The chronic rhinosinusitis with nasal polyp patient journey in the United States and Europe.

In this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate-severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.

The Unified Airway Hypothesis: Evidence From Specific Intervention With Anti-IL-5 Biologic Therapy.

The unified airway hypothesis proposes that upper and lower airway diseases reflect a single pathological process manifesting in different locations within the airway. Functional, epidemiological, and pathological evidence has supported this well-established hypothesis for some time. However, literature on the pathobiologic roles/therapeutic targeting of eosinophils and IL-5 in upper and lower airway diseases (including asthma, chronic rhinosinusitis with nasal polyps [CRSwNP], and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease) has recently emerged. This narrative review revisits the unified airway hypothesis by searching the scientific literature for recent learnings and clinical trial/real-world data that provide a novel perspective on its relevance for clinicians. According to the available literature, eosinophils and IL-5 have important pathophysiological roles in both the upper and lower airways, although the impact of eosinophils and IL-5 may vary in asthma and CRSwNP. Some differential effects of anti-IL-5 and anti-IL-5-receptor therapies in CRSwNP have been observed, requiring further investigation. However, pharmaceutical targeting of eosinophils and IL-5 in patients with upper, lower, and comorbid upper and lower airway inflammation has led to clinical benefit, supporting the hypothesis that these are linked conditions manifesting in different locations. Consideration of this approach may improve patient care and aid clinical decision making.

Real-world characterisation of patients with chronic rhinosinusitis with nasal polyps with and without surgery in England.

OBJECTIVES: To characterise the real-world burden of chronic rhinosinusitis with nasal polyps (CRSwNP) in the UK, stratified by number of surgeries. DESIGN: Retrospective cohort study. SETTING: UK Clinical Practice Research Datalink Aurum database with Hospital Episodes Statistics linkage (2007-2019). PARTICIPANTS: Adults ≥18 years of age with a first NP diagnosis (index) and 365 days of baseline and ≥180 days of follow-up data. Follow-up continued until disenrollment, death or end of data collection. MAIN OUTCOME MEASURES: Primary: primary care physician prescribed CRSwNP-related treatments, and all-cause healthcare resource utilisation (HCRU) in 90 days post-index, stratified by surgeries during follow-up. Secondary: rate of surgery and CRSwNP point prevalence. Baseline patient demographics, clinical characteristics and comorbidities were also assessed. RESULTS: Of the 33 107 patients included, 23.5% and 2.2% had ≥1 and ≥2 surgeries during follow-up, respectively (mean follow-up: 5.3 years). Patients with more surgeries (≥2/≥1/0) during follow-up were more likely to be male (67.3%/69.0%/58.0%), have asthma (37.8%/28.2%/20.2%) and have baseline blood eosinophil counts ≥300 cells/µL (68.5%/66.0%/51.5%). During the first 90-days post-index as surgery number increased, the proportion of patients using oral corticosteroids (25.8%/20.7%/14.2%) and mean (SD) number of all-cause healthcare visits (5.9 [4.2]/5.4 [4.0]/4.9 [4.2]) increased. Time between surgeries was shorter among patients with more surgeries. CRSwNP prevalence on 31 December 2018 was 476 cases per 100 000 persons. CONCLUSION: A small proportion of patients in the UK required multiple surgeries for CRSwNP and this was associated with increasing comorbidity burden, baseline blood eosinophil counts, CRSwNP-related treatment and HCRU use.

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): In-depth sinus surgery analysis.

BACKGROUND: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE. METHODS: SYNAPSE was a double-blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. RESULTS: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan-Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. CONCLUSIONS: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed.

Elucidating the Real-World Burden of Chronic Rhinosinusitis With Nasal Polyps in Patients in the USA.

