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OBJECTIVE Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease that often follows pulmonary embolism (PE). Screening for CTEPH is challenging, often delaying diagnosis and worsening prognosis. Predictive risk models for CTEPH could help identify at-risk patients, but existing models require multiple clinical inputs. We developed and validated a predictive risk model for CTEPH using health insurance claims that can be used by payers/quality-of-care organizations to screen patients post-PE. METHODS Adult patients newly diagnosed with acute PE (index date) were identified from the Optum De-identified Clinformatics Extended DataMart (January 2007-March 2018; development set) and IBM MarketScan (January 2008-June 2019; validation set) databases. Predictors were identified 12 months before or on the index PE. Risk of "likely CTEPH" was assessed post-PE based on CTEPH-related diagnoses and procedures since the CTEPH diagnosis code (ICD-10-CM: I27.24) was not available until 1 October 2017. Stepwise variable selection was used to build the model using the development set; model validation was subsequently conducted using the validation set. RESULTS The development set included 93,428 patients, of whom 11,878 (12.7%) developed likely CTEPH. Older age (odds ratios [OR] = 1.16-1.49), female (OR = 1.09), unprovoked PE (i.e. without thrombotic factors; OR = 1.14), hypertension (OR = 1.07), osteoarthritis (OR = 1.08), diabetes (OR = 1.07), chronic obstructive pulmonary disease (OR = 1.11), obesity (OR = 1.21) were associated with higher odds of likely CTEPH, and oral anticoagulants with lower odds (OR= 0.50, all p

Background As the treatment landscape for Crohn’s disease (CD) evolves, an up-to-date understanding of the burden associated with indicators of suboptimal treatment is needed. The aim of this study was to describe suboptimal treatment indicators and associated healthcare costs among CD patients initiated on a biologic or conventional agent. Methods Adults with CD were identified in a US healthcare claims database (Optum’s Clinformatics Data Mart; 01/2004–03/2019). The first biologic or conventional agent claim within 12 months of a CD diagnosis was the index date/agent. Indicators of suboptimal treatment (nonadherence, dose escalation, chronic corticosteroid use, augmentation, ≥1 CD surgery, ≥2 CD emergency department visits, ≥1 CD inpatient (IP) stay, switch, cycling, restart, inadequate induction) were identified in the 12-month postindex landmark period. The mean per-patient-per-year (PPPY) healthcare costs (2019 USD) were evaluated in the year postlandmark. Results There were 5107 patients (mean age ~44 years, 56% female) in the biologic and 6072 patients (~51 years; 59% female) in the conventional cohort. In the biologic cohort, 79.4% of patients had ≥1 suboptimal treatment indicator. Mean PPPY healthcare costs increased with the number of suboptimal treatment indicators, from $46 100 (no indicator) to $68 572 (≥4 indicators). The conventional cohort had similar patterns: 72.5% of patients presented ≥1 suboptimal treatment indicator, and mean PPPY healthcare costs increased from $17 329 (no indicator) to $67 568 (≥4 indicators). In both cohorts, IP and outpatient medical costs (excluding biologics) contributed a major portion of the increase. Conclusions Among CD patients, suboptimal treatment indicators were common and were associated with an increased burden to the healthcare system.

To quantify the long-term direct and indirect costs among patients with Crohn's disease (CD) and specific subgroups of these patients in the United States from the private payer's perspective.This retrospective study used the OptumHealth Care Solutions, Inc database (01 January 1999-31 March 2017) to match (1:5) adult patients with ≥2 claims for CD to patients without inflammatory bowel disease (IBD). Patterns observed during follow-up (i.e. biologics, opioids, or steroids; CD-related surgery; moderate-to-severe disease; and comorbidities) were used to identify CD subgroups. Comparisons of healthcare resource utilization, work loss days, and direct and indirect work loss-related costs were made between matched cohorts. Descriptive analyses of costs were conducted within each CD subgroup.There were 6,715 and 33,575 patients in the CD and non-IBD cohorts, respectively. The direct burden was significantly higher in the CD cohort compared to the non-IBD cohort, with 0.34 inpatient admissions per patient per year (PPPY) versus 0.12 (217% increase;Severity of CD was determined based on claims-based algorithms due to the lack of access to medical files. Absenteeism was imputed based on claims data, and presenteeism was not assessed.The direct healthcare and indirect work loss-related costs of patients with CD was significantly higher compared to patients without IBD over an average follow-up of 5 years.

Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US). Methods A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers’ productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates. Results The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%). Conclusions ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.

470 Background: Intravesical BCG is considered a first-line (1L) treatment for high-risk NMIBC patients. Since the presence of carcinoma in situ (CIS) in NMIBC is associated with increased disease progression rates and poor clinical outcomes, BCG is prioritized in clinical guidelines for NMIBC patients with CIS. However, BCG’s US shortage may negatively affect clinical outcomes in patients. This study evaluated the adequacy of BCG treatment patterns among NMIBC patients, including a subgroup with CIS. Methods: Adults with NMIBC treated with BCG were selected from de-identified IBM MarketScan Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Treatment patterns were assessed from the first BCG claim (triggering the start of 1L treatment) until the end of the patient’s observation. Consistent with real-world literature, adequate BCG induction was defined as ≥5 BCG claims within 70 days of the first BCG claim whereas adequate BCG induction and maintenance was defined as ≥7 BCG claims within 274 days of the first BCG claim. Proportions of patients with adequate BCG induction and maintenance were compared between CIS subgroup and overall NMIBC cohorts using chi square tests. Results: Of 5,803 NMIBC patients treated with 1L BCG, 1,182 (20.4%) had documentation of CIS. Overall and CIS cohorts had similar mean age (67 years; range 18-101 years). After 1L BCG, 56.6% and 71.8% of the overall and CIS cohorts had another treatment (P

404 Background: Intravesical BCG is a common treatment in high-risk NMIBC patients; however supply constraints and regimen demands for patients have been reported and may impact long term patient outcomes. This study examined treatment patterns in NMIBC patients receiving intravesical BCG. Methods: Adults with NMIBC treated with intravesical BCG during any line of therapy (LOT) on or after the index date (first date for transurethral resection of the bladder tumor [TURBT] or initiation of intravesical therapy) were selected from de-identified IBM MarketScan Commercial and Medicare Supplemental Databases (1/1/2010-2/28/2021) and Multi-State Medicaid Database (1/1/2010-12/31/2019). Classification of NMIBC on the index date required that patients have no prior systemic antineoplastic therapy, radiotherapy, or cystectomy. Treatment patterns were evaluated from the index date until the end of the NMIBC phase (earliest of initiation of systemic antineoplastic therapy, cystectomy, radiotherapy, diagnosis for metastatic cancer, end of insurance eligibility, or end of data availability). Discontinuation of a LOT was defined as having a treatment gap > 180 days for BCG (90 days for other agents) or switching to a new LOT. During each LOT, adequate BCG treatment was defined as having ≥5 claims during induction (first 42 days of treatment) and ≥2 claims during maintenance (beyond the first 42 days). Results: There were 5,410 NMIBC patients treated with BCG over a mean (median) follow up of 25.5 (18.9) months. The population was 79% male; mean age was 67 years. The majority of patients only received a single LOT (76%; TABLE). The predominant first LOT was BCG (93.1% of NMIBC patients); however, the majority (69.8%) did not receive adequate BCG induction/maintenance in first LOT. Nearly half (46.4%) of first LOT patients had reassessment for disease progression by TURBT. BCG retreatment after a six-month lapse was observed as the predominant second LOT, with > 90% receiving inadequate BCG induction/maintenance. Conclusions: While intravesical BCG remains the most common therapy for NMIBC, less than a third of patients receive adequate BCG treatment in the first LOT; with this percentage further decreasing in the few patients who receive a subsequent LOT. In light of supply and demand constraints, results of this study further emphasize a need for additional treatment options that are effective, safe, and tolerable for patients with NMIBC.[Table: see text]

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.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 aged16 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.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.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.

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 ( 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.

Objective: To develop and validate models allowing the prediction of major adverse chronic renal outcomes (MACRO) in patients with type 2 diabetes mellitus (T2DM) using insurance claims dat...

