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The Journal of Allergy and Clinical... Feb 2024A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β-agonists in patients with severe asthma leads to long-term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β-agonists in patients with severe asthma leads to long-term adverse events. Oral corticosteroid-sparing agents are of high priority.
OBJECTIVE
This network meta-analysis assessed biologics' comparative efficacy and safety in OCS-dependent patients with asthma.
METHODS
We performed a systematic search through PubMed, Scopus, Embase, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials that addressed the efficacy and safety of biologics compared with placebo in OCS-dependent patients with asthma from inception to July 2023. The primary outcome was an overall reduction in the OCS dose while asthma control was maintained.
RESULTS
We included seven randomized controlled trials involving 1,052 OCS-dependent patients with asthma. Compared with placebo, benralizumab every 8 weeks, benralizumab every 4 weeks, dupilumab, and mepolizumab were efficacious in achieving a reduction in the OCS dose with low to moderate confidence (odds ratio [95% CI]: 4.12 [2.22-7.64]; 4.09 [2.22-7.55]; 3.25 [1.90-5.55]; and 2.39 [1.25-4.57], respectively) whereas tralokinumab, tezepelumab, and subcutaneous reslizumab were ineffective. An indirect comparison found no significant differences among benralizumab, dupilumab, and mepolizumab. Efficacy in reducing exacerbations was consistent with the primary analysis. High baseline blood eosinophil counts benefit from anti-IL-5 therapies, whereas high FeNO levels favor dupilumab regardless of blood eosinophil counts. Adverse events between biologics and placebo were comparable, except for eosinophilia with dupilumab.
CONCLUSIONS
In OCS-dependent patients with asthma, benralizumab, dupilumab, and mepolizumab were superior to placebo in reducing the OCS dose. Evaluating baseline biomarkers helps in choosing the proper biologics to maximize treatment effects.
Topics: Humans; Anti-Asthmatic Agents; Biological Products; Network Meta-Analysis; Asthma; Adrenal Cortex Hormones; Eosinophilia
PubMed: 37972921
DOI: 10.1016/j.jaip.2023.11.007 -
JAMA Oct 2023Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.
OBJECTIVE
To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.
STUDY SELECTION
Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).
MAIN OUTCOMES AND MEASURES
Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.
RESULTS
Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).
CONCLUSIONS AND RELEVANCE
Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.
Topics: Adult; Humans; Cough; Pyrimidines; Quality of Life; Sulfonamides; Dose-Response Relationship, Drug; Treatment Outcome; Chronic Disease; Taste
PubMed: 37694849
DOI: 10.1001/jama.2023.18035 -
The Journal of Allergy and Clinical... Jun 2023Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially life-threatening drug reaction; recognizing the diversity of its clinical presentations,...
BACKGROUND
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially life-threatening drug reaction; recognizing the diversity of its clinical presentations, implicated drugs, and management modalities can aid in diagnosis and reduce morbidity and mortality.
OBJECTIVE
To review the clinical features, drug causes, and treatments deployed in DRESS.
METHODS
This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to review publications relating to DRESS published between 1979 and 2021. Only publications with a RegiSCAR score of 4 or greater were included (indicating "probable" or "definite" DRESS). The PRISMA guidelines were used for data extraction and the Newcastle-Ottawa scale for quality assessment (Pierson DJ. Respir Care 2009;54:1372-8). The main outcomes included implicated drugs, patient demographics, clinical manifestations, treatment, and sequelae for each included publication.
RESULTS
A total of 1124 publications were reviewed, and 131 met the inclusion criteria, amounting to 151 cases of DRESS. The most implicated drug classes were antibiotics, anticonvulsants, and anti-inflammatories, although up to 55 drugs were implicated. Cutaneous manifestations were present in 99% of cases, with a median onset of 24 days and maculopapular rash the most common morphology. Common systemic features were fever, eosinophilia, lymphadenopathy, and liver involvement. Facial edema was present in 67 cases (44%). Systemic corticosteroids were the mainstay of DRESS-specific treatment. A total of 13 cases (9%) resulted in mortality.
CONCLUSION
DRESS diagnosis should be considered in the presence of a cutaneous eruption, fever, eosinophilia, liver involvement, and lymphadenopathy. The class of implicated drug may influence outcome, as allopurinol was associated with 23% of cases that resulted in death (3 cases). Given potential DRESS complications and mortality, it is important that DRESS is recognized early so that any suspect drugs are ceased promptly.
Topics: Drug Hypersensitivity; Humans; Eosinophilia; Anti-Bacterial Agents
PubMed: 36893848
DOI: 10.1016/j.jaip.2023.02.035 -
International Journal of Medical... Mar 2022Drug allergy alert systems (DAAS), have been considered an effective strategy to reduce preventable adverse drug events (ADEs), improving patient's safety. To date, no... (Review)
Review
BACKGROUND AND OBJECTIVE
Drug allergy alert systems (DAAS), have been considered an effective strategy to reduce preventable adverse drug events (ADEs), improving patient's safety. To date, no review has been conducted analyzing characteristics of DAAS in the hospital setting. Therefore, the aim of this study is to identify, describe and summarize the DAAS used in hospitals. The secondary objectives are to analyse drug allergy alerts (DAA) characteristics, the override rate (OvR) and the clinical consequences of alert overrides.
