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BACKGROUND: Using federal funds from the 2009 Health Information Technology for Economic and Clinical Health Act, the Centers for Medicare and Medicaid Services funded the 2011-2021 Medicaid electronic health record (EHR) incentive programs throughout the country. OBJECTIVE: Identify the market factors associated with Meaningful Use (MU) of EHRs after primary care providers (PCPs) enrolled in the Florida-EHR incentives program through Adopting, Improving, or Upgrading (AIU) an EHR technology. RESEARCH DESIGN: Retrospective cohort study using 2011-2018 program records for 8464 Medicaid providers. MAIN OUTCOME: MU achievement after first-year incentives. INDEPENDENT VARIABLES: The resource dependence theory and the information uncertainty perspective were used to generate key-independent variables, including the county's rurality, educational attainment, poverty, health maintenance organization penetration, and number of PCPs per capita. ANALYTICAL APPROACH: All the county rates were converted into 3 dichotomous measures corresponding to high, medium, and low terciles. Descriptive and bivariate statistics were calculated. A generalized hierarchical linear model was used because MU data were clustered at the county level (level 2) and measured at the practice level (level 1). RESULTS: Overall, 41.9% of Florida Medicaid providers achieved MU after receiving first-year incentives. Rurality was positively associated with MU ( P <0.001). Significant differences in MU achievements were obtained when we compared the "high" terciles with the "low" terciles for poverty rates ( P =0.002), health maintenance organization penetration rates ( P =0.02), and number of PCPs per capita ( P =0.01). These relationships were negative. CONCLUSIONS: Policy makers and health care managers should not ignore the contribution of market factors in EHR adoption.

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This study examines the impact of county-level factors on "meaningful use" (MU) of electronic health records (EHRs) for 8415 primary care providers (PCPs) that enrolled in the Florida Medicaid EHR Incentive Program through adopting, improving, or upgrading (AIU) a certified EHR technology. PCPs received incentive payments at enrollment and if they used their EHRs in meaningful ways; ways that benefit patients and providers alike they received additional payments. We conducted a retrospective cohort study of these providers over the 2011-2018 period while linking their records to other state data. We used the core constructs of the resource dependence theory (RDT), a well-established organization theory in business management, to operationalize the county-level variables. These variables were rurality, poverty, educational attainment, managed care penetration, changes in population, and number of PCPs per capita. The unit of analysis was provider-years. For practical and computational purposes, all the county variables were dichotomized. We used analysis of variance (ANOVA) to test for differences in MU attestation rates across each county variable. Odds ratios and corresponding 95% confidence intervals were derived from pooled logistic regressions using generalized estimated equations (GEE) with the binomial family and logit link functions. Clustered standard errors were used. Approximately 42% of these providers attested to MU after receiving first-year incentives. Rurality and poverty were significantly associated with MU. To some degree, managed care penetration, change in population size, and number of PCPs per capita were also associated with MU. Policy makers and healthcare managers should not ignore the contribution of county-level factors in the diffusion of EHRs among physician practices. These county-level findings provide important insights about EHR diffusion in places where traditionally underserved populations live. This county-perspective is particularly important because of the potential for health IT to enable public health monitoring and population health management that might benefit individuals beyond the patients treated by the Medicaid providers.

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BACKGROUND: There are little available data regarding the influence of intravenous thrombolysis (IVT) on the efficacy of different first line endovascular treatment (EVT) techniques. METHODS: We used the dataset of the SWIFT-DIRECT trial which randomized 408 patients to IVT + EVT or EVT alone at 48 international sites. The protocol required the use of a stent retriever (SR), but concomitant use of a balloon guide catheter (BGC) and/or distal aspiration (DA) catheter was left to the discretion of the operators. Four first line techniques were applied in the study population: SR, SR + BGC, SR + DA, SR + DA + BGC. To assess whether the effect of allocation to IVT + EVT versus EVT alone was modified by the first line technique, interaction models were fitted for predefined outcomes. The primary outcome was first pass mTICI 2c­3 reperfusion (FPR). RESULTS: This study included 385 patients of whom 172 were treated with SR + DA, 121 with SR + DA + BGC, 57 with SR + BGC and 35 with SR. There was no evidence that the effect of IVT + EVT versus EVT alone would be modified by the choice of first line technique; however, allocation to IVT + EVT increased the odds of FPR by a factor of 1.68 (95% confidence interval, CI 1.11-2.54). CONCLUSION: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + EVT vs EVT alone in different stent retriever techniques but provides evidence for increased FPR if bridging IVT is administered before stent retriever thrombectomy.

