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Objective: To study the timing of the effect of linzagolix, an oral GnRH antagonist, on significant reduction in heavy menstrual bleeding (HMB) in women with uterine fibroids., Design: The study used pooled data from PRIMROSE1 and PRIMROSE2, two double-blind, similar placebo-controlled trials of linzagolix in US and Europe, respectively. Eligible participants were randomized equally across four treatment arms (linzagolix 100mg and 200mg, with and without concomitant hormonal add-back therapy [ABT] consisting of 1 mg estradiol and 0.5 mg norethisterone acetate) and one placebo arm. The cumulative incidence of achieving clinically significant HMB reduction and maintaining it to week 24 was compared between the linzagolix arms and the placebo arm using Kaplan-Meier plots adjusted for confounding by race and study (PRIMROSE1 vs PRIMROSE2)., Subjects: The PRIMROSE trials randomized 1,012 women aged ≥18 years with ultrasound-confirmed uterine fibroids and HMB., Intervention: Linzagolix (100mg and 200mg, with and without hormonal add-back therapy) versus placebo., Main Outcome Measures: The main outcome of this analysis was the time to achievement of clinically significant HMB reduction and its maintenance up to week 24., Results: The onset of action in achieving and maintaining clinically significant HMB reduction was significantly more rapid for the linzagolix treatment arms than for the placebo arm, with a median time of <4 weeks for most linzagolix doses (except 100mg alone). The fastest onset was seen with linzagolix 200mg with or without ABT doses, with a median time of only 3 days. The cumulative incidence of achieving clinically significant HMB reduction by week 4 and maintaining it to week 24 was also significantly higher for the linzagolix treatment arms than the placebo arm. Specifically, across the four linzagolix treatment arms, 23.2% to 68.1% achieved clinically significant HMB reduction by week 4 and maintained it to week 24 versus 7.8% for placebo arm., Conclusion: Linzagolix was associated with a quick effect on reducing clinically significant HMB compared to placebo. Linzagolix thus offers a novel non-invasive treatment approach for the rapid management of HMB symptoms in patients with uterine fibroids., (Copyright © 2025. Published by Elsevier Inc.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., (© 2022 Takeda Pharmaceutical Company Limited. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

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., (© 2021. The Author(s).)

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 → 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 → 2L enzalutamide → 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., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2021. The Author(s).)

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.

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 → NHA (29.4% of patients with ≥ 2 LOTs) and NHA → NHA → 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 → NHA was the most observed 1L → 2L LOT sequence, a plethora of other LOT sequences were observed. OS was poor, highlighting an unmet need for life-prolonging treatments., (© 2021. The Author(s).)

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.

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., Competing Interests: Conflicts of Interest: F.L. and W.J.K. are employees of Daiichi Sankyo, Inc. and may own stocks/stock options; F.L. additionally declares owning stocks of Novartis. R.I.I., I.P., W.W., and S.S. are employees of Analysis Group, Inc., which provided paid consulting services to Daiichi Sankyo, Inc. for the conduct of this study. J.A.A. declares receiving research funding from Janssen Oncology, and Novartis., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

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.

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.

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., Competing Interests: Author Relationship With Industry Dr. Greene has received a Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; has received research support from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; serves on Advisory Boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. Drs. Ionescu-Ittu and Burne and Ms. Guérin are employees of Analysis Group Inc., which has received consultancy fees from Bristol-Myers Squibb for this study. Drs. Borentain, Kessler, Tugcu, and DeSouza are employees of Bristol-Myers Squibb. Dr. Felker has received research funding from Otsuka, Novartis, Roche Diagnostics, Amgen, Merck, the American Heart Association, and the National Heart, Lung, and Blood Institute; and has served as a consultant for Novartis, Roche Diagnostics, Amgen, Trevena, Cytokinetics, Madeleine, MyoKardia, Bristol-Myers Squibb, Stealth Biotherapeutics, and GlaxoSmithKline. Dr. Chen was an employee of Bristol-Myers Squibb at the time the research was conducted. Dr. Triana has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Dr Vergeer has received research grants from Analysis Group, Inc and Novartis Pharmaceuticals Corporation and declares employment at/ownership of Redgrasp. Dr de Ranitz‐Greven reports no disclosures. Dr Neary (currently Pfizer Inc) was an employee of Novartis Pharmaceuticals Corporation at the time the study was conducted. Dr Ionescu‐Ittu, Mr Emond, and Dr Duh are employees of Analysis Group, Inc, which received research grants from Novartis Pharmaceuticals Corporation for the conduct of this study. Dr Jansen reports no disclosures. Dr Zonnenberg received personal compensation from Novartis Pharmaceuticals Corporation. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.)

