315 results on '"Adam L. Cohen"'
Search Results
2. Functional prediction of response to therapy prior to therapeutic intervention is associated with improved survival in patients with high-grade glioma
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Aubrey Ledford, Analiz Rodriguez, Lindsay Lipinski, Ajay Abad, Robert Fenstermaker, Jeffrey Edenfield, Charles Kanos, Navid Redjal, Alireza Mansouri, Brad Zacharia, Nicholas Butowski, Jesse Liu, Seunggu J. Han, Mateo Ziu, Adam L. Cohen, Andrew J. Fabiano, Katherine Miles, Melissa Rayner, Jayla Thompson, Kelley Tollison, Pedram Azimzadeh, Lillia Holmes, Matthew Gevaert, and Teresa M. DesRochers
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Medicine ,Science - Abstract
Abstract Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient’s response to this treatment regimen. Tumor tissues isolated from patients with newly diagnosed HGG enrolled in 3D PREDICT REGISTRY were evaluated for response to chemotherapeutic agents using the 3D Predict™ Glioma test. Patients receiving RT/TMZ were followed for 2 years. Clinical outcomes including imaging, assessments, and biomarker measurements were compared to patient matched test-predicted therapy response. Median survival between test-predicted temozolomide responders and test-predicted temozolomide non-responders revealed a statistically significant increase in progression-free survival when using the test to predict response across multiple subgroups including HGG (5.8 months), glioblastoma (4.7 months), and MGMT unmethylated glioblastoma (4.7 months). Overall survival was also positively separated across the subgroups at 7.6, 5.1, and 6.3 months respectively. The strong correlation of 3D Predict Glioma test results with clinical outcomes demonstrates that this functional test is prognostic in patients treated with RT/TMZ and supports aligning clinical treatment to test-predicted response across varying HGG subgroups.
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- 2024
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3. Is there an optimal time to administer postoperative stereotactic radiosurgery in patients with brain metastases? A systematic review of the literature and meta‐analysis
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Anthony Nwankwo, Danielle D. Dang, Kevin Choe, Samir Kanani, Adam L. Cohen, and Mateo Ziu
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metastatic brain cancer ,intracranial metastases ,stereotactic radiosurgery ,adjuvant radiation ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Postoperative stereotactic radiosurgery improves local tumor control in patients with metastatic brain cancer. However, the influence of timing on its therapeutic efficacy is unclear. In this study, we performed a meta‐analysis and systematic literature review examining publications that reported the timing of postoperative stereotactic radiosurgery (SRS) for patients with intracranial metastases. Our primary outcomes included median overall survival and rates of local and regional failure, while secondary outcomes examined the incidence of treatment‐related adverse events. Correlations between median SRS timing and these variables were assessed using linear regression and publication bias was appraised via Egger's test. Our study resulted in 22 articles comprising 1338 patients. The median timing of adjuvant SRS spanned 14.5 to 41 days. There was a significant negative study‐level correlation of median time to SRS with regional failure (p = 0.043, R2 = 0.32) but not with overall survival (p = 0.54, R2 = 0.03) or local failure (p = 0.16, R2 = 0.14). Additionally, there was significant heterogeneity within the reports (p
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- 2023
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4. The attributable fraction of respiratory syncytial virus among patients of different ages with influenza-like illness and severe acute respiratory illness in a high HIV prevalence setting, South Africa, 2012-2016
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Jocelyn Moyes, Stefano Tempia, Sibongile Walaza, Meredith L. McMorrow, Adam L. Cohen, Florette Treurnicht, Orienka Hellferscee, Nicole Wolter, Anne Von Gottberg, Halima Dawood, Ebrahim Variava, Kathleen Kahn, Shabir A. Madhi, and Cheryl Cohen
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Attributable fraction ,Respiratory syncytial virus ,Burden of disease ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: The detection of respiratory syncytial virus (RSV) in upper airway samples does not necessarily infer causality of illness. We aimed to calculate the attributable fraction (AF) of RSV in clinical syndromes across age groups. Methods: Using unconditional logistic regression models, we estimated the AF of RSV-associated influenza-like illness (ILI) and severe acute respiratory illness (SARI) cases by comparing RSV detection prevalence among ILI and SARI cases to those of healthy controls in South Africa, 2012-2016. The analysis, stratified by HIV serostatus, was conducted in the age categories
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- 2023
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5. The economic burden of RSV-associated illness in children aged
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Jocelyn Moyes, Stefano Tempia, Sibongile Walaza, Meredith L. McMorrow, Florette Treurnicht, Nicole Wolter, Anne von Gottberg, Kathleen Kahn, Adam L. Cohen, Halima Dawood, Ebrahim Variava, and Cheryl Cohen
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Burden ,Cost ,Respiratory syncytial virus ,Children ,Respiratory illness ,Medicine - Abstract
Abstract Background Data on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated the cost of RSV-associated illness in fine age bands to allow more accurate cost-effectiveness models to account for a limited duration of protection conferred by short- or long-acting interventions. Methods We conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests, and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalizations or clinic visits; the PDE was multiplied by the number of days of care to provide a case cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged
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- 2023
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6. The burden of RSV-associated illness in children aged
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Jocelyn Moyes, Stefano Tempia, Sibongile Walaza, Meredith L. McMorrow, Florette Treurnicht, Nicole Wolter, Anne von Gottberg, Kathleen Kahn, Adam L. Cohen, Halima Dawood, Ebrahim Variava, and Cheryl Cohen
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Burden ,Respiratory syncytial virus ,Children ,Respiratory illness ,Medicine - Abstract
Abstract Background Vaccines and monoclonal antibodies to protect the very young infant against the respiratory syncytial virus (RSV)-associated illness are effective for limited time periods. We aimed to estimate age-specific burden to guide implementation strategies and cost-effectiveness analyses. Methods We combined case-based surveillance and ecological data to generate a national estimate of the burden of RSV-associated acute respiratory illness (ARI) and severe acute respiratory illness (SARI) in South African children aged
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- 2023
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7. Clinicopathologic and sociodemographic factors associated with late relapse triple negative breast cancer in a multivariable logistic model: A multi-institution cohort study
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Adith Abraham, Carlos H. Barcenas, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Ellis G. Levine, Nancy U. Lin, Beverly Moy, Joyce C. Niland, Antonio C. Wolff, Michael J. Hassett, Sarah Asad, and Daniel G. Stover
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Triple-negative breast cancer ,Late relapse ,Body mass index ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Most metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features. Methods: We included patients diagnosed with stage I–III TNBC between 1998 and 2012 at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p
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- 2023
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8. Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020–2021
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David C. Shih, Rachel Silver, Olga L. Henao, Aynalem Alemu, Allan Audi, Godfrey Bigogo, Josh M. Colston, Elijah P. Edu-Quansah, Timothy A. Erickson, Andargachew Gashu, G. Burgess Gbelee, Sarah M. Gunter, Margaret N. Kosek, Gorbee G. Logan, Joy M. Mackey, Adrianna Maliga, Russell Manzanero, Gerhaldine Morazan, Francis Morey, Flor M. Munoz, Kristy O. Murray, Thelma V. Nelson, Maribel Paredes Olortegui, Pablo Penataro Yori, Shannon E. Ronca, Francesca Schiaffino, Adamu Tayachew, Musse Tedasse, Mesfin Wossen, Denise R. Allen, Pawan Angra, Amanda Balish, Madeline Farron, Marta Guerra, Amy Herman-Roloff, Victoria J. Hicks, Elizabeth Hunsperger, Lilit Kazazian, Matt Mikoleit, Peninah Munyua, Patrick K. Munywoki, Angella Sandra Namwase, Clayton O. Onyango, Michael Park, Leonard F. Peruski, David E. Sugerman, Emily Zielinski Gutierrez, and Adam L. Cohen
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COVID-19 ,respiratory infections ,severe acute respiratory syndrome coronavirus 2 ,SARS-CoV-2 ,SARS ,coronavirus disease ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020–October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.
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- 2022
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9. Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies
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Xiaomeng Huang, Yi Qiao, Samuel W. Brady, Rachel E. Factor, Erinn Downs-Kelly, Andrew Farrell, Jasmine A. McQuerry, Gajendra Shrestha, David Jenkins, W. Evan Johnson, Adam L. Cohen, Andrea H. Bild, and Gabor T. Marth
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Tumor evolution ,Subclone ,Metastatic breast cancer ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood. Methods Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor’s evolution at subclonal resolution. Results The most unique, previously unreported aspect of the tumor’s evolution that we observed in this patient was the presence of “subclone incubators,” defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient’s metastases for effective clinical intervention. Conclusions Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.
