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Clinical Toxicology (Philadelphia, Pa.) Dec 2022Dexmedetomidine is an alpha-2 adrenoceptor agonist which is widely used for sedation. Dexmedetomidine does not suppress the respiratory drive and produces a state of...
INTRODUCTION
Dexmedetomidine is an alpha-2 adrenoceptor agonist which is widely used for sedation. Dexmedetomidine does not suppress the respiratory drive and produces a state of cooperative sedation; it may be associated with beneficial outcomes in the general critical care population. The role of dexmedetomidine in the treatment of toxicologic conditions (excluding alcohol withdrawal) is unclear.
OBJECTIVES
To critically assess and summarize the literature regarding the use of dexmedetomidine in toxicologic conditions other than alcohol withdrawal.
METHODS
We performed a systematic review of the medical literature to identify all existing evidence regarding the use of dexmedetomidine for toxicologic conditions. We excluded reviews and commentary, studies reporting exclusively on alcohol withdrawal, and studies reporting the use of dexmedetomidine to treat iatrogenic sedative withdrawal in the intensive care unit. We also performed a review of the Toxicology Investigators Consortium (ToxIC) database for patients treated with dexmedetomidine.
RESULTS
We identified 98 studies meeting inclusion criteria; 87 of these were case reports or case series, representing 99 unique cases. Eleven articles with other designs were identified, which included 138 patients treated with dexmedetomidine for toxicologic conditions. Ninety-three cases from the ToxIC registry met inclusion criteria. Common indications for dexmedetomidine included stimulant intoxication, sedative withdrawal, serotonin syndrome, antimuscarinic toxidrome, opioid withdrawal, and cannabinoid intoxication. Dexmedetomidine was usually administered by continuous infusion; bolus administration was reported in a minority of cases. Adverse effects were uncommon. The quality of evidence was generally low, given the preponderance of case reports, the rate of missing or poorly reported data, and the near-universal co-administration of other sedatives.
TREATMENT OF STIMULANT POISONING
Fifty-nine patients with stimulant poisoning were treated with dexmedetomidine. There was reasonably good evidence that dexmedetomidine was helpful in the treatment of stimulant poisoning.
TREATMENT OF SEDATIVE WITHDRAWAL
Twenty-two patients with sedative withdrawal were treated with dexmedetomidine. Several case reports of very high-quality suggested efficacy of dexmedetomidine for this indication, particularly for baclofen withdrawal.
TREATMENT OF SEROTONIN SYNDROME
Twenty-six patients with serotonin syndrome were treated with dexmedetomidine. This evidence was of lower quality due to missing clinical details, potential overdiagnosis of serotonin syndrome, and near-universal concomitant treatment with other sedatives.
TREATMENT OF ANTIMUSCARINIC POISONING
Forty-two patients with antimuscarinic poisoning were treated with dexmedetomidine. This evidence was of low quality and was limited by infrequent use of the preferred antidote, physostigmine.
TREATMENT OF OPIOID WITHDRAWAL
Forty-four patients with opioid withdrawal were treated with dexmedetomidine. This evidence was of low quality due to missing clinical details and near-universal concomitant treatment with other agents. The one high-quality trial reported the use of dexmedetomidine in ultra-rapid opioid detoxification, which is not indicated in modern practice.
TREATMENT OF CANNABINOID INTOXICATION
Five patients with cannabinoid intoxication were treated with dexmedetomidine. No definite conclusion can be drawn from the limited available evidence.
DISCUSSION
It is important to distinguish between the use of dexmedetomidine as a general sedative, which is likely to increase as the overall utilization of dexmedetomidine in critical care settings increases, and the use of dexmedetomidine as a specific pharmacologic treatment for a toxicologic condition. Well-established pharmacologic data from animal and human studies suggest dexmedetomidine counteracts stimulant-induced norepinephrine release. The mechanism by which dexmedetomidine treats sedative withdrawal is unclear. Some animal data show that dexmedetomidine may indirectly suppress serotonin release, which may suggest a role for dexmedetomidine in this condition.
CONCLUSIONS
There is a small and generally low-quality body of evidence which suggests that dexmedetomidine may be helpful in the treatment of certain toxicologic conditions, particularly stimulant intoxication and sedative withdrawal. Further high-quality research is needed to clarify the role of dexmedetomidine in patients with toxicologic conditions.
Topics: Humans; Dexmedetomidine; Analgesics, Opioid; Alcoholism; Muscarinic Antagonists; Serotonin Syndrome; Substance Withdrawal Syndrome; Hypnotics and Sedatives; Narcotics
PubMed: 36346349
DOI: 10.1080/15563650.2022.2138761 -
Journal of Pediatric Urology Feb 2023Solifenacin is an anticholinergic that is used to treat overactive bladder syndrome (OAB) in children. It is important to ascertain the safety and tolerability of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Solifenacin is an anticholinergic that is used to treat overactive bladder syndrome (OAB) in children. It is important to ascertain the safety and tolerability of solifenacin in the paediatric population as solifenacin offers an alternative, is more bladder specific, and should have less anticholinergic side effects than other therapies.