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Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys1, Trp9, and Glu11 were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets.

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Recent evidence suggests that numerous similarities exist between the genomic landscapes of both conjunctival and cutaneous melanoma. Since alterations of several components of the MAP kinases, PI3K/mTOR, and cell cycle pathways have been reported in conjunctival melanoma, we decided to assess the sensitivity of conjunctival melanoma to targeted inhibition mostly of kinase inhibitors. A high content drug screening assay based on automated fluorescence microscopy was performed in three conjunctival melanoma cell lines with different genomic backgrounds with 489 kinase inhibitors and 53 other inhibitors. IC50 and apoptosis induction were respectively assessed for 53 and 48 compounds. The genomic background influenced the response to MAK and PI3K/mTOR inhibition, more specifically cell lines with BRAF V600E mutations were more sensitive to BRAF/MEK inhibition, while CRMM2 bearing the NRASQ61L mutation was more sensitive to PI3k/mTOR inhibition. All cell lines demonstrated sensitivity to cell cycle inhibition, being more pronounced in CRMM2, especially with polo-like inhibitors. Our data also revealed new vulnerabilities to Hsp90 and Src inhibition. This study demonstrates that the genomic background partially influences the response to targeted therapy and uncovers a large panel of potential vulnerabilities in conjunctival melanoma that may expand available options for the management of this tumor.

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BACKGROUND AND PURPOSE: Magnetic resonance imaging quantitative T2* mapping has shown reliable identification of thrombus red blood cell content in vitro. The thrombus composition has been in vivo, associated with outcomes after endovascular therapy for acute ischemic stroke. We aim to analyze the red blood cell content of thrombi retrieved from patients with large vessel occlusions in relation to the thrombus-T2* relaxation time in magnetic resonance imaging. MATERIAL AND METHODS: Consecutive acute ischemic stroke patients treated by endovascular therapy were scanned with an magnetic resonance imaging quantitative T2* mapping sequence. Quantitative histologic evaluations of red blood cell content were performed. A linear regression assessed the association between vascular risk factors, comorbidities, antithrombotic drugs intake, baseline National Institutes of Health Stroke Scale (NIHSS), intravenous thrombolysis before endovascular therapy, time between onset and groin puncture, patient's outcome at 3 months, magnetic resonance imaging quantitative T2* mapping results, and the red blood cell content of thrombi. The correlation between the mean thrombus-T2* relaxation time and red blood cell content was assessed by calculating the Pearson correlation coefficient. RESULTS: Among 31 thrombi, 16 were "Fibrin rich" and 15 "red blood cell dominant." The median red blood cell content was 39 (range, 0-90; interquartile range, 37). The median (interquartile range) thrombus-T2* relaxation time was shorter in "red blood cell dominant" thrombi (21, interquartile range 6) than in "Fibrin rich" thrombi (24, interquartile range 7), without significant difference (p = 0.15), as shown in the Box plot. An inverse correlation between thrombus-T2* relaxation time and red blood cell content was found, with a correlation coefficient of -0.41 (95% CI, -0.67 to -0.08, p = 0.02). CONCLUSION: Our study shows that a shorter thrombus-T2* relaxation time is related to a higher red blood cell content within in vivo thrombi.

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INTRODUCTION: Circulatory assistance from a SynCardia Total Artificial Heart (SynCardia-TAH) is a reliable bridge-to-transplant solution for patients with end-stage biventricular heart failure. Ischemic strokes affect about 10% of patients with a SynCardia-TAH. We report for the first time in the literature two successful thrombectomies to treat the acute phase of ischemic stroke in two patients treated with a SynCardia-TAH in the bridge-to-transplant (BTT). CASE REPORT: We follow two patients with circulatory support from a SynCardia-TAH in the bridge-to-transplant for terminal biventricular cardiac failure with ischemic stroke during the support period. An early in-hospital diagnosis enables the completion of a mechanical thrombectomy within the first 6 h of the onset of symptoms. There was no intracranial hemorrhagic complication during or after the procedure and the patients fully recovered from neurological deficits, allowing a successful heart transplant. CONCLUSION: This case report describes the possibility of treating ischemic strokes under a SynCardia-TAH by mechanical thrombectomy following the same recommendations as for the general population with excellent results and without any hemorrhagic complication during or after the procedure.

