Identification and cost of adverse events in metastatic breast cancer in taxane and capecitabine based regimens.

PurposeWe sought to compare the economic impact of treatment-related adverse events (AEs) in patients with metastatic breast cancer (mBC) using taxane- or capecitabine-based treatment regimens as either first- or second-line (FL or SL) therapy in the US.MethodsWe used healthcare claims data from the Truven Health Analytics MarketScan® Commercial Databases to conduct a retrospective cohort study comparing the economic impact of AEs amongst taxane- and capecitabine-treated mBC patients in the US. We selected women diagnosed with mBC between 2008-2010 who received a taxane or capecitabine as first- or second-line (FL or SL) chemotherapy. Costs related to hospitalization, outpatient services, emergency department visits, chemotherapy and other medications were tabulated and combined to determine total healthcare costs. The incremental monthly costs associated with the presence of AEs compared to no AEs were estimated using generalized linear models, controlling for age and Charlson Comorbidity Index.ResultsWe identified 15,443 mBC patients meeting inclusion criteria. Adjusted total monthly costs were significantly higher in those who experienced AEs than in those without AEs in both lines of treatment (FL incremental cost: taxanes $1,142, capecitabine$1,817; SL incremental cost: taxanes $1,448, capecitabine$4,437). Total costs increased with the number of AEs and were primarily driven by increased hospitalization amongst those with AEs.ConclusionsAdverse events in taxane- or capecitabine-treated mBC patients are associated with significant increases in costs. Selecting treatment options associated with fewer AEs may reduce costs and improve outcomes in these patients

Professional Organizations and Healthcare Industry Support: Ethical Conflict?

A good deal of attention has been recently focused on the presumed advertising excesses of the healthcare industry in its promotion techniques to healthcare professionals, whether through offering gratuities such as gifts, honoraria, or travel support2-6 or through deception. Two basic concerns have been expressed: Does the acceptance of gratuities bias the recipient, tainting his or her responsibilities as the patient's agent? Does acceptance of the gratuity by the healthcare professional contribute to the high cost of healthcare products? The California Society of Hospital Pharmacists was recently asked by its members to formulate a policy for an appropriate relationship between the Society and the healthcare industry, addressing these concerns. In formulating its policy, it became clear that the Society depended on healthcare industry support, gathered through journal advertising, fees for booths at its various educational events, and grants for speaker

The Decline of Coordinated Effects Enforcement and How to Reverse It

Opposition to anticompetitive coordination once animated merger policy. But evidence now suggests that coordinated effects challenges are disfavored and rarely pursued. This stark change in enforcement is both puzzling and troubling. Coordinated effects challenges are antitrust law’s best and often only opportunity to combat anticompetitive coordination in concentrated markets. Why are coordinated effects theories not being vigorously pursued? This Article exposes the decline in coordinated effects enforcement and the threat it poses to the maintenance of competitive markets. It does so in three steps. First, it surfaces the special role that coordinated effects enforcement plays in the antitrust framework. Second, it documents the decline in coordinated effects enforcement using multiple data sources. Third, it traces the causes of this decline to discrete changes in antitrust law and enforcement policy. After exposing the logical and economic errors in these changes, this Article proposes steps to restore coordinated effects enforcement to appropriate prominence

Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation

Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase in the numbers of midbrain dopaminergic neurons, in conditional Zeb2 (Nestin-Cre based) knockout mice. Therefore, these findings reveal a new mechanism for the regulation of midbrain dopaminergic axon growth during central nervous system development

Planet Sensitivity from Combined Ground- and Space-based Microlensing Observations

To move one step forward toward a Galactic distribution of planets, we present the first planet sensitivity analysis for microlensing events with simultaneous observations from space and the ground. We present this analysis for two such events, OGLE-2014-BLG-0939 and OGLE-2014-BLG-0124, which both show substantial planet sensitivity even though neither of them reached high magnification. This suggests that an ensemble of low to moderate magnification events can also yield significant planet sensitivity and therefore probability to detect planets. The implications of our results to the ongoing and future space-based microlensing experiments to measure the Galactic distribution of planets are discussed.Comment: 10 pages, 5 figures, 1 table; ApJ in pres

