Myocardial glycophagy flux dysregulation and glycogen accumulation characterize diabetic cardiomyopathy.

Diabetic heart disease morbidity and mortality is escalating. No specific therapeutics exist and mechanistic understanding of diabetic cardiomyopathy etiology is lacking. While lipid accumulation is a recognized cardiomyocyte phenotype of diabetes, less is known about glycolytic fuel handling and storage. Based on in vitro studies, we postulated the operation of an autophagy pathway in the myocardium specific for glycogen homeostasis - glycophagy. Here we visualize occurrence of cardiac glycophagy and show that the diabetic myocardium is characterized by marked glycogen elevation and altered cardiomyocyte glycogen localization. We establish that cardiac glycophagy flux is disturbed in diabetes. Glycophagy may represent a potential therapeutic target for alleviating the myocardial impacts of metabolic disruption in diabetic heart disease.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A randomised, placebo-controlled trial of carvedilol in early familial dilated cardiomyopathy.

BACKGROUND: Screening of asymptomatic relatives of patients with dilated cardiomyopathy (DCM) has identified a population of individuals with left ventricular dilatation and/or minimally impaired contraction who are believed to have early disease. A proportion of these individuals with early disease progress to overt cardiomyopathy, however to our knowledge there have been no studies that have examined the impact of early intervention on disease progression. METHODS: We evaluated 424 asymptomatic relatives in 110 families of probands with DCM and identified 102 individuals (24%) with suspected "early disease" (EDCM). Thirty-two EDCM subjects were randomised into a six-month placebo-controlled trial of the ß-blocker, carvedilol. Transthoracic echocardiography and plasma nt-proBNP levels were measured at baseline and repeated at six months. The primary trial endpoint was change in left ventricular end-systolic diameter after six months. Subjects completing six months of blinded trial therapy were offered open-label carvedilol and then observed over an extended period with repeated clinical evaluation and echocardiography. RESULTS: At baseline, left ventricular dimensions, systolic function and plasma nt-proBNP levels were similar in carvedilol and placebo groups. There were no significant changes observed in these parameters in either treatment group after six months, however reductions in end-diastolic diameter (% predicted) were observed in carvedilol-treated subjects (P=0.002) during an open-label median follow-up of 32 months (range: 13-56 months). CONCLUSIONS: In an asymptomatic population of individuals with EDCM, treatment with carvedilol for six months had no effect on echocardiographic left ventricular dimensions or systolic function, however longer-term treatment may reverse left ventricular remodelling (Australian Clinical Trials Registry N012605000204640).

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.

Hormone replacement therapy and incidence of central nervous system tumours in the Million Women Study.

We examined the relation between the use of hormone replacement therapy (HRT) and the incidence of central nervous system (CNS) tumours in a large prospective study of 1,147,894 postmenopausal women. Women were aged 56.6 years on average at entry, and HRT use was recorded at recruitment and updated, where possible, about 3 years later. During a mean follow-up of 5.3 years per woman, 1,266 CNS tumours were diagnosed, including 557 gliomas, 311 meningiomas and 117 acoustic neuromas. Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). In past users of HRT the relative risk was 1.07 (95% CI: 0.93-1.24) for all CNS tumours. Among current users of HRT, there was significant heterogeneity by the type of HRT with the users of oestrogen-only HRT at higher risk of all CNS tumours than users of oestrogen-progestagen HRT (RR = 1.42, 95% CI: 1.21-1.67 versus RR = 0.97, 95% CI: 0.82-1.16) (heterogeneity p < 0.001). Among current users of oestrogen-only and oestrogen-progestagen HRT, there was no significant heterogeneity by duration of use, hormonal constituent or mode of administration of HRT.

Type 1 diabetes mellitus and components in drinking water and diet: a population-based, case-control study in Prince Edward Island, Canada.

OBJECTIVE: To determine the relationship between the risk of type 1 diabetes (T1D) and daily intake of drinking water and dietary components, including nitrate, nitrite, and nitrosamines, during the year prior to diagnosis. METHODS: Controls (n = 105) were matched by age at diagnosis and sex to T1D cases (n = 57) newly diagnosed during 2001-2004. Food consumption was assessed using a food frequency questionnaire. Locally available samples of foods were tested for nitrate, nitrite, and nitrosamine concentrations. Water consumption was determined through an additional questionnaire, and water samples were taken from homes and tested for routine chemical components, including nitrate. RESULTS: After controlling for age, age, sex, and daily energy intake, nitrate intake from food sources showed a non-significant positive trend (odds ratios and 95% confidence intervals for quartiles = 1.00, 1.63 (0.58, 4.63), 1.71 (0.54, 5.40), 3.02 (0.78, 11.74); p for trend = 0.13). Nitrite and nitrosamine intake were not related to T1D risk (p for trend = 0.77 and 0.81, respectively). When food and water components were combined, zinc and calcium intakes were marginally and inversely related to T1D risk (p for trend = 0.07 and 0.06, respectively). After further model adjustment of possible confounders and significant risk factors, an increased intake of caffeine marginally increased the risk of T1D (p = 0.07). CONCLUSION: Dietary components from both food and water sources may influence the risk of developing T1D in young persons.

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.

Helpful Ingredients in the Treatment of Long-Term Substance Use Disorders: A Collaborative Narrative Study.

Relatively few individuals with a substance use disorder (SUD) seek or receive treatment, and knowledge about the effective ingredients in SUD treatment, from the perspective of those who receive it, is scarce. Our study purpose was to explore the experiences of those with long-term SUDs and the aspects they found helpful during treatment and long-term recovery. Semi-structured interviews were conducted with 18 participants, each of whom had been diagnosed with a long-term SUD, and who had been abstinent for at least 5 years. A resource group of peer consultants in long-term recovery from SUDs contributed to study planning, preparation, and initial analyses. Participants preferred individualized, long-term treatment, and support from both therapists and other clients. They further acknowledged the importance of their own sense of responsibility for their treatment and recovery success. Greater focus should be placed on viewing long-term SUD as a long-term condition, similar to somatic diseases, and SUD treatment services should place greater emphasis on developing partnership care models, long-term monitoring and support, and actively engaging recovered clients in the care of others in SUD treatment.

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.

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.

Colorectal cancer screening: a comparison of 35 initiatives in 17 countries.

Although in its infancy, organized screening for colorectal cancer (CRC) in the general population is increasing at regional and national levels. Documenting and describing these initiatives is critical to identifying, sharing and promoting best practice in the delivery of CRC screening. Subsequently, the International Colorectal Cancer Screening Network (ICRCSN) was established in 2003 to promote best practice in the delivery of organized screening programs. The initial aim was to identify and document organized screening initiatives that commenced before May 2004. Each identified initiative was sent 1 questionnaire per screening modality: fecal occult blood test, flexible sigmoidoscopy or total colonoscopy. Information was collected on screening methodology, testing details and initiative status. In total, 35 organized initiatives were identified in 17 countries, including 10 routine population-based screening programs, 9 pilots and 16 research projects. Fecal occult blood tests were the most frequently used screening modality, and total colonoscopy was seldom used as a primary screening test. The eligible age for screening ranged from 40 years old to no upper limit; most initiatives included participants aged 50 to 64. Recruitment was usually done by a mailed invitation or during a visit to a family physician. In conclusion, this is the first investigation describing the delivery of CRC screening protocols to various populations. The work of the ICRCSN is enabling valuable information to be shared and a common nomenclature to be established.