Treatment Patterns and Adverse Event-Related Hospitalization Among Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Metastatic Non-small Cell Lung Cancer After Treatment with EGFR Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy Regimens.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) are established first-line treatments among patients with metastatic non-small cell lung cancer harboring EGFR-sensitizing mutations. Upon EGFR TKI resistance, there are scant data supporting a standard of care in subsequent lines of therapy. OBJECTIVE: We aimed to characterize real-world treatment patterns and adverse events associated with hospitalization in later lines of therapy. METHODS: This retrospective analysis of administrative claims included adults with metastatic non-small cell lung cancer who initiated a next line of therapy (index line of therapy) following EGFR TKI and platinum-based chemotherapy discontinuation on/after 1 November, 2015. Treatment regimens and adverse event rates during the index line of therapy were described. RESULTS: Among 195 eligible patients (median age: 59 years; female: 60%), the five most common index line of therapy regimens were immune checkpoint inhibitor monotherapy (29%), EGFR TKI monotherapy (21%), platinum-based chemotherapy (19%), non-platinum-chemotherapy (13%), and EGFR TKI combinations (9%). The overall median (95% confidence interval) time to discontinuation of the index line of therapy was 2.8 (2.1-3.2) months. Common adverse events associated with hospitalizations included infection/sepsis, pneumonia/pneumonitis, and anemia (2.9, 2.8, and 2.0 per 100 person-months, respectively). CONCLUSIONS: Among EGFR TKI-resistant patients who discontinued platinum-based chemotherapy, the duration of the next line of therapy was short, treatment was highly variable, and re-treatment with EGFR TKIs and platinum-based regimens was common, suggesting a lack of standard of care in later lines. Adverse event rates associated with hospitalization were high, especially among platinum-treated patients. These results underscore the unmet need for new therapies in a later line of treatment to reduce the clinical burden among patients in this population.

Real-World Treatment Patterns and Outcomes Following First-Line Pertuzumab and Trastuzumab Among Patients with HER2+ Metastatic Breast Cancer.

INTRODUCTION: Many patients with human epidermal growth factor receptor-2-positive metastatic breast cancer (HER2+ mBC) require subsequent lines of therapy (LOTs) after being treated with pertuzumab and trastuzumab-based regimens in the first line (1L). Although the efficacy of the second-line (2L) therapies has been demonstrated in clinical trials, the real-world effectiveness of these treatments is understudied. This retrospective cohort study assessed the real-world treatment patterns and outcomes for patients with HER2+ mBC following 1L therapy with pertuzumab and trastuzumab-based regimens in the United States (US) during 2015-2019. METHODS: Adults with HER2+ mBC in the US who initiated 1L pertuzumab and trastuzumab-based regimens between 01/01/2015 and 09/30/2019 and had ≥ 60 days of follow-up after 1L initiation were identified from the IQVIA Oncology Electronic Medical Records database. The regimens utilized in 2L following 1L pertuzumab and trastuzumab-based regimens were described. Median treatment duration and time to treatment failure were reported for 2L based on Kaplan-Meier analyses. RESULTS: Of the 710 eligible patients who received pertuzumab and trastuzumab-based regimens in 1L (median age: 57.0 years [interquartile range: 48.0-65.0]; median follow-up: 20.3 months; median 1L duration: 15.3 months), 222 (31.3%) initiated 2L. The most common regimens in 2L were ado-trastuzumab emtansine (T-DM1)-based regimens (n = 159 [71.6%]), followed by lapatinib-based (n = 21 [9.5%]) and neratinib-based (n = 18 [8.1%]) regimens. The median treatment duration and time to treatment failure were 5.9 (95% CI: 5.0, 8.7) and 8.6 (7.3, 11.5) months, respectively, among patients initiating 2L, and 5.7 (4.7, 7.8) and 7.9 (6.5, 10.0) months among those receiving 2L T-DM1. CONCLUSIONS: Most patients with HER2+ mBC requiring additional treatments after 1L pertuzumab and trastuzumab-based regimens utilized T-DM1 in 2L during 2015-2019. The short median treatment duration and time to treatment failure highlight an unmet need that can potentially be fulfilled by recently approved treatment options.