To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively.Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial's inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients.Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27-$10.94) for CANVAS and $2.75 ($0.19-$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG.Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.

This study aimed to describe treatment sequencing and healthcare costs among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients treated with venetoclax in a US managed care population. CLL/SLL patients initiating venetoclax between 04/11/2016 and 06/30/2019 were selected from Optum’s de-identified Clinformatics Data Mart Database. Costs per-patient-per-month were described during the first 60 days of venetoclax-based treatment (initiation phase) and subsequent post-initiation phase. Based on venetoclax prescribing information, clinical event-related costs were identified through claims for tumor lysis syndrome (TLS) diagnosis, monitoring, prophylaxis, immunoglobulin treatment, neutropenia, thrombocytopenia, infection, renal impairment, hypertension, or cardiac arrhythmia. Statistical testing was not conducted due to small sample size. Twenty-five, 30, and 66 patients initiated venetoclax as their first observed regimen (1L), second observed regimen (2L), and third or later observed regimen (3L+), respectively. Most 2L (56.7%) and 3L+ (74.2%) venetoclax recipients previously received ibrutinib. Mean monthly all-cause costs during the initiation phase were $26,429 (1L cohort), $19,580 (2L cohort), and $23,918 (3L + cohort). Among the 2L cohort, mean monthly all-cause [clinical event-related] (including TLS) costs during initiation and post-initiation phases of venetoclax treatment were $15,506 [$6368] (initiation phase) and $14,318 [$5273] (post-initiation phase; median duration: 3.7 months) for patients receiving 1L ibrutinib, and $24,908 [$12,198] (initiation phase) and $16,905 [$7066] (post-initiation phase; median duration: 3.0 months) for patients not receiving 1L ibrutinib. In this descriptive study, highest mean costs were observed during venetoclax initiation phase. Venetoclax patients previously receiving ibrutinib had lower mean total all-cause and clinical event-related (including TLS) costs during their venetoclax line of therapy than those previously receiving non-ibrutinib therapy.

This study compared the risk of HHF in T2DM patients with macroalbuminuria initiated on CANA or DPP-4 using real-world insurance claims data. Adults with a T2DM diagnosis and a urine albumin-to-creatinine ratio >300 mg/g or albumin excretion rate >300 mg/day, initiated on CANA or DPP-4 after 03/29/2013, with at least 6 months of pre-initiation insurance eligibility were selected from Optum’s ClinformaticsTM Data Mart database (03/2012-03/2019). Patients were excluded if they notably had a diagnosis for T1DM, acute kidney injury, or stage 5 chronic kidney disease at baseline. The observation period was censored at the earliest of the index drug discontinuation, a claim for a drug from the alternate index cohort (DPP-4 or CANA), or the end of eligibility or data. Inverse probability of treatment weighting (IPTW) accounted for differences in baseline demographics, clinical characteristics, and healthcare costs. HHF events were defined as inpatient stays with a diagnosis of heart failure (ICD-9: 428.x; ICD-10: I50.x). Rates of HHF events per 100 patient-years (PY) were calculated and weighted Cox proportional hazards model accounting for repeated measurement was used to estimate the hazard ratio (HR), 95% confidence interval (CI), and p-value. A total of 759 patients were initiated on CANA and 1,892 on a DPP-4. After IPTW balanced baseline characteristics, mean age was ∼64 years old, ∼40% were female, and mean HbA1c was ∼9.0%. Among CANA and DPP-4 patients, respectively, the mean observation period was 5.4 and 6.6 months and the rate of HHF events per 100 PY was 0.57 and 3.73. At 12 months, the hazard for HHF was 74% lower among patients initiated on CANA relative to patients initiated on DPP-4 (HR [95%CI]: 0.26 [0.07-0.91]; p=0.0343). In this real-world analysis of patients with T2DM and macroalbuminuria during the initial months on therapy, patients on CANA had a significantly lower risk of HHF events compared to patients on DPP-4. Disclosure D. Pilon: Consultant; Self; Janssen Scientific Affairs, LLC. M. Durkin: Employee; Self; Janssen Scientific Affairs, LLC. A. Manceur: Employee; Self; Analysis Group, Inc. I. Ghelerter: Employee; Self; Analysis Group, Inc. M. Lafeuille: Other Relationship; Self; Janssen Scientific Affairs, LLC. P. Lefebvre: Consultant; Self; Janssen Scientific Affairs, LLC. Funding Janssen Scientific Affairs, LLC

Objective: Prior evaluations of ulcerative colitis (UC)-related costs are dated or encompassed limited follow-up. This study assessed the incremental direct and indirect work loss-related costs of ...

