having an exacerbation were similar for LAMA+LABA compared with LABA+ICS (OR 0.91, 95% CI 0.78 to 1.06; I = 61%; 13 studies, 20,960 participants; moderate-certainty evidence). The odds of having a serious adverse event were also similar (OR 1.02, 95% CI 0.91 to 1.15; I = 20%; 18 studies, 23,183 participants; high-certainty evidence). Participants receiving LAMA+LABA had a similar improvement in quality of life, as measured by the SGRQ, to those receiving LABA+ICS (MD -0.57, 95% CI -1.36 to 0.21; I = 78%; 9 studies, 14,437 participants; moderate-certainty evidence) but showed a greater improvement in trough FEV (MD 0.07, 95% CI 0.05 to 0.08; I = 73%; 12 studies, 14,681 participants; moderate-certainty evidence). Secondary outcomes LAMA+LABA decreased the odds of pneumonia compared with LABA+ICS from 5% to 3% (OR 0.61, 95% CI 0.52 to 0.72; I = 0%; 14 studies, 21,829 participants; high-certainty evidence) but increased the odds of all-cause death from 1% to 1.4% (OR 1.35, 95% CI 1.05 to 1.75; I = 0%; 15 studies, 21,510 participants; moderate-certainty evidence). The odds of achieving a minimal clinically important difference of four or more points on the SGRQ were similar between LAMA+LABA and LABA+ICS (OR 1.06, 95% CI 0.90 to 1.25; I = 77%; 4 studies, 13,614 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Combination LAMA+LABA therapy probably holds similar benefits to LABA+ICS for exacerbations and quality of life, as measured by the St George's Respiratory Questionnaire, for people with moderate to severe COPD, but offers a larger improvement in FEV and a slightly lower risk of pneumonia. There is little to no difference between LAMA+LABA and LAMA+ICS in the odds of having a serious adverse event. Whilst all-cause death may be lower with LABA+ICS, there was a very small number of events in the analysis, translating to a low absolute risk. Findings are based on moderate- to high-certainty evidence from heterogeneous trials with an observation period of less than one year. This review should be updated again in a few years.
Topics: Male; Humans; Middle Aged; Female; Muscarinic Antagonists; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Pneumonia
PubMed: 37276335
DOI: 10.1002/14651858.CD012066.pub3 -
Arquivos Brasileiros de Cardiologia 2023The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial.
OBJECTIVE
We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity.
METHODS
The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted.
RESULTS
The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study.
CONCLUSION
The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).
Topics: Adult; Humans; Renin-Angiotensin System; Stroke Volume; Cardiotoxicity; Ventricular Function, Left; Anthracyclines; Prospective Studies; Adrenergic beta-Antagonists; Antibiotics, Antineoplastic; Heart Failure
PubMed: 37255127
DOI: 10.36660/abc.20220298 -
Dermatologic Surgery : Official... Aug 2023
Topics: Humans; Timolol; Wound Healing
PubMed: 37146181
DOI: 10.1097/DSS.0000000000003829 -
Journal of Cardiovascular Pharmacology Jul 2023Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with...
Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.
Topics: Male; Humans; Female; Young Adult; Adult; Middle Aged; Postural Orthostatic Tachycardia Syndrome; Post-Acute COVID-19 Syndrome; COVID-19; Adrenergic beta-Antagonists; Midodrine; Heart Rate
PubMed: 37094584
DOI: 10.1097/FJC.0000000000001432 -
Advances in Experimental Medicine and... 2023Catecholamine stimulation over adrenergic receptors results in a state of hypercoagulability. Chronic stress involves the release and increase in circulation of...
Catecholamine stimulation over adrenergic receptors results in a state of hypercoagulability. Chronic stress involves the release and increase in circulation of catecholamines and other stress related hormones. Numerous observational studies in human have related stressful scenarios to several coagulation variables, but controlled stimulation with agonists or antagonists to adrenergic receptors are scarce. This systematic review is aimed at presenting an updated appraisal of the effect of adrenergic receptor modulation on variables related to human hemostasis by systematically reviewing the effect of adrenergic receptor-targeting drugs on scale variables related to hemostasis. By searching 3 databases for articles published between January 1st 2011 and February 16th, 2022 reporting effects on coagulation parameters from stimulation with α- or β-adrenergic receptor targeting drugs in humans regardless of baseline condition, excluding records different from original research and those not addressing the main aim of this systematic review. Risk of bias assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Tables describing a pro-thrombotic anti-fibrinolytic state induced after β-adrenergic receptor agonist stimulation and the opposite after α-, β-adrenergic receptor antagonist stimulation were synthesized from 4 eligible records by comparing hemostasis-related variables to their baseline. Notwithstanding this low number of records, experimental interventions included were sound and mostly unbiased, results were coherent, and outcomes were biologically plausible. In summary, this systematic review provides a critical systematic assessment and an updated elaboration, and its shortcomings highlight the need for further investigation in the field of hematology.
