Prevalence, incidence and healthcare burden of eosinophilic granulomatosis with polyangiitis in the UK.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease characterised by the combination of small-to-medium vessel vasculitis, blood and tissue eosinophilia, and asthma and/or sinonasal disease. This study estimated the prevalence and incidence of diagnosed EGPA in the United Kingdom (UK), and described the demographics, clinical characteristics and healthcare resource utilisation (HCRU) of this population. Methods: This retrospective longitudinal study of patients with newly diagnosed EGPA (index) (2005-2019) used the Clinical Practice Research Datalink AURUM and Hospital Episode Statistics databases. The primary outcomes were the annual prevalence (2005-2019) and incidence (2006-2019) of EGPA, and secondary outcomes included patient demographics and clinical characteristics, and HCRU in the year pre- and post-index (diagnosis). Results: Populations of patients with EGPA comprised 940 prevalent cases and 502 incident cases, of which 377 were linked to Hospital Episode Statistics. EGPA prevalence increased from 22.7 to 45.6 cases per 1 000 000 (2005-2019), driven by patients aged ≥18 years. Incidence ranged from 2.3 to 4.0 per 1 000 000 person-years (2006-2019). Pre-index, the most common clinical symptoms were respiratory related, and the most common comorbidities were asthma (80.6%) and nasal polyps (32.1%). Post-index, 19.1% had an EGPA-related inpatient stay (median length of stay 11.0 days) and 38.7% had five or more oral corticosteroid (OCS) prescriptions with a mean OCS possession ratio per patient of 47.0%. Conclusions: Although EGPA incidence in the UK remains relatively stable, prevalence is increasing, and HCRU and OCS use remain frequent, suggesting considerable healthcare burden for patients with EGPA.

Mepolizumab in Patients With Severe Asthma and Comorbidities: 1-Year REALITI-A Analysis.

BACKGROUND: Severe asthma is complex; comorbidities may influence disease outcomes. OBJECTIVE: To assess mepolizumab effectiveness in patients with severe asthma and comorbidities. METHODS: REALITI-A was a 2-year international, prospective study enrolling adults with asthma newly prescribed mepolizumab (100 mg subcutaneously) at physician's discretion. This post hoc analysis assessed 1-year outcomes stratified by comorbidities at enrollment: chronic rhinosinusitis with nasal polyps (CRSwNP), gastroesophageal reflux disease (GERD), depression/anxiety, and chronic obstructive pulmonary disease (COPD). Outcomes included the rate of clinically significant asthma exacerbations (CSEs; requiring systemic corticosteroids and/or hospital/emergency room admission) between the 12 months pre- and post-mepolizumab treatment and changes from baseline in daily maintenance oral corticosteroid dose (mo 12), Asthma Control Questionnaire-5 score (mo 12) and forced expiratory volume in 1 second (FEV1; mo 9-12). RESULTS: At enrollment (n = 822), 321 of 822 (39%), 309 of 801 (39%), 203 of 785 (26%), and 81 of 808 (10%) patients had comorbid CRSwNP, GERD, depression/anxiety, and COPD, respectively. Post- versus pre-treatment across all comorbidity subgroups: the rate of CSEs decreased by 63% or more; among 298 (39%) patients on maintenance oral corticosteroids at baseline, median dose decreased by 50% or more; Asthma Control Questionnaire-5 score decreased by 0.63 or more points; FEV1 increased by 74 mL or more. Patients with versus without CRSwNP had the greatest improvements (eg, rate of CSEs decreased by 75%). Patients without GERD, depression/anxiety, or COPD had greater improvements than those with the respective comorbidities, except for FEV1 in patients with COPD. CONCLUSIONS: Mepolizumab improved disease outcomes in patients with severe asthma irrespective of comorbidities, with additional benefit for patients with CRSwNP.

An algorithm-based approach to ascertain patients with rare diseases in electronic health records using hypereosinophilic syndrome as an example.

