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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 -
Critical Care (London, England) Dec 2019The α2 agonists, dexmedetomidine and clonidine, are used as sedative drugs during critical illness. These drugs may have anti-inflammatory effects, which might be...
BACKGROUND
The α2 agonists, dexmedetomidine and clonidine, are used as sedative drugs during critical illness. These drugs may have anti-inflammatory effects, which might be relevant to critical illness, but a systematic review of published literature has not been published. We reviewed animal and human studies relevant to critical illness to summarise the evidence for an anti-inflammatory effect from α2 agonists.
METHODS
We searched PubMed, the Cochrane library, and Medline. Animal and human studies published in English were included. Broad search terms were used: dexmedetomidine or clonidine, sepsis, and inflammation. Reference lists were screened for additional publications. Titles and abstracts were screened independently by two reviewers and full-text articles obtained for potentially eligible studies. Data extraction used a bespoke template given study diversity, and quality assessment was qualitative.
RESULTS
Study diversity meant meta-analysis was not feasible so descriptive synthesis was undertaken. We identified 30 animal studies (caecal ligation/puncture (9), lipopolysaccharide (14), acute lung injury (5), and ischaemia-reperfusion syndrome (5)), and 9 human studies. Most animal (26 dexmedetomidine, 4 clonidine) and all human studies used dexmedetomidine. In animal studies, α2 agonists reduced serum and/or tissue TNFα (20 studies), IL-6 (17 studies), IL-1β (7 studies), NFκB (6 studies), TLR4 (6 studies), and a range of other mediators. Timing and doses varied widely, but in many cases were not directly relevant to human sedation use. In human studies, dexmedetomidine reduced CRP (4 studies), TNFα (5 studies), IL-6 (6 studies), IL-1β (3 studies), and altered several other mediators. Most studies were small and low quality. No studies related effects to clinical outcomes.
CONCLUSION
Evidence supports potential anti-inflammatory effects from α2 agonists, but the relevance to clinically important outcomes is uncertain. Further work should explore whether dose relationships with inflammation and clinical outcomes are present which might be separate from sedation-mediated effects.
Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Clonidine; Critical Illness; Dexmedetomidine; Disease Models, Animal; Humans; Inflammation
PubMed: 31829277
DOI: 10.1186/s13054-019-2690-4 -
What is the evidence for mirtazapine in treating cancer-related symptomatology? A systematic review.Supportive Care in Cancer : Official... Apr 2020Cancer patients often experience multiple distressing symptoms which are challenging to manage. It would therefore be helpful to find a treatment that alleviates more... (Review)
Review
PURPOSE
Cancer patients often experience multiple distressing symptoms which are challenging to manage. It would therefore be helpful to find a treatment that alleviates more than one symptom, to avoid polypharmacy: mirtazapine has been used in several studies for this purpose. The objective of this study was to assess the effectiveness and safety of mirtazapine in alleviating one or more frequently encountered cancer-related symptoms.
METHODS
Systematic review of clinical trials in English or French. Eight databases were searched. Included studies assessed the effectiveness of mirtazapine in alleviating one or more frequently encountered cancer-related symptoms. Comparator and validated assessment tools were required. Studies were independently appraised by two investigators before data synthesis.
RESULTS
The search yielded 1898 references, from which we identified 12 relevant articles evaluating highly heterogeneous outcomes. These were two randomised-controlled (RCTs), three non-randomised controlled, and seven non-randomised non-controlled trials. In total, 392 participants were included and 185 were in RCTs. No study assessed the effectiveness of mirtazapine in alleviating symptoms at the same time, but some considered more than one symptom. Overall, the data was of poor quality, limited by small sample size and bias. However, mirtazapine showed effectiveness in treating depression, anxiety, sleep disorders, emesis and neuropathic pain. Across all studies, mirtazapine is safe to use, with drowsiness and dizziness the most common side-effects.
CONCLUSION
Study design and small sample sizes limit the ability to interpret results. Trials to assess the impact of mirtazapine or other medicines in alleviating multiple symptoms would be valuable.
Topics: Adrenergic alpha-2 Receptor Antagonists; Antidepressive Agents; Clinical Trials as Topic; Depression; Humans; Mirtazapine; Neoplasms; Palliative Care; Randomized Controlled Trials as Topic
PubMed: 31858251
DOI: 10.1007/s00520-019-05229-7 -
BMC Pulmonary Medicine Feb 2020Because of its analgesic and light sedative properties, the highly selective alpha-2 adrenergic receptor agonist dexmedetomidine (DEX) has been suggested for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Because of its analgesic and light sedative properties, the highly selective alpha-2 adrenergic receptor agonist dexmedetomidine (DEX) has been suggested for the treatment of septic patients, but its effect on the duration of mechanical ventilation remains unclear. The present study was conducted to review the extant literature in DEX and determine its influence on ventilation time in adult septic patients.
METHODS
Databases of PubMed, Cochrane, and EMBASE were applied till 20th January 2019 without language restriction. The searching strategy as following: sepsis OR septic AND mechanical ventilation AND dexmedetomidine. Two authors screened titles, abstracts, and even articles to meet the including criterion independently. In addition, references of related articles or reviews were also referred. Data was recorded in a table and analyzed using the software of Review Manager 5.0.
