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OBJECTIVE To investigate the role of systemic inflammation in reduced cognitive functioning in patients with early-stage heart failure (HF), while taking associations with other cardiovascular risk factors into account. METHODS Patients with stage B HF (n = 270; mean age 66.1 ± 10.1) were examined cross-sectionally for relationships among cardiovascular disease (CVD) and psychological risk factors, c-reactive protein (CRP) and Montreal Cognitive Assessment (MoCA) scores. A subsample (n = 83), at high-risk for stage C HF (B-type natriuretic peptide (BNP) levels >65 pg/mL) were followed for 12-months for relationships between CRP levels and cognitive function. RESULTS Baseline smoking (c2 = 6.33), unmarried (c2 = 12.0), hypertension (c2 = 5.72), greater body mass index (d = .45), and physical fatigue (d = .25) were related to higher CRP levels (p's < .05). Cross-sectionally, CRP levels were negatively related to MoCA scores, beyond CVD (DR2 = .022, b = -.170, p < .010) and psychological risk factors (DR2 = .016, b = .145, p < .027) and related to MCI criteria (odds ratio = 1.35, 95% CI 1.00 - 1.81, p = .046). Across 12-months, BNP high-risk patients with CRP levels ≥3 mg/L had lower MoCA scores (23.6; 95% CI 22.4 - 24.8) than patients with CRP levels

Klinefelter syndrome (47, XXY; Henceforth: XXY syndrome) is a high impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first neuroimaging study to map resting-state functional connectivity (rsFC) changes in XXY syndrome and ask how these might relate to brain anatomy and psychopathology. We collected resting state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males. We implemented a brain-wide screen to identify regions with altered global rsFC in XXY vs. XY males, and then used seed-based analysis to decompose these alterations. We further compared rsFC changes with regional changes in brain volume from voxel-based morphometry and tested for correlations between rsFC and symptom variation within XXY syndrome. We found that XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC), associated with overconnectivity with diverse rsFC networks. Regional rsFC changes were partly coupled to regional volumetric changes in XXY syndrome. Within the precuneus, variation in DLPFC rsFC within XXY syndrome was correlated with the severity of psychopathology in XXY individuals. Our findings provide the first view of altered functional brain connectivity in XXY syndrome and delineate links between these alterations and those relating to both brain anatomy and psychopathology. Taken together, these insights advance biological understanding of XXY syndrome as a disorder in its own right, and as a model of genetic risk for psychopathology more broadly.

Background Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome—a sex chromosome aneuploidy that is known to increase risk for psychopathology. Methods We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits. Results Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R2 ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring. Conclusions We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggest that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. Trial registrations ClinicalTrials.govNCT00001246, “89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls.” Date of registry: 01 October 1989.

Objectives Patients with cannabinoid hyperemesis syndrome (CHS) present frequently to the emergency department. Previous case studies suggest dramatic symptomatic improvement with topical capsaicin treatment. This exploratory study examined the potential effectiveness of topical capsaicin in patients with nausea and vomiting due to a suspected CHS exacerbation. Methods This was a double-blind, randomized placebo-controlled pilot trial. Adults who presented with vomiting suspected to be from CHS were eligible for enrollment. We excluded pregnant women and those with resolution of symptoms. Following randomization, topical 0.1% capsaicin or placebo cream was applied to the anterior abdomen in a uniform manner. The primary outcome was the severity of nausea on a visual analog scale (VAS) of 0 to 10 cm assessed at 30 minutes. Secondary outcomes were adverse events, occurrence of posttreatment vomiting, nausea by VAS at 60 minutes, and hospital admission. Results This pilot trial enrolled 30 patients, 17 in the capsaicin arm and 13 in the placebo arm. One patient in the capsaicin arm did not tolerate treatment due to skin irritation. Mean ± SD nausea severity at 30 minutes was 4.1 ± 2.3 cm in the capsaicin arm and 6.1 ± 3.3 cm in the placebo arm (difference = -2.0 cm, 95% confidence interval [CI] = 0.2 to -4.2 cm). At 60 minutes, mean ± SD nausea severity was 3.2 ± 3.2 cm versus 6.4 ± 2.8 cm (difference = -3.2 cm, 95% CI = -0.9 to -5.4 cm). The percent reduction in nausea at 60 minutes from baseline was 46.0% in the capsaicin arm and 24.9% in the placebo arm (difference = 21.1%, 95% CI = -5.6% to 47.9%). A higher proportion of capsaicin group patients (29.4% vs. 0%) had complete resolution of nausea (relative risk = 3.4, 95% CI = 1.6 to 7.1). Conclusion In this pilot trial, the application of topical capsaicin cream was associated with a significant reduction in nausea at 60 minutes but not at 30 minutes and provided more complete relief of nausea.

Sex chromosome aneuploidy (SCA) increases the risk for cognitive deficits, and confers changes in regional cortical thickness (CT) and surface area (SA). Neuroanatomical correlates of inter-individual variation in cognitive ability have been described in health, but are not well-characterized in SCA. Here, we modeled relationships between general cognitive ability (estimated using full-scale IQ [FSIQ] from Wechsler scales) and regional estimates of SA and CT (from structural MRI scans) in both aneuploid (28 XXX, 55 XXY, 22 XYY, 19 XXYY) and typically-developing euploid (79 XX, 85 XY) individuals. Results indicated widespread decoupling of normative anatomical–cognitive relationships in SCA: we found five regions where SCA significantly altered SA–FSIQ relationships, and five regions where SCA significantly altered CT–FSIQ relationships. The majority of areas were characterized by the presence of positive anatomy-IQ relationships in health, but no or slightly negative anatomy-IQ relationships in SCA. Disrupted anatomical–cognitive relationships generalized from the full cohort to karyotypically defined subcohorts (i.e., XX-XXX; XY-XYY; XY-XXY), demonstrating continuity across multiple supernumerary SCA conditions. As the first direct evidence of altered regional neuroanatomical–cognitive relationships in supernumerary SCA, our findings shed light on potential genetic and structural correlates of the cognitive phenotype in SCA, and may have implications for other neurogenetic disorders.

Ranibizumab and aflibercept are FDA-approved treatments for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Although these agents differ in cost and labeled dosing, it is unclear whether these differences are reflected in clinical practice.To compare the real-world frequency and cost of ranibizumab and aflibercept injections among treatment-naive and previously treated patients with nAMD and DME.Claims data from MarketScan Research Databases were retrospectively reviewed to identify treatment-naive patients with nAMD who initiated intravitreal ranibizumab or aflibercept between January 1, 2014, and January 1, 2016, and treatment-naive patients with DME who initiated intravitreal ranibizumab or aflibercept between July 29, 2014, and July 1, 2016. Patients who switched to subsequent-line aflibercept or ranibizumab during the study period were eligible to enter previously treated subgroups. Multivariable regression models were derived to compare the per-patient frequency and cost of injections between ranibizumab- and aflibercept-treated patients with nAMD over 12 months (treatment-naive: n = 1,087 and n = 1,578; previously treated: n = 221 and n = 751) and 24 months (treatment-naive: n = 454 and n = 568; previously treated: n = 93 and n = 284) and in patients with DME over 6 months (treatment-naive: n = 507 and n = 681; previously treated: n = 53 and n = 223) and 12 months (treatment-naive: n = 326 and n = 382; previously treated: n = 24 and n = 122).After adjusting for patient demographics and clinical characteristics, per-patient injection frequency and cost were not significantly different between treatment-naive patients with nAMD who received ranibizumab versus aflibercept over 12 months (5.62 vs. 5.54;Although the frequency and cost of ranibizumab and aflibercept injections were generally comparable among patients treated for nAMD, ranibizumab was associated with estimated per-patient-per-year cost savings of $3,500-$4,500 in those treated for DME. Most patients received fewer injections than any FDA-indicated dosing schedule, suggesting potential undertreatment that may result in suboptimal vision outcomes.Study funding was provided by Genentech, a member of the Roche Group. The sponsor participated in the design of the study; collection, analysis, and interpretation of the data; preparation of the manuscript; and the decision to submit the article for publication. Kiss has been a consultant for and received honoraria from Alcon, Alimera, Allergan, BioMarin, Novartis, and Spark; has been on the advisory board for, a consultant for, received honoraria from, and held stock options in Adverum and Regenxbio; has been a consultant for, received honoraria from, and held stock/stock options in Fortress; has been on the advisory board for, a consultant and investigator for, and received grants and honoraria from Genentech and Regeneron; and has been on the advisory board for, a consultant for, and received grants and honoraria from Optos. Malangone-Monaco, Wilson, Varker, Stetsovsky, and Smith are employees of IBM Watson Health, which received funding from Genentech to undertake this study. Garmo is an employee of Genentech. Data reported in this manuscript were presented in part at the Academy of Managed Care Pharmacy (AMCP) Managed Care and Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Objective: This study evaluated the real-world healthcare resource utilization (HCRU) and costs in patients diagnosed with an indolent non-Hodgkin lymphoma (iNHL) and treated with either first-line...

