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Rationale: The prevalence and diagnostic utility of bronchodilator responsiveness (BDR) in a real-life setting is unclear. Objective: To explore this uncertainty in patients aged ⩾12 years with physician-assigned diagnoses of asthma, asthma and chronic obstructive pulmonary disease (COPD), or COPD in NOVELTY, a prospective cohort study in primary and secondary care in 18 countries. Methods: The proportion of patients with a positive BDR test in each diagnostic category was calculated using 2005 (ΔFEV1 or ΔFVC ⩾12% and ⩾200 ml) and 2021 (ΔFEV1 or ΔFVC >10% predicted) European Respiratory Society/American Thoracic Society criteria. Measurements and Main Results: We studied 3,519 patients with a physician-assigned diagnosis of asthma, 833 with a diagnosis of asthma + COPD, and 2,436 with a diagnosis of COPD. The prevalence of BDR was 19.7% (asthma), 29.6% (asthma + COPD), and 24.7% (COPD) using 2005 criteria and 18.1%, 23.3%, and 18.0%, respectively, using 2021 criteria. Using 2021 criteria in patients diagnosed with asthma, BDR was associated with higher fractional exhaled nitric oxide; lower lung function; higher symptom burden; more frequent hospital admissions; and greater use of triple therapy, oral corticosteroids, or biologics. In patients diagnosed with COPD, BDR (2021) was associated with lower lung function and higher symptom burden. Conclusions: BDR prevalence in patients with chronic airway diseases receiving treatment ranges from 18% to 30%, being modestly lower with the 2021 than with the 2005 European Respiratory Society/American Thoracic Society criteria, and it is associated with lower lung function and greater symptom burden. These observations question the validity of BDR as a key diagnostic tool for asthma managed in clinical practice or as a standard inclusion criterion for clinical trials of asthma and instead suggest that BDR be considered a treatable trait for chronic airway disease.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Broncodilatadores/uso terapêutico , Estudos Prospectivos , Prevalência , Volume Expiratório Forçado , Capacidade Vital , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real-world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of 'asthma', 'COPD' or 'asthma + COPD'. METHODS: The authors selected 30 frequently occurring TTs from the NOVELTY study cohort (NOVEL observational longiTudinal studY; NCT02760329), a large (n = 11,226), global study that systematically collects data in a real-world setting, both in primary care clinics and specialized centres, for patients with 'asthma' (n = 5932, 52.8%), 'COPD' (n = 3898, 34.7%) or both ('asthma + COPD'; n = 1396, 12.4%). RESULTS: The results indicate that (1) the prevalence of the 30 TTs evaluated varied widely, with a mean ± SD of 4.6 ± 2.6, 5.4 ± 2.6 and 6.4 ± 2.8 TTs/patient in those with 'asthma', 'COPD' and 'asthma + COPD', respectively (p < 0.0001); (2) there were no large global geographical variations, but the prevalence of TTs was different in primary versus specialized clinics; (3) several TTs were specific to the diagnosis and severity of disease, but many were not; and (4) both the presence and absence of TTs formed a pattern that is recognized by clinicians to establish a diagnosis and grade its severity. CONCLUSION: These results provide the largest and most granular characterization of TTs in patients with airway diseases in a real-world setting to date.
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Asma , Doença Pulmonar Obstrutiva Crônica , Asma/diagnóstico , Asma/epidemiologia , Humanos , Estudos Longitudinais , Fenótipo , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologiaRESUMO
BACKGROUND: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort. METHODS: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis. RESULTS: Of 11â243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1â s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12â months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses. CONCLUSION: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.
