Real-world characteristics of patients with asthma initiating fluticasone furoate/umeclidinium/vilanterol single-inhaler triple therapy in Japan.

BACKGROUND: Real-world data assessing characteristics of patients with asthma initiating inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy in Japan are limited. METHODS: Descriptive, observational study of patients with asthma aged ≥15 years newly initiating single- or multiple-inhaler triple therapy (SITT: fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI], SITT: indacaterol/glycopyrronium bromide/mometasone furoate [IND/GLY/MF] or MITT) or ICS/LABA using JMDC/Medical Data Vision (MDV) health insurance databases from February 2021-February 2022 (first prescription date: index date). Patients were assigned to three non-mutually exclusive cohorts: A) new FF/UMEC/VI initiators; B) new FF/UMEC/VI, IND/GLY/MF, or MITT initiators; C) new FF/UMEC/VI, IND/GLY/MF, MITT or ICS/LABA initiators as initial maintenance therapy (IMT). Patient characteristics were assessed descriptively for 12-months pre-treatment initiation (baseline period). RESULTS: Cohort A: among new FF/UMEC/VI initiators, 12.8% and 0.1% (JMDC) and 21.7% and 0.9% (MDV) of patients had ≥1 moderate and severe exacerbation; 52.0% (JMDC) and 79.2% (MDV) had ICS/LABA use. Cohort B: most patients initiated FF/UMEC/VI and IND/GLY/MF over MITT (JMDC: 91.3% vs 8.7%; MDV: 67.8% vs 32.2%), with fewer exacerbations and lower rescue medication use. Cohort C: a greater proportion of FF/UMEC/VI initiators as IMT experienced a moderate exacerbation at index versus ICS/LABA initiators as IMT (JMDC: 17.8% vs 10.7%; MDV: 8.0% vs 5.1%). CONCLUSIONS: Patient characteristics were generally similar between treatment groups; SITT initiators had fewer exacerbations and lower rescue medication use than MITT initiators, represented by the greater proportion of IMT among SITT versus MITT initiators. Physicians may have prescribed triple over dual therapy as IMT in response to an exacerbation.

Treatment pathways, economic burden and clinical outcomes in new users of inhaled corticosteroid/long-acting B2-agonist dual therapy with chronic obstructive pulmonary disease in a primary care setting in England: a retrospective cohort study.

OBJECTIVE: Management of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) improves lung function and health status and reduces COPD exacerbation risk versus monotherapy. This study described treatment use, healthcare resource utilisation (HCRU), healthcare costs and outcomes following initiation of single-device ICS/LABA as initial maintenance therapy (IMT). DESIGN: Retrospective cohort study. SETTING: Primary care, England. DATA SOURCES: Linked data from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. PARTICIPANTS: Patients with COPD and ≥1 single-device ICS/LABA prescription between July 2015 and December 2018 were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Treatment pathways, COPD-related HCRU and healthcare costs, COPD exacerbations, time to triple therapy, medication adherence (proportion of days covered ≥80%) and indexed treatment time to discontinuation. Data for patients without prior maintenance therapy history (IMT users) and non-triple users were assessed over a 12-month follow-up period. RESULTS: Of 13 451 new ICS/LABA users, 5162 were IMT users (budesonide/formoterol, n=1056; beclomethasone dipropionate/formoterol, n=2427; other ICS/LABA, n=1679), for whom at 3 and 12 months post-index, 45.6% and 39.4% were still receiving any ICS/LABA. At >6 to ≤12 months, the proportion of IMT users with ≥1 outpatient visit (10.1%) and proportion with ≥1 inpatient stay (12.6%) had increased from those at 3 months (9.0% and 7.4%, respectively). Inpatient stays contributed most to total COPD-related healthcare costs. For non-triple IMT users, at 3 and 12 months post-index, 4.5% and 13.7% had ≥1 moderate-to-severe COPD exacerbation. Time to triple therapy initiation and time to discontinuation of index medication ranged from 45.9 to 50.2 months and 2.3 to 2.8 months between treatments. Adherence was low across all time points (21.5-27.6%). Results were similar across indexed therapies. CONCLUSIONS: In the year following treatment initiation, ICS/LABA adherence was poor and many patients discontinued or switched therapies, suggesting that more consideration and optimisation of treatment is required in England for patients initiating single-device ICS/LABA therapy.

Cancer worry at higher-risk sample of hereditary cancer in Spain.

