185 results on '"Fischer, Melissa"'
Search Results
152. Anatomy of Pelvic Support.
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Klein, Eric A., Goldman, Howard B., Vasavada, Sandip P., Fischer, Melissa, Padmanabhan, Priya, and Rosenblum, Nirit
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Female pelvic anatomy can be a conceptual challenge. To understand the function of the pelvis, one must understand the basic anatomy and then the dynamic nature of the structures that allow for urinary and bowel continence in a variety of circumstances. An understanding of normal anatomy and function provides the clinician with a framework for understanding the pathophysiology of pelvic organ prolapse and female urinary incontinence. The evaluation of female urinary incontinence often involves the recognition and treatment of concurrent pelvic abnormalities, such as cystocele, uterine prolapse, enterocele, rectocele, or perineal laxity. The factors responsible for pelvic floor relaxation rarely affect isolated anatomic areas. This chapter provides a detailed description of normal female pelvic anatomy, and an emphasis is placed on key surgical landmarks for reestablishing normal anatomy. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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153. Nontraumatic dental condition-related visits to emergency departments on weekdays, weekends and night hours: findings from the National Hospital Ambulatory Medical Care Survey.
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Okunseri, Christopher, Okunseri, Elaye, Fischer, Melissa Christine, Sadeghi, Saba Noori, Qun Xiang, and Szabo, Aniko
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NUTRITION & oral health ,EMERGENCY medical services ,DENTAL care ,TOOTHACHE ,MEDICAL care ,MEDICAID - Abstract
Objective: To determine whether the rates of nontraumatic dental condition (NTDC)-related emergency department (ED) visits are higher during the typical working hours of dental offices and lower during night hours, as well as the associated factors. Methods: We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997 through 2007 using multivariate binary and polytomous logistic regression adjusted for survey design to determine the effect of predictors on specified outcome variables. Results: Overall, 4,726 observations representing 16.4 million NTDC-related ED visits were identified. Significant differences in rates of NTDC-related ED visits were observed with 40%-50% higher rates during nonworking hours and 20% higher rates on weekends than the overall average rate of 170 visits per hour. Compared with 19-33 year olds, subjects ,18 years old had significantly higher relative rates of NTDC-related ED visits during nonworking hours [relative rate ratio (RRR) = 1.6 to 1.8], whereas those aged 73 and older had lower relative rates during nonworking hours (RRR = 0.4; overall P = 0.0005). Compared with those having private insurance, Medicaid and self-pay patients had significantly lower relative rates of NTDC visits during nonworking and night hours (RRR = 0.6 to 0.7, overall P , 0.0003). Patients with a dental reason for visit were overrepresented during the night hours (RRR = 1.3; overall P = 0.04). Conclusion: NTDC-related visits to ED occurred at a higher rate during nonworking hours and on weekends and were significantly associated with age, patient-stated reason for visit and payer type. [ABSTRACT FROM AUTHOR]
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- 2013
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154. Comparison between reduction in 24-hour pad weight, International Consultation on Incontinence-Short Form (ICIQ-SF) score, International Prostate Symptom Score (IPSS), and Post-Operative Patient Global Impression of Improvement (PGI-I) score in patient evaluation after male perineal sling
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Twiss, Christian O., Fischer, Melissa C., and Nitti, Victor W.
- Abstract
Aims We assessed the utility of three self-assessment instruments: the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the post-operative Patient Global Impression of Improvement (PGI-I) score, and the International Prostate Symptom Score (IPSS) by correlating them with an objective outcome, the change in 24-hr pad weight, after a male perineal sling. Methods Twenty-six men with urodynamically confirmed stress incontinence underwent a male perineal sling. Patients were evaluated pre-operatively and post-operatively with a 24-hr pad test, IPSS and ICIQ-SF. Patients also completed the PGI-I post-operatively. Changes in study parameters were compared via the paired t-test, and correlations were performed using Spearman's rho. Results There were significant reductions in 24-hr pad weight (−274 g, P < 0.001), percentage 24-hr pad weight (54.2%), ICIQ-SF score (−6.3, P < 0.001), and the three ICIQ-SF subscores (−1.2, −1.7, −3.4 for Questions 3, 4, and 5, respectively, P < 0.001 for all). The change in total ICIQ-SF score and the post-operative PGI-I score correlated strongly with percentage reduction in 24-hr pad weight (r = −0.68, P < 0.001; r = −0.81, P < 0.001, respectively) and with each other (r = 0.79, P < 0.001). The change in all three ICIQ-SF subscores correlated significantly with percentage reduction in 24-hr pad weight and with post-operative PGI-I score. There was no significant change in the IPSS or the voiding or storage subscores, and none correlated with any other study parameter. Conclusions This study validates the construct validity of the ICIQ-SF and PGI-I in the assessment of treatment for male stress incontinence and should make clinicians confident in comparing studies of incontinence treatment utilizing the change ICIQ-SF score, the post-operative PGI-I score, and percentage reduction in 24-hr pad weight as outcome measures. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2007
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155. Factors that Influence How Students and Residents Learn from Medical Errors.
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Fischer, Melissa A., Mazor, Kathleen M., Baril, Joann, Alper, Eric, DeMarco, Deborah, and Pugnaire, Michele
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MEDICAL errors , *SCIENTIFIC errors , *MEDICAL practice , *JOB stress , *MEDICAL students , *INTERNS (Medicine) , *INTERVIEWING , *CONTENT analysis , *COMMUNICATION methodology - Abstract
CONTEXT: Trainees are exposed to medical errors throughout medical school and residency. Little is known about what facilitates and limits learning from these experiences. OBJ'ECT/VE: To identify major factors and areas of tension in trainees' learning from medical errors. DESIGN, SETTING, AND PARTICIPANTS: Structured telephone interviews with 59 trainees (medical students and residents) from 1 academic medical center. Five authors reviewed transcripts of audiotaped interviews using content analysis. RESULTS: Trainees were aware that medical errors occur from early in medical school. Many had an intense emotional response to the idea of committing errors in patient care. Students and residents noted variation and conflict in institutional recommendations and individual actions. Many expressed role confusion regarding whether and how to initiate discussion after errors occurred. Some noted the conflict between reporting errors to seniors who were responsible for their evaluation. Learners requested more open discussion of actual errors and faculty disclosure. No students or residents felt that they learned better from near misses than from actual errors, and many believed that they learned the most when harm was caused. CONCLUSIONS: Trainees are aware of medical errors, but remaining tensions may limit learning, institutions can immediately address variability in faculty response and local culture by disseminating clear, accessible algorithms to guide behavior when errors occur. Educators should develop longitudinal curricula that integrate actual cases and faculty disclosure. Future multi-institutional work should focus on identified themes such as teaching and learning in emotionally charged situations, learning from errors and near misses and balance between individual and systems responsibility. [ABSTRACT FROM AUTHOR]
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- 2006
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156. Identification of a novel thymocyte growth-promoting factor derived from B cell lymphomas
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Suda, Takashi, primary, O'Garra, Anne, additional, MacNeil, Ian, additional, Fischer, Melissa, additional, Bond, Martha W., additional, and Zlotnik, Albert, additional
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- 1990
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157. Computers and Young Children's Development.
