Michael Sargen - Academia.edu (original) (raw)

Papers by Michael Sargen

Research paper thumbnail of Large Genomic Rearrangement in BRCA1 and BRCA2 and Clinical Characteristics of Men with Breast Cancer in the United States

Clinical Breast Cancer, 2007

Male breast cancer is rare and accounts for < 1% of all breast cancer cases. The estimated number... more Male breast cancer is rare and accounts for < 1% of all breast cancer cases. The estimated number of male breast cancer cases for 2006 in the United States was 1720. 1 Male breast cancer is associated with mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes. 2-4 Deleterious mutations are usually small insertion, deletion, or point mutations resulting in truncated nonfunctioning gene products. Large deleterious genomic rearrangements in these genes have been identified; however, they are missed by conventional polymerase chain reaction (PCR)-based mutation screening methods. In the United States, the prevalence of large genomic rearrangements in BRCA1 and BRCA2 in men with breast cancer is unknown.

Research paper thumbnail of Gaps in the Supply of Physicians, Advance Practice Nurses, and Physician Assistants

Journal of the American College of Surgeons, 2011

BACKGROUND: Based on the goals of health care reform, growth in the demand for health care will c... more BACKGROUND: Based on the goals of health care reform, growth in the demand for health care will continue to increase the demand for physicians and, as physician shortages widen, advanced practice nurses (APNs) and physician assistants (PAs) will play larger roles. Together with physicians they constitute a workforce of "advanced clinicians." The objective of this study was to assess the capacity of this combined workforce to meet the future demand for clinical services. STUDY DESIGN: Projections were constructed to the year 2025 for the supply of physicians, APNs, and PAs, and these were compared with projections of the demand for advanced clinical services, based on federal estimates of future spending and historic relationships between spending and the health care labor force.

Research paper thumbnail of Warm, Humid, and High Sun Exposure Climates Are Associated with Poorly Controlled Eczema: PEER (Pediatric Eczema Elective Registry) Cohort, 2004–2012

Journal of Investigative Dermatology, 2013

Anecdotal reports of children experiencing eczema flares during winter and summer months along wi... more Anecdotal reports of children experiencing eczema flares during winter and summer months along with global variation in eczema prevalence has fueled speculation that climate may modulate disease activity. The aim of this study was to determine whether long-term weather patterns affect the severity and persistence of eczema symptoms in children. We performed a prospective cohort study of US children (N ¼ 5,595) enrolled in PEER (Pediatric Eczema Elective Registry) between 2004 and 2012 to evaluate the effect of climate (daily temperature, daily sun exposure, daily humidity) on the severity of eczema symptoms. Odds ratios (ORs) were calculated for the patient-evaluated outcome of disease control. Multivariate logistic regression modeling adjusting for gender, race, income, and topical medication use demonstrated that higher temperature (OR ¼ 0.90, 95% confidence interval (CI): 0.87-0.93, Po0.001) and increased sun exposure (OR ¼ 0.93, 95% CI: 0.89-0.98, P ¼ 0.009) were associated with poorly controlled eczema. Higher humidity (OR ¼ 0.90, 95% CI: 0.812-0.997, P ¼ 0.04) was also associated with poorly controlled disease, but the statistical significance of this association was lost in our multivariate analysis (P ¼ 0.44).

Research paper thumbnail of Geographic variation in pharmacotherapy decisions for U.S. medicare enrollees with diabetes

Journal of Diabetes and its Complications, 2012

Prescription rates for diabetic drugs vary considerably across the United States for Medicare ben... more Prescription rates for diabetic drugs vary considerably across the United States for Medicare beneficiaries. The goal of this study was to determine if non-clinical factors (patient race, ethnicity, gender, income) are associated with regional variation in pharmacotherapy decisions for diabetic patients enrolled in Medicare. We performed a spatially-weighted, linear regression analysis of the entire diabetic population enrolled in Medicare Parts A, B, and D for the years 2006 through 2009. Our outcomes of interest were the percentage of diabetic patients being treated with metformin, a sulfonylurea, a thiazolidinedione, or insulin within a hospital referral region (HRR). Prescription rates for metformin, sulfonylureas, thiazolidinediones, and insulin varied more than two-fold between hospital referral region. Metformin prescription rates were increased in western states while prescription rates for sulfonylureas and insulins were highest in the South and Midwest. In contrast with these other diabetic drug classes, members of the thiazolidinedione drug class were prescribed more frequently in the Central United States (Great Plains, Colorado Rockies, Northern Texas, Oklahoma). Prescription rates for each drug class were increased in hospital referral regions with a lower household income. Referral regions with larger African American populations were associated with higher prescription rates for insulin (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and lower prescription rates for metformin (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Gender and Hispanic ethnicity were not associated with regional variation in prescription rates for the four major diabetic drug classes. Geographic differences exist in the management of type 2 diabetes for Medicare enrollees. Prescription patterns were associated with household income and African American race. Further studies are necessary to identify local, unidentified factors that might be influencing provider management styles.