Purpose This study examined adherence to screening for fecal immunochemical test (FIT). Methods Adults (≥ 50–75) with a FIT between 1/1/2014 and 6/30/2019 in MarketScan administrative claims were selected (index = earliest FIT). Patients were followed for 10 years pre- and 3 years post-index. Patients at increased risk for CRC or with prior screening were excluded. Year over year adherence was measured post-index. Results Of 10,253 patients, the proportion adherent to repeat testing at year 2 was 23.4% and 10.6% at year 3. Of 76.6% not adherent in year 2, 5.4% were adherent in year 3. Conclusion Results suggest adherence to FIT tests is poor, minimizing potential benefits. Future studies are needed to consider alternative test options and whether more choice will improve long-term adherence.

Importance Colorectal cancer (CRC) screening reduces CRC incidence and mortality. It is important to examine screening patterns over time, including after the introduction of new screening modalities. Objective To compare use of CRC screening tests before and after the availability of the multitarget stool DNA (mt-sDNA) test, given that endorsed options have changed. Design, Setting, and Participants This longitudinal cohort study used administrative claims data to examine CRC screening use in 2 discrete periods: before (August 1, 2011, to July 31, 2014) and after (August 1, 2016, to July 31, 2019) the mt-sDNA test became available. The MarketScan Commercial and Medicare Supplemental databases were queried for individuals aged 45 to 75 years between August 1, 2011, and July 31, 2019, with average risk of CRC and with continuous enrollment in the databases from August 1, 2001, to July 31, 2019. Main Outcomes and Measures The proportion of individuals up to date or not due for CRC screening during each measurement year and the type of screening test used among individuals due for screening. Data were reported overall and among individuals aged 45 to 49 or 50 years and older on August 1, 2011. Results A total of 97 776 individuals with average risk were identified. Individuals had a mean (SD) age of 50.8 (3.5) years, and 54 227 (55.5%) were women. The proportion of individuals with average risk aged 50 to 75 years with commercial or Medicare supplemental insurance who were up to date with CRC screening increased from 50.4% in 2011 (30 605 of 60 770) to 69.7% in 2019 (42 367 of 60 770). Among individuals due for screening and screened, the use of high-sensitivity fecal occult blood test (FOBT) decreased between 2011 (1088 of 6241 eligible individuals [17.7%]) and 2019 (195 of 2943 eligible individuals [6.6%]), and the use of mt-sDNA increased between 2016 (58 of 3014 eligible individuals [1.9%]) and 2019 (418 of 2943 eligible individuals [14.2%]). No consistent trends were observed with fecal immunochemical test (FIT) or screening colonoscopy. Computed tomography colonography, double-contrast barium enema, and flexible sigmoidoscopy were rarely performed. Conclusions and Relevance In this cohort study, the proportion of individuals with average risk who were up to date with CRC screening increased between 2011 and 2019 but remained suboptimal. There were no substantial changes in the use of the colonoscopy or FIT; however, there was an increase in the adoption of mt-sDNA and a decrease in the use of FOBT during the study period.

Aim: We evaluated treatment patterns and healthcare costs of initiating psoriatic arthritis (PsA) treatment with oral apremilast versus biologics. Methods: Claims data identified biologic-naive adults with PsA who initiated either apremilast or a biologic from 2013 to 2016. Results: Medication adherence was similar at 12 months (76.9 vs 73.4%; p = 0.175) between apremilast (n = 381) and matched biologic (n = 761) patients. Apremilast users had $12,715 lower total costs per-patient-per-month (p Conclusion: Commercially insured patients with PsA initiating apremilast had adherence similar to those initiating biologics but lower total healthcare costs.

This study evaluated the real-world healthcare resource utilization and costs in chronic lymphocytic lymphoma (CLL) patients treated with first-line ibrutinib monotherapy (IbM) therapy or bendamustine plus rituximab (BR) combination therapy.Treatment-naïve CLL patients in the IBM MarketScan Research Databases were identified based on the first prescription of either IbM or BR therapy between 1 February 2014 and 30 August 2017.A total of 1866 patients with 12 months of continuous enrollment (IbMThe results of this study suggest that further research on the real-world effectiveness of IbM in comparison to BR combination therapy, given the comparatively higher rates of inpatient admissions, longer lengths of stay, and more ER visits observed in IbM patients relative to the BR patients is needed. Given the differences in costs, it is important to further examine the impact these healthcare expenditures have on the cost-effectiveness of IbM first line treatment.

BACKGROUND Intravenous (IV) taxanes for metastatic breast cancer (mBC) are associated with toxicities, such as chemotherapy-induced peripheral neuropathy (CIPN), which can detrimentally impact outcomes. OBJECTIVE To assess the impact of CIPN on clinical and economic outcomes in women with mBC, initiating IV paclitaxel/ nab-paclitaxel. METHODS Adult women in the MarketScan Commercial and Medicare Supplemental Database with a mBC diagnosis, initiating IV paclitaxel or IV nab-paclitaxel (index date = first administration) from November 1, 2013, to September 30, 2018, who had no prior neuropathy diagnoses, and continuous enrollment 12 months prior to and ≥ 3 months following index were selected. Propensity score-matched CIPN and non-CIPN cohorts were defined, based on postindex CIPN diagnosis. Clinical characteristics and all-cause and breast cancer (BC)-related health care utilization and costs per patient per month (PPPM) were compared between matched CIPN and non-CIPN cohorts during follow-up. RESULTS Among the 5870 women with mBC initiating IV paclitaxel/nab-paclitaxel, 42.7% developed CIPN. The matched cohorts each included 1950 women. Patients with CIPN were more likely to have a dose reduction (46.1% vs 38.2%, P < .001) or develop depression, diabetes, insomnia, liver dysfunction, or arthritis compared with the non-CIPN cohort, P < .05. Patients with CIPN were more likely to have an inpatient admission (39.2% vs 34.9%, P < .01) or emergency department visit (46.7% vs 35.6%, P < .001), as well as all-cause and BC-related costs that were $1102 and $725 PPPM higher, respectively, than women without CIPN (P < .01). CONCLUSIONS CIPN was common in women, following IV paclitaxel/nab-paclitaxel treatment and was associated with dose reductions, the development of comorbidities, and elevated health care costs. Therapies for mBC that offer increased tolerability are needed to help improve patient outcomes and control costs.