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- 2021
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10. Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer
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Aritro Nath, Patrick A. Cosgrove, Hoda Mirsafian, Elizabeth L. Christie, Lance Pflieger, Benjamin Copeland, Sumana Majumdar, Mihaela C. Cristea, Ernest S. Han, Stephen J. Lee, Edward W. Wang, Sian Fereday, Nadia Traficante, Ravi Salgia, Theresa Werner, Adam L. Cohen, Philip Moos, Jeffrey T. Chang, David D. L. Bowtell, and Andrea H. Bild
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Science - Abstract
High-grade serous ovarian cancer (HGSOC) is prone to developing resistance to treatment. Here, the authors use single-cell RNA-seq and an analysis of archetypes, and find that shifts in metabolism and proliferation are associated with the response to treatment and clonal heterogeneity in HGSOC.
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- 2021
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11. Association between the 21-gene recurrence score and isolated locoregional recurrence in stage I-II, hormone receptor-positive breast cancer
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David D. Yang, Daniela L. Buscariollo, Angel M. Cronin, Shicheng Weng, Melissa E. Hughes, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Stephen B. Edge, Beverly Moy, Joyce C. Niland, Antonio C. Wolff, Michael J. Hassett, and Rinaa S. Punglia
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Breast cancer ,Locoregional recurrence ,Recurrence score ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Although the 21-gene recurrence score (RS) assay is widely used to predict distant recurrence risk and benefit from adjuvant chemotherapy among women with hormone receptor-positive (HR+) breast cancer, the relationship between the RS and isolated locoregional recurrence (iLRR) remains poorly understood. Therefore, we examined the association between the RS and risk of iLRR for women with stage I-II, HR+ breast cancer. Methods We identified 1758 women captured in the national prospective Breast Cancer-Collaborative Outcomes Research Database who were diagnosed with stage I-II, HR+ breast cancer from 2006 to 2012, treated with mastectomy or breast-conserving surgery, and received RS testing. Women who received neoadjuvant therapy were excluded. The association between the RS and risk of iLRR was examined using competing risks regression. Results Overall, 19% of the cohort (n = 329) had a RS ≥25. At median follow-up of 29 months, only 22 iLRR events were observed. Having a RS ≥25 was not associated with a significantly higher risk of iLRR compared to a RS
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- 2020
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12. Multicountry Analysis of Spectrum of Clinical Manifestations of Children
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Jillian Murray, S. Yati Soenarto, Nenny S. Mulyani, Pushpa S. Wijesinghe, Evans M. Mpabalwani, Julia C. Simwaka, Belem Matapo, Jason M. Mwenda, Gayane Sahakyan, Svetlana Grigoryan, Artavazd Vanyan, Sergey Khactatryan, Jennifer Sanwogou, Lúcia Helena de Oliveira, Gloria Rey-Benito, Gagandeep Kang, Fatima Serhan, Jacqueline E. Tate, Negar Aliabadi, and Adam L. Cohen
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multicountry analysis ,spectrum ,clinical manifestations ,children ,child surveillance ,hospitalizations ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
After introduction of rotavirus vaccine, other pathogens might become leading causes of hospitalizations for severe diarrhea among children
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- 2019
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13. SARS-CoV-2 Breakthrough Infections among US Embassy Staff Members, Uganda, May–June 2021
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Julie R. Harris, Daniel Owusu, Kevin O’Laughlin, Adam L. Cohen, Amen Ben Hamida, Jaymin C. Patel, Molly M. Freeman, Thomas Nsibambi, Rebecca Nieves, Barbara J. Marston, Samuel Wasike, Jennifer S. Galbraith, Amy L. Boore, Lisa J. Nelson, Sarah Anne J. Guagliardo, John D. Klena, Ketan Patel, and Marek Ma
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COVID-19 ,respiratory infections ,severe acute respiratory syndrome coronavirus 2 ,SARS-CoV-2 ,SARS ,coronavirus disease ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
The SARS-CoV-2 Delta variant emerged shortly after COVID-19 vaccines became available in 2021. We describe SARS-CoV-2 breakthrough infections in a highly vaccinated, well-monitored US Embassy community in Kampala, Uganda. Defining breakthrough infection rates in highly vaccinated populations can help determine public health messaging, guidance, and policy globally.
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- 2022
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14. The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database
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Sarah Hummel, Wendy Kohlmann, Thomas M. Kollmeyer, Robert Jenkins, Joshua Sonnen, Cheryl A. Palmer, Howard Colman, Diana Abbott, Lisa Cannon-Albright, and Adam L. Cohen
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Molecular epidemiology ,IDH ,rs55705857 ,Oligodendroglioma ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background IDH1/2 mutated glioma has been associated with a germline risk variant, the rs55705857 G allele. The Utah Population Database (UPDB), a computerized genealogy of people in Utah, is a unique resource to evaluate cancer risk in related individuals. Methods One hundred and two individuals with IDH1/2 mutant or 1p/19q co-deleted glioma were genotyped and linked to the UPDB. DNA came from blood (21), tumor tissue (43), or both (38). We determined congruence between somatic and germline samples and estimated the relative risk for developing cancer to first and second-degree relatives of G and A allele carriers at rs55705857. Results Somatic (glioma) DNA had 85.7% sensitivity (CI 57.2–98.2%) and 95.8% specificity (CI 78.9–99.89%) for germline rs55705857 G allele. Forty-one patients were linked to pedigrees in the UPDB with at least three generations of data. First-degree relatives of rs55705857 G allele carriers were at significantly increased risk for developing cancer (RR = 1.72, p = 0.045, CI 1.02–2.94), and specifically for oligodendroglioma (RR = 57.61, p = 0.017, CI 2.96–320.98) or prostate cancer (RR = 4.10, p = 0.008, CI 1.62–9.58); relatives of individuals without the G allele were not at increased risk. Second-degree relatives of G allele carriers also had significantly increased risk for developing cancer (RR = 1.50, p = 0.007, CI 1.15–2.01). Conclusions Tumor DNA may approximate genotype at the rs55705857 locus. We confirmed this locus confers an increased risk of all cancers and especially of oligodendroglioma. No increased cancer or brain tumor risk is seen in family members of individuals without the high-risk G allele.
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- 2019
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15. Responses to hypothetical health scenarios overestimate healthcare utilization for common infectious syndromes: a cross-sectional survey, South Africa, 2012
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Karen K. Wong, Adam L. Cohen, Neil A. Martinson, Shane A. Norris, Stefano Tempia, Claire von Mollendorf, Sibongile Walaza, Shabir A. Madhi, Meredith L. McMorrow, and Cheryl Cohen
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Pneumonia ,Influenza ,Diarrhea ,Meningitis ,South Africa ,Healthcare utilization ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Asking people how they would seek healthcare in a hypothetical situation can be an efficient way to estimate healthcare utilization, but it is unclear how intended healthcare use corresponds to actual healthcare use. Methods We performed a cross-sectional survey between August and September 2012 among households in Soweto and Klerksdorp, South Africa, to compare healthcare seeking behaviors intended for hypothetical common infectious syndromes (pneumonia, influenza-like illness [ILI], chronic respiratory illness, meningitis in persons of any age, and diarrhea in a child
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- 2018
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16. Combating subclonal evolution of resistant cancer phenotypes
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Samuel W. Brady, Jasmine A. McQuerry, Yi Qiao, Stephen R. Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, Brent S. Pedersen, Ryan H. Miller, Amanda Esch, Sara R. Selitsky, Joel S. Parker, Layla A. Anderson, Brian K. Dalley, Rachel E. Factor, Chakravarthy B. Reddy, Jonathan P. Boltax, Dean Y. Li, Philip J. Moos, Joe W. Gray, Laura M. Heiser, Saundra S. Buys, Adam L. Cohen, W. Evan Johnson, Aaron R. Quinlan, Gabor Marth, Theresa L. Werner, and Andrea H. Bild
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Science - Abstract
In metastatic breast cancer, subclonal evolution can drive drug resistance. Here, the authors genetically and transcriptionally follow the evolution of four breast cancers over time and treatment, and suggest a phenotype-targeted treatment strategy to adapt to cancer as it evolves.