Research paper thumbnail of Melanocytic Tumors Express Connexin 43 but not 26

The American Journal of Dermatopathology, 2013

Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell-cell comm... more Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell-cell communication and help to regulate cell division. The purpose of this study was to evaluate if there are diagnostically important differences in immunostaining for connexins 43 (Cx43) and 26 (Cx26) in melanoma compared with nevi. Formalin-fixed paraffin-embedded sections of 34 histologically well-characterized melanocytic lesions, 17 primary malignant melanomas (MM), and 17 nevi were stained with a polyclonal antibody to Cx43 and a polyclonal antibody to Cx26. Immunoreactivity in tumor cells was evaluated semiquantitatively based on extent (1%-100%) and intensity (0-3) of reactivity. A score of 0-300 was generated by the product of the extent and intensity readings in each case. Significantly higher Cx43 immunoreactivity was detected in MM (mean intensity score = 253.5; 95% confidence interval, 227.9-279.2; P = 0.002) compared with nevi (mean intensity score = 152.4; 95% confidence interval, 104.9-199.8). In contrast, Cx26 immunoreactivity was less than 5% or entirely absent in all melanocytic tumors (n = 34). The significantly higher Cx43 staining in MM when compared with nevi suggests an oncogenic role for this protein in melanocytic tumor progression. Consequently, the evaluation of immunohistochemical staining for Cx43 in conjunction with other ancillary stains and tumor histology may be helpful in distinguishing MM from nevi, although positive Cx26 reactivity suggests that a cutaneous neoplasm is of nonmelanocytic origin.

Research paper thumbnail of MITF Accurately Highlights Epidermal Melanocytes in Atypical Intraepidermal Melanocytic Proliferations

The American Journal of Dermatopathology, 2013

Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other ... more Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.

Research paper thumbnail of Method of Primary Tumor Detection as a Risk Factor for Local and Distant Recurrence After Breast-Conservation Treatment for Early-Stage Breast Cancer

Clinical Breast Cancer, 2008

Research paper thumbnail of Large Genomic Rearrangement in BRCA1 and BRCA2 and Clinical Characteristics of Men with Breast Cancer in the United States

Clinical Breast Cancer, 2007

Male breast cancer is rare and accounts for < 1% of all breast cancer cases. The estimated number... more Male breast cancer is rare and accounts for < 1% of all breast cancer cases. The estimated number of male breast cancer cases for 2006 in the United States was 1720. 1 Male breast cancer is associated with mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes. 2-4 Deleterious mutations are usually small insertion, deletion, or point mutations resulting in truncated nonfunctioning gene products. Large deleterious genomic rearrangements in these genes have been identified; however, they are missed by conventional polymerase chain reaction (PCR)-based mutation screening methods. In the United States, the prevalence of large genomic rearrangements in BRCA1 and BRCA2 in men with breast cancer is unknown.

Research paper thumbnail of Gaps in the Supply of Physicians, Advance Practice Nurses, and Physician Assistants

Journal of the American College of Surgeons, 2011

BACKGROUND: Based on the goals of health care reform, growth in the demand for health care will c... more BACKGROUND: Based on the goals of health care reform, growth in the demand for health care will continue to increase the demand for physicians and, as physician shortages widen, advanced practice nurses (APNs) and physician assistants (PAs) will play larger roles. Together with physicians they constitute a workforce of "advanced clinicians." The objective of this study was to assess the capacity of this combined workforce to meet the future demand for clinical services. STUDY DESIGN: Projections were constructed to the year 2025 for the supply of physicians, APNs, and PAs, and these were compared with projections of the demand for advanced clinical services, based on federal estimates of future spending and historic relationships between spending and the health care labor force.