BACKGROUND Intravenous (IV) taxane therapy for metastatic breast cancer (mBC) has been associated with toxicities and demanding dosing schedules, which can limit treatment effectiveness. OBJECTIVES To assess treatment patterns, toxicities, and costs in women with mBC initiating IV paclitaxel or IV nab-paclitaxel. METHODS Adult women diagnosed with BC from January 1, 2014, to September 30, 2018, were identified in the MarketScan Commercial and MarketScan Medicare Supplemental databases. Women had a metastatic disease diagnosis and newly initiated treatment with IV paclitaxel/nab-paclitaxel (first administration date was considered the index date), and continuous enrollment for at least 12 months prior to and at least 3 months following the index date. Treatment discontinuation, dose reductions, toxicities, and health care utilization and costs per patient per month (PPPM) were assessed over the full follow-up and the index line of IV paclitaxel/nab-paclitaxel therapy (Index LOT). RESULTS The sample included 8890 women aged 54.6 (±10.9) years, followed for 18.9 (±13.5) months. Most (82.0%) initiated IV paclitaxel/nab-paclitaxel monotherapy; 83.1% had early discontinuation (

Hypothesis: insufficiently active heart failure patients will report poorer QoL, more fatigue and depressive mood compared to active patients. Aims: To characterize clinical characteristics and health-related behaviors according to physical activity (PA). Also, to explore predicting factors of quality of life (QoL). Methods: Cross-sectional analysis of a cohort of Stage B HF patients. PA classification was set as active, moderately active or insufficiently active, according to the LTEQ questionnaire. For QoL, the SF-36 questionnaire was used. ANOVAS, Chi-Square tests or likelihood ratios and unadjusted multiple regression models were calculated. Significance was set at p ≤ 0.05. Results: In this cohort, 277 HF patients completed the PA questionnaire. The prevalence of active patients was higher than moderately active and insufficiently active (53.3% vs 15.2% and 29.6%), respectively. Younger age (p = 0.044), lower waist circumference (WC) (p = 0.002), and lower waist-to-hip ratio (p = 0.046) were associated with being active. The prevalence of Type II diabetes mellitus (T2DM) in the active groups was significantly lower (p = 0.001). Physically active groups had cases of mild LV enlargement (1.4% and 7.5%, respectively), while no cases were observed among insufficiently active patients (p = 0.017). PA was positively associated with less fatigue (p= 0.002), more vigor (p = 0.001), more self-efficacy (p < 0.001), and better quality of life (p = 0.002). Patients who were less physically active had more inflammation (CRP, p = 0.015; IL-6, p 2 = 0.449). For physical functioning (high scores reflects performing PA without limitations due to health), WC (β = - 0.28, p = 0.001), sleep (β = - 1.50, p = 0.003) and fatigue (β = - 0.32, p = 0.018) were significant predictors (R 2 = 0.422); while age (β = 0.36, p 2 = 0.696). Conclusion: Physically active heart failure patients had a better anthropometric profile and lower prevalence of T2DM. In this cohort, PA was not a significant predictor for general and physical functioning, but it remained relevant for predicting emotional well-being.

Background: Cardiopulmonary fitness and low calorie diets have been shown to reduce inflammation but few studies have been conducted in individuals with elevated blood pressure (BP) in a randomized intervention setting. Thereby, adhesion biomarkers, e.g., soluble intercellular adhesion molecule (sICAM)-3, have not been examined so far. Methods: Sixty-eight sedentary prehypertensive and mildly hypertensive individuals (mean age ± SEM: 45 ± 1 years; mean BP: 141/84 ± 1/1 mmHg) were randomized to one of three 12-week intervention groups: cardio training and caloric reduction, cardio training alone, or wait-list control group. Plasma levels of inflammatory, adhesion and prothrombotic biomarkers were assessed. In a second step, intervention groups were combined to one sample and multivariate regression analyses were applied in order to account for exercise and diet behavior changes. Results: There were no significant differences among the intervention groups. In the combined sample, greater caloric reduction was associated with a larger increase of sICAM-3 (p = 0.026) and decrease of C-reactive protein (p = 0.018) as a result of the interventions. More cardio training was associated with increases of sICAM-3 (p = 0.046) as well as interleukin-6 (p = 0.004) and a decrease of tumor necrosis factor- (p = 0.017) levels. Higher BP predicted higher plasminogen activator inhibitor (PAI)-1 (p = 0.001), and greater fitness predicted lower PAI-1 levels (p = 0.006) after the intervention. Conclusions: In prehypertensive and hypertensive patients, plasma levels of the adhesion molecule sICAM-3 and inflammatory biomarkers have different response patterns to cardio training with and without caloric reduction. Such anti-inflammatory and anti-thrombotic effects may have implications for the prevention of atherothrombotic cardiovascular disease among individuals at increased risk.

In the United States, heart failure (HF) affects approximately 6.5 million adults. While studies show that individuals with HF often suffer from adverse symptoms such as depression and anxiety, studies also show that these symptoms can be at least partially offset by the presence of spiritual wellbeing. In a sample of 327 men and women with AHA/ACC classification Stage B HF, we found that more spirituality in patients was associated with better clinically-related symptoms such as depressed mood and anxiety, emotional variables (affect, anger), well-being (optimism, satisfaction with life), and physical health-related outcomes (fatigue, sleep quality). These patients also showed better self-efficacy to maintain cardiac function. Simply belonging to a religious organization independent of spiritualty, however, was not a reliable predictor of health-related benefits. In fact, we observed instances of belonging to a religious organization unaccompanied by parallel spiritual ratings, which appeared counterproductive.

Aims: To describe healthcare utilization and cost associated with the short-term and long-term complications of cystectomy among commercially insured bladder cancer patients in the United States. Materials and methods: This retrospective, observational cohort study evaluated adults with bladder cancer receiving a transurethral resection of bladder tumor followed by a partial or radical cystectomy procedure using U.S. administrative claims from the 2005–2015 IBM MarketScan Commercial and Medicare Supplemental databases. Bladder cancer patients were classified into two cohorts: partial cystectomy or radical cystectomy. Cystectomy complications were identified during the cystectomy admission, short-term period, and long-term period. Complication-related utilization and cost outcomes were reported in aggregate during the cystectomy admission and per patient per month (PPPM) during the short-term and long-term follow-up periods. Results: Of 5136 patients who received a cystectomy, 488 (9.5%) received partial cystectomy and 4648 (90.5%) received radical cystectomy. The mean (SD) costs of complications during the cystectomy admission were $11,728 ($43,380) for radical cystectomy and $4657 ($25,668) for partial cystectomy. In the short-term period, PPPM complication-related healthcare costs were $638 [$3793] for partial cystectomy and $2681 [$14,705] for radical cystectomy. In the long-term period, PPPM complication-related healthcare costs were $544 [$2580] for partial cystectomy and $1619 [$7874] for radical cystectomy. Conclusions: Cystectomy-related complications, especially with radical cystectomy, present a substantial financial burden to patients and payers immediately after surgery as well as in the long term. Targeted interventions which improve clinical outcomes but reduce substantial costs associated with cystectomy for bladder cancer are needed.

The purpose of this article is to describe in detail how an academic hospital system took on the challenge of deep vein thrombosis (DVT) prevention. A VTE Prevention Task Force was formed in response to an increased incidence of hospital acquired DVTs. The interdisciplinary team reviewed the literature and examined the current state of organizational venous thromboembolism (VTE) prevention to identify gaps in process, determine opportunity and approaches for practice and process improvements, and develop standardized VTE prevention protocols. The article discusses the process taken in developing a highly motivated interdisciplinary team, the implementation of a care bundle, and the highly effective educational and surveillance tools used that helped improve patient outcomes by driving down the VTE rate.