Supplemental Digital Content is available in the text., 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 rehospitalizations in patients with schizophrenia treated with paliperidone palmitate (PP1M) vs oral atypical antipsychotics (OAAs), with a focus on young adults (18–35 years)...

Background: Ibrutinib is an oral once-daily Bruton's tyrosine kinase inhibitor (BTKi) and is the only targeted treatment that has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit in multiple phase 3 trials for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). With ibrutinib established as a preferred first-line (1L) treatment option, it is important to better understand the treatment sequence after 1L ibrutinib and the characteristics of patients who are treated with a second-line (2L) therapy. Using a real-world US administrative claims database, this study aimed to compare time to next treatment (TTNT), healthcare resource utilization (HRU), and healthcare costs between different 2L treatment regimens (cohorts) used after ibrutinib. Methods: Adults with CLL/SLL treated with 1L ibrutinib were identified in a US claims database (Optum's de-identified Clinformatics ® Data Mart Database; 02/12/2013-03/31/2020). Those receiving a 2L therapy were considered eligible for the study. Retreatment with ibrutinib, in-class switch to another BTKi, or treatment with anti-CD20 immunotherapy-only were not considered eligible 2L treatment options for this evaluation. The most commonly used treatment regimens were categorized into the following clinically-relevant treatment cohorts: 1) chemoimmunotherapy (CIT) or chemotherapy (CT)-only, and 2) venetoclax (VEN)- or idelalisib (IDELA)-based regimens (monotherapy or combination regimens). Comparisons of TTNT, HRU (inpatient admissions, outpatient visits, emergency room visits, other ancillary services), and per patient per month healthcare costs (inpatient admissions, outpatient visits, emergency room visits, other ancillary services, pharmacy) were evaluated based on the sum of the payer and patient paid amount during 2L treatment. Comparisons were adjusted using multivariate regression including confounders observed in the baseline period and during 1L ibrutinib therapy. For costs and HRU, 95% confidence intervals and p-values were obtained from 499 bootstrap resamples. Results: A total of 132 CLL/SLL patients who received ibrutinib as a 1L treatment and had a subsequent eligible 2L therapy were included; mean age was 74 years old, 64% were male. Eligible patients received 2L CIT/CT-only (63/132, 48%), or VEN/IDELA-based regimens (69/132, 52%). TTNT was significantly longer for 2L VEN/IDELA-based regimens than for CIT/CT (hazard ratio at 12 months: 0.37; P=0.0337) (Figure 1). The number of outpatient visits for antineoplastic drug administration was significantly lower for patients receiving 2L VEN/IDELA-based regimens compared to CIT/CT (rate ratio=0.44; P=0.004). Total mean monthly healthcare cost (includes CLL/SLL and non-CLL/SLL-related medical/pharmacy costs) was $1,754 higher, but not significantly different (P=0.593), for patients receiving VEN/IDELA-based regimens compared with CIT/CT (Figure 2). Total mean monthly medical cost (non-pharmacy) was significantly lower ($-5,202; P=0.036) for patients receiving VEN/IDELA-based regimens compared to CIT/CT (Figure 2). Conclusions: This study demonstrates that VEN/IDELA-based regimens may be a more viable treatment option post-1L ibrutinib use for CLL/SLL patients compared to CIT/CT. When compared to 2L CIT/CT, use of VEN/IDELA-based regimens post-1L ibrutinib use was associated with significantly longer TTNT and lower medical costs, signifying reduced disease burden to the patients and lessened burden to the healthcare system. These findings also suggest that treatment convenience associated with 2L oral targeted regimens may play an important role in improving treatment outcomes. These results support the need for evaluating treatment sequencing strategies in the real-world setting to further improve clinical outcomes and reduce the burden of total cost of care for patients with CLL/SLL. Figure 1 Figure 1. Disclosures Challagulla: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Emond: Janssen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; GlaxoSmithKline: Consultancy. Volodarsky: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Young: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Manceur: AbbVie: Consultancy; Actelion, part of the Janssen Pharmaceutical Companies of Johnson & Johnson: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi-Sankyo: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company.

