bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-level pooled analysis of adjudicated gastrointestinal outcomes in celecoxib clinical trials: meta-analysis of 51,000 patients enrolled in 52 randomized trials
Authors: Moore Andrew , Makinson Geoffrey , Li Chunming 
Published: January 2013

Abstract
Introduction
Although the safety of celecoxib has been investigated, limited data are available on complications affecting the entire (upper and lower) gastrointestinal (GI) tract, with no patient-level pooled analyses of upper and lower GI outcomes available. We therefore evaluated the upper and lower GI safety of celecoxib by using patient-level data from randomized controlled trials (RCTs).

Methods
This patient-level pooled analysis included 52 prospective, randomized, double-blind parallel-group studies from the Celecoxib Clinical Database. Each study had a planned duration of continuous treatment with celecoxib or a nonselective nonsteroidal antiinflammatory drug (nsNSAID), rofecoxib, or the placebo comparator arm for at least 4 weeks. All studies with final reports completed by 1 October 2007 were included. The primary end point was the combined incidence of clinically significant upper and lower GI events (CSULGIEs). An independent blinded committee reviewed and adjudicated all end points by using predefined criteria and all available reported adverse events, laboratory data, and case narratives. All doses of celecoxib and all doses of all nsNSAIDs were pooled for analysis.

Results
The pooled analysis involved 51,048 patients; 28,614 were randomized to celecoxib; 15,278 to nsNSAIDs (including 3,248 patients taking naproxen, 2,640 taking ibuprofen, 8,066 taking diclofenac, 1,234 taking loxoprofen, and 90 taking ketoprofen); 5,827 to placebo and 1,329 to rofecoxib. The mean age was 60 years, and 65% were women. Data on 1,042 patients with potential GI events were reviewed for end-points adjudication; the adjudication committee confirmed 89 patients with CSULGIEs. The majority were in the celecoxib and nsNSAID groups (with raw incidence proportions of 37 (0.1%) and 40 (0.3%), respectively). The incidence rates were 0.3, 0.9 and 0.3 per 100 patient-years in the celecoxib, nsNSAID, and placebo groups, respectively. The time to incidence of CSULGIEs was significantly longer with celecoxib than with nsNSAIDs (P = 0.0004).

Conclusions
When compared with nsNSAIDs, celecoxib is associated with a significantly lower risk of all clinically significant GI events throughout the entire GI tract. This pooled analysis of 52 RCTs significantly advances the understanding of the upper and lower GI safety profile of celecoxib and its potential benefits to patients.
Atherosclerotic cardiovascular disease and dermatomyositis: an analysis of the Nationwide Inpatient Sample survey
Authors: Linos Eleni , Fiorentino David , Lingala Bharathi , Krishnan Eswar , Chung Lorinda 
Published: January 2013

Abstract
Introduction
Increased rates of cardiovascular disease are implicated in several rheumatologic diseases. Our aim was to characterize dermatomyositis hospitalizations and evaluate cardiovascular-associated mortality in this patient population.

Methods
We examined the frequency and mortality rates of several atherosclerotic cardiovascular diagnoses and procedures among hospitalized adult patients with dermatomyositis using data from the US Nationwide Inpatient Sample (NIS) from 1993 to 2007. We compared the odds of death among hospitalized dermatomyositis patients with each cardiovascular diagnosis or procedure to those without, as well as to controls with cardiovascular diagnoses, using logistic regression.

Results
A total of 50,322 hospitalizations of dermatomyositis patients occurred between 1993 and 2007 (mean age 58 years, and 73% female). Of all dermatomyositis hospitalizations, 20% were associated with a concurrent atherosclerotic cardiovascular diagnosis or procedure. The overall in-hospital mortality was 5.7%. Dermatomyositis patients with any associated atherosclerotic cardiovascular diagnosis or procedure were twice as likely to die during the inpatient stay compared to dermatomyositis patients who did not have atherosclerotic cardiovascular disease (OR = 2.0 95% CI 1.7-2.5, p < 0.0001). The odds ratio for death in patients with both dermatomyositis and cardiovascular disease compared to controls with cardiovascular disease alone was 1.98 (95% CI 1.57-2.48) in multivariate adjusted models.