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- 2017
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17. Attributable Fraction of Influenza Virus Detection to Mild and Severe Respiratory Illnesses in HIV-Infected and HIV-Uninfected Patients, South Africa, 2012–2016
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Stefano Tempia, Sibongile Walaza, Jocelyn Moyes, Adam L. Cohen, Claire von Mollendorf, Meredith L. McMorrow, Florette K. Treurnicht, Marietjie Venter, Marthi Pretorius, Orienka Hellferscee, Nicole Wolter, Anne von Gottberg, Athermon Nguweneza, Johanna M. McAnerney, Halima Dawood, Ebrahim Variava, Shabir A. Madhi, and Cheryl Cohen
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influenza ,attributable fraction ,respiratory illness ,viruses ,HIV ,HIV-infected patients ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
The attributable fraction (AF) of influenza virus detection to illness has not been described for patients in different age groups or with different HIV infection statuses. We compared the age group–specific prevalence of influenza virus infection among patients with influenza-like illness (ILI) or severe acute or chronic respiratory illness (SARI and SCRI, respectively) with that among controls, stratified by HIV serostatus. The overall AF for influenza virus detection to illness was 92.6% for ILI, 87.4% for SARI, and 86.2% for SCRI. Among HIV-uninfected patients, the AF for all syndromes was highest among persons 65 years of age and lowest among persons 25–44 years of age; this trend was not observed among HIV-infected patients. Overall, influenza viruses when detected in patients with ILI, SARI, or SCRI are likely attributable to illness. This finding is particularly likely among children and the elderly irrespective of HIV serostatus and among HIV-infected persons irrespective of age.
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- 2017
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18. Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project
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Maria Garcia Quesada, Yangyupei Yang, Julia C. Bennett, Kyla Hayford, Scott L. Zeger, Daniel R. Feikin, Meagan E. Peterson, Adam L. Cohen, Samanta C. G. Almeida, Krow Ampofo, Michelle Ang, Naor Bar-Zeev, Michael G. Bruce, Romina Camilli, Grettel Chanto Chacón, Pilar Ciruela, Cheryl Cohen, Mary Corcoran, Ron Dagan, Philippe De Wals, Stefanie Desmet, Idrissa Diawara, Ryan Gierke, Marcela Guevara, Laura L. Hammitt, Markus Hilty, Pak-Leung Ho, Sanjay Jayasinghe, Jackie Kleynhans, Karl G. Kristinsson, Shamez N. Ladhani, Allison McGeer, Jason M. Mwenda, J. Pekka Nuorti, Kazunori Oishi, Leah J. Ricketson, Juan Carlos Sanz, Larisa Savrasova, Lena Petrova Setchanova, Andrew Smith, Palle Valentiner-Branth, Maria Teresa Valenzuela, Mark van der Linden, Nina M. van Sorge, Emmanuelle Varon, Brita A. Winje, Inci Yildirim, Jonathan Zintgraff, Maria Deloria Knoll, and the PSERENADE Team
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pneumococcal meningitis ,serotype distribution ,PCV impact ,global ,meta-analysis ,Biology (General) ,QH301-705.5 - Abstract
Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases N = 32; cases = 4503), PCV13 types caused 14% in
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- 2021
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19. Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project
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Maria Deloria Knoll, Julia C. Bennett, Maria Garcia Quesada, Eunice W. Kagucia, Meagan E. Peterson, Daniel R. Feikin, Adam L. Cohen, Marissa K. Hetrich, Yangyupei Yang, Jenna N. Sinkevitch, Krow Ampofo, Laurie Aukes, Sabrina Bacci, Godfrey Bigogo, Maria-Cristina C. Brandileone, Michael G. Bruce, Romina Camilli, Jesús Castilla, Guanhao Chan, Grettel Chanto Chacón, Pilar Ciruela, Heather Cook, Mary Corcoran, Ron Dagan, Kostas Danis, Sara de Miguel, Philippe De Wals, Stefanie Desmet, Yvonne Galloway, Theano Georgakopoulou, Laura L. Hammitt, Markus Hilty, Pak-Leung Ho, Sanjay Jayasinghe, James D. Kellner, Jackie Kleynhans, Mirjam J. Knol, Jana Kozakova, Karl Gústaf Kristinsson, Shamez N. Ladhani, Claudia S. Lara, Maria Eugenia León, Tiia Lepp, Grant A. Mackenzie, Lucia Mad’arová, Allison McGeer, Tuya Mungun, Jason M. Mwenda, J. Pekka Nuorti, Néhémie Nzoyikorera, Kazunori Oishi, Lucia Helena De Oliveira, Metka Paragi, Tamara Pilishvili, Rodrigo Puentes, Eric Rafai, Samir K. Saha, Larisa Savrasova, Camelia Savulescu, J. Anthony Scott, Kevin J. Scott, Fatima Serhan, Lena Petrova Setchanova, Nadja Sinkovec Zorko, Anna Skoczyńska, Todd D. Swarthout, Palle Valentiner-Branth, Mark van der Linden, Didrik F. Vestrheim, Anne von Gottberg, Inci Yildirim, Kyla Hayford, and the PSERENADE Team
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global ,invasive pneumococcal disease ,pneumococcal meningitis ,surveillance ,pneumococcal conjugate vaccines ,Biology (General) ,QH301-705.5 - Abstract
Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.
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- 2021
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20. Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project
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Julia C. Bennett, Marissa K. Hetrich, Maria Garcia Quesada, Jenna N. Sinkevitch, Maria Deloria Knoll, Daniel R. Feikin, Scott L. Zeger, Eunice W. Kagucia, Adam L. Cohen, Krow Ampofo, Maria-Cristina C. Brandileone, Dana Bruden, Romina Camilli, Jesús Castilla, Guanhao Chan, Heather Cook, Jennifer E. Cornick, Ron Dagan, Tine Dalby, Kostas Danis, Sara de Miguel, Philippe De Wals, Stefanie Desmet, Theano Georgakopoulou, Charlotte Gilkison, Marta Grgic-Vitek, Laura L. Hammitt, Markus Hilty, Pak-Leung Ho, Sanjay Jayasinghe, James D. Kellner, Jackie Kleynhans, Mirjam J. Knol, Jana Kozakova, Karl G. Kristinsson, Shamez N. Ladhani, Laura MacDonald, Grant A. Mackenzie, Lucia Mad’arová, Allison McGeer, Jolita Mereckiene, Eva Morfeldt, Tuya Mungun, Carmen Muñoz-Almagro, J. Pekka Nuorti, Metka Paragi, Tamara Pilishvili, Rodrigo Puentes, Samir K. Saha, Aalisha Sahu Khan, Larisa Savrasova, J. Anthony Scott, Anna Skoczyńska, Shigeru Suga, Mark van der Linden, Jennifer R. Verani, Anne von Gottberg, Brita A. Winje, Inci Yildirim, Khalid Zerouali, Kyla Hayford, and the PSERENADE Team
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invasive pneumococcal disease ,pneumococcal conjugate vaccines ,serotypes ,vaccine impact ,Biology (General) ,QH301-705.5 - Abstract
Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for
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- 2021
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21. Deaths Associated with Respiratory Syncytial and Influenza Viruses among Persons ≥5 Years of Age in HIV-Prevalent Area, South Africa, 1998–2009
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Cheryl Cohen, Sibongile Walaza, Cecile Viboud, Adam L. Cohen, Shabir A. Madhi, Marietjie Venter, Claire von Mollendorf, Jocelyn Moyes, Johanna M. McAnerney, and Stefano Tempia
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Influenza ,viruses, respiratory syncytial virus, RSV, HIV, human immunodeficiency virus, mortality rates, deaths, South Africa ,viruses ,respiratory syncytial virus ,RSV ,HIV ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We estimated deaths attributable to influenza and respiratory syncytial virus (RSV) among persons >5 years of age in South Africa during 1998–2009 by applying regression models to monthly deaths and laboratory surveillance data. Rates were expressed per 100,000 person-years. The mean annual number of seasonal influenza–associated deaths was 9,093 (rate 21.6). Persons >65 years of age and HIV-positive persons accounted for 50% (n = 4,552) and 28% (n = 2,564) of overall seasonal influenza-associated deaths, respectively. In 2009, we estimated 4,113 (rate 9.2) influenza A(H1N1)pdm09–associated deaths. The mean of annual RSV-associated deaths during the study period was 511 (rate 1.2); no RSV-associated deaths were estimated in persons >45 years of age. Our findings support the recommendation for influenza vaccination of older persons and HIV-positive persons. Surveillance for RSV should be strengthened to clarify the public health implications and severity of illness associated with RSV infection in South Africa.
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- 2015
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22. Legionnaires’ Disease in South Africa, 2012–2014
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Nicole Wolter, Maimuna Carrim, Stefano Tempia, Cheryl Cohen, Sibongile Walaza, Philip Sahr, Linda de Gouveia, Florette K. Treurnicht, Orienka Hellferscee, Adam L. Cohen, Alvaro J. Benitez, Halima Dawood, Ebrahim Variava, Jonas M. Winchell, and Anne von Gottberg
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Legionella spp. ,Legionnaires’ disease ,pneumonia ,South Africa ,Legionellosis ,legionella ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
During June 2012–September 2014, we tested patients with severe respiratory illness for Legionella spp. infection and conducted a retrospective epidemiologic investigation. Of 1,805 patients tested, Legionella was detected in samples of 21 (1.2%); most were adults who had HIV or tuberculosis infections and were inappropriately treated for Legionella.