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., Competing Interests: Financial & competing interests disclosure This study was funded by Novartis Pharmaceuticals Corporation. P Mohr: honoraria: Amgen, Bristol-Myers Squibb, Merck, Merck Sharp & Dohme, Pierre Fabre, Novartis, Sanofi and Roche. F Kiecker: advisory boards: Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche; honoraria: Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre and Roche; clinical trial participation (principal investigator): Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche. R Koneru: research funding from Novartis; advisory boards: Novartis, Bristol-Myers Squibb, Merck. O Dereure: advisory board or honoraria and travel support: Bristol-Myers Squibb, Merck Sharp and Dohme, Roche, Novartis, Pierre Fabre, Sanofi. P Saiag: personal fees: Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck-Serono, Pfizer, Roche-Genentech, Pierre Fabre and Novartis; nonfinancial support from Bristol-Myers Squibb, Merck Sharp & Dohme, Roche-Genentech and Novartis. J Utikal: advisory board or honoraria and travel support: Amgen, Bristol-Myers Squibb, GlaxoSmithKline, LeoPharma, Merck Sharp & Dohme, Novartis, Pierre Fabre and Roche. C Robert: honoraria: Amgen, Bristol-Myers Squibb, Merck, Merck Sharp & Dohme, Pierre Fabre, Novartis, Sanofi and Roche. F Cuadros received research funding from Novartis; advisory boards: Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme; speakers bureau: Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme. RU Villarroel: Advisory Board: Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb; honoraria: Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb; clinical trial participation principal investigator: Novartis, Merck Sharp & Dohme. YG Najjar: research funding: Merck; advisory board: Array Biopharma; clinical trial participation: Novartis, Genentech, Merck and Array Biopharma. L Kottschade: advisory board: Array BioPharma; research funding: Bristol-Myers Squibb. EM Couselo: advisory board: Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche; honoraria: Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre and Roche; clinical trial participation (principal investigator): Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche. R Koruth is an employee of Novartis Pharmaceutical Corporation. A Guérin, R Burne and R Ionescu-Ittu are employees of Analysis Group, Inc., which has received consulting fees from Novartis. M Perrinjaquet is an employee of Navigant Germany GmbH, whose parent company has received consulting fees from Novartis. JS Zager: research funding: Novartis, Amgen, Philogen, Provectus, Delcath Systems, Castle Biosciences; advisory boards: Merck and Array Biopharma; medical advisory board: Delcath Systems; consulting: Philogen; speakers bureau: Sun Pharma and Array Biopharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing assistance was provided by S Rochette and G DeWalt, employees of Analysis Group, Inc.; support for this assistance was provided by Novartis Pharmaceuticals Corporation. Data collection was coordinated by M Perrinjaquet and E Chater, employees of Navigant, while support for this assistance was provided by Novartis Pharmaceuticals Corporation., (© 2019 The authors.)

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.

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., (© 2019 Wiley Periodicals, Inc.)

Patients with BRAF V600 (BRAF) mutated metastatic melanoma are eligible for therapy with both immune checkpoint inhibitors and targeted therapies, making treatment choice a complex decision. The present study aimed to describe patterns of treatment with immunotherapy and targeted therapy and BRAF testing in patients with metastatic melanoma presumed to have BRAF mutations (BRAF+) in the years following the approval of the newer generation of immune checkpoint inhibitors and targeted therapies (2014-2016). Two large US commercial claims databases [Truven Health Analytics MarketScan and IQVIA Real-World Data Adjudicated Claims - USA (IQVIA RWD Adjudicated Claims - USA)] were used. Patients were presumed BRAF+ if they received at least 2 lines of therapy of which at least 1 included targeted therapy. Sequence of lines of therapy and regimens used in first (1L), second (2L), and third (3L), as well as timing of BRAF testing by sequence of therapy were described. In the Truven sample (n=162), targeted therapy was used by 66% in 1L and by 54% in 2L, and 62% had a BRAF test; in the IQVIA RWD Adjudicated Claims - USA sample (n=247), targeted therapy was used by 62% in 1L and by 50% in 2L, and 68% had a BRAF test. Among those with a claim for a BRAF test prior to 1L, over two-thirds were initiated on targeted therapy. These findings suggest that the rate of BRAF testing remained low in the years following the approval of BRAF-targeted regimens for metastatic disease. Given the recently approved adjuvant treatment options for stage III melanoma, improving the rates of BRAF testing becomes increasingly important.