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Asma , Médicos , Doença Pulmonar Obstrutiva Crônica , Asma/complicações , Asma/diagnóstico , Asma/epidemiologia , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Espirometria , Capacidade VitalRESUMO
BACKGROUND: Given the recent declines in heart attack and stroke incidence, it is unclear how women and men differ in first lifetime presentations of cardiovascular diseases (CVDs). We compared the incidence of 12 cardiac, cerebrovascular, and peripheral vascular diseases in women and men at different ages. METHODS AND RESULTS: We studied 1 937 360 people, aged ≥ 30 years and free from diagnosed CVD at baseline (51% women), using linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry, and mortality (Cardiovascular Research Using LInked Bespoke Studies and Electronic Records [CALIBER] research platform). During 6 years median follow-up between 1997 and 2010, 114 859 people experienced an incident cardiovascular diagnosis, the majority (66%) of which were neither myocardial infarction nor ischemic stroke. Associations of male sex with initial diagnoses of CVD, however, varied from strong (age-adjusted hazard ratios, 3.6-5.0) for abdominal aortic aneurysm, myocardial infarction, and unheralded coronary death (particularly >60 years), through modest (hazard ratio, 1.5-2.0) for stable angina, ischemic stroke, peripheral arterial disease, heart failure, and cardiac arrest, to weak (hazard ratio <1.5) for transient ischemic attack, intracerebral hemorrhage, and unstable angina, and inverse (0.69) for subarachnoid hemorrhage (all P<0.001). CONCLUSIONS: The majority of initial presentations of CVD are neither myocardial infarction nor ischemic stroke, yet most primary prevention studies focus on these presentations. Sex has differing associations with different CVDs, with implications for risk prediction and management strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01164371.
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Doenças Cardiovasculares/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/sangue , Anticoncepcionais Orais Hormonais , Diabetes Mellitus/epidemiologia , Registros Eletrônicos de Saúde , Feminino , Terapia de Reposição Hormonal , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. Previous studies have focussed on myocardial infarction and stroke, and these conditions are the usual outcomes chosen in clinical trials in type 2 diabetes, but other diseases such as heart failure and angina are also major causes of morbidity in diabetes. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. METHODS: We used linked electronic health records from 1997 to 2010 in the CALIBER (cardiovascular research using linked bespoke studies and electronic health records) programme to investigate the absolute and relative risks associated with type 2 diabetes in a cohort of 1·92 million patients in England. We included patients aged 30 years and older who were free from cardiovascular disease at baseline. This study is registered with ClinicalTrials.gov, number NCT01804439. FINDINGS: We observed 113â638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). 34â198 people had type 2 diabetes: 6137 experienced a first cardiovascular presentation, of which the most common were peripheral arterial disease (16·2%, n=992) and heart failure (14·1%, n=866). Type 2 diabetes was strongly positively associated with peripheral arterial disease (adjusted cause-specific hazard ratio 2·98, 95% CI 2·76-3·22), ischaemic stroke (1·72, 1·52-1·95), stable angina (1·62, 1·49-1·77), heart failure (1·56, 1·45-1·69), and non-fatal myocardial infarction (1·54 1·42-1·67), but inversely associated with abdominal aortic aneurysm (0·46, 0·35-0·59) and subarachnoid haemorrhage (0·48, 0·26-0·89). INTERPRETATION: This study suggests that associations of type 2 diabetes vary with different incident cardiovascular diseases. These findings have implications for clinical risk assessment and choice of primary endpoint in trials on type 2 diabetes. FUNDING: Wellcome Trust, National Institute for Health Research, UK Medical Research Council.
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BACKGROUND: The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS: We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS: During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION: The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING: Medical Research Council, National Institute for Health Research, and Wellcome Trust.