RESULTS
Four studies with a total of 349 patients were included. Three trials with 267 patients revealed the effect of DEX on duration of mechanical ventilation, two trials with 264 patients on ventilator-free days and four trials with 334 patients on 28-day mortality. The analyzed results indicated that DEX was not associated with significantly different durations of mechanical ventilation (MD 0.65, 95% CI, - 0.13 to 1.42, P = 0.10). However, there were significant differences in ventilator-free days (MD 3.57, 95% CI, 0.26 to 6.89, P = 0.03) and 28-day mortality (RR 0.61, 95% CI, 0.49 to 0.94, P = 0.02) in the septic patients.
CONCLUSION
Administration of DEX for sedation in septic patients was not associated with the duration of mechanical ventilation, but it increased the ventilator-free days and reduced 28-day mortality.
Topics: Dexmedetomidine; Humans; Hypnotics and Sedatives; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial; Sepsis; Treatment Outcome; Ventilator Weaning
PubMed: 32066417
DOI: 10.1186/s12890-020-1065-6 -
Medicine Nov 2021Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD.
METHODS
Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models.
RESULTS
This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47).
CONCLUSION
Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.Registration: PROSPERO (no. CRD42021265830).
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Adrenergic, alpha-2; Treatment Outcome
PubMed: 34797323
DOI: 10.1097/MD.0000000000027858 -
British Journal of Clinical Pharmacology Apr 2021The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are... (Meta-Analysis)
Meta-Analysis Review
AIMS
The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are conflicting. We conducted a meta-analysis to examine the cumulative evidence of the effects of these 2 variants on percent forced expiratory volume in 1 second (FEV1.0%) after albuterol use in asthma patients.
METHODS
We conducted a comprehensive literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies examining the association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% shortly after albuterol administration. The individual study results were combined with weights based on the inverse variance method. This systematic review was registered in the PROSPERO (registration number: CRD42019074554).
RESULTS
Among 273 initial studies identified, 7 studies met the inclusion criteria for quantitative evaluation. Results of the overall meta-analysis indicated no statistically significant mean difference of FEV1.0% between genotypes of Arg16Gly and Gln27Glu. In subgroup analyses, significant associations were found for Arg16Gly GG (vs AA) among studies where no methacholine bronchoconstriction was conducted (mean difference, -3.92; 95% confidence interval, -7.29 to -0.54; I = 0%), and for Arg16Gly GG (vs GA) among studies that included patients with no comorbidities (mean difference, -1.93; 95% confidence interval, -3.77 to -0.10; I = 0%).
CONCLUSION
Synthesis of the studies to date shows weak evidence for an association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% after albuterol use, results of which underscore significant heterogeneity across studies and the need for careful design and sample size considerations.
Topics: Albuterol; Asthma; Bronchodilator Agents; Humans; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2
PubMed: 32986886
DOI: 10.1111/bcp.14570 -
Lipids in Health and Disease May 2020Recently, some studies claim that adipokines may modulate plasma lipids. More interestingly, the ADRB3 Trp64Arg polymorphism may regulate adipokines and play an... (Meta-Analysis)
Meta-Analysis
The Trp64Arg polymorphism in β3 adrenergic receptor (ADRB3) gene is associated with adipokines and plasma lipids: a systematic review, meta-analysis, and meta-regression.
BACKGROUND
Recently, some studies claim that adipokines may modulate plasma lipids. More interestingly, the ADRB3 Trp64Arg polymorphism may regulate adipokines and play an essential role in lipids metabolism. This study aims to clarify the associations of ADRB3 Trp64Arg polymorphism with plasma adipokines and lipid levels.
METHODS
Twenty-two studies (5527 subjects) and 121 studies (54,059 subjects) were respectively identified for the association analyses of adipokines and lipids. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate the strength of the Trp64Arg variant in adipokines and plasma lipids. All results were recalculated after eliminating the studies with heterogeneity.
RESULTS
The carriers of the C allele (Arg at 64th position was encoded by the C allele) had higher levels of leptin and lower levels of adiponectin than the non-carriers. The carriers of the C allele had higher levels of triglycerides (TG), total cholesterol (TC), and lower levels of high-density lipoprotein cholesterol (HDL-C) than the non-carriers. Subgroup analysis certified an ethnicity (Asians), disease status (obesity), and gender (females) specific association. Sensitivity analysis indicated that the analysis results were robust and stable. Meta-regression indicated that obesity was related to adiponectin.
CONCLUSIONS
The C allele carriers of Trp64Arg polymorphism had a slight but significant influence on lipid levels, and the remarkable effects specific existed in obese Asian women. The associations of Trp64Arg polymorphism with dyslipidemia may partly be mediated by the effect of this polymorphism on adipokines. The association of Trp64Arg polymorphism with obesity may partly be mediated by the effect of this polymorphism on adipokines. The C allele carriers had abnormal levels of adipokines and lipids, and it indicated that the Trp64Arg polymorphism might represent a genetic risk factor for coronary artery disease (CAD).