OBJECTIVE
The aim of this study is to systematically evaluate the safety and tolerability of solifenacin in children and adolescents with OAB.
STUDY DESIGN
We included studies that reported the safety and tolerability of solifenacin in children and adolescents. All study types were included. Electronic searches were conducted in Ovid MEDLINE, Ovid Embase, TRIP, CINAHL and ICTRP on the 18th of January 2022. Risk of bias was assessed with the Cochrane Risk of Bias tool 2.0 (ROB-2) for randomised controlled trials (RCTs) and the Newcastle-Ottowa scale for cohort studies.
RESULTS
A total of twelve studies including two RCTs were included in this review. Results from the meta-analysis of RCTs showed the commonest side effects were constipation (RR 3.5, 95%CI 0.9-13.7) and dry mouth (RR 3.1 95%CI 0.2-53). In terms of tolerability, the effect estimate of ceasing solifenacin due to an adverse effect was 2.7 (95%CI 0.8-9.1). Within the cohort studies, out of the 779 patients 21.7% experienced side effects. The most common side effects were constipation (6.8%) and dry mouth/lips (6.0%) and 3.5% of patients ceased solifenacin due to adverse effects. Overall, the certainty of the evidence for side effects and tolerability were very low.
DISCUSSION
The reported incidence of side effects is low, and less than reported with oxybutynin use. However, the very low certainty of the evidence means the findings should be interpreted with caution. There is limited reporting of a prolonged QTc interval on ECG. Studies that described this only had an increase of QTc from baseline and not a clinically significant prolonged QTc that resulted in arrhythmias.
CONCLUSION
Solifenacin is an alternative anticholinergic for the treatment of OAB in children. However, given the paucity of good quality data on safety and tolerability it should be used cautiously in children with close monitoring for potential side effects.
Topics: Child; Adolescent; Humans; Solifenacin Succinate; Urinary Bladder, Overactive; Treatment Outcome; Cholinergic Antagonists; Xerostomia; Constipation; Muscarinic Antagonists
PubMed: 36336627
DOI: 10.1016/j.jpurol.2022.09.014 -
Scientific Reports Oct 2022To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in... (Meta-Analysis)
Meta-Analysis
Efficacy, according to urodynamics, of OnabotulinumtoxinA compared with antimuscarinic drugs, for neurogenic detrusor overactivity: a systematic review and network meta-analysis.
To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdet endpoints. OnabotulinumtoxinA 200U was more effective on the urodynamic endpoint of BC than other drugs or doses of OnabotulinumtoxinA. According to the MCC urodynamic results, oxybutynin, solifenacin 10 mg, and tolterodine 4 mg also had positive effects. OnabotulinumtoxinA 300U, 200U and 100U were better in improving the urodynamic results of NDO, and the current evidence also shows that selective injection of onabotulinumtoxinA can effectively improve the urodynamic results.
Topics: Humans; Botulinum Toxins, Type A; Urodynamics; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Solifenacin Succinate; Network Meta-Analysis; Tolterodine Tartrate; Bayes Theorem; Treatment Outcome; Urinary Bladder, Overactive
PubMed: 36289427
DOI: 10.1038/s41598-022-22765-1 -
Journal of Palliative Medicine Mar 2023Anticholinergics have been used to treat death rattle (DR) in dying patients with palliative care. However, the effect of anticholinergics is still controversial. No... (Meta-Analysis)
Meta-Analysis Review
Anticholinergics have been used to treat death rattle (DR) in dying patients with palliative care. However, the effect of anticholinergics is still controversial. No quantitative summary of their effects is reported. This study aimed to systematically review and quantitatively synthesize the effect of anticholinergics on DR treatment and prophylaxis. A systematic search was performed in the electronic databases (PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from inception to October 2021. Studies conducted to determine the effect of anticholinergics compared with other anticholinergics or placebo on noise reduction score in dying patients were included. A network meta-analysis was performed for DR treatment. The effect of anticholinergics at four hours was assessed. A pairwise meta-analysis was performed for DR prophylaxis. A total of nine studies were included with 1103 patients. Six studies were randomized controlled trials, and three studies were cohort studies. Seven studies were conducted for DR treatment, while two studies were conducted for DR prophylaxis. For DR treatment, no statistically significant difference was observed between each anticholinergic (hyoscine hydrobromide, hyoscine butyl bromide, atropine, and glycopyrrolate) and placebo and among any anticholinergics. However, the surface under cumulative ranking curve indicated that hyoscine butyl bromide had the highest surface under the cumulative ranking curve (SUCRA) with 71.3%. For DR prophylaxis, the relative risk of DR occurrence for hyoscine butyl bromide was 0.23 (0.04, 1.18; = 84.5%) compared with no treatment. This study showed no strong evidence of the regular use of anticholinergics for DR treatment. In addition, hyoscine butyl bromide appears to have a high potential for DR prophylaxis.