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

SpitzerSpitzer Parallax of OGLE-2018-BLG-0596: A Low-mass-ratio Planet around an M-dwarf

We report the discovery of a $Spitzer$ microlensing planet OGLE-2018-BLG-0596Lb, with preferred planet-host mass ratio $q \sim 2\times10^{-4}$. The planetary signal, which is characterized by a short $(\sim 1~{\rm day})$ "bump" on the rising side of the lensing light curve, was densely covered by ground-based surveys. We find that the signal can be explained by a bright source that fully envelops the planetary caustic, i.e., a "Hollywood" geometry. Combined with the source proper motion measured from $Gaia$, the $Spitzer$ satellite parallax measurement makes it possible to precisely constrain the lens physical parameters. The preferred solution, in which the planet perturbs the minor image due to lensing by the host, yields a Uranus-mass planet with a mass of $M_{\rm p} = 13.9\pm1.6~M_{\oplus}$ orbiting a mid M-dwarf with a mass of $M_{\rm h} = 0.23\pm0.03~M_{\odot}$. There is also a second possible solution that is substantially disfavored but cannot be ruled out, for which the planet perturbs the major image. The latter solution yields $M_{\rm p} = 1.2\pm0.2~M_{\oplus}$ and $M_{\rm h} = 0.15\pm0.02~M_{\odot}$. By combining the microlensing and $Gaia$ data together with a Galactic model, we find in either case that the lens lies on the near side of the Galactic bulge at a distance $D_{\rm L} \sim 6\pm1~{\rm kpc}$. Future adaptive optics observations may decisively resolve the major image/minor image degeneracy.Comment: 34 pages, 8 figures, Submitted to AAS journa

Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone

<p>Abstract</p> <p>Background</p> <p>Poor control of type 2 diabetes results in substantial long-term consequences. Studies of new diabetes treatments are rarely designed to assess mortality, complication rates and costs. We sought to estimate the long-term consequences of liraglutide and rosiglitazone both added to glimepiride.</p> <p>Methods</p> <p>To estimate long-term clinical and economic consequences, we used the CORE diabetes model, a validated cohort model that uses epidemiologic data from long-term clinical trials to simulate morbidity, mortality and costs of diabetes. Clinical data were extracted from the LEAD-1 trial evaluating two doses (1.2 mg and 1.8 mg) of a once daily GLP-1 analog liraglutide, or rosiglitazone 4 mg, on a background of glimepiride in type 2 diabetes. CORE was calibrated to the LEAD-1 baseline patient characteristics. Survival, cumulative incidence of cardiovascular, ocular and renal events and healthcare costs were estimated over three periods: 10, 20 and 30 years.</p> <p>Results</p> <p>In a hypothetical cohort of 5000 patients per treatment followed for 30 years, liraglutide 1.2 mg and 1.8 mg had higher survival rates compared to the group treated with rosiglitazone (15.0% and 16.0% vs. 12.6% after 30 years), and fewer cardiovascular, renal, and ocular events. Cardiovascular death rates after 30 years were 69.7%, 68.4% and 72.5%, for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively. First and recurrent amputations were lower in the rosiglitazone group, probably due to a 'survival paradox' in the liraglutide arms (number of events: 565, 529, and 507, respectively). Overall cumulative costs per patient, were lower in both liraglutide groups compared to rosiglitazone (US$38,963,$39,239, and $40,401 for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively), mainly driven by the costs of cardiovascular events in all groups.</p> <p>Conclusion</p> <p>Using data from LEAD-1 and epidemiologic evidence from the CORE diabetes model, projected rates of mortality, diabetes complications and healthcare costs over the long term favor liraglutide plus glimepiride over rosiglitazone plus glimepiride.</p> <p>Trial registration</p> <p>LEAD-1 NCT00318422; LEAD-2 NCT00318461; LEAD-3 NCT 00294723; LEAD-4 NCT00333151; LEAD-5 NCT00331851; LEAD-6 NCT00518882.</p