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PloS One 20212021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS/LAMA/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD.
METHODS AND ANALYSES
Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods.
ETHICS AND DISSEMINATION
No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients.
PROTOCOL REGISTRATION NUMBER
CRD42021240823.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Disease Progression; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Prognosis; Pulmonary Disease, Chronic Obstructive
PubMed: 34351996
DOI: 10.1371/journal.pone.0255545 -
International Journal of Clinical... Dec 2021Background Despite common use, anticholinergic medications have been associated with serious health risks. Interventions to reduce their use are being developed and... (Review)
Review
Background Despite common use, anticholinergic medications have been associated with serious health risks. Interventions to reduce their use are being developed and there is a need to understand their implementation into clinical care. Aim of review This systematic review aims to identify and analyse qualitative research studies exploring the barriers and facilitators to reducing anticholinergic burden. Methods Medline (OVID), EMBASE (OVID), CINAHL (EMBSCO) and PsycINFO (OVID) were searched using comprehensive search terms. Peer reviewed studies published in English presenting qualitative research in relation to the barriers and facilitators of deprescribing anticholinergic medications, involving patients, carers or health professionals were eligible. Normalization Process Theory was used to explore and explain the data. Results Of 1764 identified studies, two were eligible and both involved healthcare professionals (23 general practitioners, 13 specialist clinicians and 12 pharmacists). No studies were identified that involved patients or carers. Barriers to collaborative working often resulted in poor motivation to reduce anticholinergic use. Low confidence, system resources and organisation of care also hindered anticholinergic burden reduction. Good communication and relationships with patients, carers and other healthcare professionals were reported as important for successful anticholinergic burden reduction. Having a named person for prescribing decisions, and clear role boundaries, were also important facilitators. Conclusions This review identified important barriers and facilitators to anticholinergic burden reduction from healthcare provider perspectives which can inform implementation of such deprescribing interventions. Studies exploring patient and carer perspectives are presently absent but are required to ensure person-centeredness and feasibility of future interventions.
Topics: Caregivers; Cholinergic Antagonists; Health Personnel; Humans; Pharmacists; Qualitative Research
PubMed: 34173123
DOI: 10.1007/s11096-021-01293-4 -
Respiratory Research Jun 2021Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial.
METHODS
We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest.
RESULTS
We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64-0.83) and improved the QOL score and trough FEV compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18-0.48) and mortality (odds ratio 0.66, 95% CI 0.50-0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16-2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV than LAMA/LABA. Concerning the trough FEV, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference.
CONCLUSION
Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations.
CLINICAL TRIAL REGISTRATION
PROSPERO; CRD42020191978.
Topics: Adrenergic beta-2 Receptor Agonists; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 34154582
DOI: 10.1186/s12931-021-01777-x -
The Cochrane Database of Systematic... May 2021Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the 'anticholinergic burden' because of its potential to cause adverse effects. It is possible that high anticholinergic burden may be a risk factor for development of cognitive decline or dementia. There are various scales available to measure anticholinergic burden but agreement between them is often poor.
OBJECTIVES
To assess whether anticholinergic burden, as defined at the level of each individual scale, is a prognostic factor for future cognitive decline or dementia in cognitively unimpaired older adults.
SEARCH METHODS
We searched the following databases from inception to 24 March 2021: MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), and ISI Web of Science Core Collection (ISI Web of Science).
SELECTION CRITERIA
We included prospective and retrospective longitudinal cohort and case-control observational studies with a minimum of one year' follow-up that examined the association between an anticholinergic burden measurement scale and future cognitive decline or dementia in cognitively unimpaired older adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, and undertook data extraction, assessment of risk of bias, and GRADE assessment. We extracted odds ratios (OR) and hazard ratios, with 95% confidence intervals (CI), and linear data on the association between anticholinergic burden and cognitive decline or dementia. We intended to pool each metric separately; however, only OR-based data were suitable for pooling via a random-effects meta-analysis. We initially established adjusted and unadjusted pooled rates for each available anticholinergic scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. We examined variability based on severity of anticholinergic burden.