This is one of the first head-to-head real-world evidence studies comparing stroke-related and bleed-related healthcare and resource utilization (HCRU) and costs among non-valvular atrial fibrillation (NVAF) patients initiating oral anticoagulants.Adult NVAF patients newly diagnosed and treated with dabigatran, rivaroxaban, or warfarin between 10/01/2010 and 12/31/2014 were identified using MarketScan Commercial and Medicare Supplemental databases. Per-patient-per-month stroke and bleed-related HCRU and costs were reported.Dabigatran patients were matched 1:1 to 26,592 rivaroxaban and 33,024 warfarin patients (mean age=68 years). Compared to rivaroxaban, dabigatran patients had lower bleed-related inpatient and outpatient HCRU (0.004 vs. 0.005; 0.099 vs. 0.145) and significantly lower adjusted bleed-related costs ($116 vs. $172), all p 0.05. Compared to warfarin, dabigatran patients had significantly lower stroke-related outpatient visits (0.034 vs. 0.048, p0.001) and higher bleed-related outpatient visits (0.101 vs. 0.091, p=0.045). Multivariate adjusted bleed-related costs were significantly lower for dabigatran patients than warfarin patients ($94 vs. $138, p0.001).The results suggest that dabigatran patients had lower bleed-related HCRU and costs than rivaroxaban patients, and lower outpatient stroke-related HCRU, higher bleed-related outpatient HCRU, and lower bleed-related costs than warfarin patients. It provides valuable stroke-related and bleed-related HCRU and costs information among commercially insured and Medicare patients.

Objective: Cognitive deficits are common in patients with heart failure (HF), and can negatively affect self-care, predict rehospitalizations, and increase mortality rates 5-fold. Inflammation can produce vascular pathology, reducing cerebral blood flow to brain regions necessary for optimal cognitive function. The purpose of the investigation was to identify a pattern of peripheral blood inflammation-related biomarkers associated with cognitive impairment in patients with HF. Methods: Forty-five outpatients (median age = 67 years, SD = 9.9) were recruited from University of California, San Diego (UCSD) and Veterans Affairs San Diego Healthcare Systems (VASDHS), diagnosed with New York Heart Association Stages I–III HF. Participants were administered the Montreal Cognitive Assessment (MoCA) as a measure of global cognitive impairment, and blood was analyzed for plasma biomarkers, interferon-γ, tumor necrosis factor-α (TNFα), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), brain-derived neurotrophic factor (BDNF), interleukin-8 (IL-8), matrix metallopeptidase-9 (MMP-9), IL-6, C-reactive protein (CRP), and serum amyloid-A (SAA). Results: Almost half the patients scored below the threshold on the MoCA, indicating at least mild cognitive impairment. A factor analysis produced three biomarker factors: vascular inflammatory factor-1: TNFα, sICAM1, sVCAM1; neuroinflammatory factor-2: BDNF, MMP-9, IL-8; peripheral inflammatory factor-3: IL-6, CRP, SAA. Only vascular inflammatory factor-1 was significantly associated with cognitive function (MoCA) (ΔR2 = 0.214, beta = –0.468, p = 0.008). Conclusions: In this cohort with HF, vascular inflammation appears related to poorer cognitive function. This could indicate targets for treatment to reduce cognitive deficits in HF. However, this is a preliminary study, and further research is needed.

This economic evaluation examines whether adult patients in the US who have commercial or Medicare insurance pay out-of-pocket costs associated with follow-up colonoscopy within 6 months of a noninvasive stool-based test.

Compare costs and healthcare resource utilization (HCRU) among newly-diagnosed non-valvular atrial fibrillation (NVAF) patients newly treated with dabigatran vs apixaban, rivaroxaban, or warfarin.Newly-diagnosed adult NVAF patients initiating dabigatran, apixaban, rivaroxaban, or warfarin (index event) between October 1, 2010-December 31, 2014 were identified using MarketScan claims data, and followed until medication discontinuation, switch, inpatient death, enrollment end, or study end (December 31, 2015). Dabigatran patients were propensity-score matched 1:1 separately with apixaban, rivaroxaban, and warfarin patients. Per-patient-per-month (PPPM) all-cause cost, HCRU, and 30-day re-admissions were reported. Costs were analyzed using generalized linear models.Final cohorts, each matched with dabigatran patients, included 8,857 apixaban patients, 26,592 rivaroxaban patients, and 33,046 warfarin patients. Dabigatran patients had lower adjusted PPPM total healthcare, inpatient, and outpatient costs compared to rivaroxaban ($4,093 vs $4,636, $1,476 vs $1,862, and $2,016 vs $2,121, respectively, all p ≤ .001) and warfarin ($4,199 vs $4,872, $1,505 vs $1,851, and $2,049 vs $2,514, respectively, all p .001). Adjusted costs were similar for dabigatran and apixaban. Dabigatran patients had significantly fewer hospitalizations, outpatient visits, and pharmacy claims than rivaroxaban patients (0.06 vs 0.07, 4.84 vs 4.96 and 4.80 vs 4.93, respectively, all p .020) and warfarin patients (0.06 vs 0.07, 4.77 vs 6.88, and 4.76 vs 5.89, respectively, all p .001). Dabigatran patients had similar hospitalizations to apixaban, but higher outpatient visits (4.70 vs 4.31) and pharmacy claims (4.86 vs 4.61), both p .001.This real-world study found adjusted all-cause costs were lower for dabigatran compared to rivaroxaban and warfarin patients and similar to apixaban patients.

Objectives:Given the evidence of multi-parameter risk factors in shaping cognitive outcomes in aging, including sleep, inflammation, cardiometabolism, and mood disorders, multidimensional investigations of their impact on cognition are warranted. We sought to determine the extent to which self-reported sleep disturbances, metabolic syndrome (MetS) factors, cellular inflammation, depressive symptomatology, and diminished physical mobility were associated with cognitive impairment and poorer cognitive performance.Design:This is a cross-sectional study.Setting:Participants with elevated, well-controlled blood pressure were recruited from the local community for a Tai Chi and healthy-aging intervention study.Participants:One hundred forty-five older adults (72.7 ± 7.9 years old; 66% female), 54 (37%) with evidence of cognitive impairment (CI) based on Montreal Cognitive Assessment (MoCA) score ≤24, underwent medical, psychological, and mood assessments.Measurements:CI and cognitive domain performance were assessed using the MoCA. Univariate correlations were computed to determine relationships between risk factors and cognitive outcomes. Bootstrapped logistic regression was used to determine significant predictors of CI risk and linear regression to explore cognitive domains affected by risk factors.Results:The CI group were slower on the mobility task, satisfied more MetS criteria, and reported poorer sleep than normocognitive individuals (all p < 0.05). Multivariate logistic regression indicated that sleep disturbances, but no other risk factors, predicted increased risk of evidence of CI (OR = 2.00, 95% CI: 1.26–4.87, 99% CI: 1.08–7.48). Further examination of MoCA cognitive subdomains revealed that sleep disturbances predicted poorer executive function (β = –0.26, 95% CI: –0.51 to –0.06, 99% CI: –0.61 to –0.02), with lesser effects on visuospatial performance (β = –0.20, 95% CI: –0.35 to –0.02, 99% CI: –0.39 to 0.03), and memory (β = –0.29, 95% CI: –0.66 to –0.01, 99% CI: –0.76 to 0.08).Conclusions:Our results indicate that the deleterious impact of self-reported sleep disturbances on cognitive performance was prominent over other risk factors and illustrate the importance of clinician evaluation of sleep in patients with or at risk of diminished cognitive performance. Future, longitudinal studies implementing a comprehensive neuropsychological battery and objective sleep measurement are warranted to further explore these associations.

