Persistence on prostaglandin ocular hypotensive therapy: an assessment using medication possession and days covered on therapy

BACKGROUND:Prior research has demonstrated that medication persistence (continued acquisition of therapy over time) is far from optimal among patients with glaucoma. The purpose of the present study was to evaluate persistence with prostaglandin analogs among glaucoma patients in the first therapy year using a modification of a previously published technique.METHODS:This retrospective analysis of medical and pharmacy claims database included treatment-naive patients dispensed bimatoprost, latanoprost, or travoprost between 1/1/04-12/31/04. "Index agent" was defined as the first agent filled; "index date" was defined as the fill date. Follow-up continued for 358 days. Persistence measures for first therapy year were: (1) whether last fill had sufficient days supply to achieve medication possession at year's end, and (2) number of days for which the index agent was available (days covered). Associations between index agent and medication possession (logistic regression) and days covered (linear regression) were evaluated. Models were adjusted for gender, age, and previous ocular hypertension diagnosis.RESULTS:7873 patients met inclusion criteria (bimatoprost, n = 1464; latanoprost, n = 4994; travoprost, n = 1415). Medication possession was 28% and days covered was 131 when using the unadjusted (pharmacy-reported) days supply estimates and rose to 47-48% and days covered to 228-236 days when days supply was imputed. Compared to latanoprost, odds of achieving medication possession at first year's end were 26-34% lower for bimatoprost and 34-36% lower for travoprost (p [less than or equal to] 0.001 for all comparisons). Days covered in the first year were 21-29 days lower for bimatoprost and 33-42 days lower for travoprost (p [less than or equal to] 0.001 for all comparisons). Failure to refill the index agent within the initial 90 days was a strong predictor of poor persistence. CONCLUSIONS:Persistence with ocular prostaglandin therapy remains a problem. Latanoprost users had greater odds of achieving medication possession and had more days covered during the first therapy year.The results of this study were presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, April 27 to May 1, 2008, in Fort Lauderdale, Florida, USA and at the International Society for Pharmacoeconomics and Outcomes Research 13th Annual International Meeting, May 3 to May 7, 2008, in Toronto, Canada. The research was supported by Pfizer Inc, New York, New York, USA. Assistance in styling the paper for journal submission was provided by Jane G. Murphy, PhD, of Zola Associates and was funded by Pfizer Inc, New York, New York, USA. Sonali Shah, BS Pharm, RPh, MPH provided the impetus and helpful support and advice for design of this study

On Glauber modes in Soft-Collinear Effective Theory

Gluon interactions involving spectator partons in collisions at hadronic machines are investigated. We find a class of examples in which a mode, called Glauber gluons, must be introduced to the effective theory for consistency.Comment: 19 pages, three figures. Uses JHEP3.cl

Next-to-eikonal corrections to soft gluon radiation: a diagrammatic approach

We consider the problem of soft gluon resummation for gauge theory amplitudes and cross sections, at next-to-eikonal order, using a Feynman diagram approach. At the amplitude level, we prove exponentiation for the set of factorizable contributions, and construct effective Feynman rules which can be used to compute next-to-eikonal emissions directly in the logarithm of the amplitude, finding agreement with earlier results obtained using path-integral methods. For cross sections, we also consider sub-eikonal corrections to the phase space for multiple soft-gluon emissions, which contribute to next-to-eikonal logarithms. To clarify the discussion, we examine a class of log(1 - x) terms in the Drell-Yan cross-section up to two loops. Our results are the first steps towards a systematic generalization of threshold resummations to next-to-leading power in the threshold expansion.Comment: 66 pages, 19 figure

Parton Fragmentation within an Identified Jet at NNLL

The fragmentation of a light parton i to a jet containing a light energetic hadron h, where the momentum fraction of this hadron as well as the invariant mass of the jet is measured, is described by "fragmenting jet functions". We calculate the one-loop matching coefficients J_{ij} that relate the fragmenting jet functions G_i^h to the standard, unpolarized fragmentation functions D_j^h for quark and gluon jets. We perform this calculation using various IR regulators and show explicitly how the IR divergences cancel in the matching. We derive the relationship between the coefficients J_{ij} and the quark and gluon jet functions. This provides a cross-check of our results. As an application we study the process e+ e- to X pi+ on the Upsilon(4S) resonance where we measure the momentum fraction of the pi+ and restrict to the dijet limit by imposing a cut on thrust T. In our analysis we sum the logarithms of tau=1-T in the cross section to next-to-next-to-leading-logarithmic accuracy (NNLL). We find that including contributions up to NNLL (or NLO) can have a large impact on extracting fragmentation functions from e+ e- to dijet + h.Comment: expanded introduction, typos fixed, journal versio

Non-global Structure of the O({\alpha}_s^2) Dijet Soft Function

High energy scattering processes involving jets generically involve matrix elements of light- like Wilson lines, known as soft functions. These describe the structure of soft contributions to observables and encode color and kinematic correlations between jets. We compute the dijet soft function to O({\alpha}_s^2) as a function of the two jet invariant masses, focusing on terms not determined by its renormalization group evolution that have a non-separable dependence on these masses. Our results include non-global single and double logarithms, and analytic results for the full set of non-logarithmic contributions as well. Using a recent result for the thrust constant, we present the complete O({\alpha}_s^2) soft function for dijet production in both position and momentum space.Comment: 55 pages, 8 figures. v2: extended discussion of double logs in the hard regime. v3: minor typos corrected, version published in JHEP. v4: typos in Eq. (3.33), (3.39), (3.43) corrected; this does not affect the main result, numerical results, or conclusion

Inhibition of cerebrovascular raf activation attenuates cerebral blood flow and prevents upregulation of contractile receptors after subarachnoid hemorrhage

<p>Abstract</p> <p>Background</p> <p>Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH.</p> <p>Results</p> <p>Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain from the development of late cerebral ischemia at 48 h. This is accompanied by reduced phosphorylation of ERK1/2 in cerebrovascular SMC. SAH per se enhances contractile responses to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and angiotensin II (Ang II), upregulates ET_B, 5-HT_1Band AT₁receptor mRNA and protein levels. Treatment with SB-386023-b given as late as at 6 h but not at 12 h after the SAH significantly decreased the receptor upregulation, the reduction in CBF and the neurology score.</p> <p>Conclusion</p> <p>These results provide evidence for a role of the ERK1/2 pathway in regulation of expression of cerebrovascular SMC receptors. It is suggested that raf inhibition may reduce late cerebral ischemia after SAH and provides a realistic time window for therapy.</p

Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring

INTRODUCTION: In adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting. METHOD: We used MAINTRAC(® )analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients. RESULTS: MAINTRAC(® )analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy. CONCLUSION: The response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring