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1.
Artículo en Inglés | MEDLINE | ID: mdl-38701495

RESUMEN

RATIONALE: There is no consensus on criteria to include in an asthma remission definition in real-life. Factors associated with achieving remission post-biologic-initiation remain poorly understood. OBJECTIVES: To quantify the proportion of adults with severe asthma achieving multi-domain-defined remission post-biologic-initiation and identify pre-biologic characteristics associated with achieving remission which may be used to predict it. METHODS: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1-year pre- and post-biologic-initiation. A priori-defined remission cut-offs were: 0 exacerbations/year, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted forced expiratory volume in one second ≥80%. Remission was defined using 2 (exacerbations + LTOCS), 3 (+control or +lung function) and 4 of these domains. The association between pre-biologic characteristics and post-biologic remission was assessed by multivariable analysis. MEASUREMENTS AND MAIN RESULTS: 50.2%, 33.5%, 25.8% and 20.3% of patients met criteria for 2, 3 (+control), 3 (+lung function) and 4-domain-remission, respectively. The odds of achieving 4-domain remission decreased by 15% for every additional 10-years asthma duration (odds ratio: 0.85; 95% CI: 0.73, 1.00). The odds of remission increased in those with fewer exacerbations/year, lower LTOCS daily dose, better control and better lung function pre-biologic-initiation. CONCLUSIONS: One in 5 patients achieved 4-domain remission within 1-year of biologic-initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission post-biologic, indicating that biologic treatment should not be delayed if remission is the goal. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

2.
Stat Med ; 43(18): 3524-3538, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38863133

RESUMEN

Moderate calibration, the expected event probability among observations with predicted probability z being equal to z, is a desired property of risk prediction models. Current graphical and numerical techniques for evaluating moderate calibration of risk prediction models are mostly based on smoothing or grouping the data. As well, there is no widely accepted inferential method for the null hypothesis that a model is moderately calibrated. In this work, we discuss recently-developed, and propose novel, methods for the assessment of moderate calibration for binary responses. The methods are based on the limiting distributions of functions of standardized partial sums of prediction errors converging to the corresponding laws of Brownian motion. The novel method relies on well-known properties of the Brownian bridge which enables joint inference on mean and moderate calibration, leading to a unified "bridge" test for detecting miscalibration. Simulation studies indicate that the bridge test is more powerful, often substantially, than the alternative test. As a case study we consider a prediction model for short-term mortality after a heart attack, where we provide suggestions on graphical presentation and the interpretation of results. Moderate calibration can be assessed without requiring arbitrary grouping of data or using methods that require tuning of parameters.


Asunto(s)
Simulación por Computador , Modelos Estadísticos , Humanos , Medición de Riesgo/métodos , Infarto del Miocardio/mortalidad , Estadísticas no Paramétricas , Calibración , Probabilidad
3.
Ann Allergy Asthma Immunol ; 132(5): 610-622.e7, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38151100

RESUMEN

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).


Asunto(s)
Antiasmáticos , Asma , Humanos , Asma/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antiasmáticos/uso terapéutico , Estudios Longitudinales , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Corticoesteroides/uso terapéutico , Sistema de Registros , Anciano
4.
Respirology ; 29(7): 596-604, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38436522

RESUMEN

BACKGROUND AND OBJECTIVE: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. METHODS: Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non-SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre- and post-SLB. RESULTS: A total of 81 SLB patients and 468 non-SLB patients were included. In the SLB group, the post-biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p-values >0.07). In the pre-post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). CONCLUSION: No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi-centre study of patients with IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Pulmón , Sistema de Registros , Humanos , Fibrosis Pulmonar Idiopática/mortalidad , Fibrosis Pulmonar Idiopática/cirugía , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/patología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Biopsia , Pulmón/patología , Pulmón/fisiopatología , Pulmón/cirugía , Anciano , Capacidad Vital/fisiología , Trasplante de Pulmón , Canadá/epidemiología , Pruebas de Función Respiratoria , Pronóstico , Modelos de Riesgos Proporcionales , Estudios de Cohortes , Tasa de Supervivencia
5.
Can J Neurol Sci ; : 1-11, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38115804