Conclusions
Approximately one fifth of dermatomyositis hospitalizations in the US were associated with an atherosclerotic cardiovascular diagnosis or procedure. These patients have double the risk of in-hospital death in comparison with controls and dermatomyositis patients without a cardiovascular diagnosis, making identification of these groups important for both prognostic purposes and clinical care.
Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study
Authors: Gérardin Patrick , Fianu Adrian , Michault Alain , Mussard Corinne , Boussaïd Karim , Rollot Olivier , Grivard Philippe , Kassab Somar , Bouquillard Eric , Borgherini Gianandrea , Gaüzère Bernard-Alex , Malvy Denis , Bréart Gérard , Favier François 
Published: January 2013

Abstract
Introduction
Long-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.

Methods
Three hundred and forty-six infected adults (age ≥ 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.

Results
Of these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.

Conclusions
Our data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response.
Optimal Workflow Decisions for Investigators in Systems with Interruptions
Authors: Dobson Gregory , Tezcan Tolga , Tilson Vera 
Published: January 2013

We model a system that consists of a stream of customers processed through three steps by two resources. The first resource, an investigator, handles the first step, in which she collects information from the customer and decides what work will be done in the second step by the second resource, the back office. In the third step, the investigator returns to the customer armed with the additional information or analysis done by the back office and provides the customer with a conclusion, solution, or diagnosis. The investigator has to prioritize either seeing a new customer or completing the work with a customer already in the system. While serving one customer, the investigator may be interrupted by requests from the other customers in the system. Our main objective is to understand the impact of the investigator's choices on system throughput. In addition, we are interested in the occupancy of the system (and thus the flow time of customers). We create a stylized queueing model to examine the investigator's decisions and show that, when interruptions are not an issue, the investigator should prioritize new customers to maximize throughput, keeping the system as full as possible. If customers who have been in the system for a long time generate interruptions and thus additional work for the investigator, we show that it is asymptotically optimal for the investigator to keep the system occupancy low and prioritize discharging customers. Our conclusions are based on a model of a re-entrant queue with dedicated servers serving multiple stations, with two novel features: a buffer that is shared between stations, and jobs in the system generating additional work for the servers. This paper was accepted by Assaf Zeevi, stochastic models and simulation.
Nilotinib-Associated Acute Pancreatitis
Authors: Engel Tal , Justo Dan , Amitai Michal , Volchek Yulia , Mayan Haim 
Published: January 2013

OBJECTIVE To report a case of acute pancreatitis in a patient receiving nilotinib for chronic myelogenous leukemia (CML). CASE SUMMARY A 69-year-old man recently diagnosed with chronic phase CML received nilotinib 300 mg twice daily and was admitted with acute pancreatitis that appeared the day after the first dose. The patient had normal levels of triglycerides and denied alcohol use. Serum pancreatic enzymes were within normal limits the day before nilotinib initiation. Abdominal computed tomography demonstrated a normal liver, bile duct without stones, and findings that were consistent with focal pancreatitis. The patient's history was significant for concomitant use of enalapril and simvastatin; both have been associated with pancreatitis, but the patient had been taking these medications for at least 5 years without adverse effects. Nilotinib was immediately discontinued. Abdominal pain resolved and serum pancreatic enzymes levels returned to normal 2 weeks later. DISCUSSION One of the adverse effects of some tyrosine kinase inhibitors is increased levels of serum pancreatic enzymes. Accordingly, nilotinib labeling includes “high lipase levels in serum” as an adverse event. There are few case reports of acute pancreatitis associated with nilotinib in the literature and some are incomplete. We present a well-documented case of nilotinib-associated acute pancreatitis. Consistent with Badalov's new classification system for drug-induced acute pancreatitis and with the Naranjo probability scale, this case represents a possible adverse reaction of pancreatitis associated with nilotinib therapy. As rechallenge is unethical, treatment with nilotinib has not been resumed. CONCLUSIONS This case demonstrates a possible association between acute pancreatitis and nilotinib use. Although a rare phenomenon, clinicians should be alert for signs and symptoms of pancreatitis, as treatment with nilotinib for CML is becoming more common.
Carfilzomib: A Second-Generation Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma
Authors: Thompson Jennifer L 
Published: January 2013