Author(s): Mills, Paul J; Taub, Pam R; Lunde, Ottar; Pung, Meredith A; Wilson, Kathleen; Pruitt, Christopher; Rutledge, Thomas; Maisel, Alan; Greenberg, Barry H | Abstract: BackgroundThe presence of concomitant Type II diabetic mellitus (T2DM) and depressive symptoms adversely affects individuals with symptomatic heart failure (HF).HypothesisIn presymptomatic stage B HF, this study hypothesized the presence of greater inflammation and depressive symptoms in T2DM as compared to non-T2DM Stage B patients.MethodsThis cross-sectional study examined clinical parameters, inflammatory biomarkers, and depressive symptoms in 349 T2DM and non-T2DM men with asymptomatic stage B HF (mean age 66.4 years ±10.1; range 30-91).ResultsFewer diabetic HF patients had left ventricular (LV) systolic dysfunction (P l .05) although more had LV diastolic dysfunction (P l .001). A higher percentage of T2DM HF patients were taking ACE-inhibitors, beta-blockers, calcium channel blockers, statins, and diuretics (P values l .05). T2DM HF patients had higher circulating levels of interleukin-6 (IL-6) (P l .01), tumor necrosis factor-alpha (P l .01), and soluble ST2 (sST2) (P l .01) and reported more somatic/affective depressive symptoms (Beck Depression Inventory II) (P l .05) but not cognitive/affective depressive symptoms (P = .20). Among all patients, in a multiple regression analysis predicting presence of somatic/affective depressive symptoms, sST2 (P = .026), IL-6 (P = .010), B-type natriuretic peptide (P = .016), and sleep (Pittsburgh Sleep Quality Index [P l .001]) were significant predictors (overall model F = 15.39, P l .001, adjusted R2 = .207).ConclusionsSomatic/affective but not cognitive/affective depressive symptoms are elevated in asymptomatic HF patients with T2DM patients. Linkages with elevated inflammatory and cardiac relevant biomarkers suggest shared pathophysiological mechanisms among T2DM HF patients with somatic depression, and these conditions are responsive to routine interventions, including behavioral. Copyright © 2019 John Wiley a Sons, Ltd.

Objectives To describe long-term treatment patterns in migraine patients initiating prophylactic therapy and to evaluate acute medication use and adverse events associated with opioids. Methods This study used the 2005–2014 IBM MarketScan® databases to evaluate migraine patients initiating prophylactic medication. Outcome measures included persistence with prophylactic migraine medications over 2–5 years. Acute medication use and gastrointestinal-related adverse events and opioid abuse following opioid use were evaluated. Cox proportional hazards models were used to evaluate predictors of non-persistence and predictors of gastrointestinal-related AEs and opioid abuse associated with long-term opioid use. Results In total, 147,832 patients were analyzed. Non-persistence was observed in 90% of patients; 39% switched, 30% restarted, and 31% discontinued treatment. Over the follow-up, 59.9% of patients received triptans, 66.6% non-steroidal anti-inflammatory drugs, 77.4% opioids, and 2.6% ergotamines. Among opioid users, 16.6% experienced nausea/vomiting, 12.2% had constipation, and 10.4% had diarrhea. Opioid abuse was reported in Conclusions Non-persistence to prophylactic treatment was frequent among migraine patients. Opioid use was common in migraine patients and the risk of gastrointestinal-related adverse events and opioid abuse increased with long-term use of opioids. These results suggest a need for more effective prophylactic migraine treatments.

OBJECTIVE To compare 12-month healthcare costs between employees with versus without diagnosed opioid abuse within 12 months after an injury-related workers' compensation (WC) or short-term disability (STD) claim. METHODS Retrospective study using 2003 to 2014 US insurance claims linked to administrative data on WC/STD claims. Multivariable models compared healthcare costs between employees with versus without diagnosed opioid abuse. RESULTS Study included 107,975 opioid-treated employees with an injury-related WC or STD claim. Mean number of opioid prescription fills and adjusted total healthcare costs were substantially greater in employees with diagnosed opioid abuse versus without (WC: 13.4 vs. 4.5, P

Objective Stage B, asymptomatic heart failure (HF) presents a therapeutic window for attenuating disease progression and development of HF symptoms, and improving quality of life. Gratitude, the practice of appreciating positive life features, is highly related to quality of life, leading to development of promising clinical interventions. However, few gratitude studies have investigated objective measures of physical health; most relied on self-report measures. We conducted a pilot study in Stage B HF patients to examine whether gratitude journaling improved biomarkers related to HF prognosis. Methods Patients (n = 70; mean [standard deviation] age = 66.2 [7.6] years) were randomized to an 8-week gratitude journaling intervention or treatment as usual. Baseline (T1) assessments included the six-item Gratitude Questionnaire, resting heart rate variability (HRV), and an inflammatory biomarker index. At T2 (midintervention), the six-item Gratitude Questionnaire was measured. At T3 (postintervention), T1 measures were repeated but also included a gratitude journaling task. Results The gratitude intervention was associated with improved trait gratitude scores (F = 6.0, p = .017, η = 0.10), reduced inflammatory biomarker index score over time (F = 9.7, p = .004, η = 0.21), and increased parasympathetic HRV responses during the gratitude journaling task (F = 4.2, p = .036, η = 0.15), compared with treatment as usual. However, there were no resting preintervention to postintervention group differences in HRV (p values > .10). Conclusions Gratitude journaling may improve biomarkers related to HF morbidity, such as reduced inflammation; large-scale studies with active control conditions are needed to confirm these findings. Trial registration Clinicaltrials.govidentifier:NCT01615094.

Objective Almost half of patients with heart failure (HF) have cognitive impairment. While exercise relates to better cognitive health, a hallmark of HF is exercise intolerance. The study objective was to explore whether light-to-moderate exercise improves cognitive function in patients with HF. Methods This was an exploratory parallel design study of 69 patients with symptomatic HF (mean age = 65, SD = 10), recruited from VA and University of California, San Diego Healthcare Systems. Participants were randomized to Tai Chi (TC) (n = 24), resistance band (RB) exercise (n = 22) or treatment as usual (TAU) (n = 23). The primary outcome was change in Montreal Cognitive Assessment (MoCA) scores. We further explored if changes in Beck Depression Inventory – IA (BDI-IA) scores or inflammation biomarkers, CRP, TNFα and IL-6 related to altered cognitive function. Results There was a fixed effect of group for MoCA scores changes (F = 8.07, p = .001). TC and RB groups had greater MoCA score increases versus TAU, but no differences were found between TC and RB. Depression symptom changes predicted altered MoCA scores (ΔR2 = 0.15, Β = −0.413, p = .001). However, group did not interact with depression symptom levels for MoCA alterations (p = .392). Changes in CRP levels predicted MoCA scores (ΔR2 = 0.078, Β = −0.283, p = .01), but group did not interact with CRP levels for MoCA alterations (p = .689). Conclusions Light-to-moderate exercises, TC and RB may improve cognitive function. However, the mechanisms remain unclear. ClinicalTrials.gov : NCT01625819

Aim: Biologics and apremilast have advanced psoriasis management by adding treatment options. This study evaluated persistence, adherence and healthcare costs among biologic-naive patients receiving apremilast or biologics. Methods: Administrative claims data for adults starting apremilast or biologics from 1 January 2013 to 30 June 2016 were matched based on demographics. Results: Apremilast (n = 703) and biologics (n = 1378) had similar baseline characteristics. 12-month persistence and adherence rates were similar. Adjusted total healthcare costs were lower with apremilast versus biologics (p Conclusion: Real-world apremilast users had similar adherence and lower total healthcare costs versus biologic users. Apremilast's cost advantage was evident regardless of whether the patients were persistent or nonpersistent, or switched or did not switch treatments.

