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.

English tweets on allergy: Content analysis and association with surveillance data.

BACKGROUND: Analysis of X (formerly Twitter) posts can inform on the interest/perceptions that social media users have on health subjects. In this study, we aimed to analyse tweets on allergic conditions, comparing them with surveillance data. METHODS: We retrieved tweets from England on "allergy," "asthma," and "allergic rhinitis," published between 2016 and 2021. We estimated the correlation between the frequency of tweets on "asthma" and "allergic rhinitis" and English surveillance data on the incidence of asthma and allergic rhinitis medical visits. We performed sentiment analysis, computing a score informing on the emotional tone of assessed tweets. We applied a topic modelling approach to identify topics (clusters of words frequently occurring together) for tweets on each assessed condition. RESULTS: We analysed a total of 13,605 tweets on "allergy," 7767 tweets on "asthma," and 11,974 tweets on "allergic rhinitis." Food-related words were preponderant on tweets on "allergy," while "eyes" was the most frequent meaningful word on "allergy rhinitis" tweets. We observed seasonal patterns for tweets on "allergic rhinitis," both in their frequency and sentiment - the incidence of allergic rhinitis medical visits was moderately to strongly correlated with the frequency (ρ = 0.866) and sentiment (ρ = -0.474) of tweets on "allergic rhinitis." For tweets on "asthma," no such patterns/correlations were observed. The average sentiment score was negative for all assessed conditions, ranging from -0.004 ("asthma") to -0.083 ("allergic rhinitis"). CONCLUSIONS: Tweets on "allergic rhinitis" displayed a seasonal pattern regarding their frequency and sentiment, which correlated with surveillance data. No such patterns were observed for "asthma."

Patients' values and preferences for health states in allergic rhinitis-An artificial intelligence supported systematic review.

BACKGROUND: Allergic rhinitis (AR) impacts patients' physical and emotional well-being. Assessing patients' values and preferences (V&P) related to AR is an essential part of patient-centered care and of the guideline development process. We aimed to systematically summarize the information about patients' V&P on AR and its symptoms and impact on daily life. METHODS: We conducted systematic review in a MEDLINE, Embase, PsychInfo, and CINAHL databases. We included studies which quantitatively assessed patients' V&P for specific outcomes in AR by assessing utilities, applying discrete choice approaches, or rating and ranking outcomes. We grouped outcomes as AR symptoms, functional status, and care-related patient experience. Study selection and data extraction were supported by the Laser AI tool. We rated the certainty of evidence (CoE) using the GRADE approach. RESULTS: Thirty-six studies (41 records) were included: nine utility studies, seven direct-choice studies and 21 studies of rating or ranking outcomes. Utilities were lower with increased AR severity and with the concomitant presence of asthma, but not with whether AR was seasonal or perennial (CoE = low-high). Patients rated AR symptom-related outcomes as more important than those related to care-related patient experience and functional status (CoE = very low-moderate). Nasal symptoms (mainly nasal congestion) followed by breathing disorders, general and ocular symptoms were rated as the symptoms with the highest impact. CONCLUSIONS: This systematic review provides a comprehensive overview of V&P of patients with AR. Patients generally considered nasal symptoms as the most important. Future studies with standardized methods are needed to provide more information on V&P in AR.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

INTRODUCTION: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. METHODS: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. RESULTS: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. CONCLUSIONS: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Platelet transfusions in preterm infants: current concepts and controversies-a systematic review and meta-analysis.

Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken.    Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.

Neurodevelopment outcomes in the first 5 years of the life of children with transposition of the great arteries surgically corrected in the neonatal period: systematic review and meta-analysis.

OBJECTIVES: In patients with transposition of the great arteries, surgical correction may achieve definitive treatment, so a thorough knowledge of the long-term outcomes, particularly neurodevelopment outcomes, is essential. Therefore, we conducted a systematic review and meta-analysis to study the neurodevelopment outcomes in the first 5 years of the life of children submitted to corrective surgery for transposition of the great arteries in the neonatal period. METHODS: A total of 17 studies from 18 reports were included, assessing 809 individuals with surgically corrected transposition of the great arteries. The neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development (BSID) and the Wechsler Intelligence Scale for Children (WISC). RESULTS: Mean Mental Development Index (MDI) and Psychomotor Development Index (PDI) were within the average values from 1 to 3 years of age, although the proportion of children scoring more than 1 standard deviation below the mean in PDI, MDI, motor, and language composite scores was significantly higher than in the general population. From 4 to 5 years, mean full-scale global intelligence quotient (IQ), verbal IQ, and performance IQ scores did not differ significantly from the general population. CONCLUSION: This study revealed neurodevelopment scores within the normal range at 5 years of age in children submitted to corrective surgery for transposition of the great arteries in the neonatal period. However, these early outcomes may not adequately predict long-term outcomes. Further studies are needed to identify specific risk factors and early markers of later impairment to guide the establishment of early interventions.

Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference.

BACKGROUND: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. METHODS: We assessed the MASK-air® app data (May 2015-December 2020) by users self-reporting AR (16-90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. RESULTS: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71-0.80). CONCLUSION: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.

Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air® real-world data.

BACKGROUND: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. METHODS: We analysed 2015-2020 MASK-air® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms ('VAS Global Symptoms') and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. RESULTS: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p < .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H1 -antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. CONCLUSIONS: Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.

Regional, sex, and age inequities in asthma hospital admissions in Spain and Portugal.

BACKGROUND: Asthma presents a significant health challenge, imposing a considerable burden on healthcare services. Discrepancies in asthma-related hospitalisations may reflect underlying health disparities. We aimed to analyse inequities in asthma hospital admissions in mainland Portugal and Spain, from a regional perspective and considering sex and age. METHODS: We conducted a retrospective study using data from the Spanish and Portuguese national hospitalisations databases. We calculated crude national and regional yearly hospitalisation rates according per Nomenclature of Territorial Units for Statistics region. Additionally, we calculated hospitalisation rates adjusted for asthma prevalence and the female-to-male ratio in asthma hospital admissions per age group, considering the female-to-male ratio in the overall population. RESULTS: Between 2012 and 2016, there were 92,084 asthma hospital admissions in mainland Spain and 7717 in mainland Portugal. There was a trend for a higher-than-average rate of asthma-related hospitalisations in the Northern regions of both countries. Women had a hospitalisation rate that was 3.2 times higher than men. Age was associated with higher risk for asthma hospitalisation, with individuals aged 65 and older displaying a hospitalisation rate 4.5 times higher than those under 65. Additionally, while hospitalisations in women aged <65 years were 2.3 times more likely than in men of the same age, hospitalisations in women aged ≥65 years were 3.5 times higher than in men aged ≥65 years. CONCLUSION: This study suggests that marked regional inequities in asthma hospital admissions exist in Spain and Portugal. Additionally, women are particularly at risk of hospitalisation due to asthma, and such risk increases with age.

Embedding patients' values and preferences in guideline development for allergic diseases: The case study of Allergic Rhinitis and its Impact on Asthma 2024.

Recommendations for or against the use of interventions need to consider both desirable and undesirable effects as well as patients' values and preferences (V&P). In the decision-making context, patients' V&P represent the relative importance people place on the outcomes resulting from a decision. Therefore, the balance between desirable and undesirable effects from an intervention should depend not only on the difference between benefits and harms but also on the value that patients place on them. V&P are therefore one of the criteria to be considered when formulating guideline recommendations in the Evidence-to-Decision framework developed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group. Patients' V&P may be quantified through utilities, which can be elicited using direct methods (e.g., standard gamble or time trade-off) or indirect methods (using validated instruments to measure health-related quality of life, such as EQ-5D). The GRADE approach recommends conducting systematic reviews to summarise all the available evidence and assess the degree of certainty on V&P. In this article, we discuss the importance of considering patients' V&P and provide examples of how they are considered in the 2024 person-centred Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines.

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.

Poor Rhinitis and Asthma Control Is Associated With Decreased Health-Related Quality of Life and Utilities: A MASK-air Study.

