Trends in real-world biomarker testing and overall survival in US patients with advanced non-small-cell lung cancer.

Background: Trends/outcomes associated with National Comprehensive Cancer Network (NCCN)-recommended biomarker testing to guide advanced non-small-cell lung cancer (aNSCLC) treatment were assessed. Methods: Patients initiating first-line aNSCLC treatment were included using a nationwide electronic health record-derived database (1/1/2015-10/31/2021). Trends in pre-first-line biomarker testing (PD-L1, major genomic aberrations), factors associated with testing and associations between testing and outcomes were assessed. Results: PD-L1/genomic aberration testing rates increased from 33% (2016) to 81% (2018), then plateaued. Certain clinical and demographic factors were associated with a greater likelihood of PD-L1 testing. Patients tested for PD-L1 or genomic aberrations had longer overall survival (OS). Conclusion: Biomarker testing may be associated with improved OS in aNSCLC, though not all patients had equal access to testing.

Molecular diagnostics play a critical role in precision medicine. Treatment guidelines from the National Comprehensive Cancer Network (NCCN) recommend that patients newly diagnosed with advanced non-small-cell lung cancer (aNSCLC) undergo molecular testing for PD-L1 and genomic aberrations to guide treatment choices. Based on the results of such biomarker testing, physicians can select optimal treatments for individual patients. The aim of this study was to describe the latest trends and disparities in real-world biomarker testing with a focus on PD-L1 and to explore the impact of biomarker testing on outcomes in first-line treatment of aNSCLC in the United States. Patients initiating first-line aNSCLC treatment were identified in the Flatiron Health database (1/1/2015­10/31/2021; N = 30,631). Annual trends in pre-first-line biomarker testing (PD-L1, major genomic aberrations), demographic and clinical factors associated with PD-L1 testing, and associations between PD-L1 and/or ≥1 genomic aberration testing and outcomes (e.g., overall survival [OS], time-to-next treatment [TTNT]) were assessed. Biomarker testing in patients receiving first-line treatment for aNSCLC increased between 2015 and 2017 and plateaued between 2018 and 2021. By 2021, approximately 20% of patients did not receive PD-L1 testing before first-line treatment and not all patients had equal access to testing. Both PD-L1 and genomic aberration testing were associated with improved OS and TTNT. This is likely due to enhanced treatment decisions leading to optimal treatment selection. Future research is warranted to understand interventions to improve biomarker testing and reduce disparities between different patient populations to improve treatment outcomes.

Real World Use and Effects of Calcimimetics in Treating Mineral and Bone Disorder in Hemodialysis Patients.

BACKGROUND: Calcimimetics are used to treat mineral and bone disorder by reducing parathyroid hormone (PTH), calcium (Ca), and phosphorus (Phos). The study objectives were to assess the control of PTH, Ca, and Phos over time in patients receiving cinacalcet or etelcalcetide as well as dosing and time to discontinuation for etelcalcetide. METHODS: This was a retrospective cohort study using electronic medical records from small and independent dialysis centers. Adults ≥18 years of age were identified as cinacalcet or etelcalcetide users based on the first calcimimetic received in 2018 (index date). Patients were followed from the index date until parathyroidectomy, kidney transplant, death, or end of data (December 31, 2018). Analyses of mean PTH, Ca, and Phos, as well as target achievement of PTH, Ca, and Phos were conducted over a 9-month period. Discontinuation with etelcalcetide was measured with the Kaplan-Meier estimator. RESULTS: There were 1,346 cinacalcet patients (mean age 60.5 years, 43.5% female, and 47.1% Black) and 1,255 etelcalcetide patients (mean age 63.4 years, 46.6% female, and 38.5% Black). At baseline, the proportions in target were similar for etelcalcetide versus cinacalcet: 36 versus 38% for PTH, 79 versus 80% for Ca, and 43 versus 44% for Phos. Overall, 40-47% of cinacalcet users and 48-62% of etelcalcetide users were observed to be in target for PTH over 9 months. The proportion in target for Phos ranged from 41 to 46% for cinacalcet and 46-51% for etelcalcetide. The proportion in target for Ca ranged from 74 to 78% for cinacalcet and 60-73% for etelcalcetide. Etelcalcetide 12-month discontinuation was 37.4%. CONCLUSION: Both calcimimetics were effective in keeping PTH, Ca, and Phos levels within target. Patients receiving etelcalcetide tended to have lower laboratory values for PTH, Ca, and Phos over time, while patients receiving cinacalcet tended to be more likely to be in target for Ca over time.