To describe multiple myeloma (MM) treatment patterns and comorbidities over time in the US.Study patients were newly diagnosed with MM (ICD-9-CM 203.0x) between 1 July 2006 and 31 March 2014 and had ≥6 months of data prior to the initial MM diagnosis in MarketScan Research Databases. Patients were followed until inpatient death or the end of data. First-line, second-line, and third-line treatment regimens were identified following diagnosis and were described over time based upon the start date of the first line of therapy (2006-2007, 2008-2014, 2013-2014). Comorbid conditions and disease-related complications were examined during the 6 months prior to the line of therapy start dates.A total of 24,507 MM patients were examined (mean age: 65.2 years, 54.1% male, mean follow-up: 23 months, 16.2% transplant). Across all lines of therapy, the proportion of patients on thalidomide-based regimens decreased over time. In the first line, bortezomib-based regimens became more common from 2006-2007 to 2008-2014 (2006-2007: 17.0%, 2008-2014: 44.3%, 2013-2014: 49.4%). In the second line, lenalidomide- and bortezomib-based regimens were the most common (2013-2014: lenalidomide: 28.9%, bortezomib: 26.2%). The combination regimen of lenalidomide + bortezomib became more common in the first and second lines. In the third line, carfilzomib- and/or pomalidomide-based regimens were 37.0% in 2013-2014. Skeletal-related events, hypertension, anemia, and chronic kidney disease were the most prevalent comorbidities and disease-related complications. During the 6 months prior to each line of therapy, the prevalence of the majority of the comorbidities and complications increased as patients progressed to higher lines of therapy.MM treatment patterns have been dynamic over time. Comorbid conditions and myeloma-related complications increase as patients progress and may worsen MM patients' prognoses over time. Combination regimens such as lenalidomide + bortezomib are more widely used as first- and second-line therapy. Newly approved agents (carfilzomib, pomalidomide) are the prevailing treatments in the third line and are under further investigation for earlier lines of therapy.

Contemporary estimates of the prevalence of diagnosed osteoporosis among long-term care facility residents are limited.This chart review collected data between April 1, 2012 and August 31, 2013 for adult (age ≥ 30 years) residents of 11 long-term care facilities affiliated with the Louisiana State University Health Sciences Center in the New Orleans metropolitan area. Data (demographics; comorbidities; osteoporosis diagnosis, risk factors, diagnostic assessments, treatments; fracture history; fall risk; activities of daily living) were summarized. Data for residents with and without diagnosed osteoporosis were compared using χ tests and t tests.The study included 746 residents (69% women, mean [SD] age: 76.3 [13.9] years, median length of stay approximately 18.5 months). An osteoporosis diagnosis was recorded for 132 residents (18%), 30% of whom received a pharmacologic osteoporosis therapy. Fewer than 2% of residents had bone mineral density assessments; 10% had previous fracture. Calcium and vitamin D use was more prevalent in residents with diagnosed osteoporosis compared with other residents (calcium: 49% versus 12%, vitamin D: 52% versus 28%; both P0.001). Over half (304/545) of assessed residents had a high fall risk. Activities of daily living were similarly limited regardless of osteoporosis status.The prevalence of diagnosed osteoporosis was higher than previously reported for long-term care residents, but lower than epidemiologic estimates of osteoporosis prevalence for the noninstitutional U.S.In our sample, osteoporosis diagnostic testing was rare and treatment rates were low. Our results suggest that osteoporosis may be underdiagnosed and undertreated in long-term care settings.

Spirituality and gratitude are associated with wellbeing. Few if any studies have examined the role of gratitude in heart failure (HF) patients or whether it is a mechanism through which spirituality may exert its beneficial effects on physical and mental health in this clinical population. This study examined associations bet ween gratitude, spiritual wellbeing, sleep, mood, fatigue, cardiac-specific self-efficacy, and inflammation in 186 men and women with Stage B asymptomatic HF (age 66.5 years ±10). In correlational analysis, gratitude was associated with better sleep (r=-.25, p

Ustekinumab is the most recently approved biologic for the treatment of moderate-to-severe psoriasis. Real-world dosing patterns of ustekinumab are yet to be fully characterized.A retrospective, observational study was conducted using MarketScan Commercial and Medicare databases. A cohort of psoriasis patients treated with ustekinumab between 25 September 2009 and 31 October 2010 was evaluated. Main outcomes included ustekinumab dosing and treatment patterns. Kaplan-Meier estimates were calculated to adjust for the censoring of data. Subgroup analysis was conducted for biologic-experienced patients and biologic-naïve patients.One thousand ustekinumab patients were included, of whom 60% were biologic-experienced. The average age was 49.0 and 53.9% were male. 63.3% of patients initiated ustekinumab with a 45 mg dose and 34.5% initiated with a 90 mg dose. Mean (median) days from initial dose to second dose was 31.1 (28.0). During maintenance therapy, dose intervals spanned from 80.6 to 81.2 (84.0) days. About 81.4% of patients were persistent during the variable-length follow-up period.The majority of patients received the 45 mg ustekinumab dose. The mean dosing intervals were consistent with the US prescribing guidelines. Biologic-naïve and biologic-experienced patients had similar dosing patterns. Ustekinumab treatment achieved a persistency rate as high as 81.4% over an average of 186.5 (SD 114.2) days of follow-up.

Background: Peripheral neuropathy (PN) is a common consequence of multiple myeloma (MM) among those commonly treated with older-generation proteasome inhibitors (PIs). In this study, we evaluated the economic burden attributable to PN among MM patients in real-world practice settings in the US. Methods: Adults diagnosed with MM and first treated (index event) between 1 July 2006 and 28 February 2017 were identified from MarketScan® Commercial and Medicare claim databases. Continuous enrollment for at least 12 months without treatment and PN diagnoses were required pre-index. Patients were followed for at least 3 months until inpatient death or end of data. The International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes were used to identify PN. Propensity-score matching was applied to match every patient with PN to two MM patients without a PN diagnosis (controls). Healthcare utilization and expenditures per patient per month (PPPM) in the postindex period were estimated. Results: Of 11,851 patients meeting the study criteria, 15.5% had PN. After matching 1387 patients with PN and 2594 controls were identified. Baseline characteristics were well balanced between cohorts; mean follow up was 23–26 months. PPPM total costs were significantly higher by $1509 for patients with PN than controls, driven by higher hospitalization (PN 77.4%, controls 67.2%; p < 0.001) and emergency department rates (PN 67.8%, controls 58.4%; p < 0.001) and more outpatient hospital-based visits PPPM (PN 13.5 ± 14.7, controls 11.5 ± 18.0; p < 0.001). Conclusions: PN is a prevalent MM treatment complication associated with a significant economic burden adding to the complexity and cost of MM treatment. Highly effective novel treatments such as carfilzomib may reduce the overall disease burden.