Objective: To characterize healthcare burden, treatment patterns, and clinical characteristics associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Study Design: Retrospective cohort. Setting: Real-world study using US health insurance claims database. Methods: Adults with ≥1 CRSwNP diagnosis (index date: first claim for nasal polyps [NPs] between January 1, 2008, and March 31, 2019) and continuous health insurance coverage for ≥180 days preindex (baseline) and postindex were included. Follow-up spanned from index to the earliest of disenrollment, death, or data end. Assessments included patient demographics, comorbidities, and blood eosinophil count at baseline, healthcare resource utilization (HCRU), and costs during follow-up in the overall population and stratified by number of surgeries. Results: Of the 119,357 patients who met the inclusion criteria, 33,748 (28%) had ≥1 surgery during follow-up, among whom 3262 (9.7%) had ≥2 surgeries. At baseline, patients with ≥1 vs no NP surgeries had a greater comorbidity burden; a higher proportion of patients had comorbid asthma (37.8% vs 21.8%) and blood eosinophil count ≥300 cells/µL (42.6% vs 38.1%). During follow-up, patients with NP surgeries had higher all-cause and CRSwNP-related HCRU and costs than patients without NP surgery. All-cause healthcare costs per person per year increased with the number of surgeries during follow-up (no surgery, $10,628; ≥1 surgery, $20,747; ≥2 surgeries, $26,969). Conclusion: Patients with CRSwNP and surgery had a greater disease burden than those without surgery, with higher HCRU and costs, and were more likely to have comorbid conditions (most commonly asthma) and elevated blood eosinophil count, indicating a subset of patients with recalcitrant CRSwNP.

Blood eosinophil counts in the general population and airways disease: a comprehensive review and meta-analysis.

BACKGROUND: The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations. METHODS: We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants. RESULTS: Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL-1 (asthma, 22 studies); 200-400 cells·µL-1 (severe asthma, eight studies); 150-183 cells·µL-1 (COPD, six studies); and 100-160 cells·µL-1 (controls, three studies); and 100-200 cells·µL-1 (general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity. CONCLUSION: EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.

Terms and Definitions Used to Describe Recurrence, Treatment Failure and Recovery of Acute Exacerbations of COPD: A Systematic Review of Observational Studies.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are important clinical events, with many patients experiencing multiple AECOPDs annually. The terms used in the literature to define recurring AECOPD events are inconsistent and may impact the ability to describe the true burden of these events. We undertook a systematic review to identify and summarize terms and definitions used in observational studies to describe AECOPD-related events occurring after an initial AECOPD (hereafter "subsequent AECOPD"). METHODS: PubMed was searched (2000-2019) for observational studies on subsequent AECOPD events using broad search strings for "COPD", "exacerbation", and "subsequent exacerbation events". Only English-language studies were included. Small studies (n<50) and studies focusing on hospital re-admission only were excluded. Extracted data were analyzed descriptively to generate a narrative summary, using a thematic approach to group studies utilizing similar terms for subsequent AECOPD. RESULTS: Forty-seven studies were included. No single, distinct terms or definitions were used to define and identify multiple occurrences of AECOPDs, though most (46) studies used one or more of four clustered terms and definitions: reapse (n = 13), recurrence/re-exacerbation (n = 11), treatment failure (n = 12) and non-recovery/time to recovery (n = 16). Heterogeneity was observed within and between the four clusters with respect to study setting, starting point for observing subsequent AECOPDs, time frame to identify a subsequent AECOPD (except for studies using "time to recovery"), and basis for identifying a subsequent exacerbation. CONCLUSION: Our review demonstrates that subsequent AECOPDs (including events such as relapse, recurrence/re-exacerbation, treatment failure, non-recovery/time to recovery) are ill-defined in the observational study literature, emphasizing the need to reach consensus on precise and objective definitions (for example, when one AECOPD ends and another begins). Use of standardized terminology and definitions may aid comparability between, and synthesis of, studies, thus improving the understanding of the natural history and burden of exacerbations in COPD patients.

Short Physical Performance Battery: What Does Each Sub-Test Measure in Patients with Chronic Obstructive Pulmonary Disease?

