Anjali D. Deshpande

Epidemiology of Diabetes and Diabetes-Related Complications

In 2005, it was estimated that more than 20 million people in the United States had diabetes. Approximately 30% of these people had undiagnosed cases. Increased risk for diabetes is primarily associated with age, ethnicity, family history of diabetes, smoking, obesity, and physical inactivity. Diabetes-related complications—including cardiovascular disease, kidney disease, neuropathy, blindness, and lower-extremity amputation—are a significant cause of increased morbidity and mortality among people with diabetes, and result in a heavy economic burden on the US health care system. With advances in treatment for diabetes and its associated complications, people with diabetes are living longer with their condition. This longer life span will contribute to further increases in the morbidity associated with diabetes, primarily in elderly people and in minority racial or ethnic groups. In 2050, the number of people in the United States with diagnosed diabetes is estimated to grow to 48.3 million. Results from randomized controlled trials provide evidence that intensive lifestyle interventions can prevent or delay the onset of diabetes in high-risk individuals. In addition, adequate and sustained control of blood sugar levels, blood pressure, and blood lipid levels can prevent or delay the onset of diabetes-related complications in people with diabetes. Effective interventions, at both the individual and population levels, are desperately needed to slow the diabetes epidemic and reduce diabetes-related complications in the United States. This report describes the current diabetes epidemic and the health and economic impact of diabetes complications on individuals and on the health care system. The report also provides suggestions by which the epidemic can be curbed.

Surgical Removal of the Primary Tumor Increases Overall Survival in Patients With Metastatic Breast Cancer: Analysis of the 1988–2003 SEER Data

BackgroundPrimary treatments for stage IV breast cancer are chemotherapy and radiation, with surgery usually reserved for tumor-related complications. We sought to determine whether surgical removal of the primary tumor provides a survival advantage for women with metastatic breast cancer.MethodsWe conducted a retrospective, population-based cohort study by using the 1988–2003 Surveillance, Epidemiology, and End Results (SEER) program data. By use of multivariate Cox regression models, overall survival in women with stage IV disease was compared between women who underwent surgical excision of their breast tumor with women who did not, controlling for potential confounding demographic, tumor- and treatment-related variables, and propensity scores (accounting for variables associated with the likelihood of having surgery).ResultsOf 9734 SEER patients with stage IV breast cancer, 47% underwent breast cancer surgery and 53% did not. Median survival was longer for women who had surgery than for women who did not, both among women who were alive at the end of the study period (36.00 vs. 21.00 months; P < .001) and among women who had died during follow-up (18.00 vs. 7.00 months; P < .001). After controlling for potential confounding variables and propensity scores, patients who underwent surgery were less likely to die during the study period compared with women who did not undergo surgery (adjusted hazard ratio, .63, 95% confidence interval, .60–.66).ConclusionsAnalysis of the 1988–2003 SEER data indicated that extirpation of the primary breast tumor in patients with stage IV disease was associated with a marked reduction in risk of dying after controlling for variables associated with survival.

Elevated Breast Cancer Mortality in Women Younger than Age 40 Years Compared with Older Women Is Attributed to Poorer Survival in Early-Stage Disease

BACKGROUND We investigated differences in breast cancer mortality between younger (younger than 40 years of age) and older (40 years of age and older) women by stage at diagnosis to identify patient and tumor characteristics accounting for disparities. STUDY DESIGN We conducted a retrospective study of women diagnosed with breast cancer in the 1988 to 2003 Surveillance, Epidemiology, and End Results Program data. Multivariate Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals to compare overall and stage-specific breast cancer mortality in women younger than 40 years old and women 40 years and older, controlling for potential confounding variables identified in univariate tests. RESULTS Of 243,012 breast cancer patients, 6.4% were younger than 40 years old, and 93.6% were 40 years of age or older. Compared with older women, younger women were more likely to be African American, single, diagnosed at later stages, and treated by mastectomy. Younger women had tumors that were more likely to be higher grade, larger size, estrogen receptor/progesterone receptor-negative, and lymph-node positive (p < 0.001). Younger women were more likely to die from breast cancer compared with older women (crude HR = 1.39; CI, 1.34 to 1.45). Controlling for confounders, younger women were more likely to die compared with older women if diagnosed with stage I (aHR = 1.44; CI, 1.27 to 1.64) or stage II (aHR = 1.09; CI, 1.03 to 1.15) disease and less likely to die if diagnosed with stage IV disease (aHR = 0.85; CI, 0.76 to 0.95). CONCLUSIONS Higher breast cancer mortality in younger women was attributed to poorer outcomes with early-stage disease. Additional studies should focus on specific tumor biology contributing to the increased mortality of younger women with early-stage breast cancer.