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- 2016
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23. Epidemiology of Influenza Virus Types and Subtypes in South Africa, 2009–2012
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Adam L. Cohen, Orienka Hellferscee, Marthi Pretorius, Florette Treurnicht, Sibongile Walaza, Shabir Madhi, Michelle Groome, Halima Dawood, Ebrahim Variava, Kathleen Kahn, Nicole Wolter, Anne von Gottberg, Stefano Tempia, Marietjie Venter, and Cheryl Cohen
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influenza ,influenza A ,influenza B ,H3N2 ,H1N1 ,types ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
To determine clinical and epidemiologic differences between influenza caused by different virus types and subtypes, we identified patients and tested specimens. Patients were children and adults hospitalized with confirmed influenza and severe acute respiratory illness (SARI) identified through active, prospective, hospital-based surveillance from 2009–2012 in South Africa. Respiratory specimens were tested, typed, and subtyped for influenza virus by PCR. Of 16,005 SARI patients tested, 1,239 (8%) were positive for influenza virus. Patient age and co-infections varied according to virus type and subtype, but disease severity did not. Case-patients with influenza B were more likely than patients with influenza A to be HIV infected. A higher proportion of case-patients infected during the first wave of the 2009 influenza pandemic were 5–24 years of age (19%) than were patients infected during the second wave (9%). Although clinical differences exist, treatment recommendations do not differ according to subtype; prevention through vaccination is recommended.
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- 2014
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24. Severe Influenza-associated Respiratory Infection in High HIV Prevalence Setting, South Africa, 2009–2011
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Cheryl Cohen, Jocelyn Moyes, Stefano Tempia, Michelle Groom, Sibongile Walaza, Marthi Pretorius, Halima Dawood, Meera Chhagan, Summaya Haffejee, Ebrahim Variava, Kathleen Kahn, Akhona Tshangela, Anne von Gottberg, Nicole Wolter, Adam L. Cohen, Babatyi Kgokong, Marietjie Venter, and Shabir A. Madhi
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influenza ,HIV ,AIDS ,adults ,children ,pneumonia ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Data on influenza epidemiology in HIV-infected persons are limited, particularly for sub-Saharan Africa, where HIV infection is widespread. We tested respiratory and blood samples from patients with acute lower respiratory tract infections hospitalized in South Africa during 2009–2011 for viral and pneumococcal infections. Influenza was identified in 9% (1,056/11,925) of patients enrolled; among influenza case-patients, 358 (44%) of the 819 who were tested were infected with HIV. Influenza-associated acute lower respiratory tract infection incidence was 4–8 times greater for HIV-infected (186–228/100,000) than for HIV-uninfected persons (26–54/100,000). Furthermore, multivariable analysis showed HIV-infected patients were more likely to have pneumococcal co-infection; to be infected with influenza type B compared with type A; to be hospitalized for 2–7 days or >7 days; and to die from their illness. These findings indicate that HIV-infected persons are at greater risk for severe illnesses related to influenza and thus should be prioritized for influenza vaccination.
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- 2013
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25. Bevacizumab is Effective for Recurrent Papillary Tumor of the Pineal Region: First Report
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Adam L. Cohen, Karen Salzman, Cheryl Palmer, Randy Jensen, and Howard Colman
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Pineal tumor ,Bevacizumab ,Angiogenesis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Papillary tumor of the pineal region (PTPR) is a rare brain tumor that probably arises from ependymal cells. There are no known systemic treatments for PTPR once it is refractory to surgery and radiation. We present the first case of a durable radiographic and clinical response of a PTPR to bevacizumab, an antibody against vascular endothelial growth factor, despite multiple prior treatments. Bevacizumab may be an effective treatment for PTPR.
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- 2013
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26. Household Transmission of Pandemic (H1N1) 2009, San Antonio, Texas, USA, April–May 2009
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Oliver W. Morgan, Sharyn Parks, Trudi Shim, Patricia A. Blevins, Pauline M. Lucas, Roger Sanchez, Nancy Walea, Fleetwood Loustalot, Mark R. Duffy, Matthew J. Shim, Sandra Guerra, Fernando Guerra, Gwen Mills, Jennifer Verani, Bryan Alsip, Stephen Lindstrom, Bo Shu, Shannon L. Emery, Adam L. Cohen, Manoj Menon, Alicia M. Fry, Fatimah Dawood, Vincent P. Fonseca, and Sonja J. Olsen
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Human influenza ,viruses ,pandemic (H1N1) 2009 ,household transmission ,Texas ,research ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
To assess household transmission of pandemic (H1N1) 2009 in San Antonio, Texas, USA, during April 15–May 8, 2009, we investigated 77 households. The index case-patient was defined as the household member with the earliest onset date of symptoms of acute respiratory infection (ARI), influenza-like illness (ILI), or laboratory-confirmed pandemic (H1N1) 2009. Median interval between illness onset in index and secondary case-patients was 4 days (range 1–9 days); the index case-patient was likely to be 50 years of age (4%–12%). Early in the outbreak, household transmission primarily occurred from children to other household members and was lower than the transmission rate for seasonal influenza.
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- 2010
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27. Publisher Correction: Combating subclonal evolution of resistant cancer phenotypes
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Samuel W. Brady, Jasmine A. McQuerry, Yi Qiao, Stephen R. Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, Brent S. Pedersen, Ryan H. Miller, Amanda Esch, Sara R. Selitsky, Joel S. Parker, Layla A. Anderson, Brian K. Dalley, Rachel E. Factor, Chakravarthy B. Reddy, Jonathan P. Boltax, Dean Y. Li, Philip J. Moos, Joe W. Gray, Laura M. Heiser, Saundra S. Buys, Adam L. Cohen, W. Evan Johnson, Aaron R. Quinlan, Gabor Marth, Theresa L. Werner, and Andrea H. Bild
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Science - Abstract
The originally published version of this Article contained an error in Figure 4. In panel a, grey boxes surrounding the subclones associated with patients #2 and #4 obscured adjacent portions of the heatmap. This error has now been corrected in both the PDF and HTML versions of the Article.
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- 2018
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28. Methamphetamine Use and Methicillin-Resistant Staphylococcus aureus Skin Infections
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Adam L. Cohen, Carrie Shuler, Sigrid McAllister, Gregory E. Fosheim, Michael G. Brown, Debra Abercrombie, Karen F. Anderson, Linda K. McDougal, Cherie L. Drenzek, Katie Arnold, Daniel B. Jernigan, and Rachel Gorwitz
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Staphylococcus aureus ,methicillin resistance ,drug resistance ,methamphetamine ,street drugs ,rural health ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections and methamphetamine use are emerging public health problems. We conducted a case–control investigation to determine risk factors for MRSA skin and soft tissue infections (SSTIs) in residents of a largely rural southeastern community in the United States. Case-patients were persons >12 years old who had culturable SSTIs; controls had no SSTIs. Of 119 SSTIs identified, 81 (68.1%) were caused by MRSA. Methamphetamine use was reported in 9.9% of case-patients and 1.8% of controls. After we adjusted for age, sex, and race, patients with MRSA SSTIs were more likely than controls to have recently used methamphetamine (odds ratio 5.10, 95% confidence interval 1.55–16.79). MRSA caused most SSTIs in this population. Transmission of MRSA may be occurring among methamphetamine users in this community.