Research paper thumbnail of Warm, Humid, and High Sun Exposure Climates Are Associated with Poorly Controlled Eczema: PEER (Pediatric Eczema Elective Registry) Cohort, 2004–2012

Journal of Investigative Dermatology, 2013

Anecdotal reports of children experiencing eczema flares during winter and summer months along wi... more Anecdotal reports of children experiencing eczema flares during winter and summer months along with global variation in eczema prevalence has fueled speculation that climate may modulate disease activity. The aim of this study was to determine whether long-term weather patterns affect the severity and persistence of eczema symptoms in children. We performed a prospective cohort study of US children (N ¼ 5,595) enrolled in PEER (Pediatric Eczema Elective Registry) between 2004 and 2012 to evaluate the effect of climate (daily temperature, daily sun exposure, daily humidity) on the severity of eczema symptoms. Odds ratios (ORs) were calculated for the patient-evaluated outcome of disease control. Multivariate logistic regression modeling adjusting for gender, race, income, and topical medication use demonstrated that higher temperature (OR ¼ 0.90, 95% confidence interval (CI): 0.87-0.93, Po0.001) and increased sun exposure (OR ¼ 0.93, 95% CI: 0.89-0.98, P ¼ 0.009) were associated with poorly controlled eczema. Higher humidity (OR ¼ 0.90, 95% CI: 0.812-0.997, P ¼ 0.04) was also associated with poorly controlled disease, but the statistical significance of this association was lost in our multivariate analysis (P ¼ 0.44).

Research paper thumbnail of Geographic variation in pharmacotherapy decisions for U.S. medicare enrollees with diabetes

Journal of Diabetes and its Complications, 2012

Prescription rates for diabetic drugs vary considerably across the United States for Medicare ben... more Prescription rates for diabetic drugs vary considerably across the United States for Medicare beneficiaries. The goal of this study was to determine if non-clinical factors (patient race, ethnicity, gender, income) are associated with regional variation in pharmacotherapy decisions for diabetic patients enrolled in Medicare. We performed a spatially-weighted, linear regression analysis of the entire diabetic population enrolled in Medicare Parts A, B, and D for the years 2006 through 2009. Our outcomes of interest were the percentage of diabetic patients being treated with metformin, a sulfonylurea, a thiazolidinedione, or insulin within a hospital referral region (HRR). Prescription rates for metformin, sulfonylureas, thiazolidinediones, and insulin varied more than two-fold between hospital referral region. Metformin prescription rates were increased in western states while prescription rates for sulfonylureas and insulins were highest in the South and Midwest. In contrast with these other diabetic drug classes, members of the thiazolidinedione drug class were prescribed more frequently in the Central United States (Great Plains, Colorado Rockies, Northern Texas, Oklahoma). Prescription rates for each drug class were increased in hospital referral regions with a lower household income. Referral regions with larger African American populations were associated with higher prescription rates for insulin (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and lower prescription rates for metformin (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Gender and Hispanic ethnicity were not associated with regional variation in prescription rates for the four major diabetic drug classes. Geographic differences exist in the management of type 2 diabetes for Medicare enrollees. Prescription patterns were associated with household income and African American race. Further studies are necessary to identify local, unidentified factors that might be influencing provider management styles.

Research paper thumbnail of Melanocytic Tumors Express Connexin 43 but not 26

The American Journal of Dermatopathology, 2013

Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell-cell comm... more Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell-cell communication and help to regulate cell division. The purpose of this study was to evaluate if there are diagnostically important differences in immunostaining for connexins 43 (Cx43) and 26 (Cx26) in melanoma compared with nevi. Formalin-fixed paraffin-embedded sections of 34 histologically well-characterized melanocytic lesions, 17 primary malignant melanomas (MM), and 17 nevi were stained with a polyclonal antibody to Cx43 and a polyclonal antibody to Cx26. Immunoreactivity in tumor cells was evaluated semiquantitatively based on extent (1%-100%) and intensity (0-3) of reactivity. A score of 0-300 was generated by the product of the extent and intensity readings in each case. Significantly higher Cx43 immunoreactivity was detected in MM (mean intensity score = 253.5; 95% confidence interval, 227.9-279.2; P = 0.002) compared with nevi (mean intensity score = 152.4; 95% confidence interval, 104.9-199.8). In contrast, Cx26 immunoreactivity was less than 5% or entirely absent in all melanocytic tumors (n = 34). The significantly higher Cx43 staining in MM when compared with nevi suggests an oncogenic role for this protein in melanocytic tumor progression. Consequently, the evaluation of immunohistochemical staining for Cx43 in conjunction with other ancillary stains and tumor histology may be helpful in distinguishing MM from nevi, although positive Cx26 reactivity suggests that a cutaneous neoplasm is of nonmelanocytic origin.

Research paper thumbnail of MITF Accurately Highlights Epidermal Melanocytes in Atypical Intraepidermal Melanocytic Proliferations

The American Journal of Dermatopathology, 2013

Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other ... more Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.

Research paper thumbnail of Method of Primary Tumor Detection as a Risk Factor for Local and Distant Recurrence After Breast-Conservation Treatment for Early-Stage Breast Cancer

Clinical Breast Cancer, 2008