METHODS
Searches were conducted in Medline and Cochrane Library to identify studies describing DAAS. Systems characteristics, generated alerts, DAA, OvR, and its clinical consequences were extracted and analyzed.
RESULTS
Twenty-eight articles were included in the review. Seventeen different electronic DAAS were identified, of which 53% were commercially available. Systems differed in drug allergy information and rules for generating alerts. DAA were generally interruptive, triggered by non-exact match at drug prescribing and when ignored, an override reason was mandatory. The OvR ranged from 43.7% to 97%. The main override reason given by providers was that 'patient had previously tolerated or had taken the drug without allergic reaction'. Clinical consequences of overriding DAA were only analyzed in four studies, with an ADE incidence between 0% and 6%.
CONCLUSIONS
Different DAAS are used in hospitals with some degree of heterogeneity. Accurate and updated drug allergy information is important to generate only high value alerts. A regular review of DAAS and a standardization of alert rules, alert information and override reasons are necessary to optimize systems. Future studies should evaluate the impact of the DAAS aspects on preventing ADEs.
Topics: Decision Support Systems, Clinical; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Medical Order Entry Systems; Medication Systems
PubMed: 34990941
DOI: 10.1016/j.ijmedinf.2021.104673 -
Annals of Internal Medicine Nov 2020Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries.
PURPOSE
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
STUDY SELECTION
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries.
DATA EXTRACTION
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
LIMITATIONS
Only English-language studies were included. The number of head-to-head comparisons was limited.
CONCLUSION
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
PRIMARY FUNDING SOURCE
National Safety Council. (PROSPERO: CRD42018094412).
Topics: Acetaminophen; Acute Pain; Administration, Oral; Administration, Topical; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Comparative Effectiveness Research; Diclofenac; Drug Eruptions; Gastrointestinal Diseases; Humans; Musculoskeletal System; Nervous System Diseases; Network Meta-Analysis; Patient Satisfaction; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 32805127
DOI: 10.7326/M19-3601 -
International Forum of Allergy &... Jan 2024The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the... (Review)
Review
Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents' efficacy.
BACKGROUND
The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the selection of the proper biologic in treatment of chronic rhinosinusitis (CRS) with nasal polyps. The aim of this study is to summarize the current knowledge regarding the efficacy of omalizumab, dupilumab, and mepolizumab in CRS treatment. We also attempt to proceed to an indirect comparison of the agents and try to answer the tricky question: which agent to select and why?
METHODS
An extensive search in English literature was conducted in PubMed/Medline, Embase, Google Scholar, and Cochrane Database/Library. Eligibility criteria included papers with full text published in English, adult population studies, clearly described intervention protocol, and documented primary and secondary outcomes.
RESULTS
The studies included numbered 37. All agents provided significant improvement in polyp size, sinuses opacification, severity of symptoms, need for surgery and systemic corticosteroids use. Analysis of available systematic reviews, meta-analyses and indirect treatment comparison studies showed that dupilumab appeared to be the most beneficial agent, in terms of primary and secondary outcomes. However, these results are of relatively low level of evidence due to several methodological limitations.
CONCLUSIONS
Although the present analysis showed a moderate supremacy of dupilumab, there is still no evidence-based answer to the question "which biologic agent is the most effective in CRS treatment?" Improved statistical methodology, head-to-head trials, and real-life studies could lead to more robust conclusions, establishing the real role of the specific biologic agents.
Topics: Adult; Humans; Nasal Polyps; Omalizumab; Rhinosinusitis; Sinusitis; Chronic Disease; Biological Products; Rhinitis; Quality of Life; Antibodies, Monoclonal, Humanized
PubMed: 37394893
DOI: 10.1002/alr.23234 -
Journal of Anaesthesiology, Clinical... 2022Perioperative anaphylaxis is a rare, but life-threatening hypersensitivity reaction for patients undergoing surgical procedures. Sugammadex is a relatively new drug used... (Review)
Review
Perioperative anaphylaxis is a rare, but life-threatening hypersensitivity reaction for patients undergoing surgical procedures. Sugammadex is a relatively new drug used to reverse the neuromuscular blockade of specific anesthetics in surgery. Several case reports indicate that there may be a risk of anaphylaxis associated with the use of sugammadex This review examines the literature in order to evaluate the strength of the association between sugammadex use and anaphylaxis. A query of PubMed, EMBASE, and Web of Science was conducted using a combination of terms to identify relevant articles from inception until March 9, 2020. We included any primary study that identified sugammadex as a probable causative agent based on the World Allergy Organization diagnostic criteria for anaphylaxis. A total of 24 articles were reviewed. Across the three randomized controlled trials, there were only four cases of anaphylaxis identified. Incidence of anaphylaxis was reported in only one trial at 0.33%. Two retrospective observational studies conducted in Japan identified cases of anaphylaxis, with incidences of 0.02 and 0.04%. Among 19 case reports and series, 25 patient cases of anaphylaxis were confirmed via allergy testing to be caused by sugammadex or sugammadex-rocuronium complex. Commonly reported symptoms included hypotension, erythema, and decreased oxygen saturation. Based on the findings of this review, there appears to be a rare, but serious, association of sugammadex-induced perioperative anaphylaxis with an incidence between 0.02 and 0.04% in observational studies. It is unclear whether sugammadex on its own or in complex with rocuronium triggers this reaction, but it is clearly involved in inducing anaphylaxis. Further population studies are needed to get a more accurate global incidence rate, and more detailed allergy testing is required to better describe which step of the sugammadex reversal pathway initiates the anaphylactic attack.