Topics: Humans; Cholinergic Antagonists; Scopolamine; Network Meta-Analysis; Butylscopolammonium Bromide
PubMed: 36194053
DOI: 10.1089/jpm.2022.0386 -
Expert Review of Pharmacoeconomics &... Dec 2022Overactive bladder (OAB) is defined as urinary urgency, usually with urinary frequency and nocturia. . The current treatment for OAB includes conservative management,...
BACKGROUND
Overactive bladder (OAB) is defined as urinary urgency, usually with urinary frequency and nocturia. . The current treatment for OAB includes conservative management, surgery, and pharmacotherapy. Mirabegron is a new drug acting by the ß3-adrenoceptor agonism. This study aimed to review the cost-effectiveness of mirabegron in the treatment of OAB.
AREAS COVERED
We searched published articles in electronic search databases. Ten studies were included in the qualitative analysis. Various antimuscarinics, including oxybutynin, fesoterodine, tolterodine, darifenacin, and trospium were compared with mirabegron. The results were evaluated and compared according to the quality-adjusted life-years (QALY), cost/year, and incremental cost-effectiveness ratio (ICER). Of the ten studies in only three, mirabegron was not a cost-effective strategy. In seven cases, mirabegron was cost-effective.
EXPERT OPINION
The cost-effectiveness of mirabegron was variable in different regions; however, most of the studies show the cost-effectiveness of mirabegron. Our study illustrates that mirabegron's ICER in comparison with its comparators is below the willingness to pay threshold even in the countries with low GDP/Capita. Our proposal for future economic studies for OAB pharmacotherapy is to compare different doses, formulations, and administration forms in a real-world context.
Topics: Humans; Cost-Benefit Analysis; Acetanilides; Urinary Bladder, Overactive; Tolterodine Tartrate; Muscarinic Antagonists; Treatment Outcome
PubMed: 36172806
DOI: 10.1080/14737167.2022.2130761 -
Biomedicines Sep 2022Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy.... (Review)
Review
Inhaled corticosteroids (ICS) remain the mainstay of asthma treatment, along with bronchodilators serving as control agents in combination with ICS or reliever therapy. Although current pharmacological treatments improve symptom control, health status, and the frequency and severity of exacerbations, they do not really change the natural course of asthma, including disease remission. Considering the highly heterogeneous nature of asthma, there is a strong need for innovative medications that selectively target components of the inflammatory cascade. The aim of this review was to systematically assess current investigational agents in Phase I and II randomised controlled trials (RCTs) over the last five years. Sixteen classes of novel therapeutic options were identified from 19 RCTs. Drugs belonging to different classes, such as the anti-interleukin (IL)-4Rα inhibitors, anti-IL-5 monoclonal antibodies (mAbs), anti-IL-17A mAbs, anti-thymic stromal lymphopoietin (TSLP) mAbs, epithelial sodium channel (ENaC) inhibitors, bifunctional M receptor muscarinic antagonists/β-adrenoceptor agonists (MABAs), and anti-Fel d 1 mAbs, were found to be effective in the treatment of asthma, with lung function being the main assessed outcome across the RCTs. Several novel investigational molecules, particularly biologics, seem promising as future disease-modifying agents; nevertheless, further larger studies are required to confirm positive results from Phase I and II RCTs.
PubMed: 36140430
DOI: 10.3390/biomedicines10092330 -
The European Respiratory Journal Feb 2023Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting β2 agonist (LABA) combination... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting β2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD.
METHODS
Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke.
RESULTS
A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power.
CONCLUSION
Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.