The objective of this study was to identify blood-based protein biomarkers of early stage Mycobacterium tuberculosis (Mtb) infection. We utilized plasma and serum specimens from TB patients and their contacts (age ≥ 12) enrolled in a household contact study in Uganda. In the discovery phase cross-sectional samples from 104 HIV-uninfected persons classified as either active TB, latent Mtb infection (LTBI), tuberculin skin test (TST) converters, or persistent TST-negative were analyzed. Two hundred eighty-nine statistically significant (false discovery rate corrected p 0.85. Panel performance was confirmed with an independent validation set of longitudinal samples from 16 subjects. These candidate protein biomarkers may allow for the identification of recently Mtb infected individuals at highest risk for developing active TB and most likely to benefit from preventive therapy., Highlights • Changes in host proteins can be detected in M. tuberculosis infection, even prior to tuberculin skin test conversion. • Early M. tuberculosis infection provoked host responses related to inflammation, immune-response, and lipid metabolism. • Protein panels were able to predict tuberculin skin test conversion and development of latent M. tuberculosis infection. Developing a diagnostic test that identifies recent M. tuberculosis infection would allow for targeted treatment of those persons most likely to progress to active tuberculosis (TB). Current tests for M. tuberculosis infection are unable to differentiate between latent M. tuberculosis infection (LTBI) and active TB, nor distinguish recent from remote infection. This study identified human host proteins capable of predicting tuberculin skin test conversion, and the development of LTBI. These candidate protein biomarkers may allow for the identification of recently Mtb infected individuals who are at highest risk for developing active TB and would most benefit from preventive therapy.

The objective was to assess the association of Medicaid coverage gaps with health care resource utilization (HRU) and costs of patients with schizophrenia. Patients with schizophrenia were identified from the Medicaid database. The beginning of the first eligible gap was defined as the index date. Per-patient per-month (PPPM) HRU and costs before versus after a gap were assessed, and the association between gap duration and PPPM HRU and costs was examined up to 12 months post index. Together with 95% confidence intervals, HRU differences were reported in rate ratios (RRs), and cost differences were reported in 2016 US dollars. A subgroup of males with substance use disorder (SUD; risk factors for incarceration) also was analyzed. Total PPPM health care costs increased significantly by $711.04 following a coverage gap (

Which ecosystem services are addressed? Most relevant renewable food resources, i.e., provisioning ecosystem services from agriculture (crops, meat, dairy products) and aqua culture

We analysed the spatial distribution patterns of plant species’ arbuscular mycorrhizal status across an intermediate geographical scale (i.e. the country of Germany) and related these distributions to environmental drivers. Three levels of arbuscular mycorrhizal status of plant species could be defined: (1) obligate arbuscular mycorrhizal species that are always colonised by mycorrhizal fungi, (2) facultative arbuscular mycorrhizal species that are colonised under some conditions but not colonised under others and (3) non-mycorrhizal species that are never found to be colonised by mycorrhizal fungi. We aimed to investigate whether plant species assemblages at the studied grid cell scale are composed of different proportions of species regarding their arbuscular mycorrhizal status, and whether the variation of these proportions can be linked to the geographical variation of ecological and environmental factors. We fitted a vector generalised additive model (VGAM) for log-ratios of proportions of plant species’ arbuscular mycorrhizal status per grid cell (2859 grid cells, each c. 130 km 2 ). The spatially explicit plant arbuscular mycorrhizal status distribution model was based on environmental predictors related to climate, geology and land use. The spatial distribution of plant arbuscular mycorrhizal status can be explained as a function of nine environmental predictors (D 2 = 0.54). Proportion of obligate arbuscular mycorrhizal plant species per grid cell increased with increasing temperature range, mean annual temperature, urban area and area of lime as geological parent material and decreased with increasing area of mixed forest and coniferous forest. Annual temperature range was by far the most important predictor. These results extend the comparative context of former studies that established relationships between mycorrhizal status and other plant characteristics at species level, including those describing species ecological requirements, to a context at the level of assemblages and species distributions. We encourage integrating plant mycorrhizal status as a functional trait in future macroecological analyses.