Fracture risk in women with osteoporosis initiated on gastro-resistant risedronate versus immediate release risedronate or alendronate: a claims data analysis in the USA.

The study results indicate that women with osteoporosis initiated on gastro-resistant risedronate have a lower risk of fracture than those initiated on immediate release risedronate or alendronate. A large proportion of women discontinued all oral bisphosphonate therapies within 1 year of treatment start. PURPOSE: Using a US claims database (2009-2019), we compared risk of fractures between women with osteoporosis initiated on gastro-resistant (GR) risedronate and those initiated on (a) immediate release (IR) risedronate or (b) immediate release alendronate. METHODS: Women aged ≥ 60 years with osteoporosis who had ≥ 2 oral bisphosphonate prescription fills were followed for ≥ 1 year after the first observed bisphosphonates dispensing (index date). Fracture risk was compared between the GR risedronate and IR risedronate/alendronate cohorts using adjusted incidence rate ratios (aIRRs), both overall and in subgroups with high fracture risk due to older age or comorbidity/medications. Site-specific fractures were identified based on diagnosis codes recorded on medical claims using a claims-based algorithm. Persistence on bisphosphonate therapy was evaluated for all groups. RESULTS: aIRRs generally indicated lower fracture risk for GR risedronate than IR risedronate and alendronate. When comparing GR risedronate to IR risedronate, statistically significant aIRRs (p < 0.05) were observed for pelvic fractures in the full cohorts (aIRRs = 0.37), for any fracture and pelvic fractures among women aged ≥ 65 years (aIRRs = 0.63 and 0.41), for any fracture and pelvic fractures among women aged ≥ 70 years (aIRRs = 0.69 and 0.24), and for pelvic fracture among high-risk women due to comorbidity/medications (aIRR = 0.34). When comparing GR risedronate to alendronate, statistically significant aIRRs were observed for pelvic fractures in the full cohorts (aIRR = 0.54), for any fracture and wrist/arm fractures among women aged ≥ 65 years (aIRRs = 0.73 and 0.63), and for any fracture, pelvic, and wrist/arm fractures among women aged ≥ 70 years (aIRRs = 0.72, 0.36, and 0.58). In all cohorts, ~ 40% completely discontinued oral bisphosphonates within 1 year. CONCLUSIONS: Discontinuation rates of oral bisphosphonate therapy were high. However, women initiated on GR risedronate had a significantly lower risk of fracture for several skeletal sites than women initiated on IR risedronate/alendronate, particularly those aged ≥ 70 years.

Health-care resource use and costs associated with diabetic and idiopathic gastroparesis: A claims analysis of the first 3 years following the diagnosis of gastroparesis.

BACKGROUND: Due to limited treatment options, many patients with diabetic gastroparesis (DG) or idiopathic gastroparesis (IG) experience inadequate symptom control resulting in increased health-care resource utilization (HRU) and associated costs. We compared all-cause HRU and health-care costs over the 3 years after patients' first gastroparesis diagnosis with that of matched controls without gastroparesis. METHODS: Newly diagnosed adults with DG or IG were identified in Optum's de-identified Clinformatics® Data Mart Database (Q1-2007 to Q1-2019). Patients with DG/IG were matched 1:1 to controls using a mixed approach of exact matching and propensity score matching. The index date was the first gastroparesis diagnosis for cases or randomly selected for controls. All-cause HRU and direct health-care costs per person-year (PPY) were compared between DG/IG cases and controls in Years 1-3 post-index. KEY RESULTS: Demographics and comorbidities were balanced between patients with gastroparesis (n = 18,015 [DG]; n = 14,305 [IG]) and controls. In each of the Years 1-3 post-index, patients with DG or IG had significantly higher annual HRU and costs versus controls (mean total cost differences PPY: DG Year 1 $34,885, Year 2 $28,071, Year 3 $25,606; IG Year 1 $23,176, Year 2 $16,627, Year 3 $14,396) (all p < 0.05). Across all 3 years, DG/IG cohorts had approximately twice the costs of controls. HRU and costs were highest in Year 1 post-index for both DG and IG. CONCLUSIONS & INFERENCES: The economic burden of gastroparesis remains high several years after diagnosis, emphasizing the need for chronic treatment to effectively manage symptoms and consequently reduce the burden of this disorder.