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- 2007
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29. Demographic and Clinical Characteristics of Mpox in Persons Who Had Previously Received 1 Dose of JYNNEOS Vaccine and in Unvaccinated Persons — 29 U.S. Jurisdictions, May 22–September 3, 2022
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Jennifer L. Farrar, Nathaniel M. Lewis, Kennedy Houck, Michelle Canning, Amy Fothergill, Amanda B. Payne, Adam L. Cohen, Joshua Vance, Bridget Brassil, Erin Youngkin, Bailey Glenn, Anil Mangla, Nikki Kupferman, Katharine Saunders, Cristina Meza, Dawn Nims, Susan Soliva, Brandon Blouse, Tiffany Henderson, Emily Banerjee, Brooklyn White, Rachael Birn, Anna M. Stadelman, Meaghan Abrego, Meagan McLafferty, Michael G. Eberhart, Michael Pietrowski, Sandra Miranda De León, Emma Creegan, Abdoulaye Diedhiou, Caleb Wiedeman, Jade Murray-Thompson, Elizabeth McCarty, Jessica Marcinkevage, Anna Kocharian, Elizabeth A. Torrone, Logan C. Ray, and Daniel C. Payne
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Transplantation ,Immunology and Allergy ,Pharmacology (medical) - Published
- 2023
30. Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations
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Priscilla K. Brastianos, Erin L. Twohy, Elizabeth R. Gerstner, Timothy J. Kaufmann, A. John Iafrate, Jochen Lennerz, Suriya Jeyapalan, David E. Piccioni, Varun Monga, Camilo E. Fadul, David Schiff, Jennie W. Taylor, Sajeel A. Chowdhary, Chetan Bettegowda, George Ansstas, Macarena De La Fuente, Mark D. Anderson, Nicole Shonka, Denise Damek, Jose Carrillo, Lara J. Kunschner-Ronan, Rekha Chaudhary, Kurt A. Jaeckle, Francis M. Senecal, Thomas Kaley, Tara Morrison, Alissa A. Thomas, Mary R. Welch, Fabio Iwamoto, David Cachia, Adam L. Cohen, Shivangi Vora, Michael Knopp, Ian F. Dunn, Priya Kumthekar, Jann Sarkaria, Susan Geyer, Xiomara W. Carrero, Maria Martinez-Lage, Daniel P. Cahill, Paul D. Brown, Caterina Giannini, Sandro Santagata, Frederick G. Barker, and Evanthia Galanis
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Cancer Research ,Oncology - Abstract
PURPOSE Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.
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- 2023
31. Caregiver survey in glioblastoma focused on cognitive dysfunction: development and results from a multicenter study
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Trang H Au, Connor Willis, Maija Reblin, Katherine B Peters, Phioanh Leia Nghiemphu, Jennie W Taylor, Howard Colman, Adam L Cohen, David Ryan Ormond, Elizabeth C Neil, Arnab Chakravarti, Nicole Willmarth, Bea Christine Balajonda, Jyothi Menon, Junjie Ma, Hillevi Bauer, Ryan S Nelson, Malinda S Tan, Prianka Singh, Alexander Marshall, Beata Korytowsky, David Stenehjem, and Diana Brixner
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Cancer Research ,Oncology ,General Medicine - Abstract
Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases.
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- 2023
32. Pediatric Brain Abscesses, Epidural Empyemas, and Subdural Empyemas Associated with Streptococcus Species — United States, January 2016–August 2022
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Emma K, Accorsi, Sopio, Chochua, Heidi L, Moline, Matt, Hall, Adam L, Hersh, Samir S, Shah, Amadea, Britton, Paulina A, Hawkins, Wei, Xing, Jennifer, Onukwube Okaro, Lindsay, Zielinski, Lesley, McGee, Stephanie, Schrag, and Adam L, Cohen
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Empyema, Subdural ,Health (social science) ,SARS-CoV-2 ,Epidemiology ,Health, Toxicology and Mutagenesis ,Brain Abscess ,COVID-19 ,Streptococcus ,General Medicine ,United States ,Anti-Infective Agents ,Health Information Management ,Epidural Abscess ,Humans ,Child ,Empyema ,Pandemics - Abstract
In May 2022, CDC learned of three children in California hospitalized concurrently for brain abscess, epidural empyema, or subdural empyema caused by Streptococcus intermedius. Discussions with clinicians in multiple states raised concerns about a possible increase in pediatric intracranial infections, particularly those caused by Streptococcus bacteria, during the past year and the possible contributing role of SARS-CoV-2 infection (1). Pediatric bacterial brain abscesses, epidural empyemas, and subdural empyemas, rare complications of respiratory infections and sinusitis, are often caused by Streptococcus species but might also be polymicrobial or caused by other genera, such as Staphylococcus. On June 9, CDC asked clinicians and health departments to report possible cases of these conditions and to submit clinical specimens for laboratory testing. Through collaboration with the Children's Hospital Association (CHA), CDC analyzed nationally representative pediatric hospitalizations for brain abscess and empyema. Hospitalizations declined after the onset of the COVID-19 pandemic in March 2020, increased during summer 2021 to a peak in March 2022, and then declined to baseline levels. After the increase in summer 2021, no evidence of higher levels of intensive care unit (ICU) admission, mortality, genetic relatedness of isolates from different patients, or increased antimicrobial resistance of isolates was observed. The peak in cases in March 2022 was consistent with historical seasonal fluctuations observed since 2016. Based on these findings, initial reports from clinicians (1) are consistent with seasonal fluctuations and a redistribution of cases over time during the COVID-19 pandemic. CDC will continue to work with investigation partners to monitor ongoing trends in pediatric brain abscesses and empyemas.
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- 2022
33. Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States
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Nicholas P. Deputy, Joseph Deckert, Anna N. Chard, Neil Sandberg, Danielle L. Moulia, Eric Barkley, Alexandra F. Dalton, Cory Sweet, Amanda C. Cohn, David R. Little, Adam L. Cohen, Danessa Sandmann, Daniel C. Payne, Jacqueline L. Gerhart, and Leora R. Feldstein
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General Medicine - Published
- 2023
34. CLO22-033: Clinicopathologic and Sociodemographic Factors Associated With Late Relapse Triple Negative Breast Cancer
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Adith S. Abraham, Carlos H. Barcenas, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Ellis G. Levine, Nancy U. Lin, Beverly Moy, Joyce Niland, Antonio C. Wolff, Michael J. Hassett, Daniel G. Stover, and Sarah Asad
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Oncology - Published
- 2022
35. Abstract P1-17-10: H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer - A phase II study
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Erika P Hamilton, Judy S Wang, Timothy Pluard, Aki Morikawa, E Claire Dees, Robert H Jones, Barbara Haley, Anne Armstrong, Adam L Cohen, Pamela Munster, Gail S Wright, Fadi Kayali, Lisa Cantagallo, Manav Korpal, Jenny Long, Jianjun Xiao, Benoit Destenaves, Lei Gao, Tarek Sahmoud, Antonio Gualberto, and Dejan Juric
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Cancer Research ,Oncology - Abstract
Purpose: H3B-6545, a novel Selective ERα Covalent Antagonist (SERCA), inactivates both and wild-type and mutant ERα by targeting cysteine 530 and enforcing antagonist conformation. H3B-6545 demonstrated preclinical high activity in breast cancer models with constitutively active ESR1 mutations (Furman C, SABCS 2020) and clinical activity in pretreated women with ER+ breast cancer (Hamilton EP, ASCO 2021). Patients and Methods: The primary objective of the phase II is to estimate the objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and secondary objectives include safety. Results: 94 pts were treated with 450 mg daily, the recommended phase II dose: 11 in the phase I and 83 in the phase II parts of the trial. Patients and tumor characteristics were presented previously (Hamilton EP, ASCO, 2021). As of March 31, 2021, grade (gr) 2 or higher adverse events (AE) reported in ≥10% were anemia (19%), nausea (17%), fatigue (16%), and diarrhea (12%). Laboratory gr 2 or higher abnormalities reported in ≥10% pts were creatinine clearance decrease (39%), hemoglobin decrease (38%), Lymphocytes decrease (37%), ALT increase (14%), AST increase (13%), bilirubin increase (12%), and creatinine increase (12%). AE of gr 1 sinus bradycardia (asymptomatic) was reported in 35% and gr 2 (symptomatic, no intervention needed) was reported in 5%. Gr 2 and 3 QTcF prolongation were reported in 2 and 3 pts, respectively. There were no treatment-related deaths. Efficacy estimates are presented in Table 1. CI: Confidence interval. N: total number of pts in full analysis set, used in PFS analysis. n: number of response-evaluable pts, used in ORR and CBR analysis. Efficacy estimates were consistent across the various subgroups. Responses were demonstrated in heavily pretreated pts, pts with visceral metastases, pts with constitutionally active ESR1 Y537S mutations, and in pts who received chemotherapy in the metastatic setting. Numerically higher response rate and longer PFS were observed in pts with ESR1 Y537s. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was consistent across the various subgroups. Tumors harboring the constitutionally active ESR1 Y537S mutation may present higher ERα activity, and consequently enrich for luminal A traits and demonstrate greater lineage dependence on ERα. Table 1.Consistency of H3B-6545 activity across the key subgroupsEfficacyClinical CharacteristicORR % (95% CI)CBR % (95% CI)Median PFS mo (95% CI)Overall population (N=94, n=72)16.7 (8.9, 27.3)40.3 (28.9, 52.5)5.1 (3.2, 6.2)Liver and/or lung metastases (N=76, n=62)17.7 (9.2, 29.5)41.9 (29.5, 55.2)5.4 (1.8, 7.2)≥3 prior regimens (N=49, n=39)20.5 (9.3, 36.5)48.7 (32.4, 65.2)5.4 (3.5, 7.3)Prior chemotherapy (N=47, n=35)17.1 (6.6, 33.6)51.4 (34.0, 68.6)5.5 (3.6, 7.3)PgR+ (N=38, n=32)15.6 (5.3, 32.8)50.0 (31.9, 68.1)5.4 (2.0, 8.8)ESR1 clonal Y537S (N=10, n=10)30.0 (6.7, 65.2)60.0 (26.2, 87.8)7.3 (0.8, 11.2)ESR1 clonal D538G (N=19, n=17)0.0 (0.0, 19.5)35.3 (14.2, 61.7)5.4 (1.7, 7.2) Citation Format: Erika P Hamilton, Judy S Wang, Timothy Pluard, Aki Morikawa, E Claire Dees, Robert H Jones, Barbara Haley, Anne Armstrong, Adam L Cohen, Pamela Munster, Gail S Wright, Fadi Kayali, Lisa Cantagallo, Manav Korpal, Jenny Long, Jianjun Xiao, Benoit Destenaves, Lei Gao, Tarek Sahmoud, Antonio Gualberto, Dejan Juric. H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer - A phase II study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-10.
