Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly

PURPOSE: Cushing’s disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia. METHODS: Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed. RESULTS: The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3–67.0 %) than in patients with CD treated with pasireotide SC (68.4–73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791–799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875–884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320–326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914–924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues. CONCLUSIONS: Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly. Hyperglycemic effects associated with pasireotide have a predictable pattern, can be managed with antidiabetic agents, and are reversible upon discontinuation

ERTS Applications in earthquake research and mineral exploration in California

Examples that ERTS imagery can be effectively utilized to identify, locate, and map faults which show geomorphic evidence of geologically recent breakage are presented. Several important faults not previously known have been identified. By plotting epicenters of historic earthquakes in parts of California, Sonora, Mexico, Arizona, and Nevada, we found that areas known for historic seismicity are often characterized by abundant evidence of recent fault and crustal movements. There are many examples of seismically quiet areas where outstanding evidence of recent fault movements is observed. One application is clear: ERTS-1 imagery could be effectively utilized to delineate areas susceptible to earthquake recurrence which, on the basis of seismic data alone, may be misleadingly considered safe. ERTS data can also be utilized in planning new sites in the geophysical network of fault movement monitoring and strain and tilt measurements

Matrix Description of Interacting Theories in Six Dimensions

We propose descriptions of interacting (2,0) supersymmetric theories without gravity in six dimensions in the infinite momentum frame. They are based on the large $N$ limit of quantum mechanics or 1+1 dimensional field theories on the moduli space of $N$ instantons in \IR^4.Comment: 10 pages, harvmac bi

Using the West Key Number System as a Data Collection and Coding Device for Empirical Legal Scholarship: Demonstrating the Method Via a Study of Contract Interpretation

Empirical research is an increasingly important type of legal scholarship. Such research generally requires the collection and coding of large quantities of data. These tasks pose critical challenges for legal scholars. Most crucially, they are often resource-intensive. The primary purpose of this article is to explain how researchers can use the West Key Number System to dramatically streamline the process of data collection and coding. The article accomplishes this, in part, through a demonstration: it employs the Key Number System to conduct an empirical study of contract interpretation. Contract interpretation is one of the most significant areas of commercial law. And the subject has received considerable scholarly attention during the last decade. Virtually all academic work in this field is doctrinal or theoretical. But numerous contract interpretation issues cry out for empirical investigation. The secondary purpose of this article is to test one of the central claims in the judicial and academic debate over the optimal method of contract interpretation—the claim that the “contextualist” approach to interpretation results in more litigation over the meaning of contracts than does the “textualist” approach. The results of the study set forth below are inconsistent with that thesis. By thirteen of fourteen measures, there was no statistically significant difference in the amount of interpretation litigation between textualist and contextualist regimes. And for the fourteenth measure, while there was a statistically significant difference, the result was the opposite of that predicted by textualist theory: there was more litigation under textualism

Using the West Key Number System as a Data Collection and Coding Device for Empirical Legal Scholarship: Demonstrating the Method Via a Study of Contract Interpretation

Empirical research is an increasingly important type of legal scholarship. Such research generally requires the collection and coding of large quantities of data. These tasks pose critical challenges for legal scholars. Most crucially, they are often resource-intensive. The primary purpose of this article is to explain how researchers can use the West Key Number System to dramatically streamline the process of data collection and coding. The article accomplishes this, in part, through a demonstration: it employs the Key Number System to conduct an empirical study of contract interpretation. Contract interpretation is one of the most significant areas of commercial law. And the subject has received considerable scholarly attention during the last decade. Virtually all academic work in this field is doctrinal or theoretical. But numerous contract interpretation issues cry out for empirical investigation. The secondary purpose of this article is to test one of the central claims in the judicial and academic debate over the optimal method of contract interpretation—the claim that the “contextualist” approach to interpretation results in more litigation over the meaning of contracts than does the “textualist” approach. The results of the study set forth below are inconsistent with that thesis. By thirteen of fourteen measures, there was no statistically significant difference in the amount of interpretation litigation between textualist and contextualist regimes. And for the fourteenth measure, while there was a statistically significant difference, the result was the opposite of that predicted by textualist theory: there was more litigation under textualism

Hiding in Plain View: A Neglected Supreme Court Decision Resolves the Debate Over Non-Debtor Releases in Chapter 11 Reorganizations

This article presents a novel resolution of a long-standing circuit split on an issue of critical significance to bankruptcy and tort law: whether bankruptcy courts may extinguish liabilities of parties that have not filed for bankruptcy. Such non-debtor releases are similar in effect to a bankruptcy discharge and have become particularly common in both mass tort disputes and general insolvencies adjudicated through the bankruptcy process. In this article, I illustrate how an overlooked Supreme Court decision—United States v. Energy Resources, 495 U.S. 545 (1990)—offers crucial support for the pro-release position. Energy Resources demonstrates that the bankruptcy courts’ general equitable power allows them to extinguish claims against non-debtors and that such relief is not forbidden by any specific provision in the Bankruptcy Code

Using the West Key Number System as a Data Collection and Coding Device for Empirica Legal Scholsarship: Demonstrating the Method Via a Study of Contract Interpretation

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