Estimating the Population Benefits and Costs of Rituximab Therapy in the United States from 1998 to 2013 Using Real-World Data.

BACKGROUND: Rituximab was approved in 1997 and is regularly one of the largest drug expenditures for Medicare; however, its benefits and costs have not been estimated from a population perspective. OBJECTIVES: To estimate both the clinical and the economic outcomes of rituximab for its approved hematological uses at the population level. RESEARCH DESIGN: Analyses using cancer registry incidence data from the Surveillance, Epidemiology, and End Results (SEER) program, and outcomes data from SEER data linked with Medicare administrative claims (SEER-Medicare data). These results were incorporated into an epidemiological simulation model of the population over time. SUBJECTS: We modeled all United States patients from 1998 to 2013 diagnosed with diffuse large B-cell lymphoma, follicular lymphoma, or chronic lymphocytic leukemia. MEASURES: Using this model, we estimated the life-years saved, as well as their economic benefit, in the United States population. We also estimated the incremental cost of adding rituximab to chemotherapy. All economic inputs were based on Medicare reimbursed amounts inflated to 2013 dollars. RESULTS: There were 279,704 cumulative life-years saved which were valued at $25.44 billion. The incremental direct medical cost of rituximab was estimated to be $8.92 billion, resulting in an incremental economic gain of $16.52 billion. CONCLUSIONS: These analyses, based on real-world evidence, show that the introduction of rituximab into clinical practice has produced a substantial number of incremental life-years. Importantly, the economic benefit of the life-years gained greatly exceeds the added costs of treatment.

Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma.

Clinical trials have demonstrated that rituximab improves overall survival in non-Hodgkin lymphoma (NHL), except in mantle cell lymphoma (MCL). We used Surveillance Epidemiology and End Results (SEER)-Medicare data to compare survival in older MCL patients who began chemotherapy with or without rituximab within 180 days of diagnosis. Patients were followed from diagnosis (January 1999 to December 2005) until death or the end of observation (December 2007). Medicare administrative and claims data were used to identify the date and cause of death and the immunochemotherapy regimen. Of 638 patients, the mean age at diagnosis was 75 years, 75% had stage III/IV disease, 67% had extranodal involvement, and 64% received rituximab. The average length of first-line treatment was 21 weeks, with no difference between the 2 groups (P = .76). Median survival was 27 months for chemotherapy alone, compared with 37 months for chemotherapy plus rituximab (P < .001). In multivariate analysis of 2-year survival, rituximab plus chemotherapy was associated with lower all-cause (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.41-0.82; P < .01), and cancer-specific (HR 0.56; 95% CI 0.37-0.84; P < .01) mortality. Results were similar when using the entire observation period, propensity score analysis, and limiting chemotherapy to CHOP/CHOP-like. We conclude that first-line chemotherapy including rituximab is associated with significantly improved survival in older patients diagnosed with MCL.

An observational study of outcomes after initial infused therapy in Medicare patients diagnosed with chronic lymphocytic leukemia.