Background— Heart failure (HF) readmission rates are primarily derived from Medicare enrollees. Given increasing public scrutiny of HF readmissions, understanding the rate and predictors in populations covered by other payers is also important, particularly among patients with systolic dysfunction, for whom most HF-specific therapies are targeted. Methods and Results— MarketScan Commercial and Medicaid Administrative Claims Databases were used to identify all first hospitalizations with an International Classification of Diseases-9 discharge diagnosis code for HF (primary position) and systolic HF (any position) between January 1, 2005, and June 30, 2008. Among 4584 unique systolic HF index admissions (mean age 55 years), 30-day crude readmission rates were higher for Medicaid than commercially insured patients: all-cause 17.4% versus 11.8%; HF-related 6.7% versus 4.0%, respectively. In unadjusted analysis, higher comorbidity and prior healthcare utilization predicted readmission; age, sex, and plan type did not. After adjustment for case mix, the odds of all-cause and HF-related readmission were 32% and 68% higher, respectively, among Medicaid than commercially insured patients ( P Conclusions— Compared with commonly cited Medicare HF readmission rates of 20% to 25%, Medicaid patients with systolic HF had lower 30-day readmission rates, and commercially insured patients had even lower rates. Even after adjustment for case mix, Medicaid patients were more likely to be readmitted than commercially insured patients, suggesting that more attention should be focused on readmissions among socioeconomically disadvantaged populations.

Descriptions of the inpatient experience for patients hospitalized with systolic heart failure (HF) are limited and lack a cross-sectional representation of the US population. While length of stay (LOS) is a primary determinant of resource use and post-discharge events, few models exist for estimating LOS.MarketScan(®) administrative claims data from 1/1/2005-6/30/2008 were used to select hospitalized patients aged ≥18 years with discharge diagnoses for both HF (primary diagnosis) and systolic HF (any diagnostic position) without prior HF hospitalization or undergoing transplantation.Among 17,597 patients with systolic HF; 4109 had commercial; 2118 had Medicaid; and 11,370 had Medicare payer type. Medicaid patients had longer mean LOS (7.1 days) than commercial (6.3 days) or Medicare (6.7 days). In-hospital mortality was highest for patients with Medicaid (2.4%), followed by Medicare (1.3%) and commercial (0.6%). Commercial patients were more likely to receive inpatient procedures. Renal failure, pressure ulcer, malnutrition, a non-circulatory index admission DRG, receipt of a coronary artery bypass procedure or cardiac catheterization, or need for mechanical ventilation during the index admission were associated with increased LOS; receipt of a pacemaker device at index was associated with shorter LOS.Selection of patients with systolic HF is limited by completeness and accuracy of medical coding, and results may not be generalizable to patients with diastolic HF or to international populations.Inpatient care, LOS, and in-hospital survival differ by payer among patients hospitalized with systolic HF, although co-morbidity and inpatient procedures consistently influence LOS across payer types. These findings may refine risk stratification, allowing for targeted intensive inpatient management and/or aggressive transitional care to improve outcomes and increase the efficiency of care.

Aim: Hypertension is related to abnormalities in autonomic nervous system (ANS) function, with increased sympathetic output and decreased parasympathetic tone. Lifestyle interventions are the first line of treatment in hypertension, and decreased blood pressure (BP) effects may be related to changes in ANS function. Using heart rate recovery (HRR) from exercise as an index of parasympathetic tone and plasma noradrenaline as an index of sympathetic tone, we investigated the effects of lifestyle interventions on ANS function in patients with elevated BP. Methods: Sedentary participants with elevated BP were randomly assigned to either an exercise only (N = 25), exercise plus dietary approaches to stop hypertension (DASH) diet (N = 12), or waitlist control (N = 15) 12-week intervention. Plasma noradrenaline was measured at rest and participants performed a peak exercise test before and after the intervention. HRR was calculated as peak heart rate (HR) minus HR at 1 min post-exercise. Results: Heart rate recovery showed a significant group by time interaction; both intervention groups showed increases in HRR from pre- to post-intervention, while waitlist showed no change. Similarly, both exercise plus diet and exercise groups, but not waitlist, showed significant reductions in BP from pre- to post-intervention. Linear regression revealed that BP post-intervention was significantly predicted by change in HRR when controlling for pre-BP, age, gender and BMI. Conclusions: Lifestyle interventions induced training-reduced BP and altered autonomic tone, indexed by HRR. This study indicates the importance of behavioural modification in hypertension and that increased parasympathetic function is associated with success in reduction of BP.

Background and Objectives Even with the introduction of specific risk-reduction strategies, transfusion-related acute lung injury (TRALI) continues to be a leading cause of transfusion-related morbidity and mortality. Existing small animal models have not yet investigated TRALI resulting from the infusion of heat-treated supernatant from whole blood platelet concentrates. In this study, our objective was the development of a novel in vivo two-event model of TRALI in sheep. Materials and Methods Lipopolysaccharide (LPS; 15 μg/kg) as a first event, modelled clinical infection. Transfusion (estimated at 10% of total blood volume) of heat-treated pooled supernatant from date-of-expiry human whole blood platelet concentrates (d5-PLT-S/N) was used as a second event. TRALI was defined by both hypoxaemia that developed either during the transfusion or within two hours of its completion and post-mortem histological evidence of pulmonary oedema. Results LPS infusion did not cause lung injury itself, but did result in decreased circulating levels of lymphocytes and neutrophils with evidence of the latter becoming sequestered in the lungs. Sheep that received LPS (first event) followed by d5-PLT-S/N (second event) displayed decreased pulmonary compliance, decreased end tidal CO2 and increased arterial partial pressure of CO2 relative to control sheep, and 80% of these sheep developed TRALI. Conclusions This novel ovine two-event TRALI model presents a new tool for the investigation of TRALI pathogenesis. It represents the first description of an in vivo large animal model of TRALI and the first description of TRALI caused by transfusion with heat-treated pooled supernatant from human whole blood platelet concentrates.

OBJECTIVES: The purpose of this study was to examine the real-world differences in healthcare resource utilization in chronic lymphocytic lymphoma (CLL) patients treated with either first-line ibrutinib monotherapy (IM) or first-line bendamustine + rituximab (BR) therapy using U.S. administrative claims data. METHODS: The MarketScan® Research Databases were used to identify patients aged 18 years or older with commercial or Medicare supplemental insurance plans based on their first prescription (index date) of either IM or BR therapy between 02/01/2014 and 08/30/2017. Patients were required to be diagnosed with CLL and be treatment naïve, as well as be continuously enrolled (CE) for 6 months prior to and at least 30 days following the index date. All-cause and CLL-related healthcare resource utilization (e.g., inpatient admission (IP) and emergency room (ER) visits) were evaluated during a 12-month follow-up period from the index date among the subset of patients with 12 months of continuous enrollment and were reported per-patient per-month (PPPM). Statistical differences in the distribution of IP and ER visits between the IM versus BR therapy groups were estimated using chi-squared test for categorical variables and t-test for continuous variables. RESULTS: A total of 1,886 CLL patients were identified, with 1,157 patients in the IM cohort and 729 patients in the BR cohort. The IM cohort was significantly older (mean = 69.3 years; SD = 11.6) then the BR cohort (mean age = 66.4 years; SD = 9.8). There was a similar proportion of females (IM = 36%; BR = 32%), and no significant difference in the National Cancer Institute Comorbidity Index score was observed between the two cohorts (IM=0.9 vs BR=0.8, p=0.34). The results of the comparisons between the two groups with 12 months of follow-up (IM = 589; BR = 436) are provided in Table 1. For all-cause healthcare utilization, the proportion of patients experiencing at least one IP admission and the PPPM number of admissions was significantly higher in the IM cohort compared to the BR cohort. The proportion of patients with at least one ER visit was higher in the IM than in the BR cohort, but the difference was not statistically significant. However, the PPPM number of ER visits was significantly higher in the IM cohort. A similar pattern was found for the CLL-related healthcare utilization variables with two exceptions. First, the average length of stay (ALOS) per CLL-related IP admission was significantly longer for the IM than BR cohort; whereas, ALOS per all-cause IP admission was longer for the IM cohort, but the difference was not significantly different. Second, while patients in the IM cohort experienced more CLL-related ER visits, they were not significantly higher in the IM cohort than in the BR cohort. Conclusions: The current study examined differences in healthcare utilization during a 12 month period among CLL-patients initially treated in a front-line setting with either ibrutinib or BR combination therapy. Results indicated that not only did more ibrutinib patients experience an IP admission and ER visits, both all-cause and CLL-related, but they also experienced more repeat admissions and ER visits. These real-world findings highlight the importance of considering the healthcare resource utilization of CLL patients which may be associated with their first-line therapy. Disclosures Irwin: Teva: Consultancy. Zhang:Teva: Consultancy. Wilson:Teva: Consultancy. Hoehn:Teva: Employment. Szabo:Teva: Employment. Tang:Teva: Employment.

