Harvey Cohen

Overview:

Dr. Cohen's research program includes clinical research relating to aspects of the pathways to functional decline and reilience with aging, geriatric assessment, and cancer and anemia in the elderly.

Pathways to functional decline are being explored through the NIA funded Claude Pepper Older Americans Independence Center, and includes studies of the contributions of age related physiologic change, in particular changes in inflammatory parameters, comorbid diseases and conditions, environment, genetics, and the interactionas among them. Data are derived from several current studies as well as previously collected data sets from the Established Populations for Epidemiologic Studies of the Elderly (EPESE), National Long Term Care Survey, and the Chinese Longevity Study (with Dr. Zeng Yi). Previous work has demonstrated the important contributions of age related inflammation and coagulation activation to functional status. He is Co-PI of the Pepper Center Physical Performance Across the LifeSpan (PALS) study, which is a longitudinal cohort study of community dwelling adults from age 30-90+and includes functional measures and biomarkers on inflammation and metabolism.
 
Geriatric assessment approaches have been studied in a number of randomized and controlled studies and work is now concentrating on the application of Comprehensive Geriatric Assessment tools to the evaluation and treatment of elderly patients with cancer. This is an extension and continuation of a long standing interest in geriatric oncology. Previous studies have elucidated age-related patterns of disease presentation, treatment approaches, clinical trials, survivorship, quality of life, impact of comrobidities and functional outcomes. Dr. Cohen was co-chair, and now member of the Cancer in the Older Adult Committee of the Alliance for Clinical Trials in Oncology (ALLIANCE). A number of active studies and ongoing data bases aree being utilized to address these questions.


Anemia in the older adult is being addressed through an NIA funded U01 consortium (Dr. Cohen Co-PI). the current main study is an observational study followed by a pragmatic treatment trial for anemia in older adults with CHF, in collaboration with the Cardiovascular Research Network (CVRN) of the Health services research network (HSRN) 

Positions:

Professor of Medicine

Medicine, Geriatrics
School of Medicine

Walter Kempner Distinguished Professor of Medicine, in the School of Medicine

Medicine, Geriatrics
School of Medicine

Emeritus Director, Center for the Study of Aging & Human Development

Center for the Study of Aging and Human Development
School of Medicine

Faculty Research Scholar of DuPRI's Center for Population Health & Aging

Center for Population Health & Aging
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1965

State University of New York at Brooklyn

Grants:

Quantifying the genomic consequences of chronic social stress for accelerated aging

Administered By
Institutes and Provost's Academic Units
Awarded By
National Institutes of Health
Role
Advisor
Start Date
End Date

IPA-Rick Sloane

Administered By
Center for the Study of Aging and Human Development
Role
Principal Investigator
Start Date
End Date

Mentoring Intervention Development in Fall and Fracture Prevention

Administered By
Medicine, Geriatrics
Awarded By
National Institutes of Health
Role
Advisor
Start Date
End Date

Cognitive Changes and Brain Connectivity in Age-Related Macular Degeneration

Administered By
Center for the Study of Aging and Human Development
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

PACTTE-Partnership for Anemia: Clinical and Translational Trials in the Elderly

Administered By
Duke Clinical Research Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840.

BACKGROUND: Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer. PATIENTS AND METHODS: CALGB 9840 evaluated weekly paclitaxel (80 mg/m2) versus paclitaxel every 3 weeks (175 mg/m2); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m2 each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55-64 years (29%), and (iii) ≥65 years (26%). RESULTS: Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade ≥3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity. CONCLUSIONS: Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects.
Authors
Lichtman, SM; Hurria, A; Cirrincione, CT; Seidman, AD; Winer, E; Hudis, C; Cohen, HJ; Muss, HB; Cancer and Leukemia Group B,
MLA Citation
Lichtman, S. M., et al. “Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840.Ann Oncol, vol. 23, no. 3, Mar. 2012, pp. 632–38. Pubmed, doi:10.1093/annonc/mdr297.
URI
https://scholars.duke.edu/individual/pub1431711
PMID
32018654
Source
pubmed
Published In
Ann Oncol
Volume
23
Published Date
Start Page
632
End Page
638
DOI
10.1093/annonc/mdr297

Persistence, adherence, and toxicity with oral CMF in older women with early-stage breast cancer (Adherence Companion Study 60104 for CALGB 49907).

BACKGROUND: Cyclophosphamide-methotrexate-5-fluorouracil (CMF) is often selected as adjuvant chemotherapy for older patients with early-stage breast cancer due to perceived superior tolerability. We sought to measure persistence with CMF, adherence to oral cyclophosphamide, and the association of these with toxic effects. PATIENTS AND METHODS: CALGB 49907 was a randomized trial comparing standard chemotherapy (CMF or AC, provider/patient choice) with capecitabine in patients aged ≥65 with stage I-IIIB breast cancer. Those randomized to standard therapy and choosing CMF were prescribed oral cyclophosphamide 100 mg/m2 for 14 consecutive days in six 28-day cycles. Persistence was defined as being prescribed six cycles of at least one of the three CMF drugs. Adherence was the number of cyclophosphamide doses that women reported they had taken divided by the number prescribed. Persistence and adherence were based on case report forms and medication calendars. RESULTS: Of 317 randomized to standard chemotherapy, 133 received CMF. Median age was 73 (range 65-88). Seventy-one percent submitted at least one medication calendar; 65% persisted with CMF. Non-persistence was associated with node negativity (P = 0.019), febrile neutropenia (P = 0.002), and fatigue (P = 0.044). Average adherence was 97% during prescribed cycles. CONCLUSIONS: Self-reported adherence to cyclophosphamide was high, but persistence was lower, which may be attributable to toxic effects.
Authors
Ruddy, KJ; Pitcher, BN; Archer, LE; Cohen, HJ; Winer, EP; Hudis, CA; Muss, HB; Partridge, AH
MLA Citation
Ruddy, K. J., et al. “Persistence, adherence, and toxicity with oral CMF in older women with early-stage breast cancer (Adherence Companion Study 60104 for CALGB 49907).Ann Oncol, vol. 23, no. 12, Dec. 2012, pp. 3075–81. Pubmed, doi:10.1093/annonc/mds133.
URI
https://scholars.duke.edu/individual/pub1431710
PMID
32018812
Source
pubmed
Published In
Ann Oncol
Volume
23
Published Date
Start Page
3075
End Page
3081
DOI
10.1093/annonc/mds133

