Goodness-of-fit tests for the frailty distribution in proportional hazards models with shared frailty.

Frailty models account for the clustering present in grouped event time data. A proportional hazards model with shared frailties expresses the hazard for each subject. Often a one-parameter gamma distribution is assumed for the frailties. The choice of a particular frailty distribution is, most of the time, based on the availability of software, rather than on the way it fits the data. In this paper we construct formal goodness-of-fit tests to test for gamma frailties. We construct a new class of frailty models that extend the gamma frailty model by using certain polynomial expansions that are orthogonal with respect to the gamma density. For this extended family we obtain an explicit expression for the marginal likelihood of the data. The order selection test is based on finding the best fitting model in such a series of expanded models. A bootstrap is used to obtain p-values for the tests. Simulations and data examples illustrate the test's performance.Gamma distribution; Goodness-of-fit test; Frailty model; Order selection test; Orthogonal polynomial;

Patient-reported outcome assessment of inflammatory arthritis patient experience with intravenously administered biologic therapy

Objective: To evaluate patient perspectives regarding utilization of intravenous (IV) therapy for inflammatory arthritis (IA). Methods: This was a single-center, non-interventional, patient questionnaire-based study of adult IA patients currently receiving IV biologics. At a single visit, patients completed the questionnaire comprising 30 questions centered on their experience receiving an intravenously administered therapy to treat their IA. The questionnaire included questions on patient demographics, disease characteristics, and previous biologic treatment for IA (subcutaneous [SC] and IV). Patients rated their level of agreement with statements regarding satisfaction with current IV biologic therapy and potential advantages and disadvantages of IV biologic therapy using a 5-point Likert scale (1= strongly disagree, 5= strongly agree). Results: One hundred patients were enrolled and completed the survey; 66% were female and the mean age was 58 years. Before IV treatment, 97% of patients received information regarding therapy options. Ninety patients ranked their satisfaction with current IV therapy as 4 or 5. The proportion of patients with an “extremely favorable” perception of IV therapy increased from 33% to 71% following initiation of their current medication. Thirty-one patients had previously received SC therapies to treat their IA. Conclusion: These results demonstrated an overall favorable perception of IV therapy among this patient population. Patients previously treated with SC therapy also had a positive shift in the perception of IV therapy after initiating IV therapy. Patients’ perception and preference for treatment options should be highly considered by the treating physician during or as part of a shared decision-making process. © 2017 Gaylis et al

Clinical consequences of antibody formation, serum concentrations, and HLA-Cw6 status in psoriasis patients on Ustekinumab

Background: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. Methods: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for >16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or >64 of ustekinumab treatment. Results: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). Conclusions: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged

Specification testing

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Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Innovative public governance through cloud computing: Information privacy, business models and performance measurement challenges

Purpose: The purpose of this paper is to identify and analyze challenges and to discuss proposed solutions for innovative public governance through cloud computing. Innovative technologies, such as federation of services and cloud computing, can greatly contribute to the provision of e-government services, through scaleable and flexible systems. Furthermore, they can facilitate in reducing costs and overcoming public information segmentation. Nonetheless, when public agencies use these technologies, they encounter several associated organizational and technical changes, as well as significant challenges. Design/methodology/approach: We followed a multidisciplinary perspective (social, behavioral, business and technical) and conducted a conceptual analysis for analyzing the associated challenges. We conducted focus group interviews in two countries for evaluating the performance models that resulted from the conceptual analysis. Findings: This study identifies and analyzes several challenges that may emerge while adopting innovative technologies for public governance and e-government services. Furthermore, it presents suggested solutions deriving from the experience of designing a related platform for public governance, including issues of privacy requirements, proposed business models and key performance indicators for public services on cloud computing. Research limitations/implications: The challenges and solutions discussed are based on the experience gained by designing one platform. However, we rely on issues and challenges collected from four countries. Practical implications: The identification of challenges for innovative design of e-government services through a central portal in Europe and using service federation is expected to inform practitioners in different roles about significant changes across multiple levels that are implied and may accelerate the challenges' resolution. Originality/value: This is the first study that discusses from multiple perspectives and through empirical investigation the challenges to realize public governance through innovative technologies. The results emerge from an actual portal that will function at a European level. © Emerald Group Publishing Limited

Ab initio vibrational free energies including anharmonicity for multicomponent alloys

A density-functional-theory based approach to efficiently compute numerically exact vibrational free energies - including anharmonicity - for chemically complex multicomponent alloys is developed. It is based on a combination of thermodynamic integration and a machine-learning potential. We demonstrate the performance of the approach by computing the anharmonic free energy of the prototypical five-component VNbMoTaW refractory high entropy alloy

A comparison of short-term and long-term air pollution exposure associations with mortality in two cohorts in Scotland

Air pollution–mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales. We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure–mortality associations in cohort participants and with short-term exposure–mortality associations in the general population from which the cohorts were selected. We assessed short-to-medium–term exposure–mortality associations in the Renfrew–Paisley and Collaborative cohorts (using nested case–control data sets), and compared them with long-term exposure–mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium–term exposure–mortality associations in the general population (using time-series analyses). For the Renfrew–Paisley cohort (15,331 participants), BS exposure–mortality associations were observed in nested case–control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m3 increases in 3-day lag BS, respectively}. Exposure–mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: –0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m3 increases in 31-day BS in case–control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m3 increase in geometic mean BS for 1970–1979, in survival analysis]. After adjusting for individual-level exposure and potential confounders, short-term exposure–mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure–mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures

Understanding complexity: the curvilinear relationship between environmental performance and firm performance

The nature of the relationship between environmental performance (EP) and firm performance (FP) of corporations is a long standing and contentious issue in the literature. This study is intended to advance this debate by arguing for the existence of curvilinear relationship and empirically testing the same using survey data on UK manufacturing firms. FP is captured in terms of growth in sales and market share. Our results show evidence for a quadratic relationship—as firms improve their EP, they seem to achieve much higher levels of FP. These results are consistent with the resource-based view of a firm; as firms engage in EP activities, they are able to gain inimitable knowledge that helps in further learning to further improve performance. Based on our results, we suggest that new studies focus on strategies to extend the period of increasing returns and maximizing the benefits of the positive association between EP and FP