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Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Doença Aguda , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/epidemiologia , Angina Pectoris/etiologia , Anti-Hipertensivos/uso terapêutico , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/etiologia , Doenças Cardiovasculares/etiologia , Doença Crônica , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Incidência , Hemorragia Intracraniana Hipertensiva/epidemiologia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Medição de Risco/métodos , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/etiologiaRESUMO
AIMS: The population with stable coronary artery disease (SCAD) is growing but validated models to guide their clinical management are lacking. We developed and validated prognostic models for all-cause mortality and non-fatal myocardial infarction (MI) or coronary death in SCAD. METHODS AND RESULTS: Models were developed in a linked electronic health records cohort of 102 023 SCAD patients from the CALIBER programme, with mean follow-up of 4.4 (SD 2.8) years during which 20 817 deaths and 8856 coronary outcomes were observed. The Kaplan-Meier 5-year risk was 20.6% (95% CI, 20.3, 20.9) for mortality and 9.7% (95% CI, 9.4, 9.9) for non-fatal MI or coronary death. The predictors in the models were age, sex, CAD diagnosis, deprivation, smoking, hypertension, diabetes, lipids, heart failure, peripheral arterial disease, atrial fibrillation, stroke, chronic kidney disease, chronic pulmonary disease, liver disease, cancer, depression, anxiety, heart rate, creatinine, white cell count, and haemoglobin. The models had good calibration and discrimination in internal (external) validation with C-index 0.811 (0.735) for all-cause mortality and 0.778 (0.718) for non-fatal MI or coronary death. Using these models to identify patients at high risk (defined by guidelines as 3% annual mortality) and support a management decision associated with hazard ratio 0.8 could save an additional 13-16 life years or 15-18 coronary event-free years per 1000 patients screened, compared with models with just age, sex, and deprivation. CONCLUSION: These validated prognostic models could be used in clinical practice to support risk stratification as recommended in clinical guidelines.
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Doença da Artéria Coronariana/mortalidade , Idoso , Morte Súbita Cardíaca/epidemiologia , Registros Eletrônicos de Saúde , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Infarto do Miocárdio/mortalidade , Prognóstico , Medição de RiscoRESUMO
MOTIVATION: Discrimination statistics describe the ability of a survival model to assign higher risks to individuals who experience earlier events: examples are Harrell's C-index and Royston and Sauerbrei's D, which we call the D-index. Prognostic covariates whose distributions are controlled by the study design (e.g. age and sex) influence discrimination and can make it difficult to compare model discrimination between studies. Although covariate adjustment is a standard procedure for quantifying disease-risk factor associations, there are no covariate adjustment methods for discrimination statistics in censored survival data. OBJECTIVE: To develop extensions of the C-index and D-index that describe the prognostic ability of a model adjusted for one or more covariate(s). METHOD: We define a covariate-adjusted C-index and D-index for censored survival data, propose several estimators, and investigate their performance in simulation studies and in data from a large individual participant data meta-analysis, the Emerging Risk Factors Collaboration. RESULTS: The proposed methods perform well in simulations. In the Emerging Risk Factors Collaboration data, the age-adjusted C-index and D-index were substantially smaller than unadjusted values. The study-specific standard deviation of baseline age was strongly associated with the unadjusted C-index and D-index but not significantly associated with the age-adjusted indices. CONCLUSIONS: The proposed estimators improve meta-analysis comparisons, are easy to implement and give a more meaningful clinical interpretation.
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Biometria/métodos , Doenças Cardiovasculares/epidemiologia , Análise de Variância , Ensaios Clínicos como Assunto , Análise Discriminante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Many patients with asthma have type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide levels. OBJECTIVE: To assess disease burden in relation to type-2 inflammatory biomarker status (history of allergy, blood EOS count, and fractional exhaled nitric oxide level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). METHODS: Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test score (uncontrolled <20, controlled ≥20) and/or 1 or more severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and fractional exhaled nitric oxide level), symptom burden (Asthma Control Test score, modified Medical Research Council dyspnea scale), health status (St George's Respiratory Questionnaire score), exacerbations, and health care resource utilization were assessed. RESULTS: Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among those with uncontrolled asthma, 196 (44%) had 2 or more positive biomarkers, 187 (42%) had 1 positive biomarker, 325 (73%) had low blood EOS, and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (Asthma Control Test score 14.9-16.6), impaired health status (St George's Respiratory Questionnaire total score 46.7-49.4), clinically important breathlessness (modified Medical Research Council grade ≥2 in 47.3%-57.1%), and 1 or more severe exacerbation (70.6%-76.2%). CONCLUSIONS: Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed.