The study goal was to characterize older chronic lymphocytic leukemia (CLL) patients and to evaluate outcomes in those patients who initiated infused therapy. Patients 66 years of age and older in the Surveillance, Epidemiology, and End Results (SEER) program with a CLL diagnosis were matched to their Medicare Part A and Part B claims for long-term follow-up. Treatment patterns, survival after initiation of infused therapy, and both hematologic and hospitalization outcomes were assessed. There were 6433 CLL patients identified, and 2040 received infused therapy. Treated patients were categorized as receiving rituximab monotherapy (16%), rituximab plus chemotherapy (14%), and chemotherapy alone (70%) based on the initial 60 days after infusion. Rituximab plus chemotherapy compared with chemotherapy alone was associated with a 25% lower risk of overall mortality (95% confidence interval, 9%-38%). Restricting to patients age 70 years and older did not change the risk reduction for rituximab plus chemotherapy. Hematologic interventions were more common with rituximab plus chemotherapy compared with chemotherapy alone, but there was no difference in all-cause hospitalizations. These analyses, based on observational data, suggest that the benefits of initial therapy with rituximab in a heterogeneous group of older CLL patients are comparable with those demonstrated in younger patients.

Prevalence and incidence of comorbidities in elderly women with ovarian cancer.

OBJECTIVE: Studies suggest comorbidity plays an important role in ovarian cancer. We characterized the epidemiology of comorbid conditions in elderly U.S. women with ovarian cancer. METHODS: Women with ovarian cancer age ≥66 years, and matched cancer-free women, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims. Prevalence before diagnosis/index date and 3- and 12-month incidence rates (per 1000 person-years) after diagnosis/index date were estimated for 34 chronic and acute conditions across a broad range of diagnostic categories. RESULTS: There were 5087 each of women with ovarian cancer and cancer-free women. The prevalence of most conditions was similar between cancer and cancer-free patients, but exceptions included hypertension (51.8% and 43.5%, respectively), osteoarthritis (13.4% and 17.3%, respectively), and cerebrovascular disease (8.0% and 9.8%, respectively). In contrast, 3- and 12-month incidence rates (per 1000 person years) of most conditions were significantly higher in cancer than in cancer-free patients: hypertension (177.3 and 47.4, respectively); thromboembolic event (145.3 and 5.5, respectively); congestive heart failure (113.3 and 28.6, respectively); infection (664.4 and 55.2, respectively); and anemia (408.3 and 33.1, respectively) at 12 months. CONCLUSIONS: Comorbidities were common among elderly women. After cancer diagnosis, women with ovarian cancer had a much higher incidence of comorbidities than cancer-free women. The high incidence of some of these comorbidities may be related to the cancer or its treatment, but others may have been prevalent but undiagnosed until the cancer diagnosis. The presence of comorbidities may affect treatment decisions.

Comparative effectiveness and cost of adding rituximab to first-line chemotherapy for elderly patients diagnosed with diffuse large B-cell lymphoma.

BACKGROUND: Clinical trials indicate that rituximab improves the survival of patients with diffuse large B-cell lymphoma (DLBCL). Economic models using multiple data sources, including clinical trials for survival outcomes, have projected cost offsets/savings and favorable cost-effectiveness associated with rituximab. In this study, the authors evaluated survival and cost impacts of adding rituximab to first-line chemotherapy for DLBCL using a single database that reflects routine clinical practice among elderly patients in the United States. METHODS: By using Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare, the authors identified 5484 elderly patients who were diagnosed with DLBCL between January 1999 and December 2005 who had claims through December 2007. Included patients began chemotherapy with or without rituximab within 180 days of diagnosis. Multivariate analyses were conducted to estimate the impact of rituximab on mortality and costs to Medicare. The cost per life-year gained of rituximab was calculated using cost and survival estimates from the multivariate analyses. RESULTS: The mean patient age was 76 years, 43% of patients had stage III or IV disease, and 64% received rituximab. In a Cox regression model, rituximab resulted in lower 4-year all-cause mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.61-0.74) and cancer mortality, and the incremental cumulative survival was 0.37 years. In least-squares regression, rituximab resulted in higher 4-year total costs ($23,097; 95% CI, $19,129-$27,298), immunochemotherapy costs ($12,069; 95% CI, $10,687-$13,634), other cancer costs ($7655; 95% CI, $5067-$10,489), and noncancer costs ($3461; 95% CI, $1319-$5650). The cost per life-year gained was $62,424. CONCLUSIONS: In routine clinical practice, rituximab was associated with survival benefits comparable to those observed in clinical trials. However, these benefits did not translate into the previously reported cost savings.

