Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study

Objective To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs—etanercept, mometasone, and tegaserod

Black Hole Geometries in Noncommutative String Theory

We obtain a generalized Schwarzschild (GS-) and a generalized Reissner-Nordstrom (GRN-) black hole geometries in (3+1)-dimensions, in a noncommutative string theory. In particular, we consider an effective theory of gravity on a curved $D_3$-brane in presence of an electromagnetic (EM-) field. Two different length scales, inherent in its noncommutative counter-part, are exploited to obtain a theory of effective gravity coupled to an U(1) noncommutative gauge theory to all orders in $\Theta$. It is shown that the GRN-black hole geometry, in the Planckian regime, reduces to the GS-black hole. However in the classical regime it may be seen to govern both Reissner-Nordstrom and Schwarzschild geometries independently. The emerging notion of 2D black holes evident in the frame-work are analyzed. It is argued that the $D$-string in the theory may be described by the near horizon 2D black hole geometry, in the gravity decoupling limit. Finally, our analysis explains the nature of the effective force derived from the nonlinear EM-field and accounts for the Hawking radiation phenomenon in the formalism.Comment: 30 pages, 2 figure

The risk of fragility fractures in new users of dipeptidyl peptidase-4 inhibitors compared to sulfonylureas and other anti-diabetic drugs: A cohort study

Published by Elsevier via http://dx.doi.org/10.1016/j.ces.2017.10.035 © 2017. This final version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Aims Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic “fragility fractures” (upper extremity, hip, spine).Methods The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016. The primary aim was to compare new-users of DPP-4 inhibitors versus new-users of sulfonylureas (SU). The association between DPP-4 inhibitors and incident fractures was estimated using Cox proportional hazards models. Deciles of high-dimensional propensity scores and other anti-diabetic drugs were used as covariates. Results We identified 7993 and 26,636 new-users of DPP-4 inhibitors and SUs, respectively. At cohort entry, the mean age was 58.8, 40% were female, mean diabetes duration was 1.3 years, and 42% had A1c > 9%. Over 9 years (mean follow-up = 1.2 years), the incident rate of fragility fractures was lower among DPP-4 versus SU users (3.0/1000 vs. 5.2/1000 person-years; P-value = 0.007). After adjustment, there was no statistically significant difference in fracture risk (hazard ratio adjusted, aHR = 0.80, 95%CI 0.51–1.24; P-value = 0.3125). In a secondary analysis, DPP-4 inhibitors were not associated with a difference in fracture risk compared to insulin (aHR = 0.91, 95%CI 0.40–2.09); however were associated with a lower fracture risk versus thiazolidinediones (aHR = 0.47, 95%CI 0.26–0.83). Sensitivity analyses supported findings. Conclusions DPP-4 inhibitors are not associated with an increased risk of fragility fractures compared with SUs or insulin; however, are associated with a lower risk versus thiazolidinediones.JMG is supported as a New Investigator Award from the Canadian Institute of Health Research (CIHR) and a Clinician Scientist Award from Diabetes Canada. JRD is supported by a CIHR fellowship in drug safety and effectiveness. SRM holds the Endowed Chair in Patient Health Management supported by the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences at the University of Alberta, Edmonton, Alberta, Canada

Health-related quality of life deficits associated with varying degrees of disease severity in type 2 diabetes

BACKGROUND: Diabetes is a chronic medical condition accompanied by a considerable health-related quality of life (HRQL) burden. The purpose of this analysis was to use generic measures of HRQL to describe HRQL deficits associated with varying degrees of severity of type 2 diabetes. METHODS: The RAND-12 physical and mental health composites (PHC and MHC, respectively) and Health Utilities Index Mark 3 (HUI3) were self-completed by 372 subjects enrolled in a prospective, controlled study of an intervention to improve care for individuals with type 2 diabetes in rural communities. Analysis of covariance was used to assess differences in HRQL according to disease severity and control of blood glucose. Disease severity was defined in terms of treatment intensity, emergency room visits and absenteeism from work specifically attributable to diabetes. To control for potential confounding, the analysis was adjusted for important sociodemographic and clinical characteristics. RESULTS: The PHC and MHC were significantly lower for individuals treated with insulin as compared to diet alone (PHC: 41.01 vs 45.11, MHC: 43.23 vs 47.00, p < 0.05). Individuals treated with insulin had lower scores on the vision, emotion and pain attributes of the HUI3 than individuals managed with oral medication or diet. The PHC, MHC, pain attribute and overall score on the HUI3 captured substantial decrements in HRQL associated with absenteeism from work due to diabetes, while the burden associated with emergency room utilization for diabetes was seen in the PHC and HUI3 pain attribute. CONCLUSIONS: We concluded that generic measures of HRQL captured deficits associated with more severe disease in type 2 diabetes