Perceived and observed neighborhood indicators of obesity among urban adults

Objective:The global obesity epidemic has been partially attributed to modern environments that encourage inactivity and overeating, yet few studies have examined specific features of the physical neighborhood environment that influence obesity. Using two different measurement methods, this study sought to identify and compare perceived and observed neighborhood indicators of obesity and a high-risk profile of being obese and inactive.Design:Cross-sectional telephone surveys (perceived) and street-scale environmental audits (observed) were conducted concurrently in two diverse US cities to assess recreational facility access, land use, transportation infrastructure and aesthetics.Subjects:A total of 1032 randomly selected urban residents (20% obese, 32% black, 65% female).Analysis:Bivariate and multivariate logistic regression analyses were conducted to estimate the association (adjusted prevalence odds ratio (aOR)) between the primary outcome (obese vs normal weight) and perceived and observed environmental indicators, controlling for demographic variables.Results:Being obese was significantly associated with perceived indicators of no nearby nonresidential destinations (aOR=2.2), absence of sidewalks (aOR=2.2), unpleasant community (aOR=3.1) and lack of interesting sites (aOR=4.8) and observed indicators of poor sidewalk quality (aOR=2.1), physical disorder (aOR=4.0) and presence of garbage (aOR=3.7). Perceived and observed indicators of land use and aesthetics were the most robust neighborhood correlates of obesity in multivariate analyses.Conclusions:The findings contribute substantially to the growing evidence base of community-level correlates of obesity and suggest salient environmental and policy intervention strategies that may reduce population-level obesity prevalence. Continued use of both measurement methods is recommended to clarify inconsistent associations across perceived and observed indicators within the same domain.

Inflammatory Monocyte Mobilization Decreases Patient Survival in Pancreatic Cancer: A Role for Targeting the CCL2/CCR2 Axis

Purpose: To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (CCR2+/CD14+) as immunotherapeutic targets in the treatment of pancreatic cancer. Experimental Design: Survival analysis was conducted to determine if the prevalence of preoperative blood monocytes correlates with survival in patients with pancreatic cancer following tumor resection. Inflammatory monocyte prevalence in the blood and bone marrow of patients with pancreatic cancer and controls was compared. The immunosuppressive properties of inflammatory monocytes and macrophages in the blood and tumors, respectively, of patients with pancreatic cancer were assessed. CCL2 expression by human pancreatic cancer tumors was compared with normal pancreas. A novel CCR2 inhibitor (PF-04136309) was tested in an orthotopic model of murine pancreatic cancer. Results: Monocyte prevalence in the peripheral blood correlates inversely with survival, and low monocyte prevalence is an independent predictor of increased survival in patients with pancreatic cancer with resected tumors. Inflammatory monocytes are increased in the blood and decreased in the bone marrow of patients with pancreatic cancer compared with controls. An increased ratio of inflammatory monocytes in the blood versus the bone marrow is a novel predictor of decreased patient survival following tumor resection. Human pancreatic cancer produces CCL2, and immunosuppressive CCR2+ macrophages infiltrate these tumors. Patients with tumors that exhibit high CCL2 expression/low CD8 T-cell infiltrate have significantly decreased survival. In mice, CCR2 blockade depletes inflammatory monocytes and macrophages from the primary tumor and premetastatic liver resulting in enhanced antitumor immunity, decreased tumor growth, and reduced metastasis. Conclusions: Inflammatory monocyte recruitment is critical to pancreatic cancer progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease. Clin Cancer Res; 19(13); 3404–15. ©2013 AACR.

Microscopic Margins and Patterns of Treatment Failure in Resected Pancreatic Adenocarcinoma

OBJECTIVE To correlate microscopic margin status with survival and local control in a large cohort of patients from a high-volume pancreatic cancer center. DESIGN Retrospective database review. A uniform procedure for margin analysis was used with 4-color inking (neck, portal vein groove, uncinate, and posterior pancreatic margin) by the surgeon in the operating room. SETTING A tertiary care hospital. PATIENTS We reviewed patients who underwent pancreaticoduodenectomy between September 1, 1997, and December 31, 2008, from a prospective, institutional database. MAIN OUTCOME MEASURES Using Cox regression models, we identified pathologic characteristics associated with local recurrence (LR) after controlling for potential confounding variables. Overall and LR-free survival curves were generated by the Kaplan-Meier method. RESULTS Of 285 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma, 97 (34.0%) had 1 or more positive microscopic margins (uncinate, 16.5%; portal vein groove, 8.8%; neck, 7.7%; and posterior, 10.5%). A total of 198 patients (69.5%) recurred, with the first site of failure being LR only in 47 (23.7%), local plus distant recurrence in 42 (21.2%), and distant recurrence only in 109 (55.1%). Patients with LR only were significantly more likely to have lymph node involvement (adjusted hazard ratio, 2.66; 95% CI, 1.25-5.63) or a positive posterior margin (adjusted hazard ratio, 4.27; 95% CI, 2.07-8.81). Patients with a positive posterior margin had significantly poorer LR-free survival with (P < .001) or without (P = .01) lymph node involvement. CONCLUSIONS When systematically assessed, the incidence of positive microscopic margins is high. Positive posterior margins and lymph node involvement were each independently and significantly associated with LR.

Racial disparities in breast cancer survival: an analysis by age and stage.