Epidemiology and outcomes of previously undiagnosed diabetes in older women with breast cancer: an observational cohort study based on SEER-Medicare.

BACKGROUND: In breast cancer, diabetes diagnosed prior to cancer (previously diagnosed) is associated with advanced cancer stage and increased mortality. However, in the general population, 40% of diabetes is undiagnosed until glucose testing, and evidence suggests one consequence of increased evaluation and management around breast cancer diagnosis is the increased detection of previously undiagnosed diabetes. Biological factors - for instance, higher insulin levels due to untreated disease - and others underlying the association between previously diagnosed diabetes and breast cancer could differ in those whose diabetes remains undiagnosed until cancer. Our objectives were to identify factors associated with previously undiagnosed diabetes in breast cancer, and to examine associations between previously undiagnosed diabetes and cancer stage, treatment patterns, and mortality. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare, we identified women diagnosed with breast cancer and diabetes between 01/2001 and 12/2005. Diabetes was classified as previously diagnosed if it was identified within Medicare claims between 24 and 4 months before cancer diagnosis, and previously undiagnosed if it was identified from 3 months before to ≤ 3 months after cancer. Patients were followed until 12/2007 or death, whichever came first. Multivariate analyses were performed to examine risk factors for previously undiagnosed diabetes and associations between undiagnosed (compared to previously diagnosed) diabetes, cancer stage, treatment, and mortality. RESULTS: Of 2,418 patients, 634 (26%) had previously undiagnosed diabetes; the remainder had previously diagnosed diabetes. The mean age was 77.8 years, and 49.4% were diagnosed with in situ or stage I disease. Age > 80 years (40% of the cohort) and limited health system contact (primary care physician and/or preventive services) prior to cancer were associated with higher adjusted odds of previously undiagnosed diabetes. Previously undiagnosed diabetes was associated with higher adjusted odds of advanced stage (III/IV) cancer (Odds Ratio = 1.37: 95% Confidence Interval (CI) 1.05 - 1.80; P = 0.02), and a higher adjusted mortality rate due to causes other than cancer (Hazard Ratio = 1.29; 95% CI 1.02 - 1.63; P = 0.03). CONCLUSIONS: In breast cancer, previously undiagnosed diabetes is associated with advanced stage cancer and increased mortality. Identifying biological factors would require further investigation.

Inverse probability weighted least squares regression in the analysis of time-censored cost data: an evaluation of the approach using SEER-Medicare.

OBJECTIVES: To assess the accuracy and precision of inverse probability weighted (IPW) least squares regression analysis for censored cost data. METHODS: By using Surveillance, Epidemiology, and End Results-Medicare, we identified 1500 breast cancer patients who died and had complete cost information within the database. Patients were followed for up to 48 months (partitions) after diagnosis, and their actual total cost was calculated in each partition. We then simulated patterns of administrative and dropout censoring and also added censoring to patients receiving chemotherapy to simulate comparing a newer to older intervention. For each censoring simulation, we performed 1000 IPW regression analyses (bootstrap, sampling with replacement), calculated the average value of each coefficient in each partition, and summed the coefficients for each regression parameter to obtain the cumulative values from 1 to 48 months. RESULTS: The cumulative, 48-month, average cost was $67,796 (95% confidence interval [CI] $58,454-$78,291) with no censoring, $66,313 (95% CI $54,975-$80,074) with administrative censoring, and $66,765 (95% CI $54,510-$81,843) with administrative plus dropout censoring. In multivariate analysis, chemotherapy was associated with increased cost of $25,325 (95% CI $17,549-$32,827) compared with $28,937 (95% CI $20,510-$37,088) with administrative censoring and $29,593 ($20,564-$39,399) with administrative plus dropout censoring. Adding censoring to the chemotherapy group resulted in less accurate IPW estimates. This was ameliorated, however, by applying IPW within treatment groups. CONCLUSION: IPW is a consistent estimator of population mean costs if the weight is correctly specified. If the censoring distribution depends on some covariates, a model that accommodates this dependency must be correctly specified in IPW to obtain accurate estimates.