BACKGROUND: Few studies have examined the prevalence of cancer worry in the general and at-risk population. The objective of this study was to describe the prevalence of cancer worry in a sample of individuals at increased risk of developing hereditary cancer, determine differences in cancer worry by socio-demographic characteristics and assess the relationship between cancer worry and psychological distress. METHODS: A cross-sectional study was designed with 895 patients. The Cancer Worry Scale (CWS), Hospital Anxiety and Depression Scale (HADS) for psychological distress and sociodemographic characteristics were examined. The multiple linear regression model was developed to explore what variables were predicted for cancer worry. To identify variables associated with higher cancer worry scores, a logistic model was fitted. RESULTS: In the at-higher-risk sample of hereditary cancer, the mean of CWS was 10.20 (SD: 3.70). The significant predictors for cancer worry were gender, age, previous psychiatric treatment, patients affected by cancer and having children. In the sample, 38% of patients had higher scores on cancer worry, the variables associated were patients affected by cancer compared, women, widow/divorced participants, less than secondary school, patients with previous psychiatric treatment and patients less than 55 years old. Using the HADS cutoff score 29% of the sample showed significant psychological distress, more anxiety (35%) than depressive (22%) symptomatology. Psychological distress showed a higher variability (36%) on cancer worry. CONCLUSION: Findings highlighted distinctive profiles in socio-demographic characteristics according to the degree of cancer worry; therefore, genetic counseling should continue to be provided to address cancer worry and relieve psychological distress.

Comparative Effectiveness of Umeclidinium/Vilanterol versus Indacaterol/Glycopyrronium on Moderate-to-Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease in Clinical Practice in England.

Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England. Patients and Methods: This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed. Results: In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were <1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and <1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments. Conclusion: UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.

Comparison of Rescue Medication Prescriptions in Patients with Chronic Obstructive Pulmonary Disease Receiving Umeclidinium/Vilanterol versus Tiotropium Bromide/Olodaterol in Routine Clinical Practice in England.

Purpose: Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting ß2-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO. Patients and Methods: This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics. Patients with a COPD diagnosis at age ≥35 years were included (indexed) following initiation of single-inhaler UMEC/VI or TIO/OLO between July 1, 2015, and September 30, 2019. Outcomes included the number of rescue medication prescriptions at 12-months (primary), and at 6-, 18- and 24-months (secondary), adherence at 6-, 12-, 18- and 24-months post-index, defined as proportion of days covered ≥80% (secondary), and time-to-initiation of triple therapy (exploratory). Inverse probability of treatment weighting (IPTW) was used to balance potential confounding baseline characteristics. Superiority of UMEC/VI versus TIO/OLO for the primary outcome of rescue medication prescriptions was assessed using an intention-to-treat analysis with a p-value < 0.05. Results: In total, 8603 patients were eligible (UMEC/VI: n = 6536; TIO/OLO: n = 2067). Following IPTW, covariates were well balanced across groups. Patients initiating UMEC/VI had statistically significantly fewer (mean [standard deviation]; p-value) rescue medication prescriptions versus TIO/OLO in both the unweighted (4.84 [4.78] vs 5.68 [5.00]; p < 0.001) and weighted comparison (4.91 [4.81] vs 5.48 [5.02]; p = 0.0032) at 12 months; consistent results were seen at all timepoints. Adherence was numerically higher for TIO/OLO versus UMEC/VI at all timepoints. Time-to-triple therapy was similar between treatment groups. Conclusion: UMEC/VI was superior to TIO/OLO in reducing rescue medication prescriptions at 12 months after treatment initiation in a primary care cohort in England, potentially suggesting improvements in symptom control with UMEC/VI compared with TIO/OLO.

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.

Comparative Effectiveness of Umeclidinium/Vilanterol versus Inhaled Corticosteroid/Long-Acting ß2-Agonist in Patients with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in England.

