Real-world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/L1 inhibitor therapy: A Medicare claims database analysis.

BACKGROUND: Several programmed death-1 or death-ligand 1 (PD-1/L1) inhibitors are approved first- or second-line therapies for locally advanced or metastatic urothelial carcinoma (la/mUC); however, clinical trials show that only ∼20% of patients respond and all ultimately progress. This study elucidated real-world treatment patterns, healthcare resource utilization (HRU), and economic burden among Medicare beneficiaries with la/mUC who discontinue PD-1/L1 inhibitor therapies. METHODS: We conducted a retrospective claims analysis of patients aged ≥65 years diagnosed with la/mUC (2015-2017) who initiated and subsequently discontinued PD-1/L1 inhibitor therapy (index=date of last administration) using Medicare Fee-for-Service Research Identifiable Files. Included patients had ≥12 months pre- and ≥3 months post-index continuous Medicare enrollment, and were followed until disenrollment, death, or data cutoff. RESULTS: Among 28,063 patients, 17% (n=4652) received ≥1 PD-1/L1 inhibitor following la/mUC diagnosis. Of these, 791 discontinued PD-1/L1 inhibitor therapy and met inclusion criteria (study cohort); 73% male, median age 76 years. Post-discontinuation, 3% received a different PD-1/L1 inhibitor, 46% chemotherapy, and 51% no further systemic treatment. HRU was high during follow-up: 97% had ≥1 outpatient visit and 52% ≥1 hospitalization. Healthcare costs per-patient-per-month were $7153 pre- and $7745 (adjusted) post-index; systemic therapy costs were higher pre- vs. post-index ($2978 vs. $1195) but other costs were higher post-index: hospitalization ($1120 vs. $2200), outpatient ($1437 vs. $2064), hospice ($3 vs. $536), skilled nursing facility ($106 vs. $384). CONCLUSIONS: Over half of Medicare beneficiaries with la/mUC received no disease-directed therapy post-PD-1/L1 inhibitor treatment. Patients who discontinued PD-1/L1 inhibitor therapy had intensive HRU unrelated to therapy costs, highlighting the significant burden of la/mUC and need for treatments that extend survival.

Progression to Uncontrolled Severe Asthma: A Novel Risk Equation.

BACKGROUND: Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier. OBJECTIVE: To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines. METHODS: Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power. RESULTS: The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001). CONCLUSIONS: A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma. DISCLOSURES: This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.

Historical cohort study examining comparative effectiveness of albuterol inhalers with and without integrated dose counter for patients with asthma or chronic obstructive pulmonary disease.

BACKGROUND: Using a metered-dose inhaler (MDI) beyond the labeled number of actuations may result in inadequate dosing of medication, which can lead to poor clinical outcomes. This study compared respiratory-related emergency department (ED) visit rates in patients with asthma, chronic obstructive pulmonary disease, or both when they used albuterol MDIs with versus without dose counters. METHODS: This retrospective study used US claims data to identify patients (ages 4-64 years) with asthma, chronic obstructive pulmonary disease, or both, using albuterol MDIs with or without an integrated dose counter. The study comprised a 1-year baseline period for patient characterization and confounder definition and a 1-year outcome period following the first albuterol prescription. The primary end point was the incidence rate of respiratory-related ED visits, compared using a reduced zero-inflated Poisson regression model. We also compared severe exacerbation rates and rescue medication use. RESULTS: A total of 93,980 patients were studied, including 67,251 (72%) in the dose counter cohort and 26,729 (28%) in the non-dose-counter cohort. The cohorts were broadly similar at baseline (55,069 [59%] female patients; median age, 37 years). The incidence rate of respiratory-related ED visits during the outcome year was 45% lower in the dose counter cohort than in the non-dose-counter cohort (adjusted rate ratio: 0.55; 95% confidence interval: 0.47-0.64). Exacerbation rates and short-acting ß-agonist use were similar between cohorts. CONCLUSION: These findings suggest that dose counter integration into albuterol MDIs is associated with decreased ED visit rates. The presence of integrated dose counters on rescue inhalers can help patients avoid using an empty or near-empty inhaler during exacerbations, thereby ensuring available medication for relief of their symptoms. Integrated dose counters on rescue MDIs could represent a simple and effective tool to improve clinical outcomes during exacerbations, with a potential for cost savings to health care systems.