OBJECTIVE To review and summarize data on carfilzomib, which was approved by the Food and Drug Administration (FDA) in July 2012 for the treatment of patients with relapsed and refractory multiple myeloma (MM) who received prior bortezomib and thalidomide or lenalidomide. DATA SOURCES A literature search through PubMed was conducted through October 2012 using the terms carfilzomib, PR-171, proteasome inhibitor (PI), and MM. Data were also obtained through the American Society of Clinical Oncology and American Society of Hematology abstracts and FDA briefing documents. STUDY SELECTION AND DATA EXTRACTION The literature search was limited to human studies published in English. Priority was placed on trials of carfilzomib in relapsed and refractory MM. DATA SYNTHESIS Carfilzomib is a new PI that differs in pharmacology and pharmacokinetics from bortezomib, the first-in-class PI. The FDA approval was based on efficacy data from a Phase 2 study of carfilzomib in patients with relapsed and refractory MM (n = 266). All patients had received prior bortezomib and 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients were treated with intravenous carfilzomib 20 mg/m2 (cycle 1) followed by 27 mg/m2 (cycles ≥2) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The overall response rate was 23.7% (18.7–29.4), with a median duration of response of 7.8 (5.6–9.2) months. Safety data from an integrated analysis reported thrombocytopenia, anemia, fatigue, nausea, and diarrhea as the most common adverse events, with minimal dose-limiting neutropenia or peripheral neuropathy (PN) (n = 526). The incidence of grade 3 or higher thrombocytopenia was 24.9%, while that of neutropenia was 11.9%, and the incidence of all grades of treatment-emergent PN was 13%. CONCLUSIONS Carfilzomib is a safe and effective new treatment option for patients with relapsed MM refractory to bortezomib and thalidomide or lenalidomide. Randomized head-to-head trials with bortezomib will assist in formulary and treatment decisions in the context of PIs as a drug class.
Public History and Liberal Learning: Making the Case for the Undergraduate Practicum Experience
Authors: Belanger Elizabeth 
Published: January 2013

Abstract
This article explores a collaborative public history project between a small liberal arts undergraduate institution and a community social service agency. Drawing on evidence from student reflections and other course materials, it argues that undergraduate students gained important skills through the public history practicum including teamwork and problemsolving skills, intercultural awareness, and reflective practices, as well as discipline-specific learning outcomes. In documenting the student outcomes, it also demonstrates the potential of public history to contribute to undergraduate students' civic capabilities.
Exploring Identities: Public History in a Cross-Cultural Context
Authors: Lewis Catherine , Dickey Jennifer , Azhar Samir El , Brock Julia 
Published: January 2013

Abstract
The Museums Connect program, funded by the U.S. State Department's Bureau of Educational and Cultural Affairs and administered by the American Alliance of Museums, is a relatively new effort to connect international museums; the grant is set apart by its objective to sponsor projects that foster cross-cultural professional development and civic engagement in global communities. The following roundtable includes perspectives on the Museums Connect project Identities: Understanding Islam in a Cross-Cultural Context, undertaken by the Museum of History and Holocaust Education, Kennesaw State University (Georgia), and the Ben M'sik Community Museum, Université Hassan II Mohammedia, Ben M'sik (Casablanca, Morocco).
The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment
Authors: Garrison Louis P. , Wang Si-Tien , Huang Hui , Ba-Mancini Abbie , Shi Hongliang , Chen Kristina , Korves Caroline , Dhawan Ravinder , Cakana Andrew , van de Velde Helgi , Corzo Deyanira , Duh Mei Sheng 
Published: January 2013

Abstract
The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP.
Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99–06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99–06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%.
Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.
Health Care Costs and Resource Utilization, Including Patient Burden, Associated With Novel-Agent-Based Treatment Versus Other Therapies for Multiple Myeloma: Findings Using Real-World Claims Data
Authors: Teitelbaum April , Ba-Mancini Abbie , Huang Hui , Henk Henry J. 
Published: January 2013

Abstract

Background.
Treatment of multiple myeloma has dramatically improved with the introduction of bortezomib (BOR), thalidomide (THAL), and lenalidomide (LEN). Studies assessing health care costs, particularly economic burden on patients, are limited. We conducted a claims-based, retrospective analysis of total health care costs as well as patient burden (patient out-of-pocket costs and number of ambulatory/hospital visits) associated with BOR/THAL/LEN treatment versus other therapies (OTHER).

Methods.
Treatment episodes starting between January 1, 2005 and September 30, 2010 were identified from the claims database of a large U.S. health plan. Health care costs and utilization were measured during 1 year after initiation and analyzed per treatment episode. Multivariate analyses were used to adjust for patient characteristics, comorbidities, and line of treatment.