Topics: Catecholamines; Receptors, Adrenergic; Adrenergic Agents; Hemostasis; Humans; Stress, Physiological; Blood Coagulation
PubMed: 37093421
DOI: 10.1007/978-3-031-26163-3_3 -
Clinical Cardiology Jun 2023There are limited comparative data on safety and efficacy within commonly used Vaughan-Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
There are limited comparative data on safety and efficacy within commonly used Vaughan-Williams (VW) class III antiarrhythmic drugs (AADs) for maintenance of sinus rhythm in adults with atrial fibrillation (AF).
HYPOTHESIS
We hypothesized that dronedarone and sotalol, two commonly prescribed VW class III AADs with class II properties, have different safety and efficacy effects in patients with nonpermanent AF.
METHODS
A systematic literature review was conducted searching MEDLINE®, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to June 15, 2021 (NCT05279833). Clinical trials and observational studies that evaluated safety and efficacy of dronedarone or sotalol in adults with AF were included. Bayesian random-effects network meta-analysis (NMA) was used to quantify comparative safety and efficacy. Where feasible, we performed sensitivity analyses by including only randomized controlled trials (RCTs).
RESULTS
Of 3581 records identified through database searches, 37 unique studies (23 RCTs, 13 observational studies, and 1 nonrandomized trial) were included in the NMA. Dronedarone was associated with a statistically significantly lower risk of all-cause death versus sotalol (hazard ratio [HR] = 0.38 [95% credible interval, CrI: 0.19, 0.74]). The association was numerically similar in the sensitivity analysis (HR = 0.46 [95% CrI: 0.21, 1.02]). AF recurrence and cardiovascular death results were not significantly different between dronedarone and sotalol in all-studies and sensitivity analyses.
CONCLUSION
The NMA findings indicate that, across all clinical trials and observational studies included, dronedarone compared with sotalol was associated with a lower risk of all-cause death, but with no difference in AF recurrence.
Topics: Adult; Humans; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Network Meta-Analysis; Sotalol
PubMed: 37025083
DOI: 10.1002/clc.24011 -
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 -
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 -
Minerva Cardiology and Angiology Dec 2023Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical...
INTRODUCTION
Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical therapies aiming to slow down aortic growth has been tested in several trials, particularly beta-blockers and angiotensin receptor blockers, however showing conflicting results.
EVIDENCE ACQUISITION
We conducted a systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases between January and February 2022. We selected relevant articles focusing on patients with MFS treated with beta-blockers, angiotensin receptors blockers, or both, and reporting data on the effect of the drugs on 1) slowing down aortic dilatation; 2) the reduction of aortic complication (aortic dissection, mortality, aortic surgery); and with a 3) follow-up length of at least two years. A total of 16 studies were selected.
EVIDENCE SYNTHESIS
Beta-blockers remain the mainstay of therapy as they have proven to slow aortic enlargement. Angiotensin receptor blockers are a useful alternative and with proven benefit as an add-on therapy to limit aortic growth. Neither beta-blockers, nor angiotensin receptor blockers have shown meaningful results on clinical aortic endpoints.
CONCLUSIONS
The current evidence of pharmacological treatment for MFS patients is conflicting due to the lack of large, randomized clinical trials with adequate follow-up studies and homogeneous age grouping. Beta-blockers and angiotensin receptor blockers are the only available treatments to reduce aortic growth. A recently published patient-level meta-analysis confirmed that angiotensin receptor blockers and beta-blockers have a similar effect on reducing the rate of increase of the aortic root Z score, used singularly or as add-on therapy. Considering the current evidence on new features related with MFS (such as mitral annular disjunction - MAD) bearing a potential additional increased arrhythmic risk, it is of paramount importance to establish the role of beta-blockers and angiotensin receptor blockers in clinical endpoints of this population as well.
Topics: Humans; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Aorta; Aortic Diseases; Cardiovascular Diseases; Marfan Syndrome
PubMed: 36939732
DOI: 10.23736/S2724-5683.23.06184-7