e19354 Background: Ibrutinib (Ibr) is an established standard of care in CLL/SLL patients across lines, regardless of age, comorbidities and risk status. With the introduction of venetoclax (Ven) in the treatment landscape, there is a need to understand the real-world treatment sequencing of targeted oral agents, and the implication of sequencing on HRU/costs. This retrospective study evaluated HRU/costs associated with Ven treatment in various sequencing scenarios, including prior use of Ibr. Methods: Optum Clinformatics Extended DataMart De-Identified Databases (4/11/2015-6/30/2019) were used to identify adults with CLL/SLL treated with Ven (excluding investigational combination therapies). The index date was the start of the first Ven-based line of therapy (index LOT) and the baseline period was the 12-month period pre-index. Mean all-cause HRU/costs per patient per month (PPPM) were calculated during the index LOT and the Ven ramp-up period (first 30 days post-index). Results: Among a total of 11,861 CLL/SLL patients receiving ≥1 LOT, 121 patients (1.0%) were treated with Ven, including 25 patients (64.0% single agent) using Ven in first line (1L cohort), 30 (90.0% single agent) in second line (2L cohort), and 66 (83.3% single agent) in third line or later (3L+ cohort). Mean age was 71.6 years; 33.1% were female; mean baseline Quan-Charlson Comorbidity Index score was 4.7; median follow up from the start of 1L was 25.3 months; median duration of index LOT was 4.2 months. The majority of 2L+ Ven patients were previously treated with Ibr (2L: 56.7%, 3L+: 74.2%). Patients in all 3 cohorts had frequent outpatient (OP) visits PPPM during their index LOT (1L: 4.58; 2L: 4.75; 3L+: 5.71). Total costs PPPM during the index LOT were highest in the 1L cohort (1L: $21,762; 2L: $17,697; 3L+: $20,900), driven by higher OP costs (1L $9,402; 2L: $5,633; 3L+: $7,701). Increased total costs PPPM were observed during Ven ramp-up (1L: $31,707; 2L: $21,036; 3L+: $25,362). Compared to the overall 2L cohort, those treated with Ibr in 1L had lower total costs PPPM (index LOT: $15,350; V ramp-up: $15,882). Conclusions: In this descriptive study, the highest costs PPPM were observed for Ven treatment in the 1L. Prior treatment with Ibr was common among 2L and 3L+ CLL/SLL patients treated with Ven. Among 2L Ven patients, those previously treated with Ibr in 1L had $2,347 and $5,154 lower costs PPPM during 2L and Ven ramp-up, respectively, suggesting that previous Ibr treatment may help reduce costs in subsequent V treatment.

Background There exist several predictive risk models for cardiovascular disease (CVD), including some developed specifically for patients with type 2 diabetes mellitus (T2DM). However, the models developed for a diabetic population are based on information derived from medical records or laboratory results, which are not typically available to entities like payers or quality of care organizations. The objective of this study is to develop and validate models predicting the risk of cardiovascular events in patients with T2DM based on medical insurance claims data. Methods Patients with T2DM aged 50 years or older were identified from the Optum™ Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006–09/30/2016). Risk factors were assessed over a 12-month baseline period and cardiovascular events were monitored from the end of the baseline period until end of data availability, continuous enrollment, or death. Risk models were developed using logistic regressions separately for patients with and without prior CVD, and for each outcome: (1) major adverse cardiovascular events (MACE; i.e., non-fatal myocardial infarction, non-fatal stroke, CVD-related death); (2) any MACE, hospitalization for unstable angina, or hospitalization for congestive heart failure; (3) CVD-related death. Models were developed and validated on 70% and 30% of the sample, respectively. Model performance was assessed using C-statistics. Results A total of 181,619 patients were identified, including 136,544 (75.2%) without prior CVD and 45,075 (24.8%) with a history of CVD. Age, diabetes-related hospitalizations, prior CVD diagnoses and chronic pulmonary disease were the most important predictors across all models. C-statistics ranged from 0.70 to 0.81, indicating that the models performed well. The additional inclusion of risk factors derived from pharmacy claims (e.g., use of antihypertensive, and use of antihyperglycemic) or from medical records and laboratory measures (e.g., hemoglobin A1c, urine albumin to creatinine ratio) only marginally improved the performance of the models. Conclusion The claims-based models developed could reliably predict the risk of cardiovascular events in T2DM patients, without requiring pharmacy claims or laboratory measures. These models could be relevant for providers and payers and help implement approaches to prevent cardiovascular events in high-risk diabetic patients. Electronic supplementary material The online version of this article (10.1186/s12933-018-0759-z) contains supplementary material, which is available to authorized users.