RESUMEN

OBJECTIVES: We conducted a population-based study using Ontario health administrative data to describe trends in healthcare utilization and mortality in adults with epilepsy during the first pandemic year (March 2020-March 2021) compared to historical data (2016-2019). We also investigated if changes in outpatient visits and diagnostic testing during the first pandemic year were associated with increased risk for hospitalizations, emergency department (ED) visits, or death. METHODS: Projected monthly visit rates (per 100,000 people) for outpatient visits, electroencephalography, magnetic resonance, computed tomography, all-cause ED visits, hospitalizations, and mortality were calculated based on historical data by fitting monthly time series autoregressive integrated moving-average models. Two-way interactions were calculated using Quasi-Poisson models. RESULTS: In adults with epilepsy during the first quarter of the pandemic, we demonstrated a reduction in all-cause outpatient visits, diagnostic testing, ED visits and hospitalizations, and a temporary increase in mortality (observed rates of 355.8 vs projected 308.8, 95% CI: 276.3-345.1). By the end of the year, outpatient visits increased (85,535.4 vs 76,620.6, 95% CI: 71,546.9-82,059.4), and most of the diagnostic test rates returned to the projected. The increase in the rate of all-cause mortality during the pandemic, compared to pre-pandemic, was greater during months with the lower frequency of diagnostic tests than months with higher frequency (interaction p-values <.0001). CONCLUSION: We described the impact of the pandemic on healthcare utilization and mortality in adults with epilepsy during the first year. We demonstrated that access to relevant diagnostic testing is likely important for this population while planning restrictions on non-urgent health services.

7.
J Allergy Clin Immunol Pract ; 12(5): 1228-1243, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38182099

RESUMEN

BACKGROUND: Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in regular widespread use. Implementation costs are a potential barrier to uptake of such programs. OBJECTIVE: We undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on health care budget directly or via health care resource use (HCRU). METHODS: We identified relevant publications using Medline and PreMEDLINE (PubMed), Embase (Embase.com, Elsevier), and EconLit for publications between January 2000 and July 2021. We also searched clinical trial databases and selected conference proceedings. RESULTS: Of 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included an analysis of biologic medication use. When they were studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU (health care visits, hospital admissions, and/or the use of medications, including add-on/reliever treatment and antibiotics) were frequently reported. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases in which favorable outcomes were observed. CONCLUSIONS: Adherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit.


Asunto(s)
Asma , Análisis Costo-Beneficio , Cumplimiento de la Medicación , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Asma/tratamiento farmacológico , Asma/economía , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/economía , Cumplimiento de la Medicación/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos
8.
J Cancer Policy ; 41: 100496, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39032558

RESUMEN

BACKGROUND: Mutations in KRAS and NRAS are associated with a lack of response to cetuximab and panitumumab, two biologics used for third-line therapy of metastatic colorectal cancer (mCRC). In British Columbia, Canada, eligibility for cetuximab or panitumumab was first based on single-gene KRAS testing. OncoPanel, a multi-gene next-generation sequencing panel with both KRAS and NRAS, was introduced in 2016. Our objective was to estimate the real-world cost-effectiveness of OncoPanel versus to single-gene KRAS testing to inform eligibility for cetuximab or panitumumab in mCRC. METHODS: Using population-based administrative health data, we identified a cohort of mCRC patients who had received a KRAS or OncoPanel test, and completed prior chemotherapy in 2010-2019. We matched KRAS- and OncoPanel-tested patients (1:1) using genetic matching to balance baseline covariates. Mean and incremental 3-year costs, survival, and quality-adjusted survival were estimated using inverse-probability-of-censoring weighting and bootstrapping. We conducted scenario-based sensitivity analysis for key costs and assumptions. FINDINGS: All OncoPanel-tested cases (n=371) were matched to a KRAS-tested comparator. In the KRAS and OncoPanel groups, respectively, 55·8 % and 41·2 % of patients were potentially eligible for cetuximab or panitumumab based on mutation status. Incremental cost and effectiveness of OncoPanel were $72 (95 % CI: -6387, 6107), -0·004 life-years (95 % CI: -0·119, 0·113), and -0·011 quality-adjusted life-years (95 % CI: -0·094, 0·075). Reductions in systemic therapy costs were offset by increased costs in other resources. Results were moderately sensitive to time horizon and changes in testing or treatment cost. INTERPRETATION: The use of OncoPanel resulted in more precise targeting of cetuximab and panitumumab, but there was no change in incremental cost or quality-adjusted survival. Understanding the balance of costs achieved in practice can provide insight into the effect of future changes in testing policy, test cost, treatment eligibility, or drug prices in this setting.