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BACKGROUND: Intravenous (IV) milrinone, in combination with induced hypertension, has been proposed as a treatment option for cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, data on its safety and efficacy are scarce. METHODS: This was a controlled observational study conducted in an academic hospital with prospectively and retrospectively collected data. Consecutive patients with cerebral vasospasm following aSAH and treated with both IV milrinone (0.5 µg/kg/min-1, as part of a strict protocol) and induced hypertension were compared with a historical control group receiving hypertension alone. Multivariable analyses aimed at minimizing potential biases. We assessed (1) 6-month functional disability (defined as a score between 2 and 6 on the modified Rankin Scale) and vasospasm-related brain infarction, (2) the rate of first-line or rescue endovascular angioplasty for vasospasm, and (3) immediate tolerance to IV milrinone. RESULTS: Ninety-four patients were included (41 and 53 in the IV milrinone and the control group, respectively). IV milrinone infusion was independently associated with a lower likelihood of 6-month functional disability (adjusted odds ratio [aOR] = 0.28, 95% confidence interval [CI] = 0.10-0.77]) and vasospasm-related brain infarction (aOR = 0.19, 95% CI 0.04-0.94). Endovascular angioplasty was less frequent in the IV milrinone group (6 [15%] vs. 28 [53%] patients, p = 0.0001, aOR = 0.12, 95% CI 0.04-0.38). IV milrinone (median duration of infusion, 5 [2-8] days) was prematurely discontinued owing to poor tolerance in 12 patients, mostly (n = 10) for "non/hardly-attained induced hypertension" (mean arterial blood pressure < 100 mmHg despite 1.5 µg/kg/min-1 of norepinephrine). However, this event was similarly observed in IV milrinone and control patients (n = 10 [24%] vs. n = 11 [21%], respectively, p = 0.68). IV milrinone was associated with a higher incidence of polyuria (IV milrinone patients had creatinine clearance of 191 [153-238] ml/min-1) and hyponatremia or hypokalemia, whereas arrhythmia, myocardial ischemia, and thrombocytopenia were infrequent. CONCLUSIONS: Despite its premature discontinuation in 29% of patients as a result of its poor tolerance, IV milrinone was associated with a lower rate of endovascular angioplasty and a positive impact on long-term neurological and radiological outcomes. These preliminary findings encourage the conduction of confirmatory randomized trials.

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OBJECTIVE: The objective of this study was to quantify the rate of provider participation beyond year 1 incentive in the Florida Medicaid Promoting Interoperability (PI) program, formerly the Electronic Health Record Incentive program, and identify the provider and practice characteristics associated with Meaningful Use attestations. METHODS AND MATERIALS: We conducted a retrospective cohort study using the 2011-2018 records from the PI program, Provider Participation Database. Bivariate associations between Meaningful Use and categorical and ordinal variables were tested using Chi-square and Mantel-Haenszel Chi-square, respectively, with results informing logistic regressions. Adjusted odds ratios and 95 % confidence intervals are reported. RESULTS: We found that 42.56 % of Florida Medicaid providers achieved Meaningful Use after receiving first-year incentives. Logistic regression showed that pediatricians represented the largest percentage of providers who achieved Meaningful Use (65.06 %) while dentists had the lowest Meaningful Use (7.78 %). We also found that certain geographic areas and various EHR vendors were associated with higher rates of providers Meaningful Use attestation. DISCUSSION: Although the PI program successfully influenced the adoption of a basic EHR system, low Meaningful Use attestations have inadvertently created a digital "advanced use" divide among providers who serve large numbers of Medicaid patients. This is concerning because advanced EHR functions are necessary precursors to address unmet socioeconomic needs to reduce health disparities. CONCLUSION: Florida has distributed over $100 million to Medicaid providers who ultimately did not achieve Meaningful Use after collecting their first-year incentive. Policy interventions that can promote advanced EHR use functions are necessary to optimize technology in low-resourced practice settings where the potential benefits are greater.

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Porous shape-persistent organic cages have become the object of interest in recent years because they are soluble and thus processable from solution. A variety of cages can be achieved by applying dynamic covalent chemistry (DCC), but they are less chemically stable. Here the transformation of a salicylimine cage into a quinoline cage by a twelve-fold Povarov reaction as the key step is described. Besides the chemical stability of the cage over a broad pH regime, it shows a unique absorption and emission depending on acid concentration. Furthermore, thin films for the vapor detection of acids were investigated, showing color switches from pale-yellow to red, and characteristic emission profiles.