Purpose Chronic thromboembolic pulmonary hypertension (CTEPH) can develop in 1 out of 25 (4%) patients following an acute pulmonary embolism (PE). It is recommended that high risk patients on anticoagulants, who have persistent shortness of breath post-PE, should be screened for CTEPH. Ventilation-perfusion scan is considered a gold standard tool for screening for CTEPH. This retrospective study sought to describe the use of CTEPH-related diagnostic and medical procedures post-PE in the United States. Methods Adult patients newly diagnosed with acute PE (index date) without prior pulmonary hypertension (PH) were identified from a large US administrative healthcare claims database (01/2007-03/2018; > 150 million patients). Patients were required to be continuously enrolled in their healthcare plan for ≥12 months pre-index (i.e., baseline period) and post-index (i.e., observation period). CTEPH-related diagnoses, procedures, and surgeries were evaluated during the observation period. Results A total of 93,947 patients with acute PE were identified. Mean age was 65.4 years and 54.4% were females. Over an average follow-up of 3.3 years post-index, 75.3% of patients were seen for ‘shortness of breath’, of whom 93.6% had an electrocardiogram, 75.2% an echocardiography, and 57.4% a computed tomographic angiography. Specific to CTEPH screening, 18.0% had a ventilation-perfusion scan, 7.6% a pulmonary angiogram, 4.7% a right heart catheterization. Among the 93,947 patients, 14,510 (15.4%) had a diagnosis of PH documented after acute PE, and 284 (0.3%) had a CTEPH-related procedure (i.e., pulmonary endarterectomy [0.2%; n=193] or balloon pulmonary angioplasty [0.1%; n=97]). Conclusion Real-world evidence shows that patients are not systematically monitored for CTEPH using diagnostic procedures recommended by current guidelines which state. “it is recommended that high risk patients on anticoagulants, who have persistent shortness of breath post-PE, should be screened for CTEPH”. There is an ongoing need to better define the use of CTEPH diagnostic procedures in patients who have experienced acute PE as well as risk prediction tools to identify patients at high risk of developing CTEPH after PE.

Large scale land acquisitions (LSLA), and Reducing Emissions from Deforestation and forest Degradation (REDD+) are both land based phenomena which when occurring in the same area, can compete with each other for land. A quantitative analysis of country characteristics revealed that land available for agriculture, accessibility, and political stability are key explanatory factors for a country being targeted for LSLA. Surprisingly LSLA occur in countries with lower accessibility. Countries with good land availability, poor accessibility and political stability may become future targets if they do not already have LSLA. Countries which high levels of agriculture-driven deforestation and LSLA, should develop interventions which reduce forest loss driven either directly or indirectly by LSLA as part of their REDD+ strategies. Both host country and investor-side policies have been identified which could be used more widely to reduce conflicts between LSLA and REDD+. Findings from this research highlight the need for and can inform the development of national and international policies on land acquisitions including green acquisitions such as REDD+. Land management must be considered with all its objectives—including food security, biodiversity conservation, and climate change mitigation—in a coherent strategy which engages relevant stakeholders. This is not currently occurring and might be a key ingredient to achieve the targets under the Sustainable Development Goals 2 and 15 and 16 (related to food security and sustainable agriculture and the protection of forests) among others.