Purpose: To compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England. Patients and Methods: Active comparator, new-user, retrospective cohort study using CPRD-Aurum primary care data and linked Hospital Episode Statistics secondary care administrative data. Patients without exacerbations in the previous year were indexed on first/earliest prescription date of once-daily UMEC/VI or twice-daily ICS/LABA as initial maintenance therapy between July 2014-September 2019. Primary outcome: medication adherence at 12 months post-index, defined as proportion of days covered (PDC) ≥80%. PDC represented proportion of time over the treatment duration that the patient was theoretically in possession of the medication. Secondary outcomes: adherence at 6, 18, and 24 months post-index, time-to-triple therapy, time-to-first on-treatment COPD exacerbation, COPD-related and all-cause healthcare resource utilization (HCRU), and direct health-care costs. A propensity score was generated and inverse probability of treatment weighting (IPTW) was used to balance potential confounders. Superiority was defined as >0% difference between treatment groups. Results: In total, 6815 eligible patients were included (UMEC/VI:1623; ICS/LABA:5192). At 12 months post-index, weighted odds of a patient being adherent were significantly greater with UMEC/VI versus ICS/LABA (odds ratio [95% CI]: 1.71 [1.09, 2.66]; p=0.0185), demonstrating superiority of UMEC/VI. Patients taking UMEC/VI were statistically significantly more adherent than those taking ICS/LABA at 6, 18, and 24 months post-index (p<0.05). Differences in time-to-triple therapy, time-to-moderate COPD exacerbations, HCRU, and direct medical costs were not statistically significant between treatments after IPTW was applied. Conclusion: At 12 months post-treatment initiation, once-daily UMEC/VI was superior to twice-daily ICS/LABA in medication adherence among patients with COPD without exacerbations in the previous year, newly initiating dual maintenance therapy in England. The finding was consistent at 6, 18, and 24 months.

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.

Treatment Patterns, Healthcare Utilization and Clinical Outcomes of Patients with Chronic Obstructive Pulmonary Disease Initiating Single-Inhaler Long-Acting ß2-Agonist/Long-Acting Muscarinic Antagonist Dual Therapy in Primary Care in England.

Purpose: Selection of treatments for patients with chronic obstructive pulmonary disease (COPD) may impact clinical outcomes, healthcare resource use (HCRU) and direct healthcare costs. We aimed to characterize these outcomes along with treatment patterns, for patients with COPD following initiation of single-inhaler long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy in the primary care setting in England. Patients and Methods: This retrospective cohort study used linked primary care electronic medical record data (Clinical Practice Research Datalink-Aurum) and secondary care administrative data (Hospital Episode Statistics) in England to assess outcomes for patients with COPD who had a prescription for one of four single-inhaler LAMA/LABA dual therapies between 1st June 2015-31st December 2018 (indexing period). Outcomes were assessed during a 12-month follow-up period from the index date (date of earliest prescription of a single-inhaler LAMA/LABA within the indexing period). Incident users were those without previous LAMA/LABA dual therapy prescriptions prior to index; this manuscript focuses on a subset of incident users: non-triple therapy users (patients without concomitant inhaled corticosteroid use at index). Results: Of 10,991 incident users included, 9888 (90.0%) were non-triple therapy users, indexed on umeclidinium/vilanterol (n=4805), aclidinium/formoterol (n=2109), indacaterol/glycopyrronium (n=1785) and tiotropium/olodaterol (n=1189). At 3 months post-index, 63.3% of non-triple therapy users remained on a single-inhaler LAMA/LABA, and 22.1% had discontinued inhaled therapy. Most patients (86.9%) required general practitioner consultations in the first 3 months post-index. Inpatient stays were the biggest contributor to healthcare costs. Acute exacerbations of COPD (AECOPDs), adherence, time-to-triple therapy, time-to-first on-treatment moderate-to-severe AECOPD, time-to-index treatment discontinuation, HCRU and healthcare costs were similar across indexed therapies. Conclusion: Patients initiating treatment with single-inhaler LAMA/LABA in primary care in England were unlikely to switch treatments in the first three months following initiation, but some may discontinue respiratory medication. Outcomes were similar across indexed treatments.

Comparison of the accuracy of the 7-item HADS Depression subscale and 14-item total HADS for screening for major depression: A systematic review and individual participant data meta-analysis.

The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Characterisation of patients with chronic obstructive pulmonary disease initiating single-device inhaled corticosteroids/long-acting ß2-agonist dual therapy in a primary care setting in England.