PURPOSE: Improved hypereosinophilic syndrome (HES) ascertainment in electronic health record (EHR) databases may improve disease understanding and management. An algorithm to ascertain and characterize this rare condition was therefore developed and validated. METHODS: Using the UK clinical practice research datalink (CPRD)-Aurum database linked to the hospital episode statistics database (Admitted Patient Care data) from Jan 2012 to June 2019, this cross-sectional study ascertained patients with a specific HES code (index). Patients with HES were matched (age, sex and index date) 1:29 with a non-HES cohort. An algorithm was developed by identifying pre-defined variables differing between cohorts; model-fitting using Firth logistic regression and statistical determination of the top-five performing models; and internal validation using Leave-One-Out Cross Validation. Final model sensitivity and specificity were determined at an 80% probability threshold. RESULTS: The HES and non-HES cohorts included 88 and 2552 patients, respectively; 270 models with four variables each (treatment used for HES, asthma code, white blood cell condition code, and blood eosinophil count [BEC] code) plus age and sex variables were tested. Of the top five models, the sensitivity model performed best (sensitivity, 69% [95% CI: 59%, 79%]; specificity, >99%). The strongest predictors of HES versus non-HES cases (odds >1000 times greater) were an ICD-10 code for white blood cell disorders and a BEC ≥1500 cells/µL in the 24 months pre-index. CONCLUSIONS: Using a combination of medical codes, prescribed treatments data and laboratory results, the algorithm can help ascertain patients with HES from EHR databases; this approach may be useful for other rare diseases.

Hypereosinophilic syndrome in Europe: Retrospective study of treatment patterns, clinical manifestations, and healthcare resource utilization.

BACKGROUND: The burden of hypereosinophilic syndrome (HES) in Europe is not well characterized. OBJECTIVE: To evaluate real-world patient characteristics, treatment patterns, clinical manifestations, and healthcare resource utilization for patients with HES from France, Germany, Italy, Spain, and the United Kingdom. METHODS: In this retrospective, noninterventional study, data for patients with a physician-confirmed diagnosis of HES were abstracted from medical chart reviews. Patients were aged 6 years or older at the time of HES diagnosis and had 1 or more years of follow-up from the index date (first clinic visit between January 2015 and December 2019). Data on treatment patterns, comorbidities, clinical manifestations, clinical outcomes, and healthcare resource utilization were collected from diagnosis or index date to end of follow-up. RESULTS: Data for 280 patients were abstracted from medical charts by 121 physicians treating HES, with multiple specialties. Most patients (55%) had idiopathic HES, and 24% had myeloid HES; the median number (interquartile range [IQR]) of diagnostic tests per patient was 10 (6-12). The most common comorbidities were asthma (45%) and anxiety or depression (36%). Most patients (89%) used oral corticosteroids; 64% used immunosuppressants or cytotoxic agents, and 44% used biologics. Patients had a median (IQR) of 3 clinical manifestations (1-5), most commonly constitutional (63%), lung (49%), and skin (48%). Twenty-three percent of patients experienced a flare, and 40% had a complete treatment response. Some patients (30%) were hospitalized with a median (IQR) stay of 9 days (5-15) for HES-related issues. CONCLUSION: Patients with HES across 5 European countries had a substantial disease burden despite extensive oral corticosteroids treatment, highlighting the need for additional targeted therapies.