Burden of asthma with elevated blood eosinophil levels.

BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/µL) and normal eosinophil level (<400 cells/µL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76-14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma.

Value of peripheral blood eosinophil markers to predict severity of asthma.

BACKGROUND: Asthma represents a significant clinical and economic burden to the US healthcare system. Along with other clinical manifestations of the disease, elevated sputum and blood eosinophil levels are observed in patients experiencing asthma exacerbations. The aim of this study was to evaluate the association between blood eosinophil levels and asthma severity defined using Expert Panel Report 3 guidelines. METHODS: Patients with asthma diagnosis between 2004 and 2011 were extracted from the EMRClaims+ database (eMAX Health, White Plains, NY) containing electronic medical records linked to insurance claims for over 675,000 patients. The date of first asthma diagnosis was defined as the 'index date'. Patients were required to have at least 1 peripheral eosinophil test (elevated defined as ≥ 400 cells/µL) in the 12 month 'assessment' period following the index date. We classified patients as those with mild asthma and moderate-to-severe asthma based on the pattern of medication use, as recommended by the 2007 National Institutes of Health Expert Panel Report. Logistic regression models were used to determine if patients with moderate-to-severe asthma had increased likelihood of an elevated peripheral eosinophil count, after accounting for demographics and comorbidities. RESULTS: Among 1,144 patients with an asthma diagnosis, 60 % were classified as having moderate-to-severe asthma. Twenty four percent of patients with moderate-to-severe asthma and 19 % of patients with mild asthma had an elevated peripheral eosinophil count (p = 0.053). Logistic regression showed that moderate-to-severe asthma was associated with 38 % increased odds of elevated eosinophil level (OR 1.38, 95 % CI: 1.02 to 1.86, p = 0.04). CONCLUSION: Patients with moderate-severe asthma are significantly more likely to have an elevated peripheral eosinophil count than patients with mild asthma.

Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study.

BACKGROUND: Elevated sputum eosinophil counts predict asthma exacerbations and responsiveness to inhaled corticosteroids but are impractical to measure in primary care. We investigated the relation between blood eosinophil count and prospective annual asthma outcomes for a large UK cohort. METHODS: This historical cohort study used anonymised medical record data to identify primary care patients with asthma aged 12-80 years with 2 years of continuous records, including 1 year before (baseline) and 1 year after (outcome) their most recent eosinophil count. Negative binomial regression was used to compare outcome exacerbation rates and logistic regression to compare odds of asthma control for patients with blood eosinophil counts of 400 cells per µL or less versus greater than 400 cells per µL, adjusting for age, sex, body-mass index, smoking status, and Charlson comorbidity index. The study is registered at ClinicalTrials.gov, number NCT02140541. FINDINGS: Overall, 20 929 (16%) of 130 248 patients had blood eosinophil counts greater than 400 cells per µL. During the outcome year, these patients experienced significantly more severe exacerbations (adjusted rate ratio [RR] 1·42, 95% CI 1·36-1·47) and acute respiratory events (RR 1·28, 1·24-1·33) than those with counts of 400 cells per µL or less. They also had significantly lower odds of achieving overall asthma control (OR 0·74, 95% CI 0·72-0·77), defined as limited reliever use and no asthma-related hospital attendance or admission, acute course of oral corticosteroids, or prescription for antibiotics. Exacerbation rates increased progressively with nine ascending categories of blood eosinophil count as compared with a reference category of 200 cells per µL or less. INTERPRETATION: Patients with asthma and blood eosinophil counts greater than 400 cells per µL experience more severe exacerbations and have poorer asthma control. Furthermore, a count-response relation exists between blood eosinophil counts and asthma-related outcomes. Blood eosinophil counts could add predictive value to Global Initiative for Asthma control-based risk assessment. FUNDING: Teva Pharmaceuticals.