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., (Published by Elsevier B.V.)

Aim: To estimate incidence of stage III melanoma using the American Joint Committee on Cancer (AJCC) staging, 7th and 8th edition., Patients & Methods: The SEER US cancer registry was analyzed (2010-2014). AJCC7 stages were recorded in the data; AJCC8 stages were inferred., Results: Of 106,195 melanoma patients, 7669 and 7342 had stage III melanoma by AJCC7 and AJCC8, respectively (95% overlap). Nearly 30% of patients with AJCC7 stage III melanoma were reclassified in a higher stage III group by AJCC8 versus 7% in lower stage group. Regardless of the AJCC edition, incidence of stage III melanoma has increased from 2010 to 2014 both overall and within each stage III group., Conclusion: Providing appropriate management to this growing population of high-risk patients is a priority.

Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients' survival. This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences. Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017). Locoregional and distant recurrence(s) were identified on the basis of postsurgery recurrence indicators (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new surgery; secondary malignancy diagnoses). Of 6400 eligible patients, 219 (3.4%) initiated adjuvant therapy within 3 months of surgery, mostly with interferon α-2b (n=206/219, 94.1%). A total of 1191/6400 (18.6%) patients developed recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant recurrences). Among the 219 patients initiated on adjuvant therapy, 73 (33.3%) experienced recurrences (distant recurrences: 13/219, 5.9%). The mean total all-cause healthcare cost was $2645 per patient per month (PPPM) during locoregional recurrence episodes and $12 940 PPPM during distant recurrence episodes. In the year after recurrence, HRU was particularly higher in patients with distant recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions, 54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient visits (per 100 person-months), whereas all-cause healthcare costs were higher by $14 953 PPPM. It remains to be determined whether the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies, and reduce the risk of recurrences and associated HRU/cost.

Objective: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D + T; oral) and those initiated on 1 L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous)., Methods: Patients with melanoma initiated on D + T or N/P from Q1/2014 to Q2/2016 (defined as 1 L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D + T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1 L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates)., Results: Of the 445 patients included, 202 and 243 were initiated on D + T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1 L therapy than those initiated on D + T (difference = 18.6 visits PPY [95% CI = 16.0-21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference = 8.1 visits PPY [95% CI = 1.9-13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1 L therapy)., Conclusions: HRU during 1 L therapy was generally similar between patients initiated on D + T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.