Results.
A total of 4,836 treatment episodes were identified. Mean adjusted total costs were similar between BOR ($112,889) and OTHER ($111,820), but higher with THAL ($129,412) and LEN ($158,428). Mean adjusted patient out-of-pocket costs were also similar for BOR ($3,846) and OTHER ($3,900) but remained higher with THAL ($4,666) and LEN ($4,483). Mean adjusted rates of ambulatory visits were similar across therapies (BOR: 69.67; THAL: 66.31; LEN: 65.60; OTHER: 69.42).

Conclusions.
Adjusted analyses of real-world claims data show that total health care costs, as well as patient out-of-pocket costs, are higher with THAL/LEN treatment episodes than with BOR/OTHER therapies. Additionally, similar rates of ambulatory visits suggest that any perceived advantage in patient convenience of the orally administered drugs THAL/LEN is not supported by these data.
Nutrient Restriction and Radiation Therapy for Cancer Treatment: When Less Is More
Authors: Champ Colin E. , Baserga Renato , Mishra Mark V. , Jin Lianjin , Sotgia Federica , Lisanti Michael P. , Pestell Richard G. , Dicker Adam P. , Simone Nicole L. 
Published: January 2013

abstract

CME Learning Objectives
Identify molecular pathways that are potential targets of calorie restriction combined with radiation therapy. Identify cancer patients for whom calorie restriction would be contraindicated.
Calorie restriction (CR), or a diet modification aiming to reduce the total intake of calories by 20%–40%, has been shown to increase longevity across multiple species. Recently, there has been growing interest in investigating the potential role of CR as a treatment intervention for age-related diseases, such as cancer, because an increasing body of literature has demonstrated a metabolic component to both carcinogenesis and tumor progression. In fact, many of the molecular pathways that are altered with CR are also known to be altered in cancer. Therefore, manipulation of these pathways using CR can render cancer cells, and most notably breast cancer cells, more susceptible to standard cytotoxic treatment with radiation and chemotherapy. In this review article we demonstrate the laboratory and clinical evidence that exists for CR and show compelling evidence through the molecular pathways CR induces about how it may be used as a treatment in tandem with radiation therapy to improve our rates of disease control.
Interleukin-10 Gene Polymorphisms are Associated With Freedom From Treatment Failure for Patients With Hodgkin Lymphoma
Authors: Schoof Nils , Franklin Jeremy , Fürst Robert , Zander Thomas , von Bonin Frederike , Peyrade Frederic , Trümper Lorenz , Diehl Volker , Engert Andreas , Kube Dieter , Re Daniel 
Published: January 2013

Abstract

CME Learning Objectives
Discuss whether and how genetic variations influence clinical outcomes of Hodgkin lymphoma patients. Evaluate evidence that proximal IL10 promoter gene variations are associated with clinical courses of Hodgkin lymphoma patients. Compare host genetic variations from different cytokine/cytokine receptor gene variations.

Background.
Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by the production of various cytokines possibly involved in immune deregulation. Interleukin-10 (IL-10) serum levels have been associated with clinical outcome in patients with HL. Because host genetic variations are known to alter the expression and function of cytokines and their receptors, we investigated whether genetic variations influence clinical outcome of patients with HL.

Methods.
A total of 301 patients with HL who were treated within randomized trials by the German Hodgkin Study Group were included in this exploratory retrospective study. Gene variations of IL-10 (IL-10-597AC, rs1800872; IL-10-824CT, rs1800871; IL-10-1087AG, rs1800896; IL-10-3538AT, rs1800890; IL-10-6208CG, rs10494879; IL-10-6752AT, rs6676671; IL-10-7400InDel), IL-13 (IL-13-1069CT, rs1800925; IL-13Q144R, rs20541), and IL-4R (IL-4RI75V, rs1805010; IL-4RQ576R, rs1801275) were genotyped.

Results.
Inferior freedom from treatment failure (FFTF) was found in patients harboring the IL-10-597AA, IL-10-824TT, or the IL-10-1087AA genotype. In contrast, the IL-10-1087G-824C-597C haplotype present in about 48% of analyzed HL patients is nominally significant for a better FFTF in a Cox-Regression model accounting for stage and treatment. No associations were observed between the other IL-10 gene variations, IL-13-1069CT, IL-13Q144R, IL-4RI75V, IL-4RQ576R and the clinical outcome of patients with HL.

Conclusions.
Our study provides further evidence that proximal IL-10 promoter gene variations are associated with clinical course of patients with HL. However, treatment success and survival rates are already at a very high rate, supporting the need to design studies focusing on identification of predictors to reduce the side effects of therapy.