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INTRODUCTION: To examine the relationship between chronic health conditions and out-of-pocket costs (OOPC) and medical debt. METHODS: Secondary data from the 2013 Panel Study of Income Dynamics (PSID) was used. Households whose head of household and spouse (for married households) were 18 to 64 years old were included. RESULTS: Households with 1 to 3 chronic conditions had higher odds of having any OOPC compared to households with no chronic conditions (AOR 1.74, 95% CI 1.39, 2.17) (p < .01). Households with 1 to 3 and 4 or more chronic health conditions were associated with higher odds of having any medical debt (AOR 2.24, 95% CI 1.75 to 2.87; AOR 5.04, 95% CI 3.04 to 8.34) compared to those with no chronic conditions (p < 0.01). Similarly, 1 to 3 and 4 or more chronic health conditions was associated with higher amounts of OOPC (Exponentiated Coefficient 1.18, 95% CI 1.03 to 1.36; Exponentiated Coefficient 1.56, 95% CI 1.17 to 2.07) and medical debt (Exponentiated Coefficient 1.69, 95% CI 1.23 to 2.34; Exponentiated Coefficient 2.73, 95% CI 1.19 to 6.25) compared to households with no chronic conditions (p < 0.05). CONCLUSIONS: Findings from this study show that the presence of chronic health conditions impose a large financial burden on some households.

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INTRODUCTION: Studies comparing endovascular stroke treatment using mechanical thrombectomy (MT) with or without prior IV tissue plasminogen activator (tPa) have included only 30% of internal carotid artery terminus occlusions (ICA-O), a known predictor of recanalization failure with IV tPa. OBJECTIVE: To carry out a retrospective multicenter analysis of prospectively collected data of consecutive patients to investigate the impact of intravenous thrombolysis on ICA-O by comparing patients treated with MT alone or bridging therapy (BT). MATERIAL AND METHODS: Patients with ICA-O treated with MT alone or BT were retrospectively examined and compared. Demographic data, vascular risk factors, treatment modalities, complications, technical and clinical outcomes were recorded. A propensity score (PS) analysis was used to compare modified Rankin Scale (mRS) score at 3 months and intracerebral hemorrhage (ICH) between groups. RESULTS: 141 consecutive patients (60% BT/40% MT) were included between January 2014 and June 2016. Baseline characteristics did not differ between the groups. There was no significant difference in the rate of Thrombolysis in Cerebral Infarction 2b/3, distal emboli, and median number of passes between the groups. There was a significant difference between BT and MT groups in the median time between imaging and groin puncture (median 97 min vs 75, p=0.007), the rate of ICH (44% vs 27%, p=0.05), but not for symptomatic ICH (18% vs 13%, p=0.49). With PS, there was a trend towards a higher rate of ICH (OR=2.3, 95% CI 0.9 to 5.9, p=0.09) in the BT group compared with the MT alone group, with no difference in mRS score ≤2 at 3 months (OR=1.6, 95% CI 0.7 to 3.7, p=0.29). CONCLUSION: There was no significant difference in clinical outcomes between patients receiving bridging therapy versus direct thrombectomy. Bridging therapy delayed time to groin puncture and increased ICH rate.

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BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8+ T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8+ T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8+ T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8+ T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8+ T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8+ T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8+ T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8+ T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8+ T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8+ T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease.

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Recently, a tetraphenyladamantane octamethylether was shown to encapsulate a wide range of small molecules in its crystals. Uptake and release from the liquid phase were demonstrated, and crystalline inclusion complexes were prepared that act as formulation for obnoxious reagents. However, fewer than two equivalents of guest molecules were found within the crystal structures. Here we report the synthesis of 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO) and twelve X-ray crystal structures that contain up to 3.5 equivalents of guest molecules. After crystallization and drying, TEO gives a material that absorbs 30 wt % of p-xylene reversibly through the gas phase, and releases it again at 55 °C, suggesting that it may be used for the capture and release of aromatic hydrocarbons.

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Medicare spending is projected to increase over the next decade, including for substance use disorders (SUD). Our objective was to determine whether SUDs are associated with higher six-year Medicare costs (1999-2004) among participants in the Baltimore Epidemiologic Catchment Area (ECA) Study. Medicare claims data for the years 1999-2004 from the Centers for Medicare and Medicaid Services were linked to four waves of data from the Baltimore ECA cohort collected between 1981 and 2005 (n=566). A generalized linear model with a log link and gamma distribution was used to examine direct Medicare costs associated with SUD status. Medicare recipients with no history of SUD had mean six-year costs of $42,576. Those with a history of SUD based on both Baltimore ECA and Medicare data, or based on Medicare claims data alone, had significantly higher costs ($98,754 and $64,876, respectively). A history of SUD based solely on Baltimore ECA data alone had lower average costs ($25,491). Findings indicate that Medicare costs differ by source of SUD diagnosis when comparing treatment versus survey data. This may have future implications for projecting Medicare costs among SUD individuals as healthcare coverage expands under the Affordable Care Act.