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Fischer, Melissa A. and Gillespie, Catherine Wilson
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TECHNOLOGY & children ,CHILD psychology ,CHILD development ,SOCIAL conditions of children ,SOCIAL interaction ,TECHNOLOGY & society ,SOCIALIZATION ,SOCIAL psychology ,DEVELOPMENTAL psychology - Abstract
The article discusses the effects of technology on the social development of young children. For technology to have positive effects on children's development, it must be used in a developmentally appropriate manner. This article presents research and examples that give strong evidence for the benefits of introducing young children to technology. The strongest points include support for social interaction, the use of developmentally appropriate software and the teacher's role in the use of technology.
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- 2003
158. BUILDING SAFETY.
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FISCHER, MELISSA
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INDUSTRIAL safety ,SAFETY education ,INDUSTRIAL hygiene ,BUSINESS success ,PROTECTIVE clothing - Published
- 2019
159. Introduction to Estimating.
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Fischer, Melissa
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GLASS industry ,GLASS sales & prices - Published
- 2018
160. The Role of the Internal Medicine Subinternship Director in the 21st Century
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Aiyer, Meenakshy, Appel, Joel, Fischer, Melissa, Fitz, Matthew, Vu, T. Robert, Gliatto, Peter, Sweet, Michelle, Harrell, Heather, Ledford, Cynthia, Alvarez, Hugo, and Kuzma, Mary Ann
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- 2008
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161. Psychological Factors Capable of Preventing the Inhibition of Antibody Responses in Separated Infant Monkeys.
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Coe, Christopher L., Rosenberg, Leon T., Fischer, Melissa, and Levine, Seymour
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CHILD psychology , *VIRAL antibodies , *SEPARATION (Psychology) - Abstract
COE, CHRISTOPHER L, BOSENBERG, LEON T, FISCHER, MELISSA, and LEVINE, SEYMOUR Psychological Factors Capable of Preventing the inhibition of Antibody Responses in Separated Infant Monkeys CHILD DEVELOPMENT, 1987, 58, 1420-1430 The capacity of infant squirrel monkeys to mount an antibody response to viral challenge was evaluated after removal from their mothers m several social and physical environments Control and separated infants were rejected with a benign virus, the bacteriophage X174, and levels of neutralizing antibody were assessed for 3 weeks Infants separated alone m an unfamiliar environment showed a significant reduction m antibody levels as compared to control infants Allowing infants to remain in the home environment, either alone or with peers, prevented this inhibition of antibody responses from occurring Similarly, providing familiar peers in the novel environment facilitated the normal expression of antibody responses These results indicate that the trauma of maternal separation is significantly reduced when infants are familiar with the separation environment or familiar social companions are available The reduced antibody response was associated with the highest level of adrenal activation induced by the unfamiliar separation condition, but antibody titers and plasma cortisol levels could not be specifically correlated in individual infants. [ABSTRACT FROM AUTHOR]
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- 1987
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162. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.
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Lee, Taekyu, Bian, Zhiguo, Zhao, Bin, Hogdal, Leah J., Sensintaffar, John L., Goodwin, Craig M., Belmar, Johannes, Shaw, Subrata, Tarr, James C., Veerasamy, Nagarathanam, Matulis, Shannon M., Koss, Brian, Fischer, Melissa A., Arnold, Allison L., Camper, DeMarco V., Browning, Carrie F., Rossanese, Olivia W., Budhraja, Amit, Opferman, Joseph, and Boise, Lawrence H.
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MYELOID leukemia , *APOPTOSIS , *GENETIC overexpression , *PROTEIN expression , *RNA interference - Abstract
Myeloid cell leukemia 1 ( Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors. PDB ID codes Comp. 2: ; Comp. 5: . [ABSTRACT FROM AUTHOR]
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- 2017
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163. Perioperative experience of pelvic organ prolapse repair with the Prolift® and Elevate® vaginal mesh procedures.
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McLennan, Gregory, Sirls, Larry, Killinger, Kim, Nikolavsky, Dmitriy, Boura, Judith, Fischer, Melissa, and Peters, Kenneth
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PELVIC organ prolapse , *PROLAPSE of bodily organs , *UTERINE surgery , *HYSTERECTOMY , *CHI-squared test - Abstract
Introduction and hypothesis: We compared the operative and immediate postoperative experience of the trocar-based Prolift® and non-trocar-based Elevate® techniques used to repair vaginal prolapse. Methods: A retrospective review of Prolift and Elevate repairs was performed. Baseline characteristics and operative and postoperative variables evaluated included compartment(s) repaired, adjacent organ injury, operative time (OT), change in hemoglobin (ΔH), pain score, narcotic use, length of stay (LOS), and short-term complications. Categorical variables were assessed as counts and percent frequency. Data were compared using chi-squared analysis and paired t test. Results: Prolift ( n = 143) and Elevate ( n = 77) patients were similar in age ( p = 0.19). Concurrent hysterectomy was done in 22 (15.4 %) and 24 (31.2 %), respectively, and concurrent midurethral sling placed in 100 (70 %) and 50 (65 %), respectively. LOS (median, 25th,75th) after anterior/apical compartment repairs was shorter with Elevate, whether with (1.0; 1.0,1.5 vs. 2.0 days;1.0, 2.0; p = 0.003) or without (2.0; 1.0, 2.0 vs. 2.0 days; 2.0, 3.0; p = 0.024) hysterectomy, but no differences in OT, ΔH, pain score, or narcotic use occurred. Posterior compartment mean pain scores were lower with Prolift (3.6 ± 2.2 vs. 1.7 ± 1.5, p = 0.035), and three-compartment-repair pain scores were lower with Elevate (0.6 ± 1.3 vs 2.5 ± 1.9; p = 0.013). Three bladder injuries occurred with Prolift but none with Elevate. Conclusions: Operative and postoperative experiences were similar between groups; however, Elevate anterior/apical repairs had shorter LOS, which might reflect more aggressive discharge planning. There were no bowel or major vascular injuries, and the Prolift trocar bladder injuries did not alter the surgical procedure. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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164. The delta isoform of phosphatidylinositol-3-kinase predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib.