Reasons for Initiating Canakinumab among Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease in the U.S. Real-World Settings.

INTRODUCTION: The aim of this study was to understand the reasons for canakinumab initiation among patients with Still's disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), in US clinical practice. METHODS: Physicians retrospectively reviewed the medical charts of patients with Still's disease (regardless of age at symptom onset) who were prescribed canakinumab from 2016 to 2018. Patients aged < 16 years at symptom onset were classified as having SJIA and those aged ≥ 16 years at symptom onset (calculated from case-record forms) were classified as having AOSD. Patient treatment history and physician reasons for canakinumab initiation were analyzed. Overall results were presented as SJIA/AOSD. Sensitivity analyses were performed for the robustness of the results. RESULTS: Forty-three physicians in the USA (rheumatologists/dermatologists/immunologists/allergists: 51.2/27.9/11.6/9.3%; subspecialty in adults/pediatrics: 67.4/32.6%) abstracted information for 72 patients with SJIA/AOSD (SJIA/AOSD/age unknown at symptom onset: 75.0/18.1/6.9%; mean age 19.4 years; children 61.1%; females 56.9%). Most patients (90.3%) received treatment directly preceding canakinumab initiation (etanercept 27.7%; anakinra 18.5%; adalimumab 16.9%); the respective treatment was discontinued due to lack of efficacy/effectiveness (43.1%) and availability of a new treatment (27.8%). Most common reasons for canakinumab initiation were physician perceived/experienced efficacy/effectiveness of canakinumab (77.8%; children/adults: 81.8/71.4%), lack-of-response to previous treatment (45.8%; children/adults: 36.4/60.7%), convenient administration/dosing (26.4%; children/adults: 29.5/21.4%) and ability to discontinue/spare steroids (25.0%; children/adults: 20.5/32.1%). The sensitivity analysis provided similar results. CONCLUSIONS: In US clinical practice, physician perceived/experienced efficacy/effectiveness of canakinumab and lack-of-response to previous treatment were the primary reasons for canakinumab initiation among patients with SJIA/AOSD. Physician perceived/experienced efficacy/effectiveness and convenient administration/dosing of canakinumab were the most common reasons for canakinumab initiation among children, whereas lack-of-response to previous treatment and ability to discontinue/spare steroids being the most frequent reasons among adults.

Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States.

BACKGROUND: Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). METHODS: Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children (< 18 years) and adults and by subtype of PFS. RESULTS: Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). CONCLUSIONS: This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

Beyond Frontline Therapy with Abiraterone and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer: A Real-World US Study.

BACKGROUND: Real-world evidence suggest that next generation hormonal agents (NHAs) abiraterone and enzalutamide were preferred as first-line (1L) therapies for metastatic castration-resistant prostate cancer (mCRPC) in the United States (US) pre-2020, with chemotherapies, particularly docetaxel, being preferred in subsequent lines (2L+). This real-world study described patient characteristics, treatment patterns, time on treatment (ToT) and overall survival (OS) among patients with mCRPC treated with 2L and 3L docetaxel post-NHAs in the mCRPC setting. METHODS: Adults with confirmed adenocarcinoma mCRPC diagnosis and ≥1 month of follow-up post-diagnosis were selected from a US electronic health record-derived oncology de-identified database (01/2013-03/2019). Based on the observed line of therapy sequences post-mCRPC diagnosis, patients who received NHA therapy in 1L and docetaxel therapy in 2L were included in the 2L docetaxel cohort, and patients who received NHA therapy in both 1L and 2L and docetaxel therapy in 3L were included in the 3L docetaxel cohort. ToT and OS were evaluated using Kaplan-Meier analysis. RESULTS: Among 5,213 patients with mCRPC, 278 and 166 were included in the 2L and the 3L docetaxel cohorts, respectively (median age: 73 years for both cohorts). ADT was the most used class of medication pre-mCRPC (>75%). For the 2L cohort, the most common sequence post-mCRPC was 1L abiraterone â†’ 2L docetaxel (52.5%), while the median ToT and OS post-2L start were 4.1 and 10.5 months, respectively; for the 3L cohort, the most common sequence post-mCRPC was 1L abiraterone â†’ 2L enzalutamide â†’ 3L docetaxel (67.5%), while the median ToT and OS post-3L start were 3.8 and 8.7 months, respectively. CONCLUSIONS: This real-world study provides novel data on patients treated with docetaxel post-NHAs in a mCRPC setting and highlights the critical unmet need for developing more effective treatment options in this population.