Topics: Female; Humans; Male; Adiponectin; Cholesterol; Cholesterol, HDL; Dyslipidemias; Gene Expression Regulation; Genetic Predisposition to Disease; Leptin; Lipids; Obesity; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-3; Sex Factors; Triglycerides
PubMed: 32430022
DOI: 10.1186/s12944-020-01290-y -
Indian Journal of Anaesthesia Aug 2020Evaluations of adverse heart rate (HR)-responses and HR-variations during anaesthesia in beach-chair-position (BCP) for shoulder surgeries have not been done earlier. We...
Adverse heart rate responses during beach-chair position for shoulder surgeries - A systematic review and meta-analysis of their incidence, interpretations and associations.
BACKGROUND AND AIMS
Evaluations of adverse heart rate (HR)-responses and HR-variations during anaesthesia in beach-chair-position (BCP) for shoulder surgeries have not been done earlier. We analysed the incidence, associations, and interpretations of adverse HR-responses in this clinical setting.
METHODS
We performed a meta-analysis of trials that reported HR-related data in anaesthetised subjects undergoing elective shoulder surgeries in BCP. Studies included prospective, randomised, quasi-randomised and non-randomised, controlled clinical trials as well as observational cohorts. Literature search was conducted in MEDLINE, EMBASE, CINHAL and the Cochrane Central Register of Controlled Trials of the 21 century. In the first analysis, we studied the incidence and associations of bradycardia/hypotension-bradycardia episodes (HBE) with respect to the type of anaesthesia and different pharmacological agents. In the second, we evaluated anaesthetic influences, associations and inter-relationships between monitored parameters with respect to HR-behaviours.
RESULTS
Among the trials designed with bradycardia/HBE as a primary end point, the observed incidence of bradycardia was 9.1% and that of HBE, 14.9% and 22.7% [(for Interscalene block (ISB) ± sedation) subjects and general anaesthesia (GA) + ISB, respectively]. There was evidence of higher observed risk of developing adverse HR-responses for GA subjects over ISB (Risk Difference, < 0.05). Concomitant use of β-agonists did not increase risk of HBEs ( = 0.29, = 11.4%) or with fentanyl ( = 0.45, = 0%) for ISB subjects (subgroup analysis). Fentanyl significantly influenced the HR-drop over time [meta-regression, estimates (standard error), 14.9 (5.4), 9.8 (4.3) and 17 (2.6); = 0.007, 0.024 and <0.001; for early, mid and delayed periods, respectively] in GA subjects. With respect to number of subjects experiencing cerebral desaturation events (CDEs), total intravenous anaesthesia (TIVA)- propofol had higher risk over inhalational anaesthesia ( = 0.006, = 86.7%). Meta-correlation analysis showed relationships between the HR and rSO(regional cerebral oxygen saturation) or SjvO(jugular venous oxygen saturation) values (r = 0.608, 95%CI, 0.439 to 0.735, < 0.001, = 77.4% and r = 0.397, 95%CI, 0.151 to 0.597, < 0.001, = 64.3%, respectively).
CONCLUSIONS
There is not enough evidence to claim the associations of adverse HR-responses with any specific factor. HR-fall is maximal with fentanyl and its variability is associated with changes in rSO. Fall in rSO could be the common link triggering adverse HR-responses in BCP.
PubMed: 32934399
DOI: 10.4103/ija.IJA_228_20 -
BMC Pulmonary Medicine Apr 2020Inhaled bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) play a central role in the treatment of stable chronic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Inhaled bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) play a central role in the treatment of stable chronic obstructive pulmonary disease (COPD). However, it is still unclear whether LABA or LAMA should be used for the initial treatment. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LABA versus LAMA in patients with stable COPD.
METHODS
We searched relevant randomized control trials (RCTs) with a period of treatment of at least 12 weeks and analyzed the exacerbations, quality of life, dyspnea score, lung function and adverse events as the outcomes of interest.
RESULTS
We carefully excluded unblinded data and identified a total of 19 RCTs (N = 28,211). LAMA significantly decreased the exacerbations compared to LABA (OR 0.85, 95% CI 0.74 to 0.98; P = 0.02). In St George's Respiratory Questionnaire and transitional dyspnoea index score, there were no differences between LABA and LAMA treatment. Compared to LABA, there was a small but significant increase in the trough FEV after LAMA treatment (Mean difference 0.02, 95% CI 0.01 to 0.03, P = 0.0006). In the safety components, there was no difference in the serious adverse events between LABA and LAMA. However, LAMA showed a significantly lower incidence of total adverse events compared to LABA (OR 0.92, 95% CI 0.86 to 0.98; P = 0.02).
CONCLUSION
Treatment with LAMA in stable COPD provided a significantly lower incidence of exacerbation and non-serious adverse events, and a higher trough FEV compared to LABA.
TRIAL REGISTRATION
(PROSPERO: CRD42019144764).
Topics: Adrenergic beta-2 Receptor Agonists; Disease Progression; Drug Administration Schedule; Drug Combinations; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 32349720
DOI: 10.1186/s12890-020-1152-8 -
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