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Villaume, Matthew T., Arrate, M. Pia, Ramsey, Haley E., Sunthankar, Kathryn I., Jenkins, Matthew T., Moyo, Tamara K., Smith, Brianna N., Fischer, Melissa A., Childress, Merrida A., Gorska, Agnieszka E., Ferrell, P. Brent, and Savona, Michael R.
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CHRONIC leukemia , *MYELODYSPLASTIC syndromes , *ACUTE myeloid leukemia , *LEUKEMIA , *BONE marrow , *FLOW cytometry - Abstract
• PI3k-δ is the most abundant PI3K subunit among monocytic leukemia samples. • CMML patient samples are uniquely sensitive to PI3K-δ inhibition by umbralisib. • Ruxolitinib and umbralisib synergistically decrease growth in CMML patient samples. • This combination can simultaneously suppress STAT5, ERK, S6, and AKT signaling. Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome characterized by monocytic proliferation in the presence of dysplastic bone marrow changes, inflammatory symptoms, and propensity for transformation to acute myeloid leukemia (AML), with a poor prognosis and limited treatment options. Unlike the α and β isoforms, the phosphatidylinositol-3-kinase (PI3K)–δ signaling protein is predominantly expressed by hematopoietic cells and therefore has garnered interest as a potential target for the treatment of lymphomas and leukemias. We revealed a pattern of increased PIK3CD:PIK3CA ratio in monocytic M5 AML patients and cell lines, and this ratio correlated with responsiveness to pharmacological PI3K-δ inhibition in vitro. Because CMML is a disease defined by monocytic clonal proliferation, we tested the PI3K-δ inhibitor umbralisib as a single agent and in combination with the JAK1/2 inhibitor ruxolitinib, in CMML. Our ex vivo experiments with primary CMML patient samples revealed synergistic inhibition of viability and clonogenicity with this combination. Phospho-specific flow cytometry revealed that dual inhibition had the unique ability to decrease STAT5, ERK, AKT, and S6 phosphorylation simultaneously, which offers a mechanistic hypothesis for the enhanced efficacy of the combination treatment. These preclinical data indicate promising activity by co-inhibition of PI3K-δ and JAK1/2 and support the use of ruxolitinib + umbralisib combination therapy in CMML under active clinical investigation. [ABSTRACT FROM AUTHOR]
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- 2021
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165. Rapid prototyping of perfusion cell culture devices for three-dimensional imaging of mesenchymal stem cell deposition and proliferation.
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Scott TE, Boccarossa T, Florian D, Fischer MA, Peck SH, Savona MR, Pingen G, and Guelcher SA
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Perfusion of porous scaffolds transports cells to the surface to yield cellular constructs for 3D models of disease and for tissue engineering applications. While ceramic scaffolds mimic the structure and composition of trabecular bone, their opacity and tortuous pores limit the penetration of light into the interior. Scaffolds that are both perfusable and amenable to fluorescence microscopy are therefore needed to visualize the spatiotemporal dynamics of cells in the bone microenvironment. In this study, a hybrid injection molding approach was designed to enable rapid prototyping of collector arrays with variable configurations that are amenable to longitudinal imaging of attached human mesenchymal stem cells (hMSCs) using fluorescence microscopy. Cylindrical collectors were arranged in an array that is permeable to perfusion in the xy -plane and to light in the z-direction for imaging from below. The effects of the collector radius, number, and spacing on the collection efficiency of perfused hMSCs was simulated using computational fluid dynamics (CFD) and measured experimentally using fluorescence microscopy. The effect of collector diameter on simulated and experimental cell collection efficiencies followed a trend similar to that predicted by interception theory corrected for intermolecular and hydrodynamic forces for the arrays with constant collector spacing. In contrast, arrays designed with constant collector number yielded collection efficiencies that poorly fit the trend with collector radius predicted by interception theory. CFD simulations of collection efficiency agreed with experimental measurements within a factor of two. These findings highlight the utility of CFD simulations and hybrid injection molding for rapid prototyping of collector arrays to optimize the longitudinal imaging of cells without the need for expensive and time-consuming tooling., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Scott Guelcher reports financial support was provided by Incyte Corporation. Michael Savona reports financial support was provided by Incyte Corporation. Sun Peck reports financial support was provided by 10.13039/100000738US Department of Veterans Affairs. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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166. "It feels like you have to choose one or the other": a qualitative analysis of obstetrician focus groups on periviability counseling.
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Johnson KM, Delaney K, and Fischer MA
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Objectives: The objective of this study was to gain knowledge and ascertain challenges about periviability counseling among obstetricians to inform curricular development., Methods: Focus groups were utilized. A series of open-ended questions was posed to each group of obstetricians; responses were audio recorded and transcribed. Transcriptions were analyzed by two coders using thematic analysis., Results: Four focus groups were convened. Prominent themes included: (1) Obstetrician knowledge about neonatal outcomes is limited, (2) Periviability counseling is both time intensive and time-challenged, (3) Patient processing of information relies on the content, delivery and patient readiness, and (4) Obstetrician bias is toward advocating for maternal safety, which may run counter to parental instinct to "do everything." The last theme was specifically focused on the role of cesarean delivery., Conclusions: Curricula focused on improving obstetrician periviability counseling should focus on neonatal outcomes, the role of cesarean delivery, and utilization of shared decision-making., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2024
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167. Curricular Reform in Serious Illness Communication and Palliative Care: Using Medical Students' Voices to Guide Change.