Classification, Prediction, and Concordance of Cognitive and Functional Progression in Patients with Mild Cognitive Impairment in the United States: A Latent Class Analysis.

BACKGROUND: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood. OBJECTIVE: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class. METHODS: Participants with incident MCI were identified from the US National Alzheimer's Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78-15.54]), one copy of APOE ɛ4 (1.94 [1.08-3.47]), higher baseline CDR-SB (2.46 [1.56-3.88]), lower baseline MMSE (0.85 [0.75-0.97]), and higher baseline FAQ (1.13 [1.02-1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Predictors of FAQ class membership were largely similar. CONCLUSION: Approximately a third of participants experienced progression based on CDR-SB or FAQ during the  4-year follow-up period. CDR-SB and FAQ class assignment were concordant for the vast majority of participants. Identified predictors may help the selection of patients at higher risk of progression in future trials.

Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors.

INTRODUCTION: Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) patients are continuously advancing. We described mCRPC treatment patterns in the US from 2013 to 2019. METHODS: Patients with a confirmed mCRPC diagnosis and adenocarcinoma histology were included in the US Flatiron Health Electronic Health Record-derived de-identified database. Treatment patterns [including treatment per lines of therapies (LOTs), LOT sequences, and time on treatment] and overall survival (OS) have been described in mCRPC settings. RESULTS: Of 5213 patients (mean age: 72.6 years), 4374 (83.9%) were treated with ≥ 1 LOT post-mCRPC diagnosis (among those with ≥ 1 LOT, 55.3%, 29.5%, 14.7%, and 6.7% had ≥ 2, 3, 4, and 5 LOTs, respectively). In first line (1L), the main treatment class was next-generation hormonal agents (NHA; 62.5% of patients with ≥ 1 LOT), while the shortest and longest time on 1L were observed for chemotherapy (median 2.8 months) and NHA (median 5.1 months), respectively. The most common LOT sequences were NHA â†’ NHA (29.4% of patients with ≥ 2 LOTs) and NHA â†’ NHA â†’ chemotherapy (16.7% of patients with ≥ 3 LOTs). In Kaplan-Meier analyses, the median OS was 19.4, 14.6, and 11.1 months post-1L, 2L, and 3L start, respectively. Patients who moved rapidly through LOTs had an increased risk of death. CONCLUSIONS: NHA were widely used as 1L therapy in mCRPC patients from 2013 to 2019, but time on 1L NHA treatment was on average < 6 months. While NHA â†’ NHA was the most observed 1L â†’ 2L LOT sequence, a plethora of other LOT sequences were observed. OS was poor, highlighting an unmet need for life-prolonging treatments.

Real-world genetic testing patterns in metastatic castration-resistant prostate cancer.

Aim: To assess the patterns of genetic testing for homologous recombination repair mutations in patients with metastatic castration-resistant prostate cancer (mCRPC) pre-PARP inhibitors approval. Patients & methods: mCRPC patients were selected in an oncology electronic medical records database. Patterns and predictors of testing for ATM, BRCA1/2, CDK12, PALB2 and FANCA gene alterations were assessed. Results: Of 5213 mCRPC patients, 674 (13%) had a documented genetic test. The number of tested patients increased from 1 in 2013 to 313 in 2018 (out of 3161 and 3010 clinically active patients, respectively). Receiving care in an academic oncology center (versus a community-based center) strongly predicted genetic testing (hazard ratio = 2.41). Conclusion: The use of and access to genetic testing pre-PARP inhibitor approval was suboptimal.