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Asma , Eosinofilia , Hipersensibilidade , Humanos , Asma/diagnóstico , Asma/epidemiologia , Biomarcadores , Eosinófilos , Estudos Longitudinais , Óxido NítricoRESUMO
BACKGROUND: Poor asthma control is associated with high short-acting ß2-agonist (SABA) use. AIM: To assess asthma-related healthcare resource utilisation (HCRU) and medication costs associated with high versus low SABA prescriptions in the UK. DESIGN & SETTING: Analysis of SABINA I (SABA use IN Asthma I), a retrospective longitudinal study using UK electronic health records (Clinical Practice Research Datalink GOLD 2008-2019 and Hospital Episode Statistics database). METHOD: Eligible patients were ≥12 years old with SABA prescriptions in the past year. SABA prescriptions (number of canisters per year) were defined as high (≥3) or low (1-2). Association of SABA prescriptions with HCRU was assessed by negative binominal model adjusted for covariates. The UK unit costs from the NHS were applied to estimate total healthcare costs (2020). Medication costs were based on the annual average number of canisters per year per patient. RESULTS: Overall, 186 061 patients with SABA prescriptions were included, of whom 51% were prescribed high SABA. Total annual average costs (HCRU and medication) were 52% higher in the high SABA group versus the low SABA group (£2 256 091 per 1000 patients/year versus £1 480 640 per 1000 patients/year). Medication costs accounted for the majority of asthma-related costs. Across both groups, most HCRU costs were for non-exacerbation-related primary care or hospital outpatient visits. The annual average HCRU cost difference for high SABA versus low SABA was the greatest for hospitalisations (+230%; £15 521 per 1000 patients/year versus £4697 per 1000 patients/year) and exacerbation-related primary care visits (+162%; £18 770 per 1000 patients/year versus £7160 per 1000 patients/year). Asthma-related HCRU extrapolated to the broader UK asthma population was £108.5 million per year higher with high SABA versus low SABA. CONCLUSION: High SABA versus low SABA prescriptions are associated with higher asthma-related HCRU costs.
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BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are complex diseases, the definitions of which overlap. OBJECTIVE: To investigate clustering of clinical/physiological features and readily available biomarkers in patients with physician-assigned diagnoses of asthma and/or COPD in the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329). METHODS: Two approaches were taken to variable selection using baseline data: approach A was data-driven, hypothesis-free and used the Pearson dissimilarity matrix; approach B used an unsupervised Random Forest guided by clinical input. Cluster analyses were conducted across 100 random resamples using partitioning around medoids, followed by consensus clustering. RESULTS: Approach A included 3796 individuals (mean age, 59.5 years; 54% female); approach B included 2934 patients (mean age, 60.7 years; 53% female). Each identified 6 mathematically stable clusters, which had overlapping characteristics. Overall, 67% to 75% of patients with asthma were in 3 clusters, and approximately 90% of patients with COPD were in 3 clusters. Although traditional features such as allergies and current/ex-smoking (respectively) were higher in these clusters, there were differences between clusters and approaches in features such as sex, ethnicity, breathlessness, frequent productive cough, and blood cell counts. The strongest predictors of the approach A cluster membership were age, weight, childhood onset, prebronchodilator FEV1, duration of dust/fume exposure, and number of daily medications. CONCLUSIONS: Cluster analyses in patients from NOVELTY with asthma and/or COPD yielded identifiable clusters, with several discriminatory features that differed from conventional diagnostic characteristics. The overlap between clusters suggests that they do not reflect discrete underlying mechanisms and points to the need for identification of molecular endotypes and potential treatment targets across asthma and/or COPD.