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Reidy JA, Brizzi K, Chan SH, Day H, Epstein SK, Fischer M, Garg PS, Gosline A, Jaramillo C, Livne E, Mitchell S, Morgan S, Olmsted MW, Stebbins P, Stumpf I, Vesel T, Yeh IM, Young ME, and Goldman RE
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- Humans, Massachusetts, Male, Female, Qualitative Research, Adult, Critical Illness therapy, Critical Illness psychology, Palliative Care, Curriculum, Education, Medical, Undergraduate methods, Focus Groups, Students, Medical psychology, Communication
- Abstract
Purpose: To gather and leverage the voices of students to drive creation of required, integrated palliative care curricula within undergraduate medical education in Massachusetts, which is lacking in a majority of U.S. medical schools., Method: The study was conducted by the Massachusetts Medical Schools' Collaborative, a working group committed to ensuring all medical students in Massachusetts receive foundational training in serious illness communication (SIC) and palliative care. Eight focus groups (2 per participating medical school) were conducted during January-May 2021 and included a total of 50 students from Boston University Chobanian & Avedisian School of Medicine, Harvard Medical School, Tufts University School of Medicine, and the UMass Chan Medical School. Data collected from focus groups were discussed and coded. Themes were identified using the immersion/crystallization qualitative data analysis approach., Results: Six key themes emerged. Students viewed SIC as essential to high-quality medical practice regardless of specialty, and believed training in SIC skills and palliative care should be required in medical school curricula. Students preferred to learn and practice these skills using frameworks, particularly in real-world situations. Students recognized the expertise of palliative care specialists and described them as a scarce, often misunderstood resource in health care. Students reported it was mostly "luck" if they were included in family meetings and observed good role models. Finally, students desired practice in debriefing after difficult and emotional situations., Conclusions: This study confirms long-standing themes on students' experiences with SIC and palliative care topics, including feeling inadequately prepared to care for seriously ill patients as future physicians. Our study collected students' perspectives as actionable data to develop recommendations for curricular change. Collaborative faculty also created recommendations based on the focus group data for immediate and ongoing SIC and palliative care curricular change in Massachusetts, which can apply to medical schools nationwide., (Copyright © 2024 the Association of American Medical Colleges.)
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- 2024
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168. Maternity Leave Satisfaction Among Physicians Compared with Nonphysician Professionals.
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Hoang Roberts LN, Zwaans BMM, Vollstedt A, Sharrak A, Han E, Fischer M, Sirls L, and Padmanabhan P
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- Adult, Female, Humans, Infant, Newborn, Pregnancy, Mothers, Personal Satisfaction, Postpartum Period, United States, Parental Leave, Physicians
- Abstract
Objective: The objective of this study was to compare maternity leave satisfaction between physicians and nonphysicians. Currently, paid maternal leave is not guaranteed in the United States, resulting in palpable dissatisfaction among parents. Previous studies have shown associations between length of paid leave and career satisfaction and maternal happiness. Materials and Methods: A Qualtrics
® electronic survey was distributed to female professionals through email and social media from April 2019 to March 2020. Inclusion criterion was ≥1 child by birth or adoption, or active pregnancy. Continuous and categorical data were analyzed using two-sample t -test and chi-square, respectively. Results: Of 808 respondents, 77% were physicians. Mean age at birth/adoption of first child was higher in physicians versus nonphysicians (32.1 years vs. 29.7 years; p < 0.001). Physicians took shorter maternity leave than nonphysicians (10.9 weeks vs. 12.0 weeks, p = 0.017) with half of that time paid by employers (5.4 weeks vs. 5.9 weeks, p = 0.2). Dissatisfaction was high among physicians (85.1%) and nonphysicians (92.4%) that correlates with maternity leave compensation dissatisfaction (49% vs. 71.3%, p < 0.001). Thirty-four percent of physicians versus 41% of nonphysicians stated that their health was negatively impacted by maternity leave length. Physicians and nonphysicians reported similar incidences of depression, and breastfeeding, delivery, and other postpartum complications. When queried, 38.8% of physicians and 57% of nonphysicians said they would desire >16 weeks of paid maternity leave ( p < 0.001). Conclusions: In conclusion, dissatisfaction among professional women on maternity leave duration and compensation is high in the United States. Given health implications for both mother and child, this should invite further discussion and changes.- Published
- 2024
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169. Nanoparticle STING Agonist Reprograms the Bone Marrow to an Antitumor Phenotype and Protects Against Bone Destruction.
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Florian DC, Bennett NE, Odziomek M, Baljon JJ, Wehbe M, Merkel AR, Fischer MA, Savona MR, Rhoades JA, Guelcher SA, and Wilson JT
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- Mice, Animals, Bone Marrow, Cytokines, Phenotype, Tumor Microenvironment, Neoplasms, Nanoparticles
- Abstract
When breast cancer metastasizes to bone, treatment options are limited. Failure to treat bone metastases is thought to be due to therapy-resistant features of the bone marrow microenvironment. Using a murine model of bone metastatic mammary carcinoma, we demonstrate that systemic delivery of polymer nanoparticles loaded with cyclic dinucleotide (CDN) agonists of stimulator of interferon genes (STING) inhibited tumor growth and bone destruction after 7 days of treatment. Each dose of STING-activating nanoparticles trafficked to the bone marrow compartment and was retained within the tumor microenvironment for over 24 hours, enhancing antitumor immunity through proinflammatory cytokine production and early T-cell activation. While acquired resistance mechanisms, including increased levels of immunosuppressive cytokines and the infiltration of regulatory T cells, ultimately limited antitumor efficacy after 2 weeks of treatment, bone protective effects remained. Overall, these studies demonstrate that STING pathway activation, here enabled using a nanomedicine approach to enhance CDN delivery to bone metastatic sites, can reprogram the immune contexture of the bone marrow to an antitumor phenotype that inhibits bone colonization of metastatic breast cancer cells and protects from tumor-mediated bone destruction., Significance: Bone metastases are difficult to treat due to the inaccessibility of the bone marrow compartment and the immunosuppressive microenvironment that protects resident stem cells. Packaging a STING agonist into a nanoparticle that enables systemic administration and drug accumulation at tumor sites overcomes both barriers to stymie metastatic breast cancer growth., Competing Interests: N.E. Bennett reports grants from NIH during the conduct of the study. A.R. Merkel reports grants from Verteran's Administration and non-financial support from Vanderbilt University Medical Center during the conduct of the study; grants from NIH Clinical and Translational Science Award and National Center for Advancing Translational Sciences outside the submitted work. M.A. Fischer reports grants from Incyte Corporation during the conduct of the study. M.R. Savona reports grants from ALX Oncology, Astex, Incyte, Takeda, TG Therapeutics; personal fees from BMS, CTI, Forma, Geron, Novartis, Sierra Oncology, Taiho; personal fees and other from Ryvu and Karyopharm outside the submitted work. J.A. Rhoades reports grants from Veterans Administration during the conduct of the study. S.A. Guelcher reports grants from Incyte Corporation during the conduct of the study. J.T. Wilson reports a patent to 10,696,985 issued and a patent to PCT/US2019/058945 pending. No disclosures were reported by the other authors., (© 2023 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2023
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170. Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes.