BACKGROUND Black women often present with advanced-stage breast cancer compared with White women, which may result in the observed higher mortality among Black women. Age-related factors (e.g., comorbidity) also affect mortality. Whether racial disparities in mortality are evident within age and/or stage groups has not been reported, and risk factors for greater mortality among Black women are not well defined. METHODS Using the 1988-2003 Surveillance, Epidemiology, and End Results Program data, we conducted a retrospective, population-based cohort study to compare overall and stage-specific breast-cancer mortality between Black and White women within each age (<40, 40-49, 50-64, and 65+) and stage (stage 0-IV and unstaged) group at diagnosis. Cox regression models calculated unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CI), the latter controlling for potential confounders of the relationship between race and survival. RESULTS In the 1988-2003 Surveillance, Epidemiology, and End Results data, 20,424 Black and 204,506 White women were diagnosed with first primary breast cancer. In unadjusted models, Black women were more likely than White women to die from breast cancer (HR: 1.90; 95% CI: 1.83-1.96) and from all causes (HR: 1.52; 95% CI: 1.48-1.55) during follow-up. In models stratified by age and stage, Black women were at increased risk of breast-cancer-specific mortality within each stage group among women <65 y. CONCLUSION Racial disparities in breast-cancer-specific mortality were predominantly observed within each stage at diagnosis among women <65 y old. This greater mortality risk for Black women was largely not observed among women >or=65 y of age.

Temporal trends in area socioeconomic disparities in breast-cancer incidence and mortality, 1988–2005

Since an overarching goal of Healthy People 2010 was to eliminate health disparities, we determined temporal trends in socioeconomic disparities in five breast-cancer indicators (in situ, stage I, lymph-node positive, and locally advanced breast-cancer incidence, and breast-cancer mortality) by county socioeconomic deprivation using 1988–2005 population-based breast-cancer data. Using 1988–2005 data from women aged 40 and older from 200 counties in the Surveillance, Epidemiology, and End Results program, we examined trends in temporal disparities in the five breast-cancer indicators across quartiles of county socioeconomic deprivation. County-level trends were summarized using the estimated annual percentage change. Observed county rates were smoothed using Bayesian hierarchical spatiotemporal methods to calculate measures of absolute and relative disparity (using absolute and relative concentration indices) and their changes over time. Large increases in in situ breast cancer rates since 1988 were observed for each of the deprivation quartiles. Absolute and relative disparity both increased over time, suggesting increasing disparities across levels of county deprivation. Absolute and relative concentration indices were near zero for the other four breast-cancer indicators, suggesting no disparities among the four quartiles of county deprivation during 1988–2005. Efforts to target counties aimed at increasing breast-cancer screening based on their level of deprivation will not likely be beneficial.

Physical Activity and Diabetes: Opportunities for Prevention Through Policy

Over the past decade, the prevalence of type 2 diabetes mellitus has reached epidemic levels in the United States and other developed countries. With a concomitant rise in obesity levels in the United States and advances in the treatment of diabetes and its complications, the prevalence of diabetes is expected to continue to rise through the year 2050. Despite strong evidence that regular physical activity can prevent or delay the onset of diabetes, too many Americans are not meeting the recommended levels of regular physical activity. Although most physical activity interventions to date have been focused on characteristics of the individual, more-recent studies have considered how changing characteristics of the social and physical environment in which people live may ultimately have a greater impact on increasing population levels of physical activity. Policy interventions are a way to make sustainable changes in the physical environment of a community and thus provide support for other intrapersonal and interpersonal behavioral change interventions. Policy changes also can affect the social norms that shape behavior. The purposes of this perspective article are: (1) to describe the rationale for population approaches to primary prevention of type 2 diabetes, (2) to discuss how policy interventions can increase physical activity levels within populations, and (3) to provide recommendations for the role of physical therapists in interventions that can increase the level of physical activity in communities. Public health approaches to curb the diabetes epidemic are urgently needed. Policy interventions to increase population levels of physical activity show promise for diabetes prevention. Physical therapists are uniquely suited to influence primary prevention efforts for diabetes.

The Use of Sociocultural Constructs in Cancer Screening Research Among African Americans

BACKGROUND Studies are increasingly examining the role of sociocultural values, beliefs, and attitudes in cancer prevention. However, these studies vary widely in how sociocultural constructs are defined and measured, how they are conceived as affecting cancer beliefs, behaviors, and screening, and how they are applied in interventions. METHODS To characterize the current state of this research literature, we conducted a critical review of studies published between 1990 and 2006 to describe the current use of sociocultural constructs in cancer screening research among African Americans. We included quantitative and qualitative studies with cancer as a primary focus that included African American participants, assessed screening behaviors, reported race-specific analyses, and considered one or more sociocultural factors. Studies were evaluated for type of cancer and screening analyzed, study population, methodology, sociocultural constructs considered, definitions of constructs, provision of psychometric data for measures, and journal characteristics. RESULTS Of 94 studies identified for review, 35 met the inclusion criteria and were evaluated. Most focused on breast cancer screening, and thus African American women. Sociocultural constructs were seldom clearly defined, and the sources and psychometric properties of sociocultural measures were rarely reported. CONCLUSIONS A multidisciplinary approach to developing a common language and a standardized set of measures for sociocultural constructs will advance research in this area. Specific recommendations are made for future research.