9.
Ann Am Thorac Soc ; 21(7): 1007-1014, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38315632

RESUMEN

Rationale: A visual analog scale (VAS) is a simple and easily administered tool for measuring the impact of disease; however, little is known about the use of a dyspnea VAS in interstitial lung disease (ILD). Objectives: To validate the use of a dyspnea VAS in a large and heterogeneous cohort of patients with fibrotic ILD, including its minimal clinically important difference (MCID), responsiveness to change, and prognostic significance. Methods: Patients with fibrotic ILD were identified from a large prospective registry. The validity of a 100-mm dyspnea VAS was assessed by testing its correlation in change score with other measures of ILD severity, including the University of California San Diego Shortness of Breath Questionnaire, the King's Brief Interstitial Lung Disease quality of life questionnaire Breathlessness and Activities Domain, the European Quality of Life VAS, forced vital capacity, and diffusing capacity of the lung for carbon monoxide. The responsiveness of the dyspnea VAS was qualitatively confirmed on the basis of there being an observable difference in the change in dyspnea VAS across tertiles of change in anchor variables. The MCID in dyspnea VAS was calculated using both anchor (linear regression) and distribution (one-half standard deviation) approaches, with anchors including the above variables that had a correlation with dyspnea VAS (|r| ≥ 0.30). The association of dyspnea VAS with time to death or transplant was determined. Results: The cohort included 826 patients with fibrotic ILD, including 127 patients with follow-up measurements at 6 months. The mean baseline dyspnea VAS was 53 ± 24 mm. Dyspnea VAS change scores were moderately correlated with the University of California San Diego Shortness of Breath Questionnaire (|r| = 0.55) and the King's Brief Interstitial Lung Disease quality of life questionnaire Breathlessness and Activities Domain (|r| = 0.44) and weakly correlated with the European Quality of Life VAS (|r| = 0.19), forced vital capacity percent predicted (|r| = 0.21), and diffusing capacity of the lung for carbon monoxide percent predicted (|r| = 0.05). The MCID was 2.7 to 4.5 using the more reliable anchor-based methods and 12.0 based on distribution-based methods. Dyspnea VAS was associated with time to death or transplant in unadjusted models and after adjustment for age and sex (hazard ratios, 1.16 and 1.15, respectively; P < 0.05 for both). Conclusions: This study provides support for the use of the dyspnea VAS in patients with fibrotic ILD, with an estimated anchor-based MCID of 5 mm.


Asunto(s)
Disnea , Enfermedades Pulmonares Intersticiales , Calidad de Vida , Escala Visual Analógica , Humanos , Disnea/etiología , Disnea/diagnóstico , Masculino , Femenino , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Pronóstico , Sistema de Registros , Encuestas y Cuestionarios , Capacidad Vital , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/fisiopatología
10.
BMJ Open Respir Res ; 11(1)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122474

RESUMEN

BACKGROUND: Cost of illness studies are important tools to summarise the burden of disease for individuals, the healthcare system and society. The lack of standardised methods for reporting costs for cystic fibrosis (CF) makes it difficult to quantify the total socioeconomic burden. In this study, we aimed to comprehensively report the socioeconomic burden of CF in Canada. METHODS: The total cost of CF in Canada was calculated by triangulating information from three sources (Canadian CF Registry, customised Burden of Disease survey and publicly available information). A prevalence-based, bottom-up, human capital approach was applied, and costs were categorised into four perspectives (ie, healthcare system, individual/caregiver, variable (ie, medicines) and society) and three domains (ie, direct, indirect and intangible). All costs were converted into 2021 Canadian dollars (CAD) and adjusted for inflation. The cost of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies was excluded. RESULTS: The total socioeconomic burden of CF in Canada in 2021 across the four perspectives was $C414 million. Direct costs accounted for two-thirds of the total costs, with medications comprising half of all direct costs. Out-of-pocket costs to individuals and caregivers represented 18.7% of all direct costs. Indirect costs representing absenteeism accounted for one-third of the total cost. CONCLUSION: This comprehensive cost of illness study for CF represents a community-oriented approach describing the socioeconomic burden of living with CF and serves as a benchmark for future studies.


Asunto(s)
Costo de Enfermedad , Fibrosis Quística , Costos de la Atención en Salud , Humanos , Fibrosis Quística/economía , Fibrosis Quística/terapia , Fibrosis Quística/epidemiología , Canadá/epidemiología , Femenino , Masculino , Adulto , Costos de la Atención en Salud/estadística & datos numéricos , Adolescente , Adulto Joven , Niño , Gastos en Salud/estadística & datos numéricos , Preescolar , Cuidadores/economía , Factores Socioeconómicos , Lactante , Absentismo , Prevalencia , Persona de Mediana Edad , Sistema de Registros
11.
Respir Med ; 221: 107500, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38142756