OBJECTIVE: To identify phenotypic factors associated with the Short Physical Performance Battery (SPPB) and its individual sub-tests: standing balance, 4­meter gait speed (4mGS) and 5-repetition sit-to-stand (5STS). METHODS: The Evaluation of the Role of Inflammation in non-pulmonary disease manifestations in Chronic Airways disease (ERICA) study recruited adult participants with stable chronic obstructive pulmonary disease (COPD). Proportional odds models identified factors associated with the SPPB, and a principal component analysis (PCA) evaluated how much SPPB variance was explainable by each of its 3 sub-tests. RESULTS: Of 729 enrolled participants, 717 (60% male, mean age 67 years) had full SPPB data. Overall, 76% of patients had some evidence of functional limitations (SPPB total score < 12). Scores < 4 were observed in 71%, 31%, and 22% of participants for the 5STS, 4mGS, and balance sub-tests, respectively. A longer 6-minute walk test and greater quadriceps maximal voluntary contraction decreased the odds of being in a lower score category for SPPB total score and for all 3 sub-tests. Aging, self-reported hypertension and higher dyspnea increased the odds, and being married decreased the odds of being in a lower category for total score. All sub-tests contributed equally to total score. CONCLUSION: Each of the 3 sub-tests contributed independent information to the SPPB, demonstrating their usefulness for assessing COPD when considered together rather than individually. The 5STS sub-test had the greatest variation in scores and may thus have the best discriminatory power for clinical COPD studies of lower limb performance where only one SPPB test is feasible.

Exacerbation Frequency And Eosinophil Counts Among Patients With COPD Currently Prescribed Triple Therapy.

Purpose: To characterize and estimate the proportion of patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate while receiving triple therapy and further describe these patients according to blood eosinophil counts. Methods: This was an analysis of the 2017 Adelphi Real-World Respiratory Disease Specific Programme (DSP) survey of patients with COPD from France, Germany, Italy, Spain, and the United Kingdom (UK). Demographics were assessed on the date of completion of the physician/patient questionnaire; clinical characteristics were captured for the previous 12 months. The proportion of patients receiving triple therapy, who had experienced ≥2 moderate or ≥1 severe acute exacerbations of COPD (AECOPD) in the 12 months prior to index, and had blood eosinophil counts ≥150 cells/µL (T-AECOPD-EOS150) or ≥300 cells/µL (T-AECOPD-EOS300), were calculated. Results: In total, 2876 patients were included of which 762 had an eosinophil value. A higher proportion of patients in the ≥300 cells/µL eosinophil group (55.9%) compared with 150-<300 cells/µL (48.7%) and <150 cells/µL (47.1%) groups experienced ≥2 moderate and/or ≥1 severe AECOPD in the year prior to index. The ≥300 cells/µL eosinophil group had the lowest reported level of health-related quality of life (HRQoL). More severe disease in terms of comorbidities, lung function, healthcare resource use, and HRQoL was seen in patients with ≥2 moderate or ≥1 severe AECOPD in the year prior to index while receiving triple therapy, compared with patients who did not meet these criteria. In total, 10.6% and 6.2% of the COPD population, respectively, met the criteria for the T-AECOPD-EOS150 and T-AECOPD-EOS300 cohorts. Conclusion: This analysis demonstrates that there is a subpopulation of patients with COPD who continue to experience exacerbations despite receiving triple therapy; approximately three-quarters of these had eosinophils ≥150 cells/µL and one-third had eosinophils ≥300 cells/µL; these patients may benefit from eosinophil-targeted therapies.

Aortic Pulse Wave Velocity as a Measure of Cardiovascular Risk in Chronic Obstructive Pulmonary Disease: Two-Year Follow-Up Data from the ARCADE Study.