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Asma , Doença Pulmonar Obstrutiva Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asma/diagnóstico , Asma/epidemiologia , Análise por Conglomerados , Estudos Longitudinais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , FumarRESUMO
OBJECTIVE: The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity. METHODS: SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K <10/≥10) and IFNGS status (high/low). RESULTS: The study population (n=823) was 93.2% female, with mean (SD) age 45.3 (13.9) years and 11.1 (9.2) years since diagnosis; 52.4% had baseline SLICC/ACR Damage Index score ≥1. Patients with SLEDAI-2K scores ≥10 (241 of 584, 41.3%) vs <10 were younger (mean 42.8 (13.7) vs 46.6 (14.2) years; nominal p=0.001), had shorter SLE duration (10.4 (8.6) vs 12.4 (9.6) years; nominal p=0.012) and more severe flares (12.9% vs 5.3%; nominal p=0.001). IFNGS-high patients (522 of 739, 70.6%) were younger than IFNGS-low patients at first SLE manifestation (30.0 (12.7) vs 36.8 (14.6) years; nominal p<0.001). Proportions of IFNGS-high patients differed according to race (nominal p<0.001), with higher proportions among Asian (83.3%) and black (86.5%) versus white patients (63.5%). Greater proportions of IFNGS-high versus IFNGS-low patients had haematological (12.6% vs 4.1%), immunological (74.4% vs 45.6%) or dermal (69.7% vs 62.2%) involvement. CONCLUSIONS: We identified key characteristics of patients with high disease activity and/or elevated type I IFN signalling, populations with SLE with high unmet needs. Baseline SLEDAI-2K ≥10 was associated with shorter disease duration and more severe flares. IFNGS-high patients were younger at diagnosis and had distinct patterns of organ involvement, compared with IFNGS-low patients.
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Interferon Tipo I , Lúpus Eritematoso Sistêmico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Progressão da Doença , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/complicações , Estudos Prospectivos , Fatores de Tempo , Estados Unidos , AdultoRESUMO
New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks.
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Doenças Cardiovasculares/prevenção & controle , Projetos de Pesquisa Epidemiológica , Modelos de Riscos Proporcionais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/economia , Análise Custo-Benefício , Análise Discriminante , Humanos , Estimativa de Kaplan-Meier , Metanálise como Assunto , Prognóstico , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricosRESUMO
INTRODUCTION: Persistent cough with sputum production is an important clinical trait in chronic obstructive pulmonary disease (COPD). We defined "frequent productive cough" based on 2 questions from the St George's Respiratory Questionnaire (SGRQ) and sought to determine its occurrence and associated outcomes in patients with physician-assigned asthma and/or COPD from the NOVELTY study. METHODS: Frequent productive cough was defined as cough and sputum production most or several days/week for the past 3 months (scoring ≥3 for both SGRQ questions). Relationships with baseline disease characteristics and exacerbations over 12 months' follow-up were examined using logistic regression. RESULTS: Baseline SGRQ data were available for 7125 patients, of whom 31.3% had frequent productive cough. It was more common in asthma+COPD (38.8%) and COPD (38.1%) than asthma (25.0%), increasing with physician-assessed severity, and in current versus former and never smokers. Patient-reported symptomatic worsening was more common in patients with versus without frequent productive cough. Reduced post-bronchodilator FEV1 (odds ratio [OR] per 10% decrement 1.14 [95% confidence interval 1.11-1.16]) and history of pollutant exposure at home/work (OR 1.50 [1.33-1.69]) were associated with frequent productive cough in all diagnoses. Patients with baseline frequent productive cough were more likely to have ≥1 exacerbation over the subsequent 12 months (OR 1.71 [1.52-1.93]), including exacerbations requiring hospital admission and those treated with oral corticosteroids. CONCLUSIONS: Frequent productive cough represents an important indicator of adverse clinical outcomes across asthma and/or COPD. Research into the underlying pathologic mechanisms is required to support targeted therapy development. CLINICALTRIALS: GOV: NCT02760329.