INTRODUCTION: Treatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-device dual therapies in England remain unclear. This study describes the characteristics of patients with COPD before initiating treatment with a single-device inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) in primary care in England. METHODS: This is a retrospective, descriptive study of linked primary and secondary healthcare data (Clinical Practice Research Datalink Aurum, Hospital Episode Statistics). Patients with COPD were indexed on first prescription of fixed-dose, single-device ICS/LABA (June 2015-December 2018). Demographics, clinical characteristics, prescribed treatments, healthcare resource use (HCRU) and direct healthcare costs were assessed over 12 months pre-index. Incident users (indexed on first ever prescription) could be non-triple users (no concomitant long-acting muscarinic antagonist at index); a subset were initial maintenance therapy (IMT) users (no history of pre-index maintenance therapy). RESULTS: Overall, 13 451 incident users (non-triple users: 7448, 55.4%; IMT users: 5162, 38.4%) were indexed on beclomethasone dipropionate/formoterol (6122, 45.5%), budesonide/formoterol (2703, 20.1%) or Other ICS/LABA combinations (4626, 34.4%). Overall, 20.8% of incident users had comorbid asthma and 42.6% had ≥1 moderate-to-severe acute exacerbation of COPD pre-index. Baseline characteristics were similar across indexed therapies. At 3 months pre-index, 45.3% and 35.4% of non-triple and IMT users were receiving maintenance treatment. HCRU and direct healthcare costs were similar across indexed treatments. Prescribing patterns varied regionally. CONCLUSION: Patient characteristics, prior treatments, prior COPD-related HCRU and direct healthcare costs were similar across single-device ICS/LABAs in primary care in England. A high proportion of patients were not receiving any respiratory medication pre-index, indicating that prescribing in primary care in England is more closely aligned with national guidelines than global treatment strategies. Comorbid asthma may have influenced prescribing decisions. Less than half of users had preindex exacerbations, suggesting that ICS/LABA is not being prescribed principally based on exacerbation history.

Comparison of psychological distress for breast, ovarian and colorectal cancer predisposition in a Spanish sample at high risk of hereditary cancer.

OBJECTIVES: Although future treatments may speciically target the tumour phenotype, other factors should be included to confirm the efficacy of treatment and prevention strategies. The objective of this study was to compare sociodemographic characteristics and psychological distress for breast, ovarian and colorectal cancer predisposition syndrome in a sample at high risk of hereditary cancer. METHODS: A cross-sectional study was designed with 799 patients. The nonparametric test, with Kruskal-Wallis test, was used to compare three genetic cancer syndromes, with significant differences in sample size. RESULTS: There were no differences in cancer hereditary syndromes related to sociodemographic characteristics except sex, as breast/ovarian cancer mainly affects women. No group differences were observed for cancer worry (P = 0.17). Breast/ovarian cancer syndrome showed significantly higher scores in cognitive distress compared to colorectal cancer (P = 0.01). CONCLUSION: The differences in the distribution of sociodemographic characteristics in these hereditary cancer syndromes can help to better plan resources for patient care in genetic counselling units.

Characterization of Patients with Chronic Obstructive Pulmonary Disease Initiating Single-Inhaler Long-Acting Muscarinic Antagonist/Long-Acting ß2-Agonist Dual Therapy in a Primary Care Setting in England.

Purpose: Treatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-inhaler dual therapies remain unclear. We aimed to describe characteristics, prescribed treatments, healthcare resource use (HCRU) and costs of patients with COPD who initiated single-inhaler long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy in primary care in England. Patients and Methods: Retrospective study using linked data from Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. Patients with COPD with ≥1 single-inhaler LAMA/LABA prescription between June 2015 and December 2018 (index) were included. Demographic and clinical characteristics, prescribed treatments, HCRU and costs were evaluated in the 12 months pre-index. Data are presented for patients not receiving concomitant inhaled corticosteroids at index (non-triple users). Results: Of 10,991 patients initiating LAMA/LABA, 9888 were non-triple users, of whom 21.3% (n=2109) received aclidinium bromide/formoterol, 18.1% (n=1785) received indacaterol/glycopyrronium, 12.0% (n=1189) received tiotropium bromide/olodaterol and 48.6% (n=4805) received umeclidinium/vilanterol. Demographic and clinical characteristics were similar across indexed therapies. LAMA monotherapy was the most frequently prescribed respiratory therapy at 12 (18.4-25.8% of patients) and 3 months (23.9-33.7% of patients) pre-index across indexed therapies; 42.5-59.0% of patients were prescribed no respiratory therapy at these time points. COPD-related HCRU during the 12 months pre-index was similar across indexed therapies (general practitioner consultations: 62.0-68.6% patients; inpatient stays: 19.3-26.1% patients). Pre-index COPD-related costs were similar across indexed therapies, with inpatient stays representing the highest contribution. Mean total direct annual COPD-related costs ranged from £805-£1187. Conclusion: Characteristics of patients newly initiating single-inhaler LAMA/LABA dual therapy were highly consistent across indexed therapies. As half of non-triple users were not receiving respiratory therapy one year prior to LAMA/LABA initiation, there may be an opportunity for early optimization of treatment to relieve clinical burden versus current prescribing patterns in primary care in England.