Burden of illness associated with eosinophilic granulomatosis with polyangiitis: a systematic literature review and meta-analysis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease associated with vascular inflammation and multisystem organ damage. The literature reporting EGPA incidence or prevalence is limited. We performed a systematic literature review and meta-analysis to describe the incidence, prevalence, and disease burden associated with EGPA. Real-world, observational, English-language studies in MEDLINE, MEDLINE In-Process, and Embase up to 6 June, 2019, were included. A single investigator screened all identified titles/abstracts and extracted data; an additional, independent investigator repeated the screening and validated the extracted data. A random-effects meta-analysis was conducted to generate pooled estimates for EGPA incidence and prevalence. Data from 100 eligible publications were extracted (32 with incidence/prevalence data, 65 with morbidity/healthcare resource data; 3 with both types of data). Significant evidence of between-study heterogeneity for reported incidence (p = 0.0013-0.0016) and prevalence (p = 0.0001-0.0006) estimates was observed. Global and European pooled estimates (95% confidence interval) of EGPA incidence were 1.22 (0.93, 1.60) and 1.07 (0.94, 1.35) cases per million person-years, respectively; global and European pooled estimates (95% confidence interval) for EGPA prevalence were 15.27 (11.89, 19.61) and 12.13 (6.98, 21.06) cases per million individuals, respectively. The proportions of patients experiencing relapses, or who had nasal polyps or severe asthma, varied considerably across studies. EGPA healthcare resource use was high, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Our results indicate that although global and European EGPA incidence and prevalence is low, the associated disease burden is substantial. Key points • We performed a systematic literature review and meta-analysis of real-world, observational studies describing the incidence, prevalence, and disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA). • Based on meta-analysis data from 35 eligible studies reporting incidence and prevalence, the incidence and prevalence of EGPA were low (globally 1.22 cases per million person-years and 15.27 cases per million individuals, respectively). • Among the 49 studies with morbidity and/or healthcare resource data, most reported a large proportion of patients with EGPA relapses and comorbidities of nasal polyps and severe asthma. • Healthcare resource use was also high among patients with EGPA in these studies, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Taken together, these data indicate the substantial disease burden associated with EGPA.

The prevalence and patient characteristics of chronic obstructive pulmonary disease in non-smokers in Vietnam and Indonesia: An observational survey.

BACKGROUND AND OBJECTIVE: An estimated 25-40% of patients with chronic obstructive pulmonary disease (COPD) have never smoked. We investigated the prevalence and patient characteristics of COPD in non-smokers from Vietnam and Indonesia. METHODS: This population-based cross-sectional survey of participants from urban and rural Vietnam and Indonesia used a stratified multistage cluster sampling design, with sample and population weights applied to ensure representativeness. Participants were female or male (recruited in the ratio 2:1) non-smokers, 40 years or older and able to perform a spirometry test. Spirometry was performed at a single study visit. Other clinical information was collected via standardized questionnaires. RESULTS: The 1506 evaluable participants were approximately equally distributed between Vietnam and Indonesia, and rural and urban areas. Overall prevalence of COPD was found to be 6.9% (95% confidence interval (CI): 5.7-8.3), with almost three times higher prevalence in men than women (12.9% (95% CI: 9.1-18.0) vs 4.4% (95% CI: 3.0-6.5)). We found higher rates of COPD in Vietnam than Indonesia (8.1% (95% CI: 5.8-11.3) vs 6.3% (95% CI: 4.8-8.3)), with a particularly high prevalence in urban Vietnam (11.1% (95% CI: 8.1-15.1)). Very few participants (6%) diagnosed to have COPD during the study had been previously diagnosed with COPD. Respiratory symptoms and lower health-related quality of life were more common in participants with COPD. CONCLUSIONS: The prevalence of COPD in non-smoking individuals from rural and urban Vietnam and Indonesia was 6.9%, of which a significant proportion (94%) were previously undiagnosed.

Estimating physical activity energy expenditure, sedentary time, and physical activity intensity by self-report in adults.