Background and objectives: Cardiovascular (CV) disease is a major cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Patients with COPD have increased arterial stiffness, which may predict future CV risk. However, the development of arterial stiffness in COPD has not yet been studied prospectively. The Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) is a longitudinal study of CV risk and other comorbidities in COPD. The aims of this analysis were to explore factors associated with aortic pulse wave velocity (aPWV) at baseline and to describe the progression of aPWV in patients with COPD and comparators over two years. Materials and methods: At baseline, 520 patients with COPD (confirmed by spirometry) and 150 comparators free from respiratory disease were assessed for body composition, blood pressure, aPWV, noninvasive measures of cardiac output, inflammatory biomarkers, and exercise capacity. This was repeated after two years, and mortality cases and causes were also recorded. Results: At baseline, aPWV was greater in COPD patients 9.8 (95% confidence interval (CI) 9.7-10.0) versus comparators 8.7 (8.5-9.1) m/s (p < 0.01) after adjustments for age, mean arterial pressure (MAP), and heart rate. Mean blood pressure was 98 ± 11 in COPD patients and 95 ± 10 mmHg in comparators at baseline (p = 0.004). After two years, 301 patients and 105 comparators were fully reassessed. The mean (95% CI) aPWV increased similarly in patients 0.44 (0.25-0.63) and comparators 0.46 (0.23-0.69) m/s, without a change in blood pressure. At the two-year follow-up, there were 29 (6%) deaths in COPD patients, with the majority due to respiratory causes, with an overall dropout of 43% of patients with COPD and 30% of comparators. Conclusions: This was the first large longitudinal study of CV risk in COPD patients, and we confirmed greater aPWV in COPD patients than comparators after adjustments for confounding factors. After two years, patients and comparators had a similar increase of almost 0.5 m/s aPWV.

Healthcare costs and utilization associated with muscle weakness diagnosis codes in patients with chronic obstructive pulmonary disease: a United States claims analysis.

AIMS: Muscle weakness (MW)-attributable healthcare resource utilization (HCRU) and costs in patients with chronic obstructive pulmonary disease (COPD) have not been well-characterized in US insurance claims databases. The primary objective of this study was to estimate HCRU in patients with evidence of COPD with and without MW diagnosis codes. MATERIALS AND METHODS: This retrospective analysis used the MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. Between January 2007 and March 2016, we identified patients aged ≥40 years with diagnosis codes for COPD (≥1 emergency department or inpatient claim or ≥2 outpatient claims within 1 year). The cohort was divided into patients with and without ≥1 MW diagnosis code. Propensity score matching was used to generate pairs of patients with and without MW (1:1). Multivariable regression analyses were used to estimate adjusted incremental costs and utilization attributable to the presence of MW diagnosis codes among patients with COPD. RESULTS: Of 427,131 patients who met the study inclusion criteria, 14% had evidence of MW. After matching, 107,420 unique patients remained equally distributed across MW status. Patients with MW diagnosis codes had greater predicted annual HCRU, $2,465 greater total predicted annual COPD-related costs, and $15,179 greater total all-cause costs than those without MW diagnosis codes. Overall, <1% of patients received COPD-related pulmonary rehabilitation services. LIMITATIONS: Study limitations include the potential for undercoding of MW and lack of information on severity of MW in claims data. CONCLUSION: The presence of MW diagnosis codes yielded higher HCRU in this COPD population and suggests that the burden of MW affects both all-cause and COPD-related care. However, utilization of pulmonary rehabilitation, a known effective treatment for MW, remains low. Future research should expand on our results by assessing data sources that allow for clinical confirmation of MW among patients with COPD.

The COPD Biomarkers Qualification Consortium Database: Baseline Characteristics of the St George's Respiratory Questionnaire Dataset.