Disease burden of primary biliary cholangitis and associated pruritus based on a cross-sectional US claims analysis.

OBJECTIVE: In order to identify areas of unmet need in patients with primary biliary cholangitis (PBC), this study sought to use real-world observational healthcare data to characterise the burden in patients with PBC and in PBC patients with a recorded diagnosis of pruritus. DESIGN: This retrospective, cross-sectional database study compared prevalence of prespecified comorbidities and medications in the PBC population and PBC-pruritus subpopulation with non-cases using an indirect standardisation approach. The PBC population was identified from the US IBM MarketScan Commercial Claims and Medicare Supplemental Database during 2016 using International Classification of Diseases 10th Revision, Clinical Modification codes (≥2 claims for PBC); the PBC-pruritus subpopulation additionally had ≥1 claim for pruritus during this period. Non-cases had no claims for PBC. Indirect age-sex standardised prevalence ratios (iSPR) and 95% confidence intervals (CIs) were calculated for prespecified comorbidities and medications recorded during 2017. RESULTS: The PBC population (N=1963) and PBC-pruritus subpopulation (N=139) had significantly higher prevalence of fatigue (19.9%, iSPR (95% CI): 1.51 (1.36 to 1.66); 26.6%, 2.10 (1.48 to 2.90)), depression/anxiety (21.3%, 1.09 (0.99 to 1.20); 28.1%, 1.46 (1.04 to 2.00)) and sleep-related issues (6.9%, 1.18 (0.99 to 1.40); 14.4%, 2.58 (1.58 to 3.99)) compared with non-cases. Bile acid sequestrants were prescribed in 5.8% and 18.0% of the PBC and PBC-pruritus populations, respectively. In general, a higher prevalence of comorbidities and medication use was observed in the PBC-pruritus subpopulation compared with the PBC population and non-cases. CONCLUSION: Despite availability of treatments for PBC, the PBC population had a higher burden of comorbidities than non-cases. This burden was even greater among the PBC-pruritus subpopulation, with a particularly high prevalence of sleep disorders and depression/anxiety. Despite this, pruritus remains undertreated highlighting a need for treatments specifically indicated for cholestatic pruritus.

Clinical Profile and Treatment in Hypereosinophilic Syndrome Variants: A Pragmatic Review.

BACKGROUND: Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders leading to eosinophil-driven tissue damage and dysfunction. Better understanding of HES variants may facilitate improved patient management. OBJECTIVE: To describe disease characteristics, treatment, and outcomes of patients with idiopathic (I-HES), myeloproliferative (M-HES), lymphocytic (L-HES), and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) among HES case reports and aggregate data where available. METHODS: Relevant articles published between January 1, 2000, and March 20, 2020, were retrieved via PubMed; those reporting secondary, associated/reactive, overlap/single-organ, or familial HES were excluded. RESULTS: Of 188 articles included, 171 contained data on 347 separate HES cases (152 I-HES, 121 M-HES, 62 L-HES, 12 CEL-NOS). Based on individual data, mean age at diagnosis was 43 to 48 years for patients with all HES variants. Males accounted for 90% to 91% of M-HES/CEL-NOS and 55% to 65% of I-HES/L-HES cases. Cardiac symptoms were frequently observed for all HES variants (13%-22% of patients). Respiratory symptoms (I-HES), splenomegaly (M-HES and CEL-NOS), and skin conditions (L-HES) were also frequently observed. Bone marrow, heart, lung, spleen, liver, skin, and lymph nodes were commonly involved. Most patients with I-HES, L-HES, and CEL-NOS received corticosteroids (65%-85%), whereas most with M-HES received imatinib (81%); those with CEL-NOS also received interferon alpha (42%). CONCLUSIONS: Collective analysis of HES case reports supports and extends current understanding of HES variants, highlighting differences in signs and symptoms, organ involvement, and treatment approaches. Improved characterization of HES variants may facilitate the development of novel treatments.

Psychiatric symptoms in a Spanish sample with hereditary cancer risk.

