Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Intranasal antihistamines and corticosteroids in the treatment of allergic rhinitis: a systematic review and meta-analysis protocol.

INTRODUCTION: Intranasal antihistamines and corticosteroids are some of the most frequently used drug classes in the treatment of allergic rhinitis. However, there is uncertainty as to whether effectiveness differences may exist among different intranasal specific medications. This systematic review aims to analyse and synthesise all evidence from randomised controlled trials (RCTs) on the effectiveness of intranasal antihistamines and corticosteroids in rhinitis nasal and ocular symptoms and in rhinoconjunctivitis-related quality-of-life. METHODS AND ANALYSIS: We will search four electronic bibliographic databases and three clinical trials databases for RCTs (1) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis and (2) comparing the use of intranasal antihistamines or corticosteroids versus placebo. Assessed outcomes will include the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will perform a random-effects meta-analysis for each assessed medication and outcome, presenting results as pooled mean differences and standardised mean differences. Heterogeneity will be explored by sensitivity and subgroup analyses, considering (1) the risk of bias, (2) the follow-up period and (3) the drug dose. ETHICS AND DISSEMINATION: Ethical considerations will not be required. Results will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42023416573.

Control of Allergic Rhinitis and Asthma Test: A systematic review of measurement properties and COSMIN analysis.

The Control of Allergic Rhinitis and Asthma Test (CARAT) is a patient-reported outcome measurement (PROM) assessing the control of asthma and allergic rhinitis (AR) at a 4 week interval. This systematic review aimed to evaluate the measurement properties of CARAT. Following PRISMA and COSMIN guidelines, we searched five bibliographic databases and retrieved studies concerning the development, assessment of properties, validation, and/or cultural adaption of CARAT. The studies' methodological quality, the quality of measurement properties, and the overall quality of evidence were assessed. We performed meta-analysis of CARAT measurement properties. We included 16 studies. Control of Allergic Rhinitis and Asthma Test displayed sufficient content validity and very good consistency (meta-analytical Cronbach alpha = 0.83; 95% CI = 0.80-0.86;I2  = 62.6%). Control of allergic rhinitis and Asthma Test meta-analytical intraclass correlation coefficient was 0.91 (95% CI = 0.64-0.98;I2  = 93.7%). It presented good construct validity, especially for correlations with Patient-reported outcome measures assessing asthma (absolute Spearman correlation coefficients range = 0.67-0.73; moderate quality of evidence), and good responsiveness. Its minimal important difference is 3.5. Overall, CARAT has good internal consistency, reliability, construct validity and responsiveness, despite the heterogeneous quality of evidence. Control of Allergic Rhinitis and Asthma Test can be used to assess the control of asthma and AR. As first of its kind, this meta-analysis of CARAT measurement properties sets a stronger level of evidence for asthma and/or AR control questionnaires.

Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta-analysis.

BACKGROUND: Patients with a penicillin allergy label tend to have worse clinical outcomes and increased healthcare use. Drug provocation tests (DPT) are the gold-standard in the diagnostic workup of penicillin allergy, but safety concerns may hinder their performance. We aimed to assess the frequency of severe reactions following a DPT in patients with reported allergy to penicillins or other ß-lactams. METHODS: We performed a systematic review, searching MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with a penicillin allergy label who underwent a DPT. We performed a Bayesian meta-analysis to estimate the pooled frequency of severe reactions to penicillin DPTs. Sources of heterogeneity were explored by subgroup and metaregression analyses. RESULTS: We included 112 primary studies which included a total of 26,595 participants. The pooled frequency of severe reactions was estimated at 0.06% (95% credible interval [95% CrI] = 0.01%-0.13%; I2  = 57.9%). Most severe reactions (80/93; 86.0%) consisted of anaphylaxis. Compared to studies where the index reaction was immediate, we observed a lower frequency of severe reactions for studies assessing non-immediate index reactions (OR = 0.05; 95% CrI = 0-0.31). Patients reporting anaphylaxis as their index reaction were found to be at increased risk of developing severe reactions (OR = 13.5; 95% CrI = 7.7-21.5; I2  = 0.3%). Performance of direct DPTs in low-risk patients or testing with the suspected culprit drug were not associated with clinically relevant increased risk of severe reactions. CONCLUSIONS: In patients with a penicillin allergy label, severe reactions resulting from DPTs are rare. Therefore, except for patients with potentially life-threatening index reactions or patients with positive skin tests-who were mostly not assessed in this analysis -, the safety of DPTs supports their performance in the diagnostic assessment of penicillin allergy.

Clinical and economic burden of hospitalizations with registration of penicillin allergy.

BACKGROUND: Penicillin allergy is commonly reported, but only a minority of claimants has a confirmed diagnosis. Nevertheless, patients labeled as having penicillin allergy are treated with second-line antibiotics, which are more expensive and less effective, possibly increasing the risk of drug-resistant infections. OBJECTIVE: To compare hospitalizations with and without registration of penicillin allergy concerning their morbidity and hospital resource use. METHODS: We analyzed a national administrative database containing a registration of all Portuguese hospitalizations from 2000 to 2014. All episodes occurring in adults with a penicillin allergy registration were compared with an equal number of hospitalizations without such registration and matched for inpatients' age, sex, and main diagnosis. We compared those episodes concerning their length of stay, hospital price charges, comorbidities, and frequency of drug-resistant infections. Differences between medical and surgical hospitalizations were explored. RESULTS: Hospitalizations with registration of penicillin allergy (n = 102,872) had a longer average length of stay than the remainder episodes (8 vs 7 days; P < .001) and higher hospital charges (3,809.0 vs 3,490.0 USD; P < .001). Inpatients with penicillin allergy registration also had a higher mean Charlson Comorbidity Index (0.91 vs 0.76; P < .001) and a significantly higher frequency of infections by several agents, including methicillin-resistant Staphylococcus aureus, Enterococcus species, and Escherichia coli. Among surgical episodes, septicemia was 1.2-fold more frequent among penicillin allergy cases. CONCLUSION: Hospitalizations with registration of penicillin allergy are associated with increased economic costs and frequency of infections by drug-resistant agents, reinforcing the need to establish a correct diagnosis of penicillin allergy.