BACKGROUND: Few questionnaires that assess usual physical activity have been reported to be valid for all different subdimensions of physical activity. OBJECTIVE: The objective was to assess the validity and reliability of the Recent Physical Activity Questionnaire (RPAQ), which assesses usual physical activity (PA) in 4 domains (work, travel, recreation, and domestic life). DESIGN: Total energy expenditure (TEE) was measured for 14 d by using the doubly labeled water technique combined with a measure of resting metabolic rate to yield PA energy expenditure (PAEE) in 25 men and 25 women. Simultaneously, intensity of activity was measured by using combined heart rate and movement sensing for 11 d. Repeatability of the RPAQ was assessed in an independent sample of 71 women and 60 men aged 31-57 y. RESULTS: Estimated TEE and PAEE were significantly associated with criterion measures (TEE: r = 0.67; PAEE: r = 0.39) with mean (+/-SD) biases of -3452 +/- 2025 kJ/d and -13 +/- 24 kJ d(-1) kg(-1). The correlation between self-reported and measured time spent was significant for vigorous PA (r = 0.70) and marginally insignificant for sedentary time (r = 0.27, P = 0.06). The mean biases were relatively small for sedentary time and vigorous PA: 0.7 +/- 2.8 h/d and -12 +/- 24 min/d, respectively. The intraclass correlation coefficient for repeatability of total PAEE (kJ/d) was 0.76 (P < 0.0001). CONCLUSION: The RPAQ is the first questionnaire with demonstrated validity for ranking individuals according to their time spent at vigorous-intensity activity and overall energy expenditure.

Adjusting for energy intake--what measure to use in nutritional epidemiological studies?

BACKGROUND: The measurement of energy intake in epidemiological studies is difficult. However, it is important that energy intake is assessed if epidemiological analyses are to correspond to isocaloric experiments. The aim of this study was to compare self-reported energy intake, physical activity, and body weight with energy expenditure measured by 4 days of heart rate monitoring with individual calibration of the relationship between heart rate and oxygen consumption. METHODS: Volunteer sub-study of 97 men and women (mean ages 54 and 51 years respectively) within the European Investigation into Cancer (EPIC) study in Norfolk (UK). Dietary assessment of energy intake and physical activity was by self-report and weight was measured using standard techniques. Energy expenditure was assessed objectively by recording heart rate for 4 days following a calibration of the relationship between heart rate and oxygen consumption. RESULTS: Self-reported energy intake by 7-day diary (mean 8.5 MJ/day) and food frequency questionnaire (FFQ) (mean 8.8 MJ/day) were significantly lower than objectively measured total energy expenditure (mean 11.2 MJ/day). The deattenuated partial correlations between total energy expenditure were 0.33 (7-day diary), 0.34 (FFQ), 0.50 (physical activity), and 0.56 (weight). Weight accounted for 31% (deattenuated) of the sum of squares about the mean of true energy intake after adjusting for age and sex. With the addition of self-reported physical activity, the model was significantly improved (R2 = 0.57). Adding energy either assessed by the diary or FFQ did not improve the model. CONCLUSIONS: The results presented here indicate that to adjust for energy intake, for the purpose of replicating an isocaloric experiment in an observational epidemiological study, one would do considerably better adjusting for weight and physical activity, than adjusting for energy intake estimated from an FFQ.

Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

OBJECTIVE: To assess the validity and repeatability of a simple index designed to rank participants according to their energy expenditure estimated by self-report, by comparison with objectively measured energy expenditure assessed by heart-rate monitoring with individual calibration. DESIGN: Energy expenditure was assessed over one year by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole-body calorimetry and doubly labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed a physical activity questionnaire that assessed past-year activity. A simple four-level physical activity index was derived by combining occupational physical activity together with time participating in cycling and other physical exercise (such as keep fit, aerobics, swimming and jogging). SUBJECTS: One hundred and seventy-three randomly selected men and women aged 40 to 65 years. RESULTS: The repeatability of the physical activity index was high (weighted kappa=0.6, ). There were positive associations between the physical activity index from the questionnaire and the objective measures of the ratio of daytime energy expenditure to resting metabolic rate and cardio-respiratory fitness As an indirect test of validity, there was a positive association between the physical activity index and the ratio of energy intake, assessed by 7-day food diaries, to predicted basal metabolic rate. CONCLUSIONS: The summary index of physical activity derived from the questions used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study suggest it is useful for ranking participants in terms of their physical activity in large epidemiological studies. The index is simple and easy to comprehend, which may make it suitable for situations that require a concise, global index of activity.

Mammographic parenchymal patterns and self-reported soy intake in Singapore Chinese women.