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- 2022
36. Demographic and Clinical Characteristics of Mpox in Persons Who Had Previously Received 1 Dose of JYNNEOS Vaccine and in Unvaccinated Persons - 29 U.S. Jurisdictions, May 22-September 3, 2022
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Jennifer L, Farrar, Nathaniel M, Lewis, Kennedy, Houck, Michelle, Canning, Amy, Fothergill, Amanda B, Payne, Adam L, Cohen, Joshua, Vance, Bridget, Brassil, Erin, Youngkin, Bailey, Glenn, Anil, Mangla, Nikki, Kupferman, Katharine, Saunders, Cristina, Meza, Dawn, Nims, Susan, Soliva, Brandon, Blouse, Tiffany, Henderson, Emily, Banerjee, Brooklyn, White, Rachael, Birn, Anna M, Stadelman, Meaghan, Abrego, Meagan, McLafferty, Michael G, Eberhart, Michael, Pietrowski, Sandra Miranda, De León, Emma, Creegan, Abdoulaye, Diedhiou, Caleb, Wiedeman, Jade, Murray-Thompson, Elizabeth, McCarty, Jessica, Marcinkevage, Anna, Kocharian, Elizabeth A, Torrone, Logan C, Ray, Daniel C, Payne, and Rachel, Klos
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Male ,Vaccines ,Health (social science) ,Health Information Management ,Epidemiology ,Health, Toxicology and Mutagenesis ,Vaccinia ,Humans ,General Medicine ,United States ,Smallpox Vaccine ,Demography - Abstract
As of November 14, 2022, monkeypox (mpox) cases had been reported from more than 110 countries, including 29,133 cases in the United States.* Among U.S. cases to date, 95% have occurred among males (1). After the first confirmed U.S. mpox case on May 17, 2022, limited supplies of JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) were made available to jurisdictions for persons exposed to mpox. JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease.
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- 2022
37. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons - 43 U.S. Jurisdictions, July 31-October 1, 2022
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Amanda B. Payne, Logan C. Ray, Matthew M. Cole, Michelle Canning, Kennedy Houck, Hazel J. Shah, Jennifer L. Farrar, Nathaniel M. Lewis, Amy Fothergill, Elizabeth B. White, Leora R. Feldstein, Lauren E. Roper, Florence Lee, Jennifer L. Kriss, Emily Sims, Ian H. Spicknall, Yoshinori Nakazawa, Adi V. Gundlapalli, Tom Shimabukuro, Adam L. Cohen, Margaret A. Honein, Jonathan Mermin, and Daniel C. Payne
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Health (social science) ,Health Information Management ,Epidemiology ,Health, Toxicology and Mutagenesis ,General Medicine - Abstract
As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply
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- 2022
38. Caregiver burden by treatment and clinical characteristics of patients with glioblastoma
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Phioanh L. Nghiemphu, D. Ryan Ormond, Adam L. Cohen, Diana I. Brixner, Katherine B. Peters, Nicole Willmarth, Beata Korytowsky, Prianka Singh, Connor Willis, Trang H. Au, Cornelia M. Ulrich, Alexandre H. Watanabe, Arnab Chakravarti, Jyothi Menon, Alexander Marshall, Hillevi Bauer, David D. Stenehjem, Junjie Ma, Jennie Taylor, Maija Reblin, and Howard Colman
- Subjects
Adult ,Gerontology ,Aging ,Adolescent ,Caregiver Burden ,Disease ,GBM ,Medical and Health Sciences ,Rare Diseases ,Cost of Illness ,Cognitive dysfunction ,7.1 Individual care needs ,Quality of life ,Clinical Research ,Surveys and Questionnaires ,Behavioral and Social Science ,Patient experience ,Humans ,Medicine ,Oncology & Carcinogenesis ,Social determinants of health ,Cancer ,business.industry ,Nursing research ,Psychology and Cognitive Sciences ,Cognition ,Caregiver burden ,Caregiver ,Brain Disorders ,Brain Cancer ,Good Health and Well Being ,Caregivers ,Oncology ,Cohort ,Quality of Life ,Original Article ,Management of diseases and conditions ,Glioblastoma ,business - Abstract
Background Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL). Methods Caregiver–patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses. Results The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions. Conclusion This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.
- Published
- 2021
39. Toward Establishing Integrated, Comprehensive, and Sustainable Meningitis Surveillance in Africa to Better Inform Vaccination Strategies
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Adam L. Cohen, Jason M. Mwenda, Robert S. Heyderman, Brenda Kwambana-Adams, Andre Bita, Martin Antonio, Lee M. Hampton, and Aquino Albino Nhantumbo
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Economic growth ,Population ,Disease ,Meningitis, Meningococcal ,Neisseria meningitidis ,Acute bacterial meningitis ,Meningitis, Bacterial ,Commentaries ,medicine ,Humans ,Immunology and Allergy ,education ,Human resources ,Africa South of the Sahara ,education.field_of_study ,Disease surveillance ,Surveillance ,Sub-Saharan Africa ,business.industry ,Vaccination ,Outbreak ,vaccines ,medicine.disease ,Poliomyelitis ,African meningitis belt ,AcademicSubjects/MED00290 ,Streptococcus pneumoniae ,Infectious Diseases ,Business ,Sentinel Surveillance - Abstract
Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.
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- 2021
40. The Role of Molecular Testing in Pediatric Meningitis Surveillance in Southern and East African Countries, 2008–2017
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Vongai Dondo, Goitom Weldegebriel, Adam L. Cohen, Mignon du Plessis, Jason M. Mwenda, Elana Jantjies, Jeannine Uwimana, John Muyombe, Ruth Nakazwe, David Mugisha, Esther Nalumansi, Julia Liliane Raboba, Linda de Gouveia, Fernanda C. Lessa, John Macharaga, Gilbert Masona, Anne von Gottberg, Aquino Albino Nhantumbo, Budiaki Sylvie Lula, Negga Asamene Abera, Gugu Maphalala, Moses Odongkara, Fatima Serhan, Chileshe Lukwesa-Musyani, Cesar Freitas, and Nomcebo Phungwayo
- Subjects
Male ,Serotype ,medicine.medical_specialty ,pediatric bacterial meningitis surveillance ,Neisseria meningitidis ,Real-Time Polymerase Chain Reaction ,medicine.disease_cause ,Africa, Southern ,Meningitis, Bacterial ,law.invention ,Haemophilus influenzae ,meningitis pathogens ,law ,Internal medicine ,Streptococcus pneumoniae ,Humans ,Immunology and Allergy ,Medicine ,Public Health Surveillance ,Polymerase chain reaction ,molecular testing ,business.industry ,Infant, Newborn ,Laboratory Techniques for Invasive Bacterial Vaccine-Preventable Disease Surveillance ,Infant ,Odds ratio ,Africa, Eastern ,medicine.disease ,AcademicSubjects/MED00290 ,Infectious Diseases ,Real-time polymerase chain reaction ,Molecular Diagnostic Techniques ,Child, Preschool ,Bacterial Vaccines ,Africa ,Female ,real-time PCR ,business ,Meningitis ,IB-VPD - Abstract
Background As part of the global Invasive Bacterial Vaccine-Preventable Diseases Surveillance Network, 12 African countries referred cerebrospinal fluid (CSF) samples to South Africa’s regional reference laboratory. We evaluated the utility of real-time polymerase chain reaction (PCR) in detecting and serotyping/grouping Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae (HNS). Methods From 2008 to 2017, CSF samples collected from children Results The overall HNS PCR positivity rate for all countries was 10% (1195 of 11 626 samples). In samples with both PCR and culture results, HNS PCR positivity was 11% (744 of 6747 samples), and HNS culture positivity was 3% (207 of 6747). Molecular serotype/serogroup was assigned in 75% of PCR-positive specimens (762 of 1016). Compared with PCR-negative CSF samples, PCR-positive samples were more often turbid (adjusted odds ratio, 6.80; 95% confidence interval, 5.67–8.17) and xanthochromic (1.72; 1.29–2.28), had elevated white blood cell counts (6.13; 4.71–7.99) and high protein concentrations (5.80; 4.34–7.75), and were more often HNS culture positive (32.70; 23.18–46.12). Conclusion PCR increased detection of vaccine-preventable bacterial meningitis in countries where confirmation of suspected meningitis cases is impeded by limited culture capacity.