Seasonal transitions and social responsibility.

OBJECTIVE: This paper is a reflection on work transitions in an international context. PARTICIPANTS: Seasonal employees and employer of the winery Emiliana. METHODS: The following is a personal reflection by a Canadian occupational therapy student after a recent trip to Chile. RESULTS AND CONCLUSIONS: The commitment to social responsibility by the winery Emiliana guided the reflection on work transitions of seasonal employees and the employer's provision of services to improve employee's quality of life.

Where techno-science meets poverty: medical research and the economy of blood in The Gambia, West Africa.

This paper considers how internationally supported medical research is understood and interpreted by its actual and potential study subjects, exposing the limits to bioethical discourses amidst economic inequalities and contrasting socio-cultural worlds. It focuses on the Medical Research Council (MRC) Laboratories in The Gambia and particularly their Pneumococcal Vaccine Trial (PVT) that was conducted jointly with the Gambian government during 2001-2004. In many respects this was an exemplar of international best practice in trial communication and informed consent procedures. Yet ethnographic and survey research finds that Gambian parents' perspectives on participation are shaped not by trial specificities, but by broader, historically shaped views and experiences of the MRC as an institution. There is a pervasive view that the MRC offers good, free medication to participants, but that it also 'steals blood'. Widespread concerns with blood-stealing emerge from local frames of understanding in which blood is treated as a tradeable good, in which blood accumulation and depletion in bodily processes relates to its exchange in hospital and medical research practices, and in which transactions can be more or less (un)reasonable. Yet such thinking, rooted in an 'economy of blood', has been overlooked by medical research staff and indeed by historians and anthropologists of Africa whose analyses of blood-stealing have been overly transfixed on rumour and the occult. This paper argues that such cultural framings, which guide local critical commentary on trans-national research orders, require serious attention and need to inform open dialogues between scientists and the public if medical research in resource-poor settings is to continue to be sustainable and politically legitimate.

Public engagement with science? Local understandings of a vaccine trial in the Gambia.

This paper considers how parents engage with a large, internationally supported childhood pneumococcal vaccine trial in The Gambia. Current analysis and professional reflection on public engagement is strongly shaped by the imperatives of public health and research institutions, and is thus couched in terms of acceptance and refusal, and 'informed consent'. In contrast Gambian parents' perspectives on the trial are couched in conceptual and experiential terms that are linked to their wider dilemmas of raising infants amidst the hazards of globally connected village life. Ethnographic research reveals how for most parents, longer-term experiences of the organization managing the research (the UK Medical Research Council Laboratories in The Gambia) as a health-providing institution override their reflection on trial-specific aims. A decision to participate in the trial involves a perceived balance of benefit and danger -- in the extreme, of free medical treatment, versus one's child being drained of blood for sale to Europe. Social relations (especially gender relations) shape this calculus and study participation. This case suggests how the idea of 'public engagement with science' in a globalized context might be recast, with implications for debates in biomedical ethics, and the sustainability of public participation in medical research.

Avaliaçäo de um programa de assistência primária de saúde na área periurbana

Foi implantado e executado um Programa de Assistência Primária de Saúde em duas comunidades da área periurbana da cidade de Natal-RN. A finalidade deste programa foi de elevar o nível de saúde da comunidade, e seu elemento-chave era a participaçäo comunitária através, principalmente, do trabalho da promotora de saúde. Será detalhado o desenvolvimento do programa e apresentada uma avaliaçäo baseada em mudanças mensuráveis de práticas de saúde e utilizaçäo dos serviços de saúde, como observado nestas comunidades no período de dois anos