Summary Plant diversity is globally threatened by anthropogenic land use including management and modification of the natural environment. At regional and local scales, numerous studies world-wide have examined land use and its effects on plant diversity, but evidence for declining species diversity is mixed. This is because, first, land use comes in many variations, hampering comparisons of studies. Second, land use directly affects the environment, but indirect effects extend beyond the boundaries of the land in use. Third, land-use effects greatly depend on the environmental, historical and socio-economic context. To evaluate the generality and variation of studies’ findings about land-use effects, we undertook a quantitative synthesis using meta-analytic techniques. Using 572 effect sizes from 375 studies distributed globally relating to 11 classes of land use, we found that direct and indirect effects of land use on plant diversity (measured as species richness) are variable and can lead to both local decreases and increases. Further, we found evidence (best AIC model) that land-use-specific covariables mostly determine effect-size variation and that in general land-use effects differ between biomes. Synthesis and applications. This extensive synthesis provides the most comprehensive and quantitative overview to date about the effects of the most widespread and relevant land-use options on plant diversity and their covariables. We found important covariables of specific land-use classes but little evidence that land-use effects can be generally explained by their environmental and socio-economic context. We also found a strong regional bias in the number of studies (i.e. more studies from Europe and North America) and highlight the need for an overarching and consistent land-use classification scheme. Thereby, our study provides a new vantage point for future research directions.

Summary For several data bases in species distribution modelling (SDM), presences are known but absences are uncertain and can be non-detections. The environment influences both the non-detections and the species occurrences (preferential sampling), affecting model predictions. The objective is to estimate model-based probability of occurrence when absences are uncertain and sampling is preferential. Our Bayesian image restoration (BIR) model has an environmental, spatial and non-detection component. The latter is based on the number of ‘control species’ (selected by expert knowledge to have wide geographic range and occupy several habitats) observed. Control species are assumed present in all grid cells so an observed absence of the control species is a non-detection. The observed absence of a focal species is likely a non-detection when the environment is conducive, the focal species was observed in the neighbourhood, and the number of control species is small. Simulating an artificial species (true prevalence 0·31) and preferential sampling (observed prevalence 0·18), the BIR modelled prevalence was 0·32 (0·30–0·34). The estimation was robust to failure of assumptions with a mis-specified environmental model. The restored map was close to the true map, and the true realized niche of the species was inferred (with uncertainty). The link between the non-detection and control species is crucial, and a sensitivity analysis is recommended. BIR restored the simulated atlas map more accurately than a covariate adjustment method. When applied to the vascular plant Asarum europaeum L., BIR changed the interpretation. The uncertainty maps assisted decision-making. A BIR implementation new to the SDM field is presented. BIR using control species is most fruitfully applied at coarse scale and intermediate extent, with limited environmental extremes and sufficient expert knowledge (e.g. many Central European countries). BIR is a framework, and we studied one implementation. Any proxy (road density, distance to city, direct expert knowledge, detectability traits, etc.) associated with non-detection can be used so BIR can be applied in diverse settings. Including non-detections reduces model indeterminacy but often requires expert knowledge. However, the benefits of using a priori knowledge and Bayesian estimation are expected to outweigh the risks of model-based inference.

We present modified likelihood ratio tests (LRTs) for simple and double separability of a variance–covariance structure, unbiased in finite samples. The modification is a penalty-based homothetic transformation of the LRT statistic. Optimal penalties, depending on the mean model, contain novel information.

In 2004 and 2005, the yield, leaf area, dry weight and dry weight partitions of soybeans were determined at the Agroforestry Research Site (ARS) (est. 1987, Ontario, Canada). Soybean was intercropped with poplar (Populus deltoides x nigra DN-177 L., 556 m3crown tree−1), silver maple (Acer saccharinum L., 308 m3), black walnut (Juglans nigra L., 148 m3) and pecan (Carya illinoensis Wangenh., 114 m3), or grown alone (monoculture). Yield of soybean was not different in either year between the monoculture and the black walnut or pecan intercrops. In the poplar and silver maple treatments, yield was 66 and 85% (2004 and 2005) lower than in the monoculture. Despite the fact that different tree species were used, there was a significant negative linear regression between yield and tree crown volume (R 2 = 0.76, P = 0.0049 and R 2 = 0.93, P