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Asma , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/uso terapêutico , Asma/complicações , Asma/tratamento farmacológico , Asma/epidemiologia , Tosse/complicações , Tosse/etiologia , Progressão da Doença , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Reliance on short-acting ß-2 agonists and nonadherence to maintenance medication are associated with poor clinical outcomes in asthma. Digital health solutions could support optimal medication use and therefore disease control in patients with asthma; however, their use in community settings has not been determined. OBJECTIVE: The primary objective of this study is to investigate community implementation of the Turbu+ program designed to support asthma self-management, including adherence to budesonide and formoterol (Symbicort) Turbuhaler, a combination inhaler for both maintenance therapy or maintenance and reliever therapy. The secondary objective is to provide health care professionals with insights into how patients were using their medication in real life. METHODS: Patients with physician-diagnosed asthma were prescribed budesonide and formoterol as maintenance therapy, at a dose of either 1 inhalation twice daily (1-BID) or 2 inhalations twice daily (2-BID), or as maintenance and reliever therapy (1-BID and reliever or 2-BID and reliever in a single inhaler), and they received training on Turbu+ in secondary care centers across Italy. An electronic device attached to the patients' inhaler for ≥90 days (data cutoff) securely uploaded medication use data to a smartphone app and provided reminders, visualized medication use, and motivational nudge messages. Average medication adherence was defined as the proportion of daily maintenance inhalations taken as prescribed (number of recorded maintenance actuations per day or maintenance inhalations prescribed per day) averaged over the monitoring period. The proportion of adherent days was defined as the proportion of days when all prescribed maintenance inhalations were taken on a given day. The Wilcoxon test was used to compare the proportion of adherent days between patients in the maintenance regimen and patients in the maintenance and reliever regimen of a given dose. RESULTS: In 661 patients, the mean (SD) number of days monitored was 217.2 (SD 109.0) days. The average medication adherence (maintenance doses taken/doses prescribed) was 70.2% (108,040/153,820) overall and was similar across the groups (1-BID: 6332/9520, 66.5%; 1BID and reliever: 43,578/61,360, 71.0%; 2-BID: 10,088/14,960, 67.4%; 2-BID and reliever: 48,042/67,980, 70.7%). The proportion of adherent days (prescribed maintenance doses/doses taken in a given day) was 56.6% (31,812/56,175) overall and was higher with maintenance and reliever therapy (1-BID and reliever vs 1-BID: 18,413/30,680, 60.0% vs 2510/4760, 52.7%; P<.001; 2-BID and reliever vs 2-BID: 8995/16,995, 52.9% vs 1894/3740, 50.6%; P=.02). Rates of discontinuation from the Turbu+ program were significantly lower with maintenance and reliever therapy compared with maintenance therapy alone (P=.01). CONCLUSIONS: Overall, the high medication adherence observed during the study might be attributed to the electronic monitoring and feedback mechanism provided by the Turbu+ program.
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Asma , Tutoria , Humanos , Broncodilatadores/uso terapêutico , Broncodilatadores/efeitos adversos , Etanolaminas/efeitos adversos , Nebulizadores e Vaporizadores , Asma/tratamento farmacológico , Budesonida/efeitos adversos , Fumarato de Formoterol/uso terapêutico , TecnologiaRESUMO
BACKGROUND: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. METHODS: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. RESULTS: Overall, 2004 patients with mild asthma were included; 22.8% experienced ≥1 exacerbation in the previous 12 months, of whom 72.3% experienced ≥1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation ± 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score <20), increasing to 55.6% for those with ≥2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring ≥1 emergency department visit and 1.1% requiring ≥1 hospital admission. CONCLUSIONS: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.