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Antigen-specific effector CD8+ T cells play a critical role in controlling hepatic infections, such as the one caused by hepatitis B virus (HBV). We review here recent results where we coupled advanced dynamic imaging with dedicated mouse models of HBV pathogenesis to show that circulating effector CD8+ T cells aimed at viral clearance initially arrest in liver sinusoids by preferentially docking onto platelets that have previously adhered to liver sinusoids. Upon detachment from platelets, effector CD8+ T cells crawl within the sinusoids irrespective of bloodstream direction, and probe underlying hepatocytes for the presence of antigen by extending filopodia-like protrusions through the sinusoidal fenestrae. Effector CD8+ T cells recognize hepatocellular antigen and perform effector functions (i.e., IFN-γ production and hepatocyte killing) while still in the intravascular space. They later extravasate in the parenchyma. Finally, we provide our perspective on how, in the next few years, intravital microscopy might shed new light on yet unresolved issues with particular regard to identifying the determinants of hepatic effector CD8+ T cell trafficking, antigen recognition and effector functions during hepatocellular carcinoma and understanding the mechanisms whereby intrahepatic T cell priming induces functionally defective T cell responses. A better understanding of how adaptive immunity mediates pathogen clearance and tumor elimination may lead to improved vaccination and treatment strategies for immunotherapy of infectious diseases and cancer.

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T cells play critical roles in controlling hepatotropic viral infections and liver tumors. The protective capacity of these cells is mediated by antigen-experienced effector cells and depends on their ability to migrate to and traffic within the liver, recognize pathogen- or tumor-derived antigens, get activated and deploy effector functions.While some of the rules that characterize T cell behavior in the healthy and cancerous antigen-expressing liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of T cell interactions with different kinds of liver cells at the single-cell level. Here, we describe in detail an intravital microscopy technique that allows the analysis of T cell dynamic behavior in the liver of anesthetized mice at high spatial and temporal resolution. A detailed understanding of the spatiotemporal dynamics of T cells within the liver is important for the rational design of targeted immunotherapeutic approaches for chronic liver infections and tumors.

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BACKGROUND: Many persons with depressive disorder are not treated and associated costs are not recorded. AIMS OF THE STUDY: To determine whether major depressive disorder (MDD) is associated with higher medical cost among Medicare recipients. METHODS: Four waves of the Baltimore-Epidemiologic Catchment Area (Baltimore ECA) Study conducted between 1981 and 2004 were linked to Medicare claims data for the years 1999 to 2004 from the Centers for Medicare and Medicaid Services (CMS). Generalized linear models specified with a gamma distribution and log link function were used to examine direct medical care costs associated with MDD. RESULTS: Medicare recipients with no history of MDD in either the ECA or CMS data had mean six-year medical costs of US $40,670, compared to $87,445 for Medicare recipients with MDD as recorded in CMS data and $43,583 for those with MDD as recorded in Baltimore-ECA data. Multivariable regressions found that compared to Medicare recipients with no history of depression, those with depression identified in the CMS data had significantly higher medical costs; about 1.87 times (95% confidence interval (CI) 1.32 to 2.67) higher. Medicare recipients with a history of depression identified in the ECA data were no more likely to have higher costs than were Medicare recipients with no history of depression (relative ratio 1.33, 95% CI 0.87 to 2.02). DISCUSSION: Medicare recipients with a history of depression identified in claims data had significantly higher medical costs than recipients with no history of depression. However, no significant differences were found between Medicare recipients with depression in the community-based Baltimore ECA data and those with no history of depression. The results show that the source of diagnosis, in treatment versus survey data, produces differences in results as regards costs. LIMITATIONS: This study involved only Medicare recipients with claims data over the six years 1999 to 2004. Many of the ECA respondents were too young to qualify for Medicare. IMPLICATIONS FOR HEALTH POLICY: Depressive disorder involves substantial medical care costs. The findings provide information on the economic burden of depression, an important but often omitted dimension and perspective of the burden of mental illnesses.

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