RESUMEN

BACKGROUND: Interstitial pneumonia with autoimmune features (IPAF) has features of connective tissue disease-associated interstitial lung disease (CTD-ILD), but without meeting criteria for a specific CTD. We compared baseline characteristics, survival, and response to treatment of IPAF to both CTD-ILD and unclassifiable ILD. METHODS: Measurements were extracted from a prospective registry. Baseline features and survival were compared in IPAF against both CTD-ILD and unclassifiable ILD. Linear trajectory of lung function decline (%-predicted forced vital capacity [FVC%] and diffusion capacity of the lung for carbon monoxide [DLCO%]) before and after initiation of mycophenolate or azathioprine were compared in IPAF against both CTD-ILD and unclassifiable ILD using linear mixed models. RESULTS: Compared to CTD-ILD (n = 1240), patients with IPAF (n = 128) were older, more frequently male, and had greater smoking history. Compared to unclassifiable ILD (n = 665), patients with IPAF were younger, more frequently female, and had worse baseline lung function. IPAF had higher mortality compared to CTD-ILD and similar risk of mortality compared to unclassifiable ILD. Mycophenolate initiation was associated with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% in patients with IPAF, and azathioprine initiation with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% decline in IPAF and DLCO% decline in CTD-ILD. CONCLUSION: Patients with IPAF had worse survival compared to those with CTD-ILD and similar mortality to unclassifiable ILD, with treatment being associated with stabilization in lung function in all three ILDs. It is uncertain whether IPAF should be considered a distinct ILD diagnostic subgroup.


Asunto(s)
Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Humanos , Masculino , Femenino , Azatioprina/uso terapéutico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Pulmón , Enfermedades del Tejido Conjuntivo/diagnóstico , Inmunosupresores/uso terapéutico , Factores de Riesgo
12.
Chest ; 166(1): 28-38, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38395297

RESUMEN

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.


Asunto(s)
Asma , Progresión de la Enfermedad , Sistema de Registros , Índice de Severidad de la Enfermedad , Humanos , Asma/tratamiento farmacológico , Asma/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Hospitalización/estadística & datos numéricos , Corticoesteroides/uso terapéutico
13.
Front Immunol ; 15: 1361891, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711495

RESUMEN

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.


Asunto(s)
Asma , Productos Biológicos , Biomarcadores , Eosinófilos , Inmunoglobulina E , Humanos , Asma/tratamiento farmacológico , Asma/diagnóstico , Asma/inmunología , Masculino , Femenino , Persona de Mediana Edad , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Adulto , Eosinófilos/inmunología , Productos Biológicos/uso terapéutico , Antiasmáticos/uso terapéutico , Resultado del Tratamiento , Sistema de Registros , Índice de Severidad de la Enfermedad , Recuento de Leucocitos , Óxido Nítrico/metabolismo , Anciano , Estudios de Cohortes
14.
Artículo en Inglés | MEDLINE | ID: mdl-38768896

RESUMEN

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

15.
Front Public Health ; 11: 1251020, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38169852

RESUMEN

Background: The COVID-19 pandemic led to global disruptions in non-urgent health services, affecting health outcomes of individuals with ambulatory-care-sensitive conditions (ACSCs). Methods: We conducted a province-based study using Ontario health administrative data (Canada) to determine trends in outpatient visits and hospitalization rates (per 100,000 people) in the general adult population for seven ACSCs during the first pandemic year (March 2020-March 2021) compared to previous years (2016-2019), and how disruption in outpatient visits related to acute care use. ACSCs considered were chronic obstructive pulmonary disease (COPD), asthma, angina, congestive heart failure (CHF), hypertension, diabetes, and epilepsy. We used time series auto-regressive integrated moving-average models to compare observed versus projected rates. Results: Following an initial reduction (March-May 2020) in all types of visits, primary care outpatient visits (combined in-person and virtual) returned to pre-pandemic levels for asthma, angina, hypertension, and diabetes, remained below pre-pandemic levels for COPD, and rose above pre-pandemic levels for CHF (104.8 vs. 96.4, 95% CI: 89.4-104.0) and epilepsy (29.6 vs. 24.7, 95% CI: 22.1-27.5) by the end of the first pandemic year. Specialty visits returned to pre-pandemic levels for COPD, angina, CHF, hypertension, and diabetes, but remained above pre-pandemic levels for asthma (95.4 vs. 79.5, 95% CI: 70.7-89.5) and epilepsy (53.3 vs. 45.6, 95% CI: 41.2-50.5), by the end of the year. Virtual visit rates increased for all ACSCs. Among ACSCs, reductions in hospitalizations were most pronounced for COPD and asthma. CHF-related hospitalizations also decreased, albeit to a lesser extent. For angina, hypertension, diabetes, and epilepsy, hospitalization rates reduced initially, but returned to pre-pandemic levels by the end of the year. Conclusion: This study demonstrated variation in outpatient visit trends for different ACSCs in the first pandemic year. No outpatient visit trends resulted in increased hospitalizations for any ACSC; however, reductions in rates of asthma, COPD, and CHF hospitalizations persisted.


Asunto(s)
Asma , COVID-19 , Diabetes Mellitus , Epilepsia , Hipertensión , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Humanos , Pandemias , Pacientes Ambulatorios , Pacientes Internos , Atención Ambulatoria , COVID-19/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Asma/epidemiología , Asma/terapia , Hipertensión/epidemiología , Ontario/epidemiología
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