BACKGROUND: Allergic rhinitis (AR) and asthma may affect health-related quality of life. However, national estimates on the quality of life of patients with AR or asthma are lacking. OBJECTIVE: To provide estimates for utility scores and EuroQoL five-dimension (EQ-5D) visual analog scale (VAS) for patients with AR or asthma. METHODS: We conducted a cross-sectional study using direct patient data from the MASK-air app on European MASK-air users with self-reported AR or asthma. We used a multi-attribute instrument (EQ-5D) to measure quality of life (as utility scores and EQ-5D VAS values). Mean scores were calculated per country and disease control level using multilevel regression models with poststratification, accounting for age and sex biases. RESULTS: We assessed data from 7905 MASK-air users reporting a total of up to 82,737 days. For AR, utilities ranged from 0.86 to 0.99 for good control versus 0.72 to 0.85 for poor control; EQ-5D VAS levels ranged from 78.9 to 87.9 for good control versus 55.3 to 64.2 for poor control. For asthma, utilities ranged from 0.84 to 0.97 for good control versus 0.73 to 0.87 for poor control; EQ-5D VAS levels ranged from 68.4 to 81.5 for good control versus 51.4 to 64.2 for poor control. Poor disease control was associated with a mean loss of 0.14 utilities for both AR and asthma. For the same control levels, AR and asthma were associated with similar utilities and EQ-5D VAS levels. However, lower values were observed for asthma plus AR compared with AR alone. CONCLUSIONS: Poor AR or asthma control are associated with reduced quality of life. The estimates obtained from mobile health data may provide valuable insights for health technology assessment studies.

Impact of Allergic Rhinitis Control on Work Productivity and Costs: A Real-World Data MASK-air Study.

BACKGROUND: Allergic rhinitis (AR) has a substantial socioeconomic impact associated with impaired work productivity. OBJECTIVE: To study the impact of AR on work productivity and estimate the corresponding indirect costs for 40 countries. METHODS: We conducted a cross-sectional study using direct patient data from the MASK-air app on users with self-reported AR. We used the Work Productivity and Activity Impairment Questionnaire: Allergy Specific to measure the impact of AR on work productivity (presenteeism and absenteeism). Weekly indirect costs were estimated per country for each level of rhinitis control. Patients with and without asthma were considered. RESULTS: We assessed data from 677 weeks (364 patients), 280 of which were reported by patients with asthma. Regarding presenteeism, the median impact of AR in weeks of poor disease control was 60.7% (percentiles 25-75 [P25-P75] 24.9%-74.2%), whereas partial and good disease control were, respectively, associated with an impact of 25.0% (P25-P75 12.1%-42.4%) and 4.4% (P25-P75 0.8%-12.9%). In poorly controlled weeks, presenteeism was associated with indirect costs ranging from 65.7 US$ purchase power parities (PPPs) (P25-P75 29.2-143.2) in Brazil to 693.6 US$ PPP (P25-P75 405.2-1,094.9) in Iceland. Median absenteeism per week was of 0% for all levels of rhinitis control. Patients with AR + asthma showed higher overall work impairment than patients with AR alone, particularly in poorly controlled weeks (median work impairment in AR alone 39.1% [P25-P75 12.5%-71.9%]; median work impairment in AR + asthma 68.4% [P25-P75 54.6%-80.2%]). CONCLUSIONS: Poor AR control was associated with decreased work productivity and increased indirect costs, particularly in patients with AR + asthma. The estimates from this study underpin the economic burden of AR.

Detection of subclinical microvascular changes in systemic lupus erythematous using optical coherence tomography angiography: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune connective tissue disease that affects several vascular territories. We sought to assess the role of optical coherence tomography angiography in detecting subclinical microvascular alterations in SLE patients. PubMed, Scopus, and Web of Science databases were systematically searched until January 21, 2023. Studies using optical coherence tomography angiography as a primary diagnostic method to evaluate the macular microvasculature of SLE patients versus healthy controls were included. Primary outcomes were macular vessel density and foveal zone parameters. A meta-analysis was performed using a random-effects model. Of 301 screened abstracts, 15 were found eligible, enrolling 1,246 eyes from 1,013 patients. SLE patients presented a reduction of macular vessel density at both plexuses in all zones (whole scan, fovea, parafovea, and perifovea), and of foveal density compared with healthy controls. No differences were found at foveal avascular zone parameters. SLE patients presented a reduction of macular vessel density without signs or symptoms of SLE ocular involvement. Optical coherence tomography angiography application for the assessment of subclinical microvascular changes needs to be elucidated with longitudinal studies.

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.

Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study.

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78). INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. FUNDING: None.

Cutoff Values of MASK-air Patient-Reported Outcome Measures.

BACKGROUND: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested. OBJECTIVE: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms. METHODS: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs. RESULTS: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100). CONCLUSIONS: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management.