Longitudinal evaluation of treatment patterns, risk factors and outcomes in patients with cardiovascular disease treated with lipid-lowering therapy in the UK.

OBJECTIVES: To compare treatment patterns, risk factors and cardiovascular disease (CVD) event rates in the UK from 2008 to 2017. DESIGN: Retrospective cohort study using the Clinical Practice Research Datalink. SETTING: UK primary care. PARTICIPANTS: We selected 10 annual cohorts of patients with documented CVD receiving lipid-lowering therapy and the subsets with myocardial infarction (MI). Each cohort included patients ≥18 years old, with ≥1 year of medical history and ≥2 lipid-lowering therapy prescriptions in the prior year. PRIMARY AND SECONDARY OUTCOME MEASURES: For each annual cohort, we identified cardiovascular risk factors and lipid-lowering therapy and estimated the 1-year composite rate of fatal and non-fatal MI, ischaemic stroke (IS) or revascularisation. RESULTS: The documented CVD cohort mean age was 71.6 years in 2008 (N=173 424) and 72.5 (N=94 418) in 2017; in the MI subset, mean age was 70.1 years in 2008 (N=38 999) and 70.4 in 2017 (N=25 900). Both populations had larger proportions of men. In the documented CVD cohort, the proportion receiving high-intensity lipid-lowering therapy from 2008 to 2017 doubled from 16% to 32%; in the MI subset, the increase was 20% to 48%. In the documented CVD cohort, the proportion of patients with low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L increased from 28% to 38%; in the MI subset, the proportion with LDL-C <1.8 mmol/L increased from 32% to 42%. The composite event rate per 100 person-years declined over time, from 2.5 to 2.0 in the documented CVD cohort, and from 3.7 to 2.8 in the MI subset. After excluding revascularisation from the composite outcome, the decline in the event rate in both populations was substantially attenuated. CONCLUSIONS: Despite an increase in high-intensity therapy use and a decline in revascularisation, more than half of patients did not receive high-intensity lipid-lowering therapy by 2017 and incidence rates of MI and IS remained virtually unchanged.

Treatment patterns and outcomes in older patients with advanced malignant pleural mesothelioma: Analyses of Surveillance, Epidemiology, and End Results-Medicare data.

BACKGROUND: Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population. AIM: To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013. METHODS: This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90 days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes. RESULTS: There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n = 209) received pemetrexed-platinum. Of these 209 patients, 41% (n = 86) initiated second-line therapy, and 26% (n = 22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2 months. Patients with epithelioid histology had better median overall survival (12.2 months) compared with other histologies (4.4-5.6 months). Within 90 days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100 000 for all patients with advanced MPM treated with first-line pemetrexed-platinum. CONCLUSIONS: Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.

Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL).

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. RESULTS: Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1.35; P = 0.01), but not mortality due to NHL (HR 1.16; P = 0.19). CONCLUSIONS: In elderly patients diagnosed with DLBCL, there are large differences in treatment access and survival between blacks and whites.