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- 2021
41. Vaccine preventable diseases surveillance in Nepal: How much does it cost?
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Sudhir Joshi, Pasang Rai, Xiao Xian Huang, Jhalak Sharma Gautam, Binod Prasad Gupta, Anindya Sekhar Bose, Bhim Singh Tinkari, Adam L. Cohen, Jos Vandelaer, and Minal K. Patel
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Cost ,Developing country ,Context (language use) ,World Health Organization ,Article ,Country study ,Nepal ,Vaccine-Preventable Diseases ,Poliomyelitis eradication ,Economic cost ,Vaccine preventable diseases ,Per capita ,medicine ,Humans ,Socioeconomics ,Surveillance ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,medicine.disease ,Poliomyelitis ,Infectious Diseases ,Cost driver ,Molecular Medicine ,Vaccine-preventable diseases ,Business ,Health Expenditures ,Polio transition - Abstract
Assessing the cost of vaccine preventable diseases (VPD) surveillance is becoming more important in the context of the Global Polio Eradication Initiative (GPEI) funding transition, since GPEI support to polio surveillance helped the incremental building of VPD surveillance systems in many countries, including low income countries such as Nepal. However, there is limited knowledge on the cost of conducting VPD surveillance, especially the national cost for surveillance of multiple vaccine-preventable diseases. The current study sought to calculate the economic and financial costs of Nepal’s comprehensive VPD surveillance systems from July 2016 to July 2017. At thecentral level, all surveillance units were included in the sample. At sub-national level, a purposive sampling strategy was used to select a representative sample from locations involved in conducting surveillance. The sub-national sample costs were extrapolated to the nationwide VPD surveillance system. Nepal’s total annual economic cost of VPD surveillance was USD 4.81 million or USD 0.18 per capita, while the total financial cost was USD 4.38 million or USD 0.16 per capita. Government expenditures accounted for 56% of the total economic cost, and World Health Organization accounting for 44%. The biggest cost driver was personnel accounting for 51% of the total economic cost. WHO supported trained surveillance personnel through donor funding, mainly from Global Polio Eradication Initiative. As a polio transition priority country, Nepal will need to make strategic choices to fully self-finance or seek full donor support or a mixed-financing model as polio program funding diminishes.
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- 2021
42. Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic
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Priscilla K, Brastianos, Erin L, Twohy, Elizabeth R, Gerstner, Timothy J, Kaufmann, A John, Iafrate, Jochen, Lennerz, Suriya, Jeyapalan, David E, Piccioni, Varun, Monga, Camilo E, Fadul, David, Schiff, Jennie W, Taylor, Sajeel A, Chowdhary, Chetan, Bettegowda, George, Ansstas, Macarena, De La Fuente, Mark D, Anderson, Nicole, Shonka, Denise, Damek, Jose, Carrillo, Lara J, Kunschner-Ronan, Rekha, Chaudhary, Kurt A, Jaeckle, Francis M, Senecal, Thomas, Kaley, Tara, Morrison, Alissa A, Thomas, Mary R, Welch, Fabio, Iwamoto, David, Cachia, Adam L, Cohen, Shivangi, Vora, Michael, Knopp, Ian F, Dunn, Priya, Kumthekar, Jann, Sarkaria, Susan, Geyer, Xiomara W, Carrero, Maria, Martinez-Lage, Daniel P, Cahill, Paul D, Brown, Caterina, Giannini, Sandro, Santagata, Frederick G, Barker, and Evanthia, Galanis
- Abstract
Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship withEligible patients whose tumors screened positively forOf 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients withGSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive
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- 2022
43. A global comprehensive vaccine-preventable disease surveillance strategy for the immunization Agenda 2030
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Minal K. Patel, Heather M. Scobie, Fatima Serhan, Benjamin Dahl, Christopher S. Murrill, Tomoka Nakamura, Sarah W. Pallas, and Adam L. Cohen
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Infectious Diseases ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Molecular Medicine - Published
- 2022
44. Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022
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Miwako, Kobayashi, Jennifer L, Farrar, Ryan, Gierke, Andrew J, Leidner, Doug, Campos-Outcalt, Rebecca L, Morgan, Sarah S, Long, Katherine A, Poehling, Adam L, Cohen, and Sarah, Schillie
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Adult ,Pneumococcal Vaccines ,Vaccines, Conjugate ,Adolescent ,Advisory Committees ,Vaccination ,Humans ,Diphtheria Toxin ,Child ,Immunization Schedule ,United States - Abstract
The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck SharpDohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck SharpDohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)
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- 2022
45. Serial single-cell genomics reveals convergent subclonal evolution of resistance as patients with early-stage breast cancer progress on endocrine plus CDK4/6 therapy
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Anne O'Dea, Jinfeng Chen, Frederick R. Adler, Patrick A. Cosgrove, Andrea Bild, Jason I. Griffiths, Aditya Bardia, Ruth O'Regan, Meghna S. Trivedi, Cynthia X. Ma, Issam Makhoul, Qamar J. Khan, Laura Spring, Jeffrey T. Chang, Kevin Kalinsky, Adam L. Cohen, Priyanka Sharma, and Kari B. Wisinski
- Subjects
Cancer Research ,Combination therapy ,medicine.drug_class ,business.industry ,Letrozole ,medicine.disease ,Somatic evolution in cancer ,Breast cancer ,Oncology ,Growth factor receptor ,Estrogen ,Cancer cell ,medicine ,Cancer research ,business ,CDK inhibitor ,medicine.drug - Abstract
Combining cyclin-dependent kinase (CDK) inhibitors with endocrine therapy improves outcomes for patients with metastatic estrogen receptor-positive breast cancer but its value in earlier-stage patients is unclear. We examined evolutionary trajectories of early-stage breast cancer tumors, using single-cell RNA sequencing of serial biopsies from the FELINE clinical trial of endocrine therapy (letrozole) alone or combined with the CDK inhibitor ribociclib. Despite differences in subclonal diversity evolution across patients and treatments, common resistance phenotypes emerged. Resistant tumors treated with combination therapy showed accelerated loss of estrogen signaling with convergent upregulation of JNK signaling through growth factor receptors. In contrast, cancer cells maintaining estrogen signaling during mono- or combination therapy showed potentiation of CDK4/6 activation and ERK upregulation through ERBB4 signaling. These results indicate that combination therapy in early-stage estrogen receptor-positive breast cancer leads to emergence of resistance through a shift from estrogen to alternative growth signal-mediated proliferation. Bild and colleagues identify convergent clonal evolution mechanisms through single-cell genomic analyses, explaining therapy resistance in patients with early-stage breast cancer treated with endocrine and CDK4/6 therapy in the FELINE trial.
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- 2021
46. The burden of RSV-associated illness in children aged <5 years, South Africa, 2011 to 2016
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Jocelyn Moyes, Stefano Tempia, Sibongile Walaza, Meredith L. McMorrow, Florette Treurnicht, Nicole Wolter, Anne von Gottberg, Kathleen Kahn, Adam L Cohen, Halima Dawood, Ebrahim Variava, and Cheryl Cohen
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General Medicine - Abstract
Background Vaccines and monoclonal antibodies to protect the very young infant against the respiratory syncytial virus (RSV)-associated illness are effective for limited time periods. We aimed to estimate age-specific burden to guide implementation strategies and cost-effectiveness analyses. Methods We combined case-based surveillance and ecological data to generate a national estimate of the burden of RSV-associated acute respiratory illness (ARI) and severe acute respiratory illness (SARI) in South African children aged Results We estimated a mean annual total (medically and non-medically attended) of 264,112 (95% confidence interval (CI) 134,357–437,187) cases of RSV-associated ARI and 96,220 (95% CI 66,470–132,844) cases of RSV-associated SARI (4.7% and 1.7% of the population aged Conclusions Due to the high burden of RSV-associated illness, specifically SARI cases in young infants, maternal vaccination and monoclonal antibody products delivered at birth could prevent significant RSV-associated disease burden.
