Impact of Initiating Insulin Glargine Disposable Pen Versus Vial/Syringe on Real-World Glycemic Outcomes and Persistence Among Patients with Type 2 Diabetes Mellitus in a Large Managed Care Plan: A Claims Database Analysis

Background: Diabetes accounts for almost 15% of all direct healthcare expenditures. Managed care organizations try to reduce costs and improve patient outcomes. Increasing patient persistence with antidiabetes treatment could help achieve these goals. Subjects and Methods: A retrospective study was conducted using the Optum Research Database (Optum, Eden Prairie, MN) to analyze clinical and economic outcomes associated with initiation of insulin glargine via a disposable pen (GLA-P) or vial and syringe (GLA-V) among adult, insulin-naive patients with type 2 diabetes mellitus (T2DM). Propensity-matched patient cohorts were assessed for persistence with insulin therapy, glycated hemoglobin (A1C), hypoglycemic events (based on diagnosis codes), and healthcare costs (total paid amount of adjudicated claims) after follow-up at 1 year. Results: In 1,308 matched patients, persistence was significantly higher (P=0.011) and longer (P=0.001) with GLA-P. Follow-up A1C values were significantly lower (P=0.038), and decreases in A1C from baseline significantly larger (P=0.043), in GLA-P than in GLA-V. Significantly fewer hypoglycemic events (P=0.042) were experienced, and a lower rate of diabetes-related inpatient admissions (P=0.008) was reported in GLA-P than GLA-V. Despite higher study drug costs with GLA-P than GLA-V, all-cause and diabetes-related healthcare costs were similar. Conclusions: In insulin-naive patients with T2DM, initiation of insulin glargine using the disposable pen rather than the vial and syringe is associated with higher persistence, better A1C control, and lower rates of hypoglycemia. The higher study drug costs associated with pen use do not increase total all-cause or diabetes-related healthcare costs. This may help treatment selection for patients with T2DM in a managed care setting.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140354/1/dia.2013.0312.pd

Renormalization of Tamm-Dancoff Integral Equations

During the last few years, interest has arisen in using light-front Tamm-Dancoff field theory to describe relativistic bound states for theories such as QCD. Unfortunately, difficult renormalization problems stand in the way. We introduce a general, non-perturbative approach to renormalization that is well suited for the ultraviolet and, presumably, the infrared divergences found in these systems. We reexpress the renormalization problem in terms of a set of coupled inhomogeneous integral equations, the ``counterterm equation.'' The solution of this equation provides a kernel for the Tamm-Dancoff integral equations which generates states that are independent of any cutoffs. We also introduce a Rayleigh-Ritz approach to numerical solution of the counterterm equation. Using our approach to renormalization, we examine several ultraviolet divergent models. Finally, we use the Rayleigh-Ritz approach to find the counterterms in terms of allowed operators of a theory.Comment: 19 pages, OHSTPY-HEP-T-92-01

Spontaneous symmetry breaking of (1+1)-dimensional ϕ4\bf \phi^4 theory in light-front field theory (III)

We investigate (1+1)-dimensional $\phi^4$ field theory in the symmetric and broken phases using discrete light-front quantization. We calculate the perturbative solution of the zero-mode constraint equation for both the symmetric and broken phases and show that standard renormalization of the theory yields finite results. We study the perturbative zero-mode contribution to two diagrams and show that the light-front formulation gives the same result as the equal-time formulation. In the broken phase of the theory, we obtain the nonperturbative solutions of the constraint equation and confirm our previous speculation that the critical coupling is logarithmically divergent. We discuss the renormalization of this divergence but are not able to find a satisfactory nonperturbative technique. Finally we investigate properties that are insensitive to this divergence, calculate the critical exponent of the theory, and find agreement with mean field theory as expected.Comment: 21 pages; OHSTPY-HEP-TH-94-014 and DOE/ER/01545-6

Spontaneous Symmetry Breaking of phi4(1+1) in Light Front Field Theory

We study spontaneous symmetry breaking in phi^4_(1+1) using the light-front formulation of the field theory. Since the physical vacuum is always the same as the perturbative vacuum in light-front field theory the fields must develop a vacuum expectation value through the zero-mode components of the field. We solve the nonlinear operator equation for the zero-mode in the one-mode approximation. We find that spontaneous symmetry breaking occurs at lambda_critical = 4 pi(3+sqrt 3), which is consistent with the value lambda_critical = 54.27 obtained in the equal time theory. We calculate the value of the vacuum expectation value as a function of the coupling constant in the broken phase both numerically and analytically using the delta expansion. We find two equivalent broken phases. Finally we show that the energy levels of the system have the expected behavior within the broken phase.Comment: 17 pages, OHSTPY-HEP-TH-92-02

Tube Model for Light-Front QCD

We propose the tube model as a first step in solving the bound state problem in light-front QCD. In this approach we neglect transverse variations of the fields, producing a model with 1+1 dimensional dynamics. We then solve the two, three, and four particle sectors of the model for the case of pure glue SU(3). We study convergence to the continuum limit and various properties of the spectrum.Comment: 29 page

Spontaneous symmetry breaking of (1+1)-dimensional ϕ4\phi^4 theory in light-front field theory (II)

We discuss spontaneous symmetry breaking of (1+1)-dimensional $\phi^4$ theory in light-front field theory using a Tamm-Dancoff truncation. We show that, even though light-front field theory has a simple vacuum state which is an eigenstate of the full Hamiltonian, the field can develop a nonzero vacuum expectation value. This occurs because the zero mode of the field must satisfy an operator valued constraint equation. In the context of (1+1)-dimensional $\phi^4$ theory we present solutions to the constraint equation using a Tamm-Dancoff truncation to a finite number of particles and modes. We study the behavior of the zero mode as a function of coupling and Fock space truncation. The zero mode introduces new interactions into the Hamiltonian which breaks the $Z_2$ symmetry of the theory when the coupling is stronger than the critical coupling.Comment: 25 page

Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis

Although direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug-drug interactions. Here, we report adherence, efficacy, safety and patient-reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1-6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co-medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post-treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2-98.5) and 97.5% (1689/1733; 95% CI = 96.7-98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co-medication classes. Overall, most adverse events (AEs) were mild-to-moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well-tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders

Mean sojourn time, overdiagnosis, and reduction in advanced stage prostate cancer due to screening with PSA: implications of sojourn time on screening

This study aimed to assess the mean sojourn time (MST) of prostate cancer, to estimate the probability of overdiagnosis, and to predict the potential reduction in advanced stage disease due to screening with PSA. The MST of prostate cancer was derived from detection rates at PSA prevalence testing in 43 842 men, aged 50–69 years, as part of the ProtecT study, from the incidence of non-screen-detected cases obtained from the English population-based cancer registry database, and from PSA sensitivity obtained from the medical literature. The relative reduction in advanced stage disease was derived from the expected and observed incidences of advanced stage prostate cancer. The age-specific MST for men aged 50–59 and 60–69 years were 11.3 and 12.6 years, respectively. Overdiagnosis estimates increased with age; 10–31% of the PSA-detected cases were estimated to be overdiagnosed. An interscreening interval of 2 years was predicted to result in 37 and 63% reduction in advanced stage disease in men 65–69 and 50–54 years, respectively. If the overdiagnosed cases were excluded, the estimated reductions were 9 and 54%, respectively. Thus, the benefit of screening in reducing advanced stage disease is limited by overdiagnosis, which is greater in older men