Cost and mortality associated with hospitalizations in patients with immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is associated with low platelet counts and, consequently, a high risk of adverse events leading to hospitalization. However, there are few data on the clinical and economic burden of hospitalizations for ITP. The Nationwide Inpatient Sample (NIS) database of discharges, a stratified 20% sample of all United States (US) community hospitals across all payers, was used to evaluate discharges in ITP patients. We developed nationally representative numbers of discharges in ITP patients from 2003 to 2006 based on diagnosis codes. Using appropriate weights for each NIS discharge, we created national estimates of average cost, length of stay, and in-hospital mortality for specific groups of ITP-related hospitalizations. Approximately 129,000 discharges occurred between 2003 and 2006 in ITP patients. The average cost associated with all discharges in 2008 dollars was 16,476, with a 6.4-day length of stay and in-hospital mortality of 3.8%. In contrast, the average cost of all hospitalizations in the US population during the same period was 10,039, the average length of stay was 4.8 days, and in-hospital mortality was 2.5%. Mortality risk was higher for ITP patients than for the standard US population adjusted for age and gender, with a relative mortality ratio of 1.5 (95% CI: 1.4-1.6). On the basis of a nationally representative sample of US discharge records from 2003 to 2006, hospitalization with ITP represents an economically and clinically important event. ITP was associated with higher costs, longer stays, and more in-hospital deaths on average than all other hospitalized patients combined.

Estimated Life Expectancy and Income of Patients With Sickle Cell Disease Compared With Those Without Sickle Cell Disease.

Importance: Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. Objective: To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. Design, Setting, and Participants: Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. Main Outcomes and Measures: Life expectancy, quality-adjusted life expectancy, and projected lifetime income. Results: The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. Conclusions and Relevance: In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.

Treatment patterns, survival, and hospitalization in adult patients with acute lymphoblastic leukemia: an observational cohort study using SEER Medicare data.

There is little evidence about whether additional risk stratification for adult patients with acute lymphoblastic leukemia age 65 and older is warranted. Using the Surveillance, Epidemiology, and End Results data linked to Medicare claims, we examined the effects of age, comorbid conditions, and mobility limitations on treatment and survival in a cohort of 795 patients diagnosed with ALL between 1 January 2000 and 31 December 2009. In the cohort, 54% received chemotherapy within the first 90 days, of whom 74% were hospitalized during the first chemotherapy administration. Unadjusted median survival was 172 days (95% CI = 244-379) for the overall cohort, 325 days (95% CI = 244-379) for those age 65-69, but only 59 days (95% CI = 45-76) for those age ≥80. In multivariate analyses, older age groups (70-74, 75-79, and ≥80) and comorbidity score ≥2 were independently associated with poorer survival. Treatment and outcomes vary considerably among subgroups of older patients suggesting that further risk stratification may be useful.

Self-reported healthcare utilization by adults with diabetic retinopathy in the United States.

PURPOSE: To assess healthcare utilization patterns across diabetic retinopathy (DR) severity levels in the United States (US). DESIGN: Cross-sectional study of 699 adults, participating in the 2005-2008 National Health and Nutritional Examination Surveys. METHODS: Diagnosis of DR was based on fundus photographs and categorized as: (1) no DR; (2) mild/moderate nonproliferative DR (NPDR); and (3) severe NPDR/proliferative DR (PDR). Healthcare utilization patterns were assessed during a household questionnaire where survey participants self-reported: (1) awareness that diabetes had affected their eyes; (2) pupil-dilation during the past year; and (3) visits to a diabetes education/nutrition specialist during the past year. RESULTS: Among adults with self-reported diabetes, the proportion of those that were aware that diabetes had affected their eye was 15.3% [95% confidence interval (C.I.)] 10.9-19.6%), 21.7% (95% C.I. 14.6-28.7%), and 81.5% (95% C.I. 66.5-96.5%) across those with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p < 0.01). The utilization of a diabetic education/nutrition specialist during the past year was 30.4% (95% C.I. 24.8-36.0%), 31.8% (95% C.I 23.4-40.2%), and 55.9% (95% C.I. 32.3-79.6%) across those with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.13). Pupil dilation within the past year was 62.2% (95% C.I. 56.3-68.1%), 62.1% (95% C.I. 53.4-70.8%), and 93.8% (95% C.I. 87.3-100.0%) across those with no DR, mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.01). CONCLUSIONS: Adults with diabetes in the United States, even those with the most severe forms of DR, do not fully utilize healthcare services for diabetic eye disease. Future studies should aim to address barriers to appropriate diabetes care.