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Asma , Corticosteroides/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Progressão da Doença , Humanos , Estudos Longitudinais , Aceitação pelo Paciente de Cuidados de Saúde , Estudos ProspectivosRESUMO
[This corrects the article DOI: 10.2196/25879.].
RESUMO
The aim of the present study was to identify factors associated with the risk of development of gastrointestinal acute graft-versus-host disease (GI-aGVHD), as well as to evaluate the impact of various baseline parameters on response to treatment, nonrelapse mortality (NRM), and overall survival (OS) in pediatric patients with GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT). We retrospectively analyzed 300 pediatric patients who underwent allo-SCT from HLA-matched related or volunteer unrelated donors in our institution. GI tract involvement was observed in 46 out of 133 patients with aGVHD grade II-IV. Severe aGVHD (grade III-IV) was more frequently observed among patients with GI-aGVHD in comparison with patients without GI involvement (P < .001). Treatment with steroids resulted in durable responses in 22/46 patients; 14 additional patients responded to salvage therapy, whereas 10 were refractory to all treatments administered. Using Cox regression analysis, we observed that serum albumin level ≥ 3 mg/dL on day 5 after the initiation of therapy with steroids was statistically significantly associated with decreased hazard of NRM and improved OS (P = .021 and P = .026, respectively). In our study, serum albumin level, early (+ day 5) after the onset of steroids in patients with GI-aGVHD, was a predictor of treatment outcome. Prospective randomized trials need to be performed to verify the predictive significance of serum albumin and the need for early intensification of immunosuppressive treatment.
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Albuminúria/etiologia , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Aguda , Adolescente , Albuminúria/urina , Anemia Aplástica/cirurgia , Biomarcadores , Transplante de Medula Óssea/efeitos adversos , Causas de Morte , Criança , Pré-Escolar , Diarreia/tratamento farmacológico , Diarreia/etiologia , Diarreia/imunologia , Diarreia/prevenção & controle , Diarreia/urina , Feminino , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/imunologia , Gastroenteropatias/prevenção & controle , Gastroenteropatias/urina , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/urina , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Lactente , Estimativa de Kaplan-Meier , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Neoplasias/cirurgia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Lung cancer stigma negatively impacts the clinical care and outcomes of those diagnosed, resulting in enduring disparities. The objective of this study was to determine whether attitudes toward lung cancer and the stigmatization of people diagnosed have changed over a decade. METHODS: A cross-sectional survey was administered to the general public, oncologists, and people with lung cancer 10 years apart (2008 and 2018) using the same instrument and methodology. The measures of stigma agreement ratings on a five-point Likert scale were compared between 2008 and 2018 for all three sample groups. RESULTS: In 2018, a total of 1001 members of the general public, 205 oncologists, and 208 people with lung cancer were enrolled. Improvements were noted over the decade, including the availability of more treatment options. Greater disease awareness was also found, with 94% of the public reporting knowledge of lung cancer (versus 82.5% in 2008, p < 0.0001). However, no change was found in the percentage of the public reporting that patients with lung cancer are at least partially to blame for their illness (60.3% in 2018). In 2018, more people with lung cancer agreed there is a stigma associated with lung cancer (72.1 versus 54.5%, p < 0.001) and that those diagnosed are viewed or treated differently by society in general (69.4% versus 50.8%, p < 0.001). CONCLUSIONS: The results reflect recognition of treatment gains and increased visibility of lung cancer but also highlight that stigma remains a significant problem. Of critical importance to the care of those diagnosed was the unexpected increase in stigma reported by the patient population.
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Neoplasias Pulmonares , Oncologistas , Atitude , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neoplasias Pulmonares/terapia , Estigma Social , Inquéritos e QuestionáriosRESUMO
Objectives To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption.Design Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years).Setting CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records).Participants 1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline.Main outcome measures 12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm.Results 114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00).Conclusions Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary.Registration clinicaltrails.gov (NCT01864031).