Objective: To compare kidney size (used as proxy for total renal angiomyolipoma [rAML] size) and kidney function outcomes between patients with tuberous sclerosis complex (TSC) and rAML treated and not treated with everolimus., Methods: Medical charts of adults with TSC-associated rAML followed at a specialty medical center in the Netherlands (1990-2015). Included patients treated with everolimus (n = 33, of which 27 were included in the kidney size analyses and 27 in the kidney function analyses [21 patients in both]; index date = everolimus initiation) and non-treated patients (n = 39, of which 29 were included in the kidney size analyses and 33 in the kidney function analyses [23 patients in both]; index date = one date among all dates with outcome measurement).Percent change in kidney size and kidney function from the index date to the best measurement in the two years post-index date (best response) compared between patients treated and not treated with everolimus., Results: Compared with non-treated patients, significantly more everolimus-treated patients experienced a reduction in the size of their largest kidney in the two years post-index date (85.2% vs. 37.9%, p < 0.01). Also, there was a tendency towards more improvement in the estimated glomerular filtration rate (eGFR) among the everolimus-treated patients (55.6% vs. 33.3%, p = 0.08)., Conclusions: The study results suggest that everolimus is effective in controlling and even reversing the growth of the kidneys, used as a proxy for rAML size, as well as preserving or improving kidney function in patients with TSC and rAML treated in a real-world, observational setting., Competing Interests: The authors of this manuscript have the following competing interests: BAZ is a former employee of University Medical Center Utrecht (now retired) and reports personal compensation from Novartis and funding from Analysis Group. MSD, RII, JF, and FV are employees of Analysis Group/Groupe d'analyse and report consultancy fees from Novartis. Analysis Group/Groupe d'analyse is an economic consulting firm that is engaged by a variety of clients in the bio-medical arena for a range of services including the development of protocols, posters, abstracts, and manuscripts for health economics and outcomes research across many therapeutic areas. Analysis Group's/Groupe d'analyse's services for each client are confidential and independent of services for other clients. MPN is an employee of Novartis. Novartis had a role, together with the authors, in the study design, statistical analysis plan, interpretation of study results, decision to publish, and preparation of the manuscript. The commercial affiliation of MPN (Novartis) and MSD, RII, JF, and FV (Analysis Group/Groupe d'analyse) does not alter the authors' adherence to PLOS ONE policies.

Background: To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults., Methods: This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT) post-echinocandin initiation. Adjusted incidence rate ratios (IRRs) were estimated for anidulafungin versus caspofungin and micafungin, overall and in patients with normal baseline LFT (Grade 0)., Results: Treatments included anidulafungin (n = 1700), caspofungin (n = 4431), or micafungin (n = 6547). The proportions with LFT Grade ≥ 3 pre-echinocandin initiation were: anidulafungin 40.4% versus caspofungin 25.9% (p <  0.001) and micafungin 25.6% (p <  0.001). Rates of severe underlying diseases or comorbidities were: critical care admissions: 75.3% versus 52.6 and 48.6%; and organ failures: 69.4% versus 46.7 and 51.5%. Adjusted IRRs of severe hepatotoxicity for anidulafungin versus caspofungin and micafungin were 1.43 (p = 0.002) and 1.19 (p = 0.183) overall, and 0.88 (P = 0.773) and 0.97 (P = 0.945) for normal baseline LFT, respectively., Conclusions: Accounting for confounders, severe hepatotoxicity risk was not significantly different across echinocandins in this real-world head-to-head study. Anidulafungin was used more frequently in patients with more comorbidities. Those with normal baseline LFT (least susceptible to confounding by indication), showed no elevated hepatotoxicity risk for anidulafungin.

Objective: Glioblastoma (GBM) is an aggressive disease with limited therapeutic options. While bevacizumab was approved in 2009 for the treatment of patients with progressive GBM, its impact on overall survival (OS) remains unclear. Using US population-based cancer registry data (SEER), this study compared OS of patients diagnosed with GBM before and after bevacizumab approval., Methods: Adult patients from SEER with a GBM diagnosis were divided into two cohorts: patients diagnosed in 2006-2008 (pre-bevacizumab cohort, n = 6,120) and patients diagnosed in 2010-2012 (post-bevacizumab cohort, n = 6,753). Patients were included irrespective of the treatments received. OS post-diagnosis was compared between the study cohorts utilizing Kaplan-Meier analyses and multivariate Cox proportional hazards regression., Results: Among 12,873 patients with GBM, the median age was 62 years, 41% were women, 31% underwent gross total resection, and 75% received radiation therapy. Survival was stable within the 2006-2008 period (median survival = 9 months for each year), but increased after year 2009 (median survival = 10 and 11 months for years 2010/2011 and 2012, respectively). The adjusted hazard of death was significantly lower in the post-bevacizumab approval cohort (hazard ratio = 0.91, p < .01)., Conclusions: The results of this large population-based study suggested an improvement in OS among patients with a GBM diagnosis in 2010-2012 compared to 2006-2008. While the cause of this improvement cannot be proven in a retrospective analysis, the timing of the survival increase coincides with the approval of bevacizumab for the treatment of patients with progressive GBM, indicating a possible benefit of bevacizumab in this population.