Association of a Combined Measure of Adherence and Treatment Intensity With Cardiovascular Outcomes in Patients With Atherosclerosis or Other Cardiovascular Risk Factors Treated With Statins and/or Ezetimibe.

Importance: Both adherence and treatment intensity can alter the effectiveness of lipid-lowering therapy in routine clinical practice. Objective: To evaluate the association of adherence and treatment intensity with cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD or chronic kidney disease (CKD), and CKD without CVD. Design, Setting, and Participants: Retrospective cohort study using the Clinical Practice Research Datalink from January 2010 through February 2016. United Kingdom primary care was the setting. Participants were newly treated patients who received their first statin and/or ezetimibe prescription between January 1, 2010, and December 31, 2013, plus an additional prescription for statins and/or ezetimibe during the following year. Exposures: Adherence was assessed annually using the proportion of days covered, with adherent defined as a proportion of days covered of 80% or higher. Treatment intensity was classified according to guidelines based on the expected percentage of low-density lipoprotein cholesterol (LDL-C) reduction as low (<30% reduction), moderate (30% to <50% reduction), or high (≥50% reduction). Adherence and treatment intensity were multiplied to create a combined measure, reflecting treatment intensity after accounting for adherence. Main Outcomes and Measures: Composite end point of cardiovascular death or hospitalization for myocardial infarction, unstable angina, ischemic stroke, heart failure, or revascularization. Hazard ratios (HRs) were estimated against patients not treated for 1 year or longer. Results: Among a total of 29 797 newly treated patients, there were 16 701, 12 422, and 674 patients with documented CVD, type 2 diabetes without CVD or CKD, and CKD without CVD, respectively; mean (SD) ages were 68.3 (13.2), 59.3 (12.4), and 67.3 (15.1) years, and male proportions were 60.6%, 55.0%, and 47.0%. In the documented CVD cohort, patients receiving high-intensity therapy were more likely to be adherent over time (84.1% in year 1 and 72.3% in year 6) than patients receiving low-intensity therapy (57.4% in year 1 and 48.4% in year 6). Using a combined measure of adherence and treatment intensity, a graded association was observed with both LDL-C reduction and CVD outcomes: each 10% increase in the combined measure was associated with a 10% lower risk (HR, 0.90; 95% CI, 0.86-0.94). Adherent patients receiving a high-intensity regimen had the lowest risk (HR, 0.60; 95% CI, 0.54-0.68) vs patients untreated for 1 year or longer. Findings in the other 2 cohorts were similar. Conclusions and Relevance: Results of this study demonstrate that the lowest cardiovascular risk was observed among adherent patients receiving high-intensity therapy, and the highest cardiovascular risk was observed among nonadherent patients receiving low-intensity therapy. Strategies that improve adherence and greater use of intensive therapies could substantially improve cardiovascular risk.

Methods for estimating costs in patients with hyperlipidemia experiencing their first cardiovascular event in the United Kingdom.

AIMS: Methods for integrating external costs into clinical databases are not well-characterized. The purpose of this research was to describe and implement methods for estimating the cost of hospitalizations, prescriptions, and general practitioner and specialist visits used to manage hyperlipidemia patients experiencing cardiovascular (CV) events in the United Kingdom (UK). METHODS: This study was a retrospective cohort study using the Clinical Practice Research Datalink and Hospital Episode Statistics data. Costs were incorporated based on reference costs from the National Health Service, and labor costs from the Personal Social Services Research Unit. The study population included patients seen by general practitioners in the UK from 2006-2012. Patients ≥18 years were selected at the time of their first CV-related hospitalization defined as myocardial infarction, ischemic stroke, heart failure, transient ischemic attack, unstable angina, or revascularization. To be included, patients must have received ≥2 lipid-lowering therapies. Outcome measures included healthcare utilization and direct medical costs for hospitalizations, medications, general practitioner visits, and specialist visits during the 6-month acute period, starting with the CV hospitalization, and during the subsequent 30-month long-term period. RESULTS: There were 24,093 patients with a CV hospitalization included in the cohort. This study identified and costed 69,240 hospitalizations, 673,069 GP visits, 32,942 specialist visits, and 2,572,792 prescriptions, representing 855 unique drug and dose combinations. The mean acute period and mean annualized long-term period costs (2014£) were £4,060 and £1,433 for hospitalizations, £377 and £518 for GP visits, £59 and £103 for specialist visits, and £98 and £209 for medications. CONCLUSIONS: Hospital costs represent the largest portion of acute and long-term costs in this population. Detailed costing using utilization data is feasible and representative of UK clinical practice, but is labor intensive. The availability of a standardized coding system in the UK drug costing data would greatly facilitate drug costing.

Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States.

Importance: Among adults with diabetes in the United States, severe forms of diabetic retinopathy (DR) are significantly associated with a greater vision-related functional burden. Objective: To assess the functional burden of DR across severity levels in the United States. Design, Setting, and Participants: This cross-sectional study was based on 1004 participants 40 years or older with diabetes and valid ocular and sociodemographic outcomes in the National Health and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic retinopathy was based on fundus photograph grading, using the Early Treatment Diabetic Retinopathy Study severity scale. The analysis was performed from October 15, 2016, to June 15, 2017. Main Outcomes and Measures: Functional difficulties secondary to vision were assessed during a household questionnaire in which participants self-reported difficulty with reading, visuospatial tasks (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking down steps, stairs, or curbs), and driving. The main outcome measure was vision-related functional burden, which was defined as present for individuals reporting moderate or greater difficulty in any of the aforementioned tasks. Results: Of the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95% CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI, 44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR or proliferative diabetic retinopathy (PDR). The prevalence of vision-related functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy, 20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95% CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable analysis, the odds of vision-related functional burden were significantly greater among those with severe NPDR or PDR relative to those with no retinopathy (adjusted odds ratio [aOR], 3.59; 95% CI, 1.29-10.05; P = .02). Those with severe NPDR or PDR did not have a statistically significant greater odds of vision-related functional burden than did those with mild or moderate NPDR (aOR, 2.70; 95% CI, 0.93-7.78; P = .07). Conclusions and Relevance: Among US adults with diabetes, approximately half of those with severe NPDR or PDR had difficulty with at least one visual function task. Moreover, vision-related functional burden was significantly greater among those with severe NPDR or PDR than among those with no retinopathy. These data suggest the importance of preventing severe forms of DR to mitigate the vision-related functional burden among US adults with diabetes. Future studies should complement our study by assessing the association of worsening retinopathy with objectively measured functional outcomes.

Management of lipid-lowering therapy in patients with cardiovascular events in the UK: a retrospective cohort study.

OBJECTIVES: To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event. DESIGN: Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data. SETTING: Routine clinical practice in the UK from 2006 to 2012. PARTICIPANTS: Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand. Patients were stratified into four mutually exclusive subgroups based on the presence or absence of vascular disease and of diabetes. Those with a second CV hospitalisation within 36 months were included in a separate cohort (second event cohort). PRIMARY AND SECONDARY OUTCOME MEASURES: LDL levels in the year prior to the CV event and 12 months later as well as measures of adherence to lipid-lowering therapy during the 12 months after the CV hospitalisation. RESULTS: There were 24 093 patients in the first event cohort, of whom 5274 were included in the second event cohort. Most received moderate intensity statins at baseline and 12 months. Among the four first event cohort subgroups at baseline, the proportions with an LDL of <1.8 mmol/L was similar between the two diabetic cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The proportion of adherent patients (medication possession ratio of≥0.8) was highest for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%, and for fibrates, it was 48% to 62%. CONCLUSIONS: Despite the existence of effective therapies for lowering cholesterol, patients do not reach achievable LDL targets.