Profitability, productivity and price recovery patterns in the U.S. telecommunications industry

We undertake a study where we examine changes in the profitability, productivity and price recovery of firms in the U.S. telecommunications industry over a sixteen-year period. We assess the performance of thirty-three major companies in the local-exchange sector over six time periods 1975, 1978, 1981, 1984, 1987 and 1990, using a performance analysis model which disaggregates the profitability measure into two components: productivity and price recovery. We demonstrate the computation of performance using this technique. Our study indicates that the opening up of markets has had a significant impact on different dimensions of performance in the telecommunications industry, also validating a number of theoretical assumptions about the impact that industry changes are expected to have on firms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43575/1/11151_2004_Article_BF00163594.pd

MTX-cIBR Conjugate for Targeting Methotrexate to Leukocytes: Conjugate Stability and in vivo Efficacy in Suppressing Rheumatoid Arthritis

Methotrexate (MTX) has been used to treat rheumatoid arthritis at low doses and leukemia at high doses; however, this drug can produce severe side effects. Our hypothesis is that MTX side effects can be attenuated by directing the drug to the target cells (i.e., leukocytes) using cIBR peptide. To test this hypothesis, MTX was conjugated to the N-terminus of cIBR peptide to give MTX-cIBR conjugate. MTX-cIBR (5.0 mg/kg) suppressed joint arthritis in adjuvant arthritis rats and prevented periarticular inflammation and bone resorption of the limb joints. In vitro, the toxicity of MTX-cIBR peptide against Molt-3 T cells was inhibited by anti-LFA-1 antibody and cIBR peptide in a concentration-dependent manner, suggesting that the uptake of MTX-cIBR was partially mediated by LFA-1. Chemical stability studies indicated that MTX-cIBR was most stable at pH 6.0. The MTX portion of MTX-cIBR was unstable under acidic conditions whereas the cIBR portion was unstable under basic conditions. In biological media, MTX-cIBR had short half-lives in rat plasma (44 min) and homogenized rat heart tissue (38 min). This low plasma stability may contribute to the low in vivo efficacy of MTX-cIBR; therefore, there is a need to design a more stable conjugate to improve the in vivo efficacy

Group versus individual academic detailing to improve the use of antihypertensive medications in primary care: a cluster-randomized controlled trial

Purpose To compare group versus individual academic detailing to increase diuretic or β-blocker use in hypertension. Methods We conducted a cluster-randomized controlled trial in a large health maintenance organization. Subjects (N=9820) were patients with newly treated hypertension in the year preceding the intervention (N=3692), the 9 months following the intervention (N=3556), and the second year following intervention (N=2572). We randomly allocated 3 practice sites to group detailing (N=227 prescribers), 3 to individual detailing (N=235 prescribers), and 3 to usual care (N=319 prescribers). Individual detailing entailed a physician-educator meeting individually with clinicians to address barriers to prescribing guideline-recommended medications. The group detailing intervention incorporated the same social marketing principles in small groups of clinicians. Results In the first year following the intervention, the rates of diuretic or β-blocker use increased by 13.2% in the group detailing practices, 12.5% in the individual detailing practices, and 6.2% in the usual care practices. As compared with usual care practices, diuretic or β-blocker use was more likely in group detailing practices (adjusted odds ratio (OR), 1.40; 95% confidence interval (CI), 1.11 – 1.76) and individual detailing practices (adjusted OR, 1.30; 95% CI, 0.95 – 1.79). Neither intervention affected blood pressure control. Two years following this single-visit intervention, there was still a trend suggesting a persistent effect of individual (OR, 1.22; 95% CI, 0.92 – 1.62), but not group, detailing (OR, 1.06; 95% CI, 0.80 – 1.39), as compared with usual care. Conclusion Both group and individual academic detailing improved antihypertensive prescribing over and above usual care but may require reinforcement to sustain improvements

Effect of pay for performance on the management and outcomes of hypertension in the United Kingdom: interrupted time series study

Objective To assess the impact of a pay for performance incentive on quality of care and outcomes among UK patients with hypertension in primary care