UMass Memorial Health Care

About: UMass Memorial Health Care is a healthcare organization based out in Worcester, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 1102 authors who have published 1018 publications receiving 21896 citations.

Recommendations for standards regarding preclinical neuroprotective and restorative drug development

Abstract: The plethora of failed clinical trials with neuroprotective drugs for acute ischemic stroke have raised justifiable concerns about how best to proceed for the future development of such interventions. Preclinical testing of neuroprotective drugs is an important aspect of assessing their therapeutic potential, but guidelines concerning how to perform preclinical development of purported neuroprotective drugs for acute ischemic stroke are lacking. This conference of academicians and industry representatives was convened to suggest such guidelines for the preclinical evaluation of neuroprotective drugs and to recommend to potential clinical investigators the data they should review to reassure themselves that a particular neuroprotective drug has a reasonable chance to succeed in an appropriately designed clinical trial. Without rigorous, robust, and detailed preclinical evaluation, it is unlikely that novel neuroprotective drugs will prove to be effective when tested in large, time-consuming, and expensive clinical trials. Additionally, similar recommendations are provided for drugs with the potential to enhance recovery after acute ischemic stroke, a burgeoning new field with great potential but little currently available data. The suggestions contained in this document are meant to serve as overall guidelines that must be adapted to the individual characteristics related to particular drugs and their preclinical and clinical development needs.

Pd-l1 expression is characteristic of a subset of aggressive b-cell lymphomas and virus-associated malignancies

Abstract: Purpose: Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed–Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors. Experimental Design: Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1. Results: Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1. Conclusion: Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies. Clin Cancer Res; 19(13); 3462–73. ©2013 AACR .

Initial symptoms of nicotine dependence in adolescents

Abstract: Objectives—It has been assumed that nicotine dependence has a slow onset and occurs only after prolonged daily use of tobacco. A cohort of young adolescents was followed to determine when the first symptoms of nicotine dependence occur with respect to the duration and frequency of tobacco use. Design—A cohort of 681 seventh grade students (age 12‐13 years) from seven schools in two small cities in central Massachusetts was followed over one year. Detailed information regarding tobacco use was obtained in individual confidential interviews conducted in school three times over the year. The latency time to the onset of symptoms of nicotine dependence was measured from the time a subject first smoked at a frequency of at least once per month. Results—22% of the 95 subjects who had initiated occasional smoking reported a symptom of nicotine dependence within four weeks of initiating monthly smoking. One or more symptoms were reported by 60 (63%) of these 95 subjects. Of the 60 symptomatic subjects, 62% had reported experiencing their first symptom before smoking daily or began smoking daily only upon experiencing their first symptom. Discussion—The first symptoms of nicotine dependence can appear within days to weeks of the onset of occasional use, often before the onset of daily smoking. The existence of three groups of individuals—rapid onset, slower onset, and resistant—distinguishable from one another by their susceptibility to nicotine dependence, is postulated. (Tobacco Control 2000;9:313‐319)

The run chart: a simple analytical tool for learning from variation in healthcare processes

Abstract: Background Those working in healthcare today are challenged more than ever before to quickly and efficiently learn from data to improve their services and delivery of care. There is broad agreement that healthcare professionals working on the front lines benefit greatly from the visual display of data presented in time order. Aim To describe the run chart—an analytical tool commonly used by professionals in quality improvement but underutilised in healthcare. Methods A standard approach to the construction, use and interpretation of run charts for healthcare applications is developed based on the statistical process control literature. Discussion Run charts allow us to understand objectively if the changes we make to a process or system over time lead to improvements and do so with minimal mathematical complexity. This method of analyzing and reporting data is of greater value to improvement projects and teams than traditional aggregate summary statistics that ignore time order. Because of its utility and simplicity, the run chart has wide potential application in healthcare for practitioners and decision-makers. Run charts also provide the foundation for more sophisticated methods of analysis and learning such as Shewhart (control) charts and planned experimentation.