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Fischer MA, Song Y, Arrate MP, Gbyli R, Villaume MT, Smith BN, Childress MA, Stricker TP, Halene S, and Savona MR
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- Animals, Mice, Myeloid Cell Leukemia Sequence 1 Protein metabolism, Proto-Oncogene Proteins c-bcl-2, Disease Models, Animal, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Apoptosis, Cell Line, Tumor, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes metabolism
- Abstract
Treatment for myelodysplastic syndromes (MDS) remains insufficient due to clonal heterogeneity and lack of effective clinical therapies. Dysregulation of apoptosis is observed across MDS subtypes regardless of mutations and represents an attractive therapeutic opportunity. Venetoclax (VEN), a selective inhibitor of anti-apoptotic protein B-cell lymphoma- 2 (BCL2), has yielded impressive responses in older patients with acute myeloid leukemia (AML) and high risk MDS. BCL2 family anti-apoptotic proteins BCL-XL and induced myeloid cell leukemia 1 (MCL1) are implicated in leukemia survival, and upregulation of MCL1 is seen in VEN-resistant AML and MDS. We determined in vitro sensitivity of MDS patient samples to selective inhibitors of BCL2, BCL-XL and MCL1. While VEN response positively correlated with MDS with excess blasts, all MDS subtypes responded to MCL1 inhibition. Treatment with combined VEN + MCL1 inhibtion was synergistic in all MDS subtypes without significant injury to normal hematopoiesis and reduced MDS engraftment in MISTRG6 mice, supporting the pursuit of clinical trials with combined BCL2 + MCL1 inhibition in MDS.
- Published
- 2023
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171. Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost-tutorial and efficacy of complete directional hippocampal blocking.
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Popp I, Grosu AL, Fennell JT, Fischer M, Baltas D, and Wiehle R
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- Cranial Irradiation methods, Hippocampus, Humans, Organ Sparing Treatments methods, Organs at Risk, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted methods, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Radiotherapy, Intensity-Modulated methods
- Abstract
Purpose: Hippocampus-avoidance whole brain radiotherapy with simultaneous integrated boost (HA-WBRT+SIB) is a complex treatment option for patients with multiple brain metastases, aiming to prevent neurocognitive decline and simultaneously increase tumor control. Achieving efficient hippocampal dose reduction in this context can be challenging. The aim of the current study is to present and analyze the efficacy of complete directional hippocampal blocking in reducing the hippocampal dose during HA-WBRT+SIB., Methods: A total of 30 patients with multiple metastases having undergone HA-WBRT+SIB were identified. The prescribed dose was 30 Gy in 12 fractions to the whole brain, with 98% of the hippocampus receiving ≤ 9 Gy and 2% ≤ 17 Gy and with SIB to metastases/resection cavities of 36-51 Gy in 12 fractions. Alternative treatment plans were calculated using complete directional hippocampal blocking and compared to conventional plans regarding target coverage, homogeneity, conformity, dose to hippocampi and organs at risk., Results: All alternative plans reached prescription doses. Hippocampal blocking enabled more successful sparing of the hippocampus, with a mean dose of 8.79 ± 0.99 Gy compared to 10.07 ± 0.96 Gy in 12 fractions with the conventional method (p < 0.0001). The mean dose to the whole brain (excluding metastases and hippocampal avoidance region) was 30.52 ± 0.80 Gy with conventional planning and 30.28 ± 0.11 Gy with hippocampal blocking (p = 0.11). Target coverage, conformity and homogeneity indices for whole brain and metastases, as well as doses to organs at risk were similar between planning methods (p > 0.003)., Conclusion: Complete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB., (© 2022. The Author(s).)
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- 2022
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172. Selective Inhibition of JAK1 Primes STAT5-Driven Human Leukemia Cells for ATRA-Induced Differentiation.
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Ramsey HE, Stengel K, Pino JC, Johnston G, Childress M, Gorska AE, Arrate PM, Fuller L, Villaume M, Fischer MA, Ferrell PB Jr, Roe CE, Zou J, Lubbock ALR, Stubbs M, Zinkel S, Irish JM, Lopez CF, Hiebert S, and Savona MR
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- Cell Differentiation, Humans, Janus Kinase 1, Proteomics, STAT5 Transcription Factor, Tretinoin pharmacology, Leukemia, Leukemia, Myeloid, Acute
- Abstract
Background: All-trans retinoic acid (ATRA), a derivate of vitamin A, has been successfully used as a therapy to induce differentiation in M3 acute promyelocytic leukemia (APML), and has led to marked improvement in outcomes. Previously, attempts to use ATRA in non-APML in the clinic, however, have been underwhelming, likely due to persistent signaling through other oncogenic drivers. Dysregulated JAK/STAT signaling is known to drive several hematologic malignancies, and targeting JAK1 and JAK2 with the JAK1/JAK2 inhibitor ruxolitinib has led to improvement in survival in primary myelofibrosis and alleviation of vasomotor symptoms and splenomegaly in polycythemia vera and myelofibrosis., Objective: While dose-dependent anemia and thrombocytopenia limit the use of JAK2 inhibition, selectively targeting JAK1 has been explored as a means to suppress inflammation and STAT-associated pathologies related to neoplastogenesis. The objective of this study is to employ JAK1 inhibition (JAK1i) in the presence of ATRA as a potential therapy in non-M3 acute myeloid leukemia (AML)., Methods: Efficacy of JAK1i using INCB52793 was assessed by changes in cell cycle and apoptosis in treated AML cell lines. Transcriptomic and proteomic analysis evaluated effects of JAK1i. Synergy between JAK1i+ ATRA was assessed in cell lines in vitro while efficacy in vivo was assessed by tumor reduction in MV-4-11 cell line-derived xenografts., Results: Here we describe novel synergistic activity between JAK1i inhibition and ATRA in non-M3 leukemia. Transcriptomic and proteomic analysis confirmed structural and functional changes related to maturation while in vivo combinatory studies revealed significant decreases in leukemic expansion., Conclusions: JAK1i+ ATRA lead to decreases in cell cycle followed by myeloid differentiation and cell death in human leukemias. These findings highlight potential uses of ATRA-based differentiation therapy of non-M3 human leukemia., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2021
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173. Development of a multi-component intervention to promote participation of Black and Latinx individuals in biomedical research.