The COPD Biomarkers Qualification Consortium (CBQC) is a public-private partnership formed in 2010 with a goal of qualifying biomarkers and clinical assessment tools for use in clinical or nonclinical decision-making and particularly within the regulatory context. The St George's Respiratory Questionnaire (SGRQ) is a measure of health-related quality of life widely used in clinical research. The aim of the CBQC working group on SGRQ was to construct an individual patient level database of clinical trial data that included the SGRQ, to use this to confirm the reliability and validity of the SGRQ as an outcome measure of health status, and investigate its use as a predictor of future events (exacerbations and mortality). This manuscript describes the formulation of the CBQC database and presents the baseline demographic and clinical characteristics of the integrated SGRQ database overall, and by study type (short-term [≤1 year], medium-term [2-4 years] and observational studies). Distribution of baseline SGRQ scores varied little by demographic determinants except for income region in the observational data set (low-middle income countries +10 units compared with high income, p<0.0001) and this observation held across studies. SGRQ scores increased with increasing modified Medical Research Council dyspnea scores (mean differences ranged 6.9-17.9 units) and with increasing airflow limitations (Global initiative for chronic Obstructive Lung Disease grades 1 to 4; differences ranged 4.5-16.1 units), consistent across study types. As a method of cross-sectional comparison, the SGRQ appears to be relatively free of bias from demographic factors although care should be taken when making cross sectional comparisons of scores between patients in countries at different levels of socio-economic development/.

St George's Respiratory Questionnaire Score Predicts Outcomes in Patients with COPD: Analysis of Individual Patient Data in the COPD Biomarkers Qualification Consortium Database.

Background: We aimed to estimate the usefulness of a disease specific health status measure, the St George's Respiratory Questionnaire (SGRQ), to predict outcomes in patients with chronic obstructive pulmonary disease (COPD). Methods: Individual patient-data of 12043 patients from long-term randomized clinical trials (2-4 years' duration) in the COPD Biomarkers Qualification Consortium database were analyzed. The adverse COPD outcomes were: exacerbations of COPD, hospital admissions due to exacerbation and all-cause mortality. Cox proportional hazards regression was used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for quartiles of SGRQ scores at baseline and time to first event, and time from first to second event, where appropriate. Results: The risk of adverse COPD outcomes increased with each increasing quartile of SGRQ score for all time to first event analyses. When comparing the lowest versus the highest quartile, the event risk (HRs [95% CIs]) increased by 40% for exacerbations (1.40 [1.29, 1.51]); 2-fold for hospital admissions (2.01 [1.78, 2.28]) and more than 2-fold for all-cause mortality (2.30 [1.91, 2.78]). For second event analyses in a subset of eligible patients, these trends persisted albeit with reduced risk estimates for exacerbations. Conclusions: Among patients with COPD, health status measured by a SGRQ score predicted exacerbations of COPD, hospital admissions due to exacerbations and their recurrence and death after adjustment. These data support the rationale for a health status measure use as a drug development tool and suggest that a health status measure may also have a role in risk assessment for COPD patients in routine medical care.

Socioeconomic Status as a Determinant of Health Status Treatment Response in COPD Trials.

Background: Randomized controlled trials (RCTs) often recruit patients from low and high socioeconomic status (SES) countries, but little is known about the effect of SES on clinical outcomes, particularly patient-centered measures of symptomatic benefit. Methods: Combined individual chronic obstructive pulmonary disease (COPD) patient data from the placebo and long-acting bronchodilator arms of 17 RCTs (from the COPD Biomarkers Qualification Consortium database) were analyzed. Health status was measured using the St George's Respiratory Questionnaire (SGRQ) (minimum clinically important difference [MCID]: 4 units). Trials were grouped into short-term (≤12 months) and medium-term (>12 months to 48 months). A participant's country of residence was categorized into Low/Medium or High SES using World Health Organization criteria. Results: Data from 19765 individuals (6109 Low/Medium SES) were available. Patients in Low/Medium SES countries had more severe disease at baseline. Improvement in SGRQ score with placebo was ≈2 units greater in Low/Medium than in High SES countries; at its greatest, the improvement from baseline exceeded the MCID in Low/Medium countries. This difference was maintained for at least 1 year. Improvement with bronchodilator was also greater in Low/Medium versus High SES countries; overall there was no evidence that the treatment effect versus placebo was different between countries of different SES status. Conclusions: Participants in Low/Medium SES countries experienced significantly larger treatment effects, irrespective of treatment group (placebo and bronchodilator). Despite this, COPD patients in Low/Medium SES countries experienced a health status gain from long-acting bronchodilator treatment that is similar to that seen in High SES countries.