The study aimed to investigate whether self-reported dietary variables were associated with mammographic parenchymal patterns, which have been shown to predict risk of breast cancer. Among the 3,421 women, ages 45-74 years, common to two independent population-based cohorts, mammographic parenchymal patterns and current dietary habits were assessed for 406 randomly chosen participants. Logistic regression methods were used to compare dietary and other lifestyle profiles between subjects classified as displaying high (cases) and low risk (controls) parenchymal patterns. After adjustment for energy intake and other potential confounders, dietary soy protein intake was inversely related to risk of high-risk parenchymal pattern (odds ratio, 0.41; 95% confidence interval, 0.18-0.94, highest versus lowest quartile of intake). Similarly, the highest versus lowest quartile of dietary soy isoflavone intake was significantly related to low-risk parenchymal patterns (odds ratio, 0.44; 95% confidence interval, 0.20-0.98). The association between high soy intake and a reduced risk of mammographic parenchymal patterns that are associated with high breast cancer risk may have important implications in breast cancer prevention.

Physical inactivity is associated with lower forced expiratory volume in 1 second : European Prospective Investigation into Cancer-Norfolk Prospective Population Study.

Forced expiratory volume in 1 second (FEV(1)) is a strong risk factor for cardiovascular disease, stroke, lung cancer, and all-cause mortality. One possible explanation for this association is that FEV(1) is a marker of other determinants of mortality risk, such as obesity and physical inactivity. In a population-based cohort study of 12,283 men and women aged 45-74 years from the European Prospective Investigation into Cancer-Norfolk Study recruited in 1993-1997, the cross-sectional association between physical activity and FEV(1) and that between physical activity and change in FEV(1) were analyzed. Indices of physical activity, including participation in vigorous recreational activity, stair climbing, and television viewing, were assessed with a validated questionnaire designed to assess activity in the previous year. Television viewing was negatively associated with FEV(1) in men and women (p < 0.001), whereas stair climbing and participation in vigorous leisure time activities were positively associated with FEV(1) in men and women (p < 0.001). The associations remained after adjustment for known confounders, including age, height, vitamin C, and smoking. Climbing more stairs and participating in vigorous leisure-time activity predicted a slower rate in annual percent decline in FEV(1) (p < 0.004 and p < 0.002, respectively). In conclusion, physical activity is associated with higher levels of FEV(1), whereas television viewing is associated with lower levels.

Validity and repeatability of the EPIC-Norfolk Physical Activity Questionnaire.

BACKGROUND: Physical activity is an important lifestyle which is often poorly assessed in epidemiological studies. The European Prospective Investigation into Cancer Study-Norfolk cohort (EPIC-Norfolk), a large population-based cohort study, has developed a comprehensive questionnaire to assess activity in different domains of life aimed at assessing total energy expenditure. We report the repeatability of this instrument and its validity against repeated objective measures of fitness and energy expenditure undertaken throughout the time frame of reference of the questionnaire. METHODS: The validity of the instrument was measured in 173 individuals randomly selected from a continuing population-based cohort study. Energy expenditure was assessed by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole body calorimetry and doubly-labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed the physical activity questionnaire that assesses past-year activity at home, work and in recreation. Repeatability was assessed in a separate group of 399 randomly selected participants in EPIC who completed the physical activity questionnaire twice with a 3-month interval. RESULTS: The age- and sex-adjusted correlation between the objective measure of daytime energy expenditure and the sum of recreational and occupational reported physical activity (in MET h per week) was 0.28 (P < 0.001). The reported time spent in vigorous activity was correlated with cardio-respiratory fitness (0.16, P < 0.05) and with the proportion of time when energy expenditure was more than five times basal (0.17, P < 0.05). The repeatability of the sum of recreational and occupational reported activity was high, r = 0.73. CONCLUSIONS: The indices of physical activity derived from this questionnaire have levels of validity and repeatability comparable to other physical activity instruments that are used in large epidemiological studies and which have undergone such intense development and testing.