MAIN RESULTS
We identified 25 studies that met our inclusion criteria (968,428 older adults). Twenty studies were conducted in the community care setting, two in primary care clinics, and three in secondary care settings. Eight studies (320,906 participants) provided suitable data for meta-analysis. The Anticholinergic Cognitive Burden scale (ACB scale) was the only scale with sufficient data for 'scale-based' meta-analysis. Unadjusted ORs suggested an increased risk for cognitive decline or dementia in older adults with an anticholinergic burden (OR 1.47, 95% CI 1.09 to 1.96) and adjusted ORs similarly suggested an increased risk for anticholinergic burden, defined according to the ACB scale (OR 2.63, 95% CI 1.09 to 6.29). Exploratory analysis combining adjusted ORs across available scales supported these results (OR 2.16, 95% CI 1.38 to 3.38), and there was evidence of variability in risk based on severity of anticholinergic burden (ACB scale 1: OR 2.18, 95% CI 1.11 to 4.29; ACB scale 2: OR 2.71, 95% CI 2.01 to 3.56; ACB scale 3: OR 3.27, 95% CI 1.41 to 7.61); however, overall GRADE evaluation of certainty of the evidence was low.
AUTHORS' CONCLUSIONS
There is low-certainty evidence that older adults without cognitive impairment who take medications with anticholinergic effects may be at increased risk of cognitive decline or dementia.
Topics: Aged; Aged, 80 and over; Analysis of Variance; Bias; Cholinergic Antagonists; Cognitive Dysfunction; Confidence Intervals; Dementia; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Odds Ratio; Prognosis; Syndrome; Treatment Outcome
PubMed: 34097766
DOI: 10.1002/14651858.CD013540.pub2 -
JAMA Jun 2021The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.
OBJECTIVE
To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.
DATA SOURCES
MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.
STUDY SELECTION
Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.
MAIN OUTCOMES AND MEASURES
Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.
RESULTS
Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).
CONCLUSIONS AND RELEVANCE
Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Child; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Quality of Life; Severity of Illness Index; Symptom Flare Up; Xerostomia
PubMed: 34009257
DOI: 10.1001/jama.2021.7872 -
Respiration; International Review of... 2021Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for... (Comparative Study)
Comparative Study Meta-Analysis
Comparisons of Efficacy and Safety between Triple (Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist) Therapies in Chronic Obstructive Pulmonary Disease: Systematic Review and Bayesian Network Meta-Analysis.
BACKGROUND
Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD).
OBJECTIVE
Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia.
METHOD
We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757).
RESULTS
Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0-0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0-0.97]}.
CONCLUSION
There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.
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: 33971649
DOI: 10.1159/000515133 -
Advances in Therapy Jun 2021In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic... (Meta-Analysis)
Meta-Analysis
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 33929661
DOI: 10.1007/s12325-021-01703-z -
The Cochrane Database of Systematic... Apr 2021This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder,...
BACKGROUND
This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment.
OBJECTIVES
To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia.
SEARCH METHODS
We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020.
SELECTION CRITERIA
Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event.
MAIN RESULTS
We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness).
AUTHORS' CONCLUSIONS
We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.
Topics: Botulinum Toxins, Type A; Humans; Muscarinic Antagonists; Neuromuscular Agents; Torticollis; Trihexyphenidyl
PubMed: 33852744
DOI: 10.1002/14651858.CD004312.pub3 -
Developmental Medicine and Child... Sep 2021To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and... (Meta-Analysis)
Meta-Analysis
AIM
To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia.
METHOD
Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE.
RESULTS
Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis.
INTERPRETATION
Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.
Topics: Baclofen; Botulinum Toxins; Cerebral Palsy; Clonidine; Deep Brain Stimulation; Dystonia; Humans; Injections, Spinal; Levodopa; Neurosurgical Procedures; Trihexyphenidyl
PubMed: 33772789
DOI: 10.1111/dmcn.14874 -
International Journal of Chronic... 2021Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is... (Review)
Review
Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.
Topics: Bronchodilator Agents; Humans; Inflammation; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Receptors, Muscarinic; Tiotropium Bromide
PubMed: 33603353
DOI: 10.2147/COPD.S285867