PubMed: 36505200
DOI: 10.4103/joacp.JOACP_573_20 -
Allergy Jul 2021As the rise in prevalence of allergic diseases worldwide corresponds in time with increasing infant vaccination, it has been hypothesized that childhood vaccination may... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
As the rise in prevalence of allergic diseases worldwide corresponds in time with increasing infant vaccination, it has been hypothesized that childhood vaccination may increase the risk of allergic disease. We aimed to synthesize the literature on the association between childhood vaccination and allergy.
DESIGN
We searched the electronic databases PubMed and EMBASE (January 1946-January 2018) using vaccination and allergy terms.
METHODS
Two authors selected papers according to the inclusion criteria. Pooled effects across studies were estimated using random-effects meta-analysis. Due to inadequate number of homogeneous publications on newer and underused vaccines, meta-analysis was limited to allergic outcomes following administration of (Bacillus Calmette-Guérin) BCG, measles or pertussis vaccination. The review was prospectively registered in the PROSPERO systematic review registry (NO: CRD42017071009).
RESULTS
A total of 35 publications based on cohort studies and 7 publications based on randomized controlled trials (RCTs) met the inclusion criteria. RCTs: From 2 studies, early vaccination with BCG vaccine was associated with a reduced risk of eczema (RR = 0.83; 95% CI = 0.73-0.93; I = 0%) but not food allergy or asthma. No association was found between pertussis vaccine and any allergic outcome based on a single RCT.
COHORT STUDIES
Childhood measles vaccination was associated with a reduced risk of eczema (RR = 0.65; 95% CI = 0.47-0.90, I = 0.0%), asthma (RR = 0.78; 95% CI = 0.62-0.98, I = 93.9%) and, with a similar, statistically non-significant reduction in sensitization (RR = 0.78; 95% CI = 0.61-1.01, I = 19.4%).
CONCLUSIONS
We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease. Our results from pooled analysis of both RCTs and cohort studies suggest that vaccination with BCG and measles vaccines were associated with a reduced risk of eczema.
Topics: Asthma; BCG Vaccine; Eczema; Food Hypersensitivity; Humans; Infant; Vaccination
PubMed: 33569761
DOI: 10.1111/all.14771 -
Pediatric Research Jan 2023Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test.
METHODS
We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021.
RESULTS
The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I = 38%) from 18 studies.
CONCLUSIONS
The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare.
IMPACT
Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.
Topics: Humans; Child; beta-Lactams; Hypersensitivity; Prevalence
PubMed: 35449396
DOI: 10.1038/s41390-022-02076-x -
Frontiers in Allergy 2022Gadolinium-based contrast agents (GBCAs) are frequently used in magnetic resonance imaging (MRI) examinations to increase sensitivity in diagnoses. Recently, an increase...
Gadolinium-based contrast agents (GBCAs) are frequently used in magnetic resonance imaging (MRI) examinations to increase sensitivity in diagnoses. Recently, an increase in the description of hypersensitivity reactions to GBCAs has been detected. We performed research in PubMed, PubMed, SCOPUS, and EMBASE until September 2021, searching for studies regarding immediate and delayed hypersensitivity reactions to gadolinium-based contrast agents in which an allergy study was performed. The initial research identified 149 articles written in English. After excluding articles duplicated and articles that had irrelevant designs, 26 articles were included. Finally, 17 studies concerning immediate reactions, six studies concerning non-immediate reactions, and three concerning both that performed allergy evaluations were selected. In the review, we analyzed the characteristics of immediate and delayed reactions and the results of the allergy study and cross-reactivity. Skin tests seem to have acceptable accuracy, but drug provocation tests are still needed when skin tests are negative o to find alternative agents. Although cross-reactivity patterns are not well established, cross-reactivity seems to exist among macrocyclic agents. Notwithstanding, the number of patients analyzed is low and further studies are required. A management algorithm is suggested.
PubMed: 35386665
DOI: 10.3389/falgy.2022.813927