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Danila MI, Allison JJ, Goins KV, Chiriboga G, Fischer M, Puliafico M, Mudano AS, Rahn EJ, Merchant J, Lawrence CE, Dunkel L, Israel T, Barton B, Jenoure F, Alexander T, Cruz D, Douglas M, Sims J, Richmond A, Roberson ED, Chambless C, Harris PA, Saag KG, and Lemon SC
- Abstract
Introduction: Barriers to research participation by racial and ethnic minority group members are multi-factorial, stem from historical social injustices and occur at participant, research team, and research process levels. The informed consent procedure is a key component of the research process and represents an opportunity to address these barriers. This manuscript describes the development of the Strengthening Translational Research in Diverse Enrollment (STRIDE) intervention, which aims to improve research participation by individuals from underrepresented groups., Methods: We used a community-engaged approach to develop an integrated, culturally, and literacy-sensitive, multi-component intervention that addresses barriers to research participation during the informed consent process. This approach involved having Community Investigators participate in intervention development activities and using community engagement studios and other methods to get feedback from community members on intervention components., Results: The STRIDE intervention has three components: a simulation-based training program directed toward clinical study research assistants that emphasizes cultural competency and communication skills for assisting in the informed consent process, an electronic consent (eConsent) framework designed to improve health-related research material comprehension and relevance, and a "storytelling" intervention in which prior research participants from diverse backgrounds share their experiences delivered via video vignettes during the consent process., Conclusions: The community engaged development approach resulted in a multi-component intervention that addresses known barriers to research participation and can be integrated into the consent process of research studies. Results of an ongoing study will determine its effectiveness at increasing diversity among research participants., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)
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- 2021
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174. In Reply to Ramotshwana et al.
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Flotte TR, Larkin AC, Fischer MA, Chimienti SN, DeMarco DM, Fan PY, and Collins MF
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- Humans, Pandemics, SARS-CoV-2, COVID-19, Physicians
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- 2021
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175. BET Inhibition Enhances the Antileukemic Activity of Low-dose Venetoclax in Acute Myeloid Leukemia.
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Ramsey HE, Greenwood D, Zhang S, Childress M, Arrate MP, Gorska AE, Fuller L, Zhao Y, Stengel K, Fischer MA, Stubbs MC, Liu PCC, Boyd K, Rathmell JC, Hiebert SW, and Savona MR
- Subjects
- Acute Disease, Animals, Antineoplastic Agents pharmacology, Apoptosis drug effects, Apoptosis genetics, Cell Cycle drug effects, Cell Cycle genetics, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation genetics, Dose-Response Relationship, Drug, Drug Synergism, Female, Gene Expression Regulation, Leukemic drug effects, HL-60 Cells, Humans, K562 Cells, Leukemia, Myeloid genetics, Leukemia, Myeloid metabolism, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Mice, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Leukemia, Myeloid drug therapy, Organic Chemicals pharmacology, Proteins antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Sulfonamides pharmacology
- Abstract
Purpose: The BCL2 inhibitor, venetoclax, has transformed clinical care in acute myeloid leukemia (AML). However, subsets of patients do not respond or eventually acquire resistance. Venetoclax-based regimens can lead to considerable marrow suppression in some patients. Bromodomain and extraterminal inhibitors (BETi) are potential treatments for AML, as regulators of critical AML oncogenes. We tested the efficacy of novel BET inhibitor INCB054329, and its synergy with venetoclax to reduce AML without induction of hematopoietic toxicity., Experimental Design: INCB054329 efficacy was assessed by changes in cell cycle and apoptosis in treated AML cell lines. In vivo efficacy was assessed by tumor reduction in MV-4-11 cell line-derived xenografts. Precision run-on and sequencing (PRO-seq) evaluated effects of INCB054329. Synergy between low-dose BETi and venetoclax was assessed in cell lines and patient samples in vitro and in vivo while efficacy and toxicity was assessed in patient-derived xenograft (PDX) models., Results: INCB054329 induced dose-dependent apoptosis and quiescence in AML cell lines. PRO-seq analysis evaluated the effects of INCB054329 on transcription and confirmed reduced transcriptional elongation of key oncogenes, MYC and BCL2 , and genes involved in the cell cycle and metabolism. Combinations of BETi and venetoclax led to reduced cell viability in cell lines and patient samples. Low-dose combinations of INCB054329 and venetoclax in cell line and PDX models reduced AML burden, regardless of the sensitivity to monotherapy without development of toxicity., Conclusions: Our findings suggest low dose combinations of venetoclax and BETi may be more efficacious for patients with AML than either monotherapy, potentially providing a longer, more tolerable dosing regimen., (©2020 American Association for Cancer Research.)
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- 2021
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176. University of Massachusetts Medical School.
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Larkin AC and Fischer MA
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- 2020
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177. Venetoclax response is enhanced by selective inhibitor of nuclear export compounds in hematologic malignancies.
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Fischer MA, Friedlander SY, Arrate MP, Chang H, Gorska AE, Fuller LD, Ramsey HE, Kashyap T, Argueta C, Debler S, Byrne M, Villaume MT, Shaver AC, Senapedis W, Landesman Y, Baloglu E, Shacham S, and Savona MR
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- Active Transport, Cell Nucleus, Cell Line, Tumor, Humans, Sulfonamides, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Hematologic Neoplasms drug therapy
- Abstract
The selective inhibitor of nuclear export (SINE) compounds selinexor (KPT-330) and eltanexor (KPT-8602) are from a novel class of small molecules that target exportin-1 (XPO1 [CRM1]), an essential nucleo-cytoplasmic transport protein responsible for the nuclear export of major tumor suppressor proteins and growth regulators such as p53, p21, and p27. XPO1 also affects the translation of messenger RNAs for critical oncogenes, including MYC, BCL2, MCL1, and BCL6, by blocking the export of the translation initiation factor eIF4E. Early trials with venetoclax (ABT-199), a potent, selective inhibitor of BCL2, have revealed responses across a variety of hematologic malignancies. However, many tumors are not responsive to venetoclax. We used models of acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) to determine in vitro and in vivo responses to treatment with venetoclax and SINE compounds combined. Cotreatment with venetoclax and SINE compounds demonstrated loss of viability in multiple cell lines. Further in vitro analyses showed that this enhanced cell death was the result of an increase in apoptosis that led to a loss of clonogenicity in methylcellulose assays, coinciding with activation of p53 and loss of MCL1. Treatment with SINE compounds and venetoclax combined led to a reduction in tumor growth in both AML and DLBCL xenografts. Immunohistochemical analysis of tissue sections revealed that the reduction in tumor cells was partly the result of an induction of apoptosis. The enhanced effects of this combination were validated in primary AML and DLBCL patient cells. Our studies reveal synergy with SINE compounds and venetoclax in aggressive hematologic malignancies and provide a rationale for pursuing this approach in a clinical trial., (© 2020 by The American Society of Hematology.)
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- 2020
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178. Developing an opioid curriculum for medical students: A consensus report from a national symposium.