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- 2022
47. The economic burden of RSV-associated illness in children aged <5 years, South Africa 2011-2016
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Jocelyn Moyes, Stefano Tempia, Sibongile Walaza, Meredith L. McMorrow, Florette Treurnicht, Nicole Wolter, Anne von Gottberg, Kathleen Kahn, Adam L Cohen, Halima Dawood, Ebrahim Variava, and Cheryl Cohen
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General Medicine - Abstract
Background Data on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated the cost of RSV-associated illness in fine age bands to allow more accurate cost-effectiveness models to account for a limited duration of protection conferred by short- or long-acting interventions. Methods We conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests, and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalizations or clinic visits; the PDE was multiplied by the number of days of care to provide a case cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged Results The estimated mean annual cost of RSV-associated illness in children aged Conclusions Among children
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- 2022
48. ANETT: PhAse II trial of NEoadjuvant TAK-228 plus Tamoxifen in patients with hormone receptor-positive breast cancer
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Emre Koca, Virginia G. Kaklamani, Adam L. Cohen, Sindhu Nair, Jorge Darcourt, Asha Murthy, Anna Belcheva, Helen Wong, Toniva Boone, Joe Ensor, Pej Hemati, Polly A. Niravath, Wei Qian, Priya V. Ramshesh, Jing Zhao, Jenny C. Chang, Tejal Patel, and Xiaoxian Li
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Nausea ,medicine.drug_class ,medicine.medical_treatment ,Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Nitriles ,medicine ,Clinical endpoint ,Humans ,Neoadjuvant therapy ,Benzoxazoles ,medicine.diagnostic_test ,business.industry ,Triazoles ,medicine.disease ,Hormones ,Neoadjuvant Therapy ,Tamoxifen ,Pyrimidines ,Treatment Outcome ,030104 developmental biology ,Receptors, Estrogen ,Estrogen ,030220 oncology & carcinogenesis ,Toxicity ,Female ,medicine.symptom ,Oncotype DX ,business ,medicine.drug - Abstract
Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed. Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p
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- 2021
49. Abstract PS11-05: Updated data from SERENA-1: A Phase 1 dose escalation and expansion study of the next generation oral SERD AZD9833 as a monotherapy and in combination with palbociclib, in women with ER-positive, HER2-negative advanced breast cancer
- Author
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Andy Sykes, Christopher J. Morrow, Richard D. Baird, Teresa Klinowska, Rhiannon Maudsley, Marta Capelán Rodríguez, Manuel Ruiz-Borrego, Tim Brier, Bistra Kirova, Justin P.O. Lindemann, Nitharsan Sathiyayogan, Christina Hernando, Julia Lai-Kwon, Javier Garcia-Corbacho, Judy S. Wang, Begoña Bermejo de las Heras, Steven Fox, Mafalda Oliveira, Chris Leach, Eva Maria Ciruelos Gil, Anne C Armstrong, Richard Mather, Erika Hamilton, Manish R. Patel, Jason Incorvati, Udai Banerji, Valentina Boni, Chris Twelves, Ivan Victoria Ruiz, Bruno de Paula, Alejandro González, Li Zhang, Anosheh Afghani, Peter Kabos, Christos Vaklavas, and Adam L. Cohen
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Fulvestrant ,Combination therapy ,business.industry ,Population ,Phases of clinical research ,Palbociclib ,medicine.disease ,Discontinuation ,Breast cancer ,Tolerability ,Internal medicine ,medicine ,business ,education ,medicine.drug - Abstract
Background: AZD9833 is an oral selective estrogen receptor (ER) antagonist and degrader (SERD) in Phase 2 clinical development for the treatment of ER+ HER2− breast cancer. Here we report data from Parts C and D of the ongoing Phase 1 study (SERENA-1) examining AZD9833 in combination with palbociclib, together with updated data from Parts A and B examining AZD9833 monotherapy. Methods: SERENA-1 (NCT03616587) is an ongoing open-label Phase 1 study of AZD9833 in pre- and post-menopausal women with ER+, HER2− advanced breast cancer who have previously received ≥1 endocrine therapy and ≤2 prior chemotherapies. Prior treatment with fulvestrant and/or CDK4/6 inhibitors was permitted. The primary objective is to determine the safety and tolerability of once daily (QD) AZD9833, with dose-limiting toxicities (DLTs) in the first 28 days defining the maximum tolerated dose. Secondary objectives include anti-tumor response (including circulating tumor [ct] DNA response) and pharmacokinetics. Parts A (escalation) and B (expansion) assess AZD9833 as a monotherapy, and Parts C (escalation) and D (expansion) assess AZD9833 in combination with palbociclib. Results: At a data cut-off of March 24 2020, 17 patients had received either 150 mg or 300 mg AZD9833 in combination with palbociclib, given according to its product labeling. Eighty patients had received AZD9833 monotherapy at doses of 25, 75, 150, 300, and 450 mg QD. In patients treated with AZD9833 and palbociclib, treatment-related adverse events (AEs; experienced by ≥10% of patients) included visual disturbances*, bradycardia*, asthenia, anemia, QTcF prolongation, nausea, neutropenia, decreased white blood cell count, and vomiting (*combined terms). All instances of AZD9833-related bradycardia were Grade 1. One DLT was observed in the 150 mg cohort: CTCAE Grade 2 visual disturbances, which began on Cycle 1 Day 8 and resolved by Cycle 1 Day 9 following dose interruption. The patient restarted treatment on Cycle 1 Day 15 at 75 mg and continued this dose until data cut-off. No causally related AEs led to discontinuation of AZD9833. The tolerability of AZD9833 with palbociclib was consistent with the observed tolerability profile of AZD9833 monotherapy, and the known tolerability profile of palbociclib. Pharmacokinetic analysis showed similar AZD9833 exposure for monotherapy and palbociclib combination therapy. Similarly, palbociclib exposure was comparable with simulations using a published population pharmacokinetic model. In Part A, ESR1 hotspot mutations were detected in ctDNA at baseline in 26/56 (46%) patients; 13/26 (50%) of these patients achieved a partial response or stable disease at 24 weeks, including 5/10 (50%) with a Y537S ESR1 mutation. Further, in patients with ESR1 mutations and samples available for longitudinal ctDNA analysis, 17/20 (85%) exhibited a reduction or loss of mutant ESR1 on treatment with AZD9833. Efficacy data to be presented include objective response rate and clinical benefit rate at 24 weeks. Of note, unconfirmed partial responses have been observed in Part C after the data cut-off for this abstract. Conclusions: AZD9833 continues to show an encouraging efficacy and dose-dependent safety profile as a monotherapy or in combination with palbociclib. A Phase 2 study comparing the efficacy and safety of three doses of AZD9833 versus fulvestrant (NCT04214288), and a Phase 2 pre-surgical ‘window of opportunity’ study (EUDRA-CT; 2019-003706-2) are ongoing. Citation Format: Richard Baird, Mafalda Oliveira, Eva Maria Ciruelos Gil, Manish R Patel, Begoña Bermejo de las Heras, Manuel Ruiz-Borrego, Javier García-Corbacho, Anne Armstrong, Udai Banerji, Chris Twelves, Valentina Boni, Jason Incorvati, Peter Kabos, Adam L Cohen, Bruno de Paula, Marta Capelán Rodríguez, Judy S Wang, Christina Hernando, Alejandro Falcón Gonzalez, Ivan Victoria Ruiz, Julia Lai-Kwon, Anosheh Afghani, Christos Vaklavas, Tim Brier, Steven Fox, Bistra Kirova, Teresa Klinowska, Chris Leach, Justin PO Lindemann, Richard Mather, Rhiannon Maudsley, Christopher J Morrow, Nitharsan Sathiyayogan, Andy Sykes, Li Zhang, Erika Hamilton. Updated data from SERENA-1: A Phase 1 dose escalation and expansion study of the next generation oral SERD AZD9833 as a monotherapy and in combination with palbociclib, in women with ER-positive, HER2-negative advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-05.
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- 2021
50. ENDORSE: a prognostic model for endocrine therapy in estrogen-receptor-positive breast cancers
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Aritro Nath, Adam L Cohen, and Andrea H Bild
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Computational Theory and Mathematics ,General Immunology and Microbiology ,Receptors, Estrogen ,Drug Resistance, Neoplasm ,Applied Mathematics ,Humans ,Breast Neoplasms ,Estrogens ,Female ,General Agricultural and Biological Sciences ,Prognosis ,General Biochemistry, Genetics and Molecular Biology ,Information Systems - Abstract
Advanced and metastatic estrogen receptor-positive (ER
- Published
- 2022
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