OBJECTIVE: An integral part of the genetic counselling process is the assessment of psychiatric morbidity. The objectives of this study were first to assess psychometric properties of the General Health Questionnaire (GHQ-28items) in a Spanish sample at increased risk of hereditary cancer, and second evaluated the prevalence of psychiatric morbidity and the contribution of socio-demographic and clinical characteristics to predict distress. METHODS: A cross-sectional study was designed with 766 patients. Psychometric analysis with exploratory factor analysis was performed. The influences of socio-demographic characteristics were investigated by multiple linear regression analyses. RESULTS: Factor analysis supported the four-factor solution of the original GHQ-28; Depression and Social dysfunction scales were more stable than Anxiety and Somatic symptom scales. Psychiatric morbidity was detected in 212 (27.9%) patients. The variables predicting psychiatric morbidity were gender, age, patient affected by cancer, previous psychiatric treatment, and patients with relatives affected by cancer. The higher prevalence of psychiatric symptoms was in the age group from 41 to 59 years (16.73%), women (24.37%), patients affected by cancer (19.89%), patients without previous psychiatric treatment (20.82%), and patients with relatives affected by cancer (21.74%). CONCLUSION: Screening psychological distress should consider socio-demographic and clinical characteristics with reference to improve the quality of care. TRIAL REGISTRATION: Clinical trials identifier: NCT04428710.

The increasing incidence and prevalence of hypereosinophilic syndrome in the United Kingdom.

INTRODUCTION: Data on the burden of hypereosinophilic syndrome (HES) are limited. This study investigated the incidence and prevalence of HES using real-world data from patients in the United Kingdom. METHODS: Primary care data from the Clinical Practice Research Datalink were analyzed. The patients of interest were identified using medical codes specific for HES. Annual incidence rates and prevalence were estimated for the years 2010-2018 (inclusive) using patients observed for a minimum period of one year. RESULTS: Between 2010 and 2018, 93 patients were identified with HES. During the study period the incidence of HES ranged from less than 0.04, 95% confidence interval (CI) (0.01-0.07) to 0.17, 95% CI (0.10-0.26) per 100,000 person-years and the prevalence ranged from 0.15, 95% CI (0.10-0.25) to 0.89, 95% CI (0.74-1.09) cases per 100,000 persons. Sensitivity analyses varying the minimum observation period required to identify HES patients gave similar results. CONCLUSION: These results provide estimates of the burden of HES in the United Kingdom and indicate that whilst HES is a very rare disease, there is evidence that is increasingly being recorded in UK primary care.

The Utilization and Safety of Umeclidinium and Umeclidinium/Vilanterol in UK Primary Care: A Retrospective Cohort Study.

BACKGROUND: Umeclidinium bromide (UMEC) and umeclidinium/vilanterol (UMEC/VI) received European approval for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) in 2014. This study examined prescribing patterns, possible off-label prescribing, potential safety-related outcomes and adherence of these medications in routine clinical practice post-approval. METHODS: This retrospective, multi-database, longitudinal observational study of new users of UMEC, UMEC/VI, or other long-acting bronchodilators (LABD) analyzed data from UK electronic health record databases (primary care cohort), linked to hospital data (linked cohort). Off-label prescribing, safety outcomes (cardiovascular, respiratory, and mortality), treatment patterns, and medication adherence were assessed. RESULTS: In the primary care cohort (new users of UMEC n=3875; UMEC/VI n=2224; other LABD n=32,809), two-thirds of UMEC users were prescribed concomitant inhaled corticosteroids/long-acting ß2-agonists. Possible off-label prescribing, defined as use in patients without COPD, was similar for UMEC (7.0%) and UMEC/VI (8.8%), but higher for new users of other LABD (18.0%). There were 547 UMEC users and 512 UMEC/VI users in the linked cohort. In both cohorts, incidence rates (IRs) of cardiovascular outcomes were similar for UMEC and UMEC/VI users (myocardial infarction IR per 1000 person-years [95% CIs]: UMEC 6.9 [4.4, 10.2]; UMEC/VI 6.8 [3.5, 11.9]). IRs of pneumonia and acute COPD exacerbations (AECOPD) were slightly higher among UMEC users compared with UMEC/VI users (AECOPD IR per 1000 person-years [95% CIs]: UMEC 979 [931, 1030]; UMEC/VI 746 [687, 811]). Adherence (medication possession ratio ≥80%) was 64% for UMEC and UMEC/VI. CONCLUSION: Most new users of UMEC were receiving multiple-inhaler triple therapy. Off-label prescribing was uncommon for new users of UMEC and UMEC/VI. Incidence of cardiovascular and respiratory outcomes was as expected for these drug classes. This study provides evidence that UMEC and UMEC/VI are being prescribed appropriately and their safety profile remains unchanged.