Lay abstract In 2017, US guidelines recommended the use of genetic testing in patients with metastatic castration-resistant prostate cancer (mCRPC). While the initial goal of genetic testing was to guide referral to genetic counselling and clinical trial enrollment, it is now also used to identify patients who could benefit from new drugs that target specific molecular defects. Using medical record data of US patients with mCRPC, we found that the rates of genetic testing and the breadth of molecular defects tested were suboptimal from 2013 to 2019. We also found lower rates of genetic testing in patients treated in community-based centers compared with those treated in academic oncology centers. These results underscore the importance of increasing the take up rate of genetic testing in patients with mCRPC to help guide treatment decisions.

Disease Management and Outcomes in Patients Hospitalized for Acute Heart Failure in Japan.

INTRODUCTION: This study described patients hospitalized for acute heart failure (AHF) in Japan who received intravenous (IV) diuretics and/or vasodilators as the initial therapy. METHODS: The Japan Medical Data Vision database was used to identify adult patients hospitalized for AHF during 2013-2017, who were hemodynamically stable at presentation and treated with IV diuretics and/or IV vasodilators as initial therapy. Treatment patterns and use of cardiac rehabilitation, as well as outcomes (e.g., length of stay [LOS], in-hospital mortality, HF-readmission) were reported overall and by year of AHF hospitalization. RESULTS: Of 30,360 patients (mean age = 80.0 years; 52.2% male), 87.0% were treated during the hospitalization with IV diuretics, 63.9% with IV vasodilators, and 13.8% with intensified therapies. On average, the duration of IV therapy was 10.6 days. In-hospital cardiac rehabilitation was utilized by 51.7% of the patients for 11.7 days on average. Mean LOS was 23.3 days, while in-hospital mortality and 30-day HF readmission post-discharge were 13.2 and 9.5%, respectively. Hospitalization outcomes remained stable between 2013 and 2017 despite important changes in AHF management such as a decrease in carperitide use (55.9-40.0% in 2017), and increases in use of tolvaptan (from 14.2% in 2013 to 31.3% in 2017) and of cardiac rehabilitation (from 43.2% in 2013 to 56.1% in 2017). Patients with intensified therapies had the longest IV therapy duration (mean 23.8 days vs. 5.5-9.9 days), the highest cardiac rehabilitation services use (60.2 vs. 38.3-57.0%), the longest LOS (mean 36.7 vs. 16.3-22.2 days), and the highest in-hospital mortality (37.4 vs. 3.1-12.4%) compared to the other treatment groups. CONCLUSIONS: Contemporary treatment for AHF hospitalization in Japan comprises a long duration of IV therapy followed by extended use of oral medications and in-hospital cardiac rehabilitation prior to discharge. Patients requiring intensified therapies had much longer LOS and higher in-hospital mortality.

The Economic Burden of Tenosynovial Giant Cell Tumors Among Employed Workforce in the United States.

OBJECTIVE: To assess the economic burden of tenosynovial giant cell tumor (TGCT) among US employed workforce. METHODS: Patients with TGCT medical claims (N = 1395) and matched controls (1:10) without TGCT claims (N = 13,950) were identified from the OptumHealth Care Solutions, Inc. database (January 1, 1999 to March 31, 2017). Adjusted regression models were used to compare healthcare resource utilization, time lost from work, and associated costs between cohorts. RESULTS: In patients with TGCT, the rates of inpatient admissions, emergency room visits, outpatient visits, and work loss days were 2.8, 1.5, 2.2, and 2.6 times those of matched controls, respectively (all P < 0.001). Total annual all-cause healthcare costs and work loss-related costs were $9368 and $2708 higher for TGCT patients than for matched controls, respectively (all P < 0.001). CONCLUSIONS: TGCT was associated with a significant healthcare and work loss burden on US employers.