Topics: Humans; Bronchodilator Agents; Cardiovascular Diseases; Administration, Inhalation; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Adrenal Cortex Hormones; Drug Therapy, Combination; Adrenergic beta-2 Receptor Agonists
PubMed: 36137586
DOI: 10.1183/13993003.00302-2022 -
Scientific Reports Sep 2022A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids... (Meta-Analysis)
Meta-Analysis
A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids (ICS) in stable chronic obstructive pulmonary disease (COPD). We selected 26 parallel randomized controlled trials (41,366 patients) comparing triple therapy with ICS/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), and LAMA in patients with stable COPD for ≥ 12 weeks from PubMed, EMBASE, the Cochrane Library, and clinical trial registries (search from inception to June 30, 2022). Triple therapy with high dose (HD)-ICS exhibited a lower risk of total exacerbation in pre-specified subgroups treated for ≥ 48 weeks than that with low dose (LD)-ICS (odds ratio [OR] = 0.66, 95% credible interval [CrI] = 0.52-0.94, low certainty of evidence) or medium dose (MD)-ICS (OR = 0.66, 95% CrI = 0.51-0.94, low certainty of evidence). Triple therapy with HD-ICS exhibited a lower risk of moderate-to-severe exacerbation in pre-specified subgroups with forced expiratory volume in 1 s < 65% (OR = 0.6, 95% CrI = 0.37-0.98, low certainty of evidence) or previous exacerbation history (OR = 0.6, 95% CrI = 0.36-0.999, very low certainty of evidence) than triple therapy with MD-ICS. Triple therapy with HD-ICS may reduce acute exacerbation in patients with COPD treated with other drug classes including triple therapy with LD- or MD-ICS or dual therapies.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive
PubMed: 36127353
DOI: 10.1038/s41598-022-18353-y -
Contrast Media & Molecular Imaging 2022Chronic obstructive pulmonary disease (COPD) is a major and difficult disease of the chronic respiratory system that is common and frequent, with a huge disease burden....
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a major and difficult disease of the chronic respiratory system that is common and frequent, with a huge disease burden. The aim of this study was to investigate the efficacy and safety of budesonide/glyburide/formoterol fumarate (BGF) in the treatment of COPD.
METHODS
A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The basic features of the seven pieces of literature were identified using the search strategy. The sample size range was 130∼1264.
RESULTS
The effects of BGF increased FEV1 in patients with COPD (mean difference = 2.86, 95%CI: 2.71-3.01, < 0.00001). The effects of BGF improved in patients with ≥1 TEAE in patients with COPD, and was not statistically significant after treatment (Odds rate = 1.00, 95%CI: 0.85-1.17, =0.97). The effects of BGF increased in patients with TEAEs related a to study treatment in patients with COPD (odds rate = 1.27, 95% CI: 1.03-1.57, =0.02). The effects of BGF in decreased patients with serious TEAEs in patients with COPD (odds rate = -0.02, 95% CI: -0.03--0.00, =0.04). The effects of BGF decreased the death rate in patients with COPD, and were not statistically significant after treatment (odds rate = 0.77, 95% CI: 0.31-1.97, =0.59). The effects of BGF decreased the hypertension rate in patients with COPD (odds rate = 0.92, 95% CI: 0.44-1.89, =0.81), and was not statistically significant after treatment. The effects of BGF increased pneumonia in patients with COPD (odds rate = 1.55, 95% CI: 0.81-2.97, =0.19), and were not statistically significant after treatment. The effects of BGF increased FEV1, increased patients with TEAEs related a to study treatment, and decreased patients with serious TEAEs in patients with COPD.
CONCLUSION
This study elucidates the efficacy and safety of BGF in the treatment of COPD with a view to providing a clinical reference.
Topics: Aged; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Glycopyrrolate; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 36072633
DOI: 10.1155/2022/8382295 -
Respiratory Research Aug 2022Although asthma is more prevalent in women and the prevalence of COPD is increasing in women, the current international recommendations for the management and prevention...
BACKGROUND
Although asthma is more prevalent in women and the prevalence of COPD is increasing in women, the current international recommendations for the management and prevention of asthma and COPD provide no sex-related indication for the treatment of these diseases. Therefore, we systematically reviewed the evidence across literature on the sex-related effectiveness of asthma and COPD therapy.
METHODS
This systematic review has been registered in PROSPERO and performed according to PRISMA-P. The PICO framework was applied for the literature search strategy: "patient problem" included adult patients suffering from asthma or COPD, "Intervention" regarded the pharmacological treatments for asthma or COPD, "Comparison" was vs. baseline, active controls, or placebo, "Outcome" was any difference sex-related in the effectiveness of interventions.
RESULTS
In asthma 44% of the evidence reported that men responded better than women to the therapy, whereas this percentage was 28% in COPD. ICS was generally less effective in women than in men to treat asthma, and consistent evidence suggests that in asthmatic patients ICS/LABA/LAMA combination may be equally effective in both men and women. Due to the inconsistent available evidence, it is not possible to identify specific treatments whose effectiveness is related to sex difference in COPD patients.
CONCLUSIONS
There is a strong need of investigating the sex-related impact of asthma and COPD treatments. Pre-specified analyses in men and women should be planned in future trial protocols, a necessary condition that should be requested also by the regulatory agencies to overcome the anachronistic "one-size-fits-all" approach to therapeutics associated with suboptimal outcomes for patients.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Sex Characteristics
PubMed: 36038873
DOI: 10.1186/s12931-022-02140-4