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Wallace PM, Warrier S, Kahn MJ, Welsh C, and Fischer M
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- Analgesics, Opioid, Consensus, Curriculum, Humans, Education, Medical, Undergraduate, Students, Medical
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In June 2018, the Warren Alpert Medical School of Brown University hosted a national, multidisciplinary, interprofessional symposium on opioid curricula in undergraduate medical education. This article presents the consensus of an interprofessional group who attended a session focused on elements of an opioid curriculum, including key areas of content, teaching modalities, and learner assessment. This report also includes further directions and next steps for undergraduate medical education collaboration on opioid curricula.
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- 2020
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179. Simulation-based power and sample size calculation for designing interrupted time series analyses of count outcomes in evaluation of health policy interventions.
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Liu W, Ye S, Barton BA, Fischer MA, Lawrence C, Rahn EJ, Danila MI, Saag KG, Harris PA, Lemon SC, Allison JJ, and Zhang B
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Objective: The purpose of this study was to present the design, model, and data analysis of an interrupted time series (ITS) model applied to evaluate the impact of health policy, systems, or environmental interventions using count outcomes. Simulation methods were used to conduct power and sample size calculations for these studies., Methods: We proposed the models and analyses of ITS designs for count outcomes using the Strengthening Translational Research in Diverse Enrollment (STRIDE) study as an example. The models we used were observation-driven models, which bundle a lagged term on the conditional mean of the outcome for a time series of count outcomes., Results: A simulation-based approach with ready-to-use computer programs was developed to calculate the sample size and power of two types of ITS models, Poisson and negative binomial, for count outcomes. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9, with various effect sizes. The power to detect the same magnitude of parameters varied largely, depending on the testing level change, the trend change, or both. The relationships between power and sample size and the values of the parameters were different between the two models., Conclusion: This article provides a convenient tool to allow investigators to generate sample sizes that will ensure sufficient statistical power when the ITS study design of count outcomes is implemented., Competing Interests: None., (© 2019 The Authors.)
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- 2019
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180. Perioperative Outcomes, Complications, and Efficacy of Robotic-Assisted Prolapse Repair: A Single Institution Study of 196 Patients.
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Gupta P, Ehlert M, Bartley J, Gilleran J, Killinger KA, Boura JA, Nagaraju P, and Fischer M
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- Female, Humans, Laparoscopy adverse effects, Middle Aged, Operative Time, Postoperative Complications etiology, Retrospective Studies, Robotic Surgical Procedures adverse effects, Surgical Mesh, Treatment Outcome, Laparoscopy methods, Pelvic Organ Prolapse surgery, Robotic Surgical Procedures methods
- Abstract
Abdominal pelvic organ prolapse repair is efficacious for uterovaginal and apical prolapse. We describe the safety and efficacy of robotic prolapse repair in a large teaching institution., Methods: Consecutive robotic-assisted prolapse repairs at a single institution between 2006 and 2014 were retrospectively reviewed for patient characteristics, operative information, and outcomes., Results: A total of 196 women (mean age, 61 ± 9 years) underwent robotic prolapse repair (189 sacrocolpopexy, 6 sacrohysteropexy, 1 enterocele repair). Concomitant procedures included hysterectomy (88), midurethral sling (84), and/or Burch colposuspension (7). Mean odds ratio time was 242 ± 69.9 minutes, and median length of stay was 1 day. Intraoperative complications were as follows: cystotomy (4), vaginotomy (4), conversion to open (2), bowel injury/aborted (1), adhesions/aborted (1), and ureteral injury (1). Women with complications had greater blood loss than those without complications (P = 0.0015). Immediate (<30 days) postoperative complications were rare: port-site hernia (2), discitis (1), ileus (1), and ulnar neuropraxia (3). At median follow-up of 9 months (range, 0-85 months), 14 women had recurrent grade 3 prolapse, and 4 had grade 2 apical prolapse. Nine of 14 women had additional prolapse repair at a mean of 9.5 ± 6.3 months. Vaginal mesh exposure was detected in 12 (6.3%) of 192 women. There were 6 procedures for mesh exposure and 2 procedures for exposed sutures. One mesh erosion into the bladder required open excision., Conclusions: In this large series of robotic prolapse repair, complications are infrequent. Short-term apical outcomes are excellent. Few women required additional compartment repairs within 1 year with 6% rate of mesh exposure.
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- 2018
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181. Education Research: A framework for global health curricula for neurology trainees.
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Deb A, Fischer M, and DePold Hohler A
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- Humans, Program Development, Program Evaluation, Curriculum, Global Health education, Internship and Residency organization & administration, Neurology education
- Abstract
As the global burden of neurologic disease increases, educating future neurologists about the principles of global health through global health curricula is of utmost importance. However, few neurology residency training programs have developed and implemented comprehensive global health curricula. This report outlines the design, implementation, and evaluation of the University of Massachusetts Medical School neurology residency global health curriculum. Using accepted curriculum development methods and incorporating an innovative use of technology, we created a global health curriculum focused on neurology to engage trainees. The implementation of curricula and organization of elective opportunities also incorporates learning objectives and an evaluation process. The University of Massachusetts Medical School neurology global health curriculum can be used as a framework for other residency programs developing global health programs. Global health education increases young neurologists' awareness of the growing burden of neurologic disease and, subsequently, may motivate them to address the need for neurologic expertise around the world., (© 2018 American Academy of Neurology.)
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- 2018
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182. Biotechnologically produced microbial alginate dressings show enhanced gel forming capacity compared to commercial alginate dressings of marine origin.
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Hoefer D, Schnepf JK, Hammer TR, Fischer M, and Marquardt C
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- Azotobacter vinelandii classification, Biological Products chemistry, Biotechnology methods, Glucuronic Acid biosynthesis, Glucuronic Acid chemistry, Hexuronic Acids chemistry, Materials Testing, Species Specificity, Wound Healing, Alginates chemistry, Azotobacter vinelandii metabolism, Biological Dressings, Gels chemical synthesis, Glycerol metabolism
- Abstract
Marine alginate fibre dressings are well established in wound management. Alginate fibres can absorb plenty of wound exudate due to their gel forming abilities and ion exchange. Alginates from bacteria have never been studied for medical applications so far, although the microbial polymer raises expectations for improved gelling capacity due to its unique O-acetylation. To prove the gelling capacity of bacterial alginate, we extracted the co-polymer from fermentation of the soil bacterium Azotobacter vinelandii ATCC 9046, cultivated on crude glycerol as an alternative carbon source. Bacterial alginate was isolated in high purity and extruded by a wet spinning method. Fibre structure and properties were characterised by infrared spectroscopy, NMR, GPC, scanning electron microscopy and tensile testing. The fibres could be processed into biocompatible needle web dressings, which showed more than twice the gel formation in saline compared to commercial dressings made of marine alginates. Gelled dressings of bacterial alginate formed stable hydrogels of sufficient shape and strength for wound healing applications. This work suggests that the increased gel formation of bacterial alginate from A. vinelandii may be optimal for the preparation of novel wound dressings.