Associations between gastro-oesophageal reflux, its management and exacerbations of chronic obstructive pulmonary disease.

AIM: To determine factors, overall and by sex, associated with self-reported gastro-oesophageal reflux disease (GORD) in chronic obstructive pulmonary disease (COPD) patients, and to evaluate relationships between GORD, its modification by acid suppression medications (Proton Pump Inhibitors [PPI]/histamine-2 receptor antagonists [H2RA]) and exacerbations of COPD and mortality. METHODS: Logistic regression was used to determine factors associated with GORD; Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for GORD and risk of exacerbation and death. RESULTS: Among 2135 COPD patients from the ECLIPSE cohort, 547 patients self-reported GORD, with female preponderance; 237 were taking PPI/H2RA. Risk factors for GORD did not differ by sex. When compared to patients who did not report GORD or use of PPI/H2RA, patients with GORD and taking PPI/H2RA had a significantly increased risk of exacerbation (HR = 1.58, 95%CI = 1.35-1.86); risk was also increased for patients reporting GORD only or PPI/H2RA use only (HR = 1.21 [1.04-1.40] and 1.33 [1.08-1.65], respectively). Similar findings were observed for risk of hospitalised exacerbation. GORD was not associated with mortality. CONCLUSION: GORD in COPD patients is highly prevalent, and risk factors did not differ by sex. Use of PPI/H2RA and self-reported GORD were associated with increased risk of moderate-to-severe and hospitalised exacerbations.

Menopausal hormone therapy and central nervous system tumor risk: large UK prospective study and meta-analysis.

Female sex hormones are thought to affect women's risk of developing central nervous system (CNS) tumors. Some have reported an increased risk in users of menopausal hormone therapy (HT) but evidence is limited. In the UK General Practice Research Database we compared prospectively collected information on HT prescriptions in women aged 50-79 years with CNS tumors diagnosed in 1987-2011 with that in matched controls (four per case). Relative risks (RRs) in relation to prescribed HT were calculated overall and by CNS tumor subtype. Statistical tests are two-sided. For all CNS tumors (n = 3,500), glioma (n = 689), meningioma (n = 1,197), acoustic neuroma (n = 439), and pituitary tumors (n = 273) adjusted RRs for women prescribed HT versus not were, respectively, 1.21 (95% confidence intervals (CI) = 1.10-1.32, p < 0.0001), 1.14 (0.93-1.40, p = 0.2), 1.30 (1.11-1.51, p = 0.001), 1.37 (1.06-1.75, p = 0.01), and 1.35 (0.99-1.85, p = 0.06). There was no significant difference in risk by tumor subtype (p(heterogeneity) = 0.6). A meta-analysis was conducted, combining our results with those from other published studies with prospectively collected exposure information. The meta-analyses yielded significantly increased risks for all CNS tumors, glioma and meningioma in users of estrogen-only [1.35 (1.22-1.49), 1.23 (1.06-1.42) and 1.31 (1.20-1.43), respectively] but not estrogen-progestin HT [1.09 (0.99-1.19), 0.92 (0.78-1.08) and 1.05 (0.95-1.16), respectively]; these differences were statistically significant (p < 0.005 for each tumor type). There was no significant difference between glioma and meningioma risk in users of estrogen-only HT. The totality of the available evidence suggests an increased risk of all CNS tumors (and of glioma and meningioma separately) in users of estrogen-only HT. Absolute excess risk (2 per 10,000 users over 5 years) is small.