Progressive Metabolic Dysfunction and Nutritional Variability Precedes Necrotizing Enterocolitis.

Necrotizing Enterocolitis (NEC) is associated with prematurity, enteral feedings, and enteral dysbiosis. Accordingly, we hypothesized that along with nutritional variability, metabolic dysfunction would be associated with NEC onset. Methods: We queried a multicenter longitudinal database that included 995 preterm infants (<32 weeks gestation) and included 73 cases of NEC. Dried blood spot samples were obtained on day of life 1, 7, 28, and 42. Metabolite data from each time point included 72 amino acid (AA) and acylcarnitine (AC) measures. Nutrition data were averaged at each of the same time points. Odds ratios and 95% confidence intervals were calculated using samples obtained prior to NEC diagnosis and adjusted for potential confounding variables. Nutritional and metabolic data were plotted longitudinally to determine relationship to NEC onset. Results: Day 1 analyte levels of alanine, phenylalanine, free carnitine, C16, arginine, C14:1/C16, and citrulline/phenylalanine were associated with the subsequent development of NEC. Over time, differences in individual analyte levels associated with NEC onset shifted from predominantly AAs at birth to predominantly ACs by day 42. Subjects who developed NEC received significantly lower weight-adjusted total calories (p < 0.001) overall, a trend that emerged by day of life 7 (p = 0.020), and persisted until day of life 28 (p < 0.001) and 42 (p < 0.001). Conclusion: Premature infants demonstrate metabolic differences at birth. Metabolite abnormalities progress in parallel to significant differences in nutritional delivery signifying metabolic dysfunction in premature newborns prior to NEC onset. These observations provide new insights to potential contributing pathophysiology of NEC and opportunity for clinical care-based prevention.
Authors
Sinclair, TJ; Ye, C; Chen, Y; Zhang, D; Li, T; Ling, XB; Cohen, HJ; Shaw, GM; Stevenson, DK; Chace, D; Clark, RH; Sylvester, KG
MLA Citation
Sinclair, Tiffany J., et al. “Progressive Metabolic Dysfunction and Nutritional Variability Precedes Necrotizing Enterocolitis.Nutrients, vol. 12, no. 5, Apr. 2020. Epmc, doi:10.3390/nu12051275.
URI
https://scholars.duke.edu/individual/pub1441649
PMID
32365850
Source
epmc
Published In
Nutrients
Volume
12
Published Date
DOI
10.3390/nu12051275

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia.

BACKGROUND: Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms. METHODS: Serum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice. RESULTS: An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs. CONCLUSIONS: Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.
Authors
Hao, S; You, J; Chen, L; Zhao, H; Huang, Y; Zheng, L; Tian, L; Maric, I; Liu, X; Li, T; Bianco, YK; Winn, VD; Aghaeepour, N; Gaudilliere, B; Angst, MS; Zhou, X; Li, Y-M; Mo, L; Wong, RJ; Shaw, GM; Stevenson, DK; Cohen, HJ; Mcelhinney, DB; Sylvester, KG; Ling, XB
MLA Citation
Hao, Shiying, et al. “Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia.Plos One, vol. 15, no. 3, 2020, p. e0230000. Pubmed, doi:10.1371/journal.pone.0230000.
URI
https://scholars.duke.edu/individual/pub1439772
PMID
32126118
Source
pubmed
Published In
Plos One
Volume
15
Published Date
Start Page
e0230000
DOI
10.1371/journal.pone.0230000

A proteomic clock for malignant gliomas: The role of the environment in tumorigenesis at the presymptomatic stage.

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies.
Authors
Zheng, L; Zhang, Y; Hao, S; Chen, L; Sun, Z; Yan, C; Whitin, JC; Jang, T; Merchant, M; McElhinney, DB; Sylvester, KG; Cohen, HJ; Recht, L; Yao, X; Ling, XB
MLA Citation
Zheng, Le, et al. “A proteomic clock for malignant gliomas: The role of the environment in tumorigenesis at the presymptomatic stage.Plos One, vol. 14, no. 10, 2019, p. e0223558. Pubmed, doi:10.1371/journal.pone.0223558.
URI
https://scholars.duke.edu/individual/pub1416906
PMID
31600288
Source
pubmed
Published In
Plos One
Volume
14
Published Date
Start Page
e0223558
DOI
10.1371/journal.pone.0223558