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- 2015
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183. HDAC3 is essential for DNA replication in hematopoietic progenitor cells.
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Summers AR, Fischer MA, Stengel KR, Zhao Y, Kaiser JF, Wells CE, Hunt A, Bhaskara S, Luzwick JW, Sampathi S, Chen X, Thompson MA, Cortez D, and Hiebert SW
- Subjects
- Animals, Bone Marrow Cells physiology, Bone Marrow Transplantation, Cell Differentiation, Cell Proliferation, Cells, Cultured, Hematopoietic Stem Cells physiology, Lymphopoiesis, Mice, Mice, Inbred C57BL, Mice, Knockout, S Phase, Spleen pathology, Transcriptome, DNA Replication, Hematopoietic Stem Cells enzymology, Histone Deacetylases physiology
- Abstract
Histone deacetylase 3 (HDAC3) contributes to the regulation of gene expression, chromatin structure, and genomic stability. Because HDAC3 associates with oncoproteins that drive leukemia and lymphoma, we engineered a conditional deletion allele in mice to explore the physiological roles of Hdac3 in hematopoiesis. We used the Vav-Cre transgenic allele to trigger recombination, which yielded a dramatic loss of lymphoid cells, hypocellular bone marrow, and mild anemia. Phenotypic and functional analysis suggested that Hdac3 was required for the formation of the earliest lymphoid progenitor cells in the marrow, but that the marrow contained 3-5 times more multipotent progenitor cells. Hdac3(-/-) stem cells were severely compromised in competitive bone marrow transplantation. In vitro, Hdac3(-/-) stem and progenitor cells failed to proliferate, and most cells remained undifferentiated. Moreover, one-third of the Hdac3(-/-) stem and progenitor cells were in S phase 2 hours after BrdU labeling in vivo, suggesting that these cells were impaired in transit through the S phase. DNA fiber-labeling experiments indicated that Hdac3 was required for efficient DNA replication in hematopoietic stem and progenitor cells. Thus, Hdac3 is required for the passage of hematopoietic stem/progenitor cells through the S phase, for stem cell functions, and for lymphopoiesis.
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- 2013
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184. Prescribers and pharmaceutical representatives: why are we still meeting?
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Fischer MA, Keough ME, Baril JL, Saccoccio L, Mazor KM, Ladd E, Von Worley A, and Gurwitz JH
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- Adult, Aged, Female, Focus Groups, Humans, Male, Middle Aged, Qualitative Research, Cognitive Dissonance, Conflict of Interest, Drug Industry ethics, Ethics, Medical, Marketing ethics, Physicians ethics, Practice Patterns, Physicians' ethics
- Abstract
Context: Research suggests that pharmaceutical marketing influences prescribing and may cause cognitive dissonance for prescribers. This work has primarily been with physicians and physician-trainees. Questions remain regarding why prescribers continue to meet with pharmaceutical representatives (PRs)., Objective: To describe the reasons that prescribers from various health professions continue to interact with PRs despite growing evidence of the influence of these interactions., Design, Setting, and Participants: Multi-disciplinary focus groups with 61 participants held in practice settings and at society meetings., Results: Most prescribers participating in our focus groups believe that overall PR interactions are beneficial to patient care and practice health. They either trust the information from PRs or feel that they are equipped to evaluate it independently. Despite acknowledgement of study findings to the contrary, prescribers state that they are able to effectively manage PR interactions such that their own prescribing is not adversely impacted. Prescribers describe few specific strategies or policies for these interactions, and report that policies are not consistently implemented with all members of a clinic or institution. Some prescribers perceive an inherent contradiction between academic centers and national societies receiving money from pharmaceutical companies, and then recommending restriction at the level of the individual prescriber. Prescribers with different training backgrounds present a few novel reasons for these meetings., Conclusions: Despite evidence that PR detailing influences prescribing, providers from several health professions continue to believe that PR interactions improve patient care, and that they can adequately evaluate and filter information presented to them by PRs. Focus group comments suggest that cultural change is necessary to break the norms that exist in many settings. Applying policies consistently, considering non-physician members of the healthcare team, working with trainees, restructuring the current primary care model and offering convenient, individualized, non-biased educational options may aid success.
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- 2009
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185. Between two worlds: a multi-institutional qualitative analysis of students' reflections on joining the medical profession.
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Fischer MA, Harrell HE, Haley HL, Cifu AS, Alper E, Johnson KM, and Hatem D
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- Career Choice, Humans, Writing, Clinical Clerkship, Internal Medicine education, Students, Medical psychology
- Abstract
Background: Recent changes in healthcare system and training mandates have altered the clinical learning environment. We incorporated reflective writing into Internal Medicine clerkships (IMcs) in multiple institutions so students could consider the impact of clerkship experiences on their personal and professional development. We analyzed student reflections to inform curricula and support learning., Methods: We qualitatively analyzed the reflections of students at 3 US medical schools during IMcs (N = 292) to identify themes, tone, and reflective quality using an iterative approach. Chi-square tests assessed differences between these factors and across institutions., Findings: Students openly described powerful experiences. Major themes focused on 4 categories: personal issues (PI), professional development (PD), relational issues (RI), and medical care (MC). Each major theme was represented at each institution, although with significant variability between institutions in many of the subcategories including student role (PI), development-as-a-physician (PD), professionalism (PD) (p < 0.001). Students used positive tones to describe student role, development-as-a-physician and physician-patient relationship (PD) (p < 0.01-0.001), and negative tones for quality and safety (MC) (p < 0.05). Only 4% of writings coded as professionalism had a positive tone. Students employed a "reporting" voice in writing about clinical problem-solving, healthcare systems, and quality/safety (MC)., Discussion: Reflection is considered important to professional development. Our analysis suggests that students at 3 institutions reflect on similar experiences. Theme variability across institutions implies curricula should be tailored to local culture. Reflective quality analysis suggests students are better equipped to reflect on certain experiences over others, which may impact learning. Student reflections can function as a mirror for our organizations, offer institutional feedback for support and improvement, and inform curricula for learners and faculty.
- Published
- 2008
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