Mobile phone use and risk of brain neoplasms and other cancers: prospective study.

BACKGROUND: Results from some retrospective studies suggest a possible increased risk of glioma and acoustic neuroma in users of mobile phones. METHODS: The relation between mobile phone use and incidence of intracranial central nervous system (CNS) tumours and other cancers was examined in 791,710 middle-aged women in a UK prospective cohort, the Million Women Study. Cox regression models were used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Women reported mobile phone use in 1999 to 2005 and again in 2009. RESULTS: During 7 years' follow-up, 51,680 incident invasive cancers and 1,261 incident intracranial CNS tumours occurred. Risk among ever vs never users of mobile phones was not increased for all intracranial CNS tumours (RR = 1.01, 95% CI = 0.90-1.14, P = 0.82), for specified CNS tumour types nor for cancer at 18 other specified sites. For long-term users compared with never users, there was no appreciable association for glioma (10+ years: RR = 0.78, 95% CI = 0.55-1.10, P = 0.16) or meningioma (10+ years: RR = 1.10, 95% CI = 0.66-1.84, P = 0.71). For acoustic neuroma, there was an increase in risk with long term use vs never use (10+ years: RR = 2.46, 95% CI = 1.07-5.64, P = 0.03), the risk increasing with duration of use (trend among users, P = 0.03). CONCLUSIONS: In this large prospective study, mobile phone use was not associated with increased incidence of glioma, meningioma or non-CNS cancers.

Toward standardizing and reporting colorectal cancer screening indicators on an international level: The International Colorectal Cancer Screening Network.

The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and indicators. To test the feasibility of data collection, we requested data on these variables and basic program characteristics from 26 organized full programs and 9 pilot programs in 24 countries. The size of the target population for each program varied considerably from a few thousand to 36 million. The majority of programs used fecal occult blood tests for primary screening, with more using guaiac than immunochemical tests. There was wide variation in the ability of screening programs to report the requested measures and in the values reported. In general, pilot programs were more likely to provide screening measure values than were full programs. As expected, detection rates for polyps and neoplasia were substantially higher in programs screening with endoscopy than in those using fecal occult blood tests. It is hoped that the screening measures and indicators, once revised in the light of this survey, will be adopted and used by existing programs and those in the early planning stages, allowing international comparison with the goal of improved colorectal cancer screening quality.

Development and evaluation of the Oxford WebQ, a low-cost, web-based method for assessment of previous 24 h dietary intakes in large-scale prospective studies.

OBJECTIVES: To describe the development of the Oxford WebQ, a web-based 24 h dietary assessment tool developed for repeated administration in large prospective studies; and to report the preliminary assessment of its performance for estimating nutrient intakes. DESIGN: We developed the Oxford WebQ by repeated testing until it was sufficiently comprehensive and easy to use. For the latest version, we compared nutrient intakes from volunteers who completed both the Oxford WebQ and an interviewer-administered 24 h dietary recall on the same day. SETTING: Oxford, UK. SUBJECTS: A total of 116 men and women. RESULTS: The WebQ took a median of 12·5 (interquartile range: 10·8-16·3) min to self-complete and nutrient intakes were estimated automatically. By contrast, the interviewer-administered 24 h dietary recall took 30 min to complete and 30 min to code. Compared with the 24 h dietary recall, the mean Spearman's correlation for the 21 nutrients obtained from the WebQ was 0·6, with the majority between 0·5 and 0·9. The mean differences in intake were less than ±10 % for all nutrients except for carotene and vitamins B12 and D. On rare occasions a food item was reported in only one assessment method, but this was not more frequent or systematically different between the methods. CONCLUSIONS: Compared with an interviewer-based 24 h dietary recall, the WebQ captures similar food items and estimates similar nutrient intakes for a single day's dietary intake. The WebQ is self-administered and nutrients are estimated automatically, providing a low-cost method for measuring dietary intake in large-scale studies.