The Economic Value of Improved Productivity from Treatment of Chronic Hepatitis C Virus Infection: A Retrospective Analysis of Earnings, Work Loss, and Health Insurance Data.

INTRODUCTION: Patients with chronic hepatitis C virus infection (HCV) may incur significant indirect costs due to health-related work loss. However, the impact of curative HCV therapy on work productivity is not well characterized. We estimated the economic value of improved productivity following HCV treatment. METHODS: Adults diagnosed with HCV infection (Optum Healthcare Solutions data; Q1 1999 to Q1 2017) were stratified into two cohorts: (1) treated cohort, patients who received HCV therapy and (2) untreated cohort, therapy-naïve patients. For the treated cohort, the index date was set at the end of the post-treatment monitoring period, assumed to be 6 months after the end of treatment for patients with cirrhosis or for those treated with interferon-based therapy, and 3 months after the end of treatment for patients without cirrhosis who received interferon-free therapy. For the untreated cohort, an index date was randomly selected post-HCV diagnosis. Time from the index date to the first work-loss event was assessed using time to event analyses. An economic modeling approach was used to monetize the improved productivity from reduced risk of work-loss event in the 4 years post-index. RESULTS: Patients in the treated cohort had a lower risk of experiencing a work-loss event compared to untreated patients [unadjusted and adjusted hazard ratios and 95% CI 0.72 (0.61-0.86), and 0.68 (0.55-0.85), respectively; p < 0.001 for both]. The mean cumulative added productivity value associated with HCV treatment was US$4511 (CI $2778-$6278) at 1 year post-index and $21,429 (CI $12,733-$30,199) at 4 years post-index. CONCLUSION: HCV treatment reduces the risk of work loss resulting in productivity gains for employers and employees. The monetary value associated with these productivity gains is substantial, and, after about 4 years, it is comparable to the wholesale acquisition cost of some direct-acting antiviral regimens in the United States. Employers may derive economic benefits from adopting HCV elimination strategies.

In-Hospital Therapy for Heart Failure With Reduced Ejection Fraction in the United States.

OBJECTIVES: This study sought to characterize in-hospital treatment patterns and associated patient outcomes among patients hospitalized for heart failure (HF) in U.S. clinical practice. BACKGROUND: Hospitalizations for HF are common and associated with poor patient outcomes. Real-world patterns of in-hospital treatment, including diuretic therapy, in contemporary U.S. practice are unknown. METHODS: Using Optum de-identified Electronic Health Record data from 2007 through 2018, patients hospitalized for a primary diagnosis of HF (ejection fraction ≤40%) and who were hemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patients were categorized into 1 of 4 mutually exclusive hierarchical treatment groups defined by complexity of treatment during hospitalization (intensified treatment with mechanical support or IV vasoactive therapy, IV diuretic therapy reinitiated after discontinuation for ≥1 day without intensified treatment, IV diuretic dose increase/combination diuretic treatment without intensified treatment or IV diuretic reinitiation, or uncomplicated). RESULTS: Of 22,677 patients hospitalized for HF with reduced ejection fraction (HFrEF), 66% had uncomplicated hospitalizations without escalation of treatment beyond initial IV diuretic therapy. Among 7,809 remaining patients, the highest level of therapy received was IV diuretic dose increase/combination diuretic treatment in 25%, IV diuretic reinitiation in 36%, and intensified therapy in 39%. Overall, 19% of all patients had reinitiation of IV diuretic agents (26% of such patients had multiple instances), 12% were simultaneously treated with multiple diuretics, and 61% were transitioned to oral diuretic agents before discharge. Compared with uncomplicated treatment, IV diuretic reinitiation and intensified treatment were associated with significantly longer median length of stay (uncomplicated: 4 days; IV diuretic reinitiation: 8 days; intensified: 10 days) and higher rates of in-hospital (uncomplicated: 1.6%; IV diuretic reinitiation: 4.2%; intensified: 13.2%) and 30-day post-discharge mortality (uncomplicated: 5.2%; IV diuretic reinitiation: 9.7%; intensified: 12.7%). CONCLUSIONS: In this contemporary real-world population of U.S. patients hospitalized for HFrEF, one-third of patients had in-hospital treatment escalated beyond initial IV diuretic therapy. These more complex treatment patterns were associated with highly variable patterns of diuretic use, longer hospital lengths of stay, and higher mortality. Standardized and evidence-based approaches are needed to improve the efficiency and effectiveness of in-hospital HFrEF care.

Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review.

AIM: To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011-2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait. METHODS: Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe. RESULTS: Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy. CONCLUSION: Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.

Epilepsy, impaired functioning, and quality of life in patients with tuberous sclerosis complex.

OBJECTIVE: To estimate health-related quality of life (HRQoL) in patients with tuberous sclerosis complex (TSC) and associated manifestations and to identify potential factors associated with HRQoL in this population of patients. METHODS: We performed a retrospective chart review of adults with TSC who attended the outpatient clinic of the University Medical Center Utrecht in the Netherlands from 1990 to 2015 (N = 363; on average 33.6 years of follow-up). HRQoL data were assessed in 2012 using the Health Utility Index version 3 (HUI-3) questionnaire completed by patients or caregivers (N = 214 with HUI score and ≥1 TSC manifestation, including renal angiomyolipomas [rAMLs], subependymal giant cell astrocytoma [SEGA], or epilepsy). RESULTS: Of 214 patients in the study sample, 171 had TSC-associated epilepsy (with or without rAML/SEGA), 37 had TSC and rAML (without epilepsy or SEGA), and 6 had other combinations of manifestations. The median HUI score for the 214 patients with ≥1 TSC manifestation was 0.51 (-0.371 to 1 scale, 1 = perfect health, 0 = death, <0 = worse than death). Among all components used to build the overall HUI score, the cognition component had the lowest score (mean = 0.47; 0-1 scale). Patients with TSC-epilepsy had significantly lower overall HUI than patients with TSC and rAML only (median HUI = 0.31 vs 0.95, P < .05), especially those who were in refractory state for prolonged periods of time (median HUI = -0.11 among patients with seizures during the entire duration of their follow-up time). In multivariate analyses, severe impairment of daily functioning was the strongest predictor of HRQoL decrement (adjusted HUI difference between patients with severe vs. no impairment = -0.55, P < .05). SIGNIFICANCE: This study showed that TSC-related epilepsy is associated with lower HUI, especially for patients who have refractory seizures for prolonged periods of time. Early and effective interventions to control or reduce seizures and preserve patients' cognitive functions may help to improve patients' quality of life.

Second-line rituximab-bendamustine versus rituximab-gemcitabine-oxaliplatin in diffuse large B-cell lymphoma in the real world.

Aim: Despite long-term responses to first-line immunochemotherapy, many patients with diffuse large B-cell lymphoma (DLBCL) have relapsed/refractory disease. Second-line treatment options are available. However, a large proportion of patients are ineligible for transplantation/intensive therapy. Patients & methods: This observational study of 702 patients in the USA, who used second-line therapies for relapsed/refractory DLBCL, evaluated treatment patterns and overall survival (OS). The study focused on the OS outcome of patients receiving second-line rituximab-bendamustine or rituximab-gemcitabine-oxaliplatin. Results & conclusion: Rituximab-bendamustine and rituximab-gemcitabine-oxaliplatin were received by 4.6 and 1.4% of patients, respectively (N = 42/702). Median and 1-year OS rates were similar between regimens. Many of the 200 different treatment regimens observed in second line were modified versions of National Comprehensive Cancer Network regimens.

Secular trends in pregnancy rates, delivery outcomes, and related health care utilization among women with congenital heart disease.

