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.

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.

Potential for organ donation after controlled circulatory death: a retrospective analysis.

Objectives: Despite the discrepancy between demand and availability of organs for transplantation, controlled circulatory death donation has not been implemented in Portugal. This study aimed to estimate the potential increase in organ donation from implementing such a program. Material and Methods: All deceased patients within the intensive care medicine department at Centro Hospitalar Universitário de São João, throughout the year 2019, were subjected to retrospective analysis. Potential gain was estimated comparing the results with the number of donors and organs collected during the same period at this hospital center. Differences in variables between groups were assessed using t tests for independent samples or Mann-Whitney U tests for continuous variables, and chi-squared tests were used for categorical variables. Results: During 2019, 152 deaths occurred after withdrawal of life-sustaining therapies, 10 of which would have been potentially eligible for donation after controlled circulatory death. We can anticipate a potential increase of 10 prospective donors, a maximum 21% growth in yearly transplantation activity, with a greater impact on kidney transplantation. For most patients, the time between withdrawal of organ support and death surpassed 120 minutes, an outcome explained by variations in withdrawal of life-sustaining measures and insufficient clinical records, underestimating the potential for controlled circulatory arrest donation. Conclusion: This study effectively highlights public health benefits of controlled circulatory arrest donation. Legislation allowing donation through this method represents a social gain and enables patients who will never meet brain death criteria to donate organs as part of the end-of-life process in intensive care medicine, within a framework of complete ethical alignment.

Reaction Risk to Direct Penicillin Challenges: A Systematic Review and Meta-Analysis.

Importance: While direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier. Objective: To evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions. Data Sources: Three electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk. Study Selection: Two reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy. Data Extraction and Synthesis: Two reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies. Main Outcomes and Measures: The primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions. Results: A total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal. Conclusions and Relevance: This systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.

Protocol for the systematic reviews on the desirable and undesirable effects of pharmacological treatments of allergic rhinitis informing the ARIA 2024 guidelines.

There is insufficient evidence regarding the comparative efficacy and safety of pharmacological treatments of allergic rhinitis (AR). In the context of informing the 2024 revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, we plan to perform three systematic reviews of randomized controlled trials (RCTs) comparing the desirable and undesirable effects (i) between intranasal and oral medications for AR; (ii) between combinations of intranasal and oral medications versus nasal or oral medications alone; and (iii) among different intranasal specific medications. We will search four electronic bibliographic databases and three clinical trials databases for RCTs examining patients ≥ 12 years old with seasonal or perennial AR. Assessed outcomes will include the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. If appropriate, we will perform a pairwise random-effects meta-analysis for each pair of assessed medication classes and outcomes, as well as a network meta-analysis to assess the comparative efficacy of intranasal medications among each other. Heterogeneity will be explored by sensitivity and subgroup analyses. This set of systematic reviews will allow for a comprehensive assessment of the effectiveness and safety of pharmacological interventions for AR and inform recommendations in the context of the ARIA guidelines.

Intranasal versus oral treatments for allergic rhinitis: A systematic review with meta-analysis.

BACKGROUND: Treatments for allergic rhinitis include intranasal or oral medications. OBJECTIVE: To perform a systematic review with meta-analysis comparing the effectiveness of intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists in improving allergic rhinitis symptoms and quality of life. METHODS: We searched four bibliographic databases and three clinical trial datasets for randomised controlled trials (i) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis, and (ii) comparing intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists. We performed a meta-analysis of the Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), development of adverse events, and withdrawals due to adverse events. Certainty of evidence was assessed using GRADE. RESULTS: We included 35 studies, most of which assessed patients with seasonal allergic rhinitis and displayed an unclear risk of bias. Superiority of intranasal treatments was found for all assessed outcomes. Intranasal corticosteroids were more effective than oral antihistamines at improving the TNSS (MD=-0.86; 95%CI=-1.21;-0.51; I2=70%), TOSS (MD=-0.36; 95%CI=-0.56;-0.17; I2=0%) and RQLQ (MD=-0.88; 95%CI=-1.15;-0.61; I2=0%), being mostly associated with clinically meaningful improvements. Superiority of intranasal corticosteroids at improving the TNSS was also found against oral leukotriene receptor antagonists (MD=-1.05; 95%CI=-1.33;-0.77). Intranasal antihistamines were more effective than oral antihistamines at improving the TNSS (MD=-0.47; 95%CI=-0.81;-0.14; I2=0%) and RQLQ (MD=-0.31; 95%CI=-0.56;-0.06; I2=0%). CONCLUSIONS: Randomized controlled trials suggest that intranasal treatments are more effective than oral treatments at improving symptoms and quality of life in seasonal allergic rhinitis.

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.