Objective: Very preterm neonates are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit any lung disease but giving 30 mL/kg of perfluorocarbon when starting PLV increases cortical cerebral blood flow velocity. We aimed to determine if varying the initial dose of perfluorocarbon alters the effect on cerebral blood flow velocity when starting PLV. Methods: In this randomised, controlled trial with historical comparison 24 preterm lambs received one of three loading doses of intratracheal perfluorocarbon liquid over 20 min when starting PLV: 20, 30 or 40 mL/kg. Data on respiratory mechanics, haemodynamics and cerebral blood flow velocity, measured with laser Doppler, were collected continuously for 30 min from the start of dosing. Results: Cortical cerebral blood flow velocity increased over time in all three groups (two-way ANOVA, P= 0.007). There was no difference between groups (two-way ANOVA, P= 0.26). There was no difference between groups in cortical cerebral blood flow velocity variability (P= 0.68), blood pressure (P= 0.96) or heart rate (P= 0.46). The was no statistically significant difference in PaCO2 between groups measured at baseline and at 30 min after starting PLV (P= 0.51). Conclusions: Cortical cerebral blood flow velocity and its variability are not affected by varying doses of tracheal perfluorocarbon (20, 30 or 40 mL/kg) at the start of PLV in preterm lambs.

Objective To review the evidence and provide recommendations for the counselling and management of obese parturients. Outcomes Outcomes evaluated include the impact of maternal obesity on the provision of antenatal and intrapartum care, maternal morbidity and mortality, and perinatal morbidity and mortality. Evidence Literature was retrieved through searches of Statistics Canada, Medline, and The Cochrane Library on the impact of obesity in pregnancy on antepartum and intrapartum care, maternal morbidity and mortality, obstetrical anaesthesia, and perinatal morbidity and mortality. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to April 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The evidence obtained was reviewed and evaluated by the Maternal Fetal Medicine and Clinical Practice Obstetric Committees of the SOGC under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Benefits, Harms, and Costs Implementation of the recommendations in this guideline should increase recognition of the issues clinicians need to be aware of when managing obese women in pregnancy, improve communication and consultation amongst the obstetrical care team, and encourage federal and provincial agencies to educate Canadians about the values of entering pregnancy with as healthy a weight as possible.

Resume Objectif Analyser les donnees et formuler des recommandations en ce qui concerne le counseling et la prise en charge des parturientes obeses. Issues Parmi les issues evaluees, on trouve les effets de l’obesite maternelle sur l’offre de soins prenatals et intrapartum, ainsi que sur la morbidite et la mortalite maternelles et perinatales. Resultats Des recherches ont ete menees aupres de Statistique Canada, de Medline et de The Cochrane Library en vue d’en tirer la litterature portant sur les effets de l’obesite pendant la grossesse sur les soins prenatals et intrapartum, la morbidite et la mortalite maternelles, l’anesthesie obstetricale, et la morbidite et la mortalite perinatales. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles. Aucune restriction en fonction de la date ou de la langue n’a ete mise en œuvre. Les recherches ont ete regulierement mises a jour et leurs resultats ont ete incorpores a la directive clinique jusqu’en avril 2009. La litterature grise (non publiee) a ete identifiee par l’intermediaire de recherches menees dans les sites Web d’organismes s’interessant a l’evaluation des technologies dans le domaine de la sante et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs Les resultats cumules ont ete analyses et evalues par le comite de medecine fœto-maternelle et le comite de pratique clinique-obstetrique de la SOGC, sous la gouverne des auteurs principaux, et les recommandations ont ete formulees conformement aux lignes directrices elaborees par le Groupe d’etude canadien sur les soins de sante preventifs. Avantages, desavantages et couts :La mise en œuvre des recommandations formulees dans la presente directive clinique devraient sensibiliser davantage les cliniciens aux aspects qui doivent etre pris en consideration dans le cadre de la prise en charge des femmes obeses pendant la grossesse, ameliorer la communication et la consultation au sein de l’equipe de soins obstetricaux, et inciter les organismes federaux et provinciaux a sensibiliser les Canadiennes aux bienfaits du maintien d’un poids aussi sante que possible avant la grossesse. Recommandations 1. Les examens de sante periodiques et les autres consultations de nature gynecologique se deroulant avant la grossesse constituent des occasions ideales d’aborder le sujet de la perte de poids avant la conception. Les femmes devraient etre incitees a presenter, avant la grossesse, un IMC 2 et, idealement, 2 . (III-B) 2. L’IMC devrait etre calcule en fonction de la taille et du poids pregrossesses. Les femmes qui presentent un IMC pregrossesse > 30 kg/m 2 sont considerees comme etant obeses. Ce renseignement peut s’averer utile dans le cadre du counseling visant les risques pour la grossesse qui sont associes a l’obesite. (II-2B) 3. Les femmes enceintes obeses devraient se voir offrir des services de counseling au sujet du gain ponderal, de la nutrition et des choix alimentaires. (II-2B) 4. Les femmes obeses devraient etre avisees qu’elles sont exposees a des risques de complications medicales telles que les maladies cardiaques, les maladies pulmonaires, l’hypertension gestationnelle, le diabete gestationnel et l’apnee obstructive du sommeil. La pratique reguliere d’exercices pendant la grossesse peut contribuer a attenuer certains de ces risques. (II-2B) 5. Les femmes obeses devraient etre avisees que leur fœtus est expose a un risque accru d’anomalies congenitales; un depistage approprie devrait etre mis en œuvre. (II-2B) 6. Les fournisseurs de soins obstetricaux devraient tenir compte de l’IMC au moment de prendre des dispositions en vue de la tenue d’une evaluation anatomique fœtale au cours du deuxieme trimestre. Une evaluation anatomique menee a 20–22 semaines pourrait s’averer mieux indiquee pour ce qui est des patientes enceintes obeses. (II-2B) 7. Les femmes enceintes obeses courent un risque accru de subir une cesarienne; de plus, leur taux de reussite en ce qui concerne l’accouchement vaginal a la suite d’une cesarienne connait une baisse. (II-2B) 8. Le tenue d’une consultation prenatale aupres d’un anesthesiste devrait etre envisagee, afin de passer en revue les options en matiere d’analgesie et de s’assurer de la mise en place d’un plan de prise en charge lorsque l’option de l’anesthesie regionale est retenue. (III-B) 9. Le risque de thromboembolie veineuse de chaque femme obese devrait etre evalue. Dans certaines situations cliniques, le fait d’envisager une thromboprophylaxie devrait etre personnalise. (III-B)