BACKGROUND: The number of women with congenital heart disease (CHD) of reproductive age is increasing, yet a description of trends in pregnancy and delivery outcomes in this population is lacking. OBJECTIVE: To assess secular trends in pregnancy rates, delivery outcomes, and related health care utilization in the adult female CHD population in Quebec, Canada. METHODS: The Quebec CHD database was used to construct a cohort with all women with CHD aged 18-45 years between 1992 and 2004. Pregnancy and delivery rates were determined yearly and compared to the general population. Secular trends in pregnancy and delivery rates were assessed with linear regression. The cesarean delivery rate in the CHD population was compared to the general population. Predictors of cesarean section were determined with multivariable logistic regression. Cox regression, adjusted for comorbidities, was used to analyze the impact of cesarean sections on 1-year health care use following delivery. RESULTS: About 14 878 women were included. A total of 10 809 pregnancies were identified in 5641 women, of whom 4551 (80%) and 2528 (45%) experienced at least one delivery and/or abortion, respectively. Absolute yearly numbers and rates of pregnancies and deliveries increased during the study period (P < .05). The increment in cesarean section rates was more pronounced among women with CHD than among the general population. Gestational diabetes (OR 1.50, 95% CI [1.13, 1.99]), gestational hypertension (OR 1.81, 95% CI [1.27, 2.57]), and preeclampsia (OR 1.59, 95% CI [1.11, 2.8]) were independent predictors of cesarean delivery. Cesarean sections were associated with postpartum cardiac-hospitalization within 1 year following delivery (HR = 2.35, 95% CI [1.05, 5.28]). CONCLUSIONS: Yearly numbers and rates of pregnancies and deliveries in adult females with CHD rose significantly during the study period. Cesarean sections led to increased health care utilization. Further research is required to determine causes of high cesarean section rates in this patient population.

Comparative Effectiveness of Non-cisplatin First-line Therapies for Metastatic Urothelial Carcinoma: Phase 2 IMvigor210 Study Versus US Patients Treated in the Veterans Health Administration.

BACKGROUND: First-line treatments for cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC) include carboplatin-based chemotherapy and checkpoint inhibitors such as atezolizumab (anti-PD-L1). OBJECTIVE: To compare overall survival (OS) among patients with mUC treated in the first-line setting with atezolizumab versus carboplatin-based chemotherapies (any carboplatin-based regimens or carboplatin-gemcitabine). DESIGN, SETTING, AND PARTICIPANTS: Cisplatin-ineligible patients with mUC from the phase 2 trial IMvigor210 (ClinicalTrials.gov NCT02951767) treated with atezolizumab and patients from the Veterans Health Administration (VHA) health care system (2006-2017, with IMvigor210 eligibility criteria applied using proxy measurements) treated according to normal clinical practice. INTERVENTIONS: IMvigor210 cohort 1 patients were treated with atezolizumab, and real-world VHA cohorts were treated with carboplatin-based regimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Entropy-balance weighting was applied to balance prespecified baseline patient characteristics. OS was analyzed using weighted Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The median OS was 15.0 mo with atezolizumab (n = 110), 12.1 mo with any carboplatin-based chemotherapy (n = 282), and 8.7 mo with carboplatin-gemcitabine (n = 120). An OS benefit occurred with atezolizumab versus carboplatin-based regimens after 9 mo (hazard ratio [HR] 0.43; p = 0.004) and with atezolizumab versus carboplatin-gemcitabine after 5 mo (HR 0.52; p = 0.005). Study limitations include a predominantly male VHA cohort and ≤24-mo follow-up. Adjustment for confounding, a potential limitation of nonrandomized studies, was limited by the availability of clinical measurements in the VHA data, which allowed for replication of IMvigor210 exclusions in the VHA cohorts. CONCLUSIONS: First-line atezolizumab for cisplatin-ineligible mUC may provide an OS benefit over carboplatin-based treatments after 5-9 mo, depending on the regimen. PATIENT SUMMARY: Many patients with metastatic urothelial carcinoma are ineligible for cisplatin-based chemotherapy. This study compared patients from a clinical trial receiving the immunotherapeutic agent atezolizumab with those in Veterans Health Administration clinical practice receiving carboplatin-based chemotherapy. Atezolizumab provided a survival benefit over chemotherapy after 5-9 mo.