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This study examined the effects of a digital diabetes prevention program (DPP) on health care costs and utilization among Medicare Advantage participants. Patients (n = 501) received access to a plan-sponsored, digitally-delivered DPP accessible through computer, tablet, or smartphone. Prior research demonstrated a 7.5% reduction in body weight at 12 months. A comparison group who did not participate in the DPP was constructed by matching on demographic, health plan, health status, and health care costs and utilization. The authors assessed effects on cost and utilization outcomes using difference-in-differences regressions, controlling for propensities to participate and engage in the DPP, in the 12 months prior to DPP enrollment and 24 months after. Though post-enrollment data showed trends in decreased drug spending and emergency department use, increased inpatient utilization, and no change in total nondrug costs or outpatient utilization, the findings did not reach statistical significance, potentially because of sample size. The population had low costs and utilization at baseline, which may be responsible for the lack of observed effects in the short time frame. This study demonstrates the challenges of studying the effectiveness of preventive programs in a population with low baseline costs and the importance of using a large enough sample and follow-up period, but remains an important contribution to exploring the effects of digital DPPs in a real-world sample of individuals who were eligible and willing to participate.

Objectives: In patients with type 2 diabetes (T2D), comorbidity-related hospitalizations can have significant impact on longitudinal care. This study aimed to estimate incremental all-cause health care resource utilization (HCRU) and costs between patients with T2D who experienced cardiovascular (CV)-, heart failure (HF)-, or renal-related hospitalizations vs those who did not., Study Design: This was a retrospective cohort study using data from a large national health plan., Methods: Patients with T2D aged 18 to 90 years with CV, HF, or renal hospitalizations were identified from the Humana claims database from October 1, 2009, to September 30, 2015, and separated into CV, HF, and renal cohorts. Patients had 12 months of continuous enrollment prior to the date of first hospitalization (index) and were followed for up to 12 months. Per-patient per-month (PPPM) all-cause HCRU and costs for hospitalized patients were compared with those of no-CV, no-HF, and no-renal cohorts. Differences in baseline characteristics between cohorts were controlled for using generalized linear models., Results: A total of 221,229, 68,126, and 120,105 patients were included in the CV, HF, and renal cohorts, respectively; these patients were older and had higher Deyo-Charlson Comorbidity Index scores than patients in the no-CV, no-HF, and no-renal cohorts. Adjusted for baseline covariates, they had higher mean PPPM inpatient stays, outpatient visits, emergency department visits, and total health care costs., Conclusions: Among patients with T2D, concurrent CV, HF, or renal events present significant disease burden leading to poor quality of life. This information can be used to guide disease management strategies and interventions aimed at reducing comorbidity-related hospitalizations and health care costs, thus providing improved quality of life for these patients.

The objective was to identify individuals with undiagnosed prediabetes from administrative data using adaptive techniques. The data source was a national Medicare Advantage Prescription Drug (MAPD) plan administrative data set. A retrospective, cross-sectional study developed and evaluated data adaptive logistic regression, decision tree, neural network, and ensemble predictive models for metabolic syndrome and prediabetes using 3 mutually exclusive cohorts (N = 279,903). The misclassification rate (MCR), average squared error (ASE), c-statistics, sensitivity (SN), and false positive (FP) rates were compared to select the final predictive models. MAPD individuals with continuous enrollment from 2013 to 2014 were included. Metabolic syndrome and prediabetes were defined using clinical guidelines, diagnosis, and laboratory data. A total of 512 variables identified through subject matter expertise in addition to utilizing all data available were evaluated for the modeling. The ensemble model demonstrated better discrimination (c-statistics, MCR, and ASE of 0.83, 0.24, and 0.16, respectively), high SN, and low FP rate in predicting metabolic syndrome than the individual data adaptive modeling techniques. Logistic regression demonstrated better discrimination (c-statistics, MCR, and ASE of 0.67, 0.13, and 0.11 respectively), high SN, and low FP rate in predicting prediabetes than the other adaptive modeling techniques or ensemble methods. The scored data predicted prediabetes in 44% of the MAPD population, which is comparable to 2005-2006 National Health and Nutrition Examination Survey prediabetes rates of 41%. The logistic regression model demonstrated good performance in predicting undiagnosed prediabetes in MAPD individuals.

Objective: To examine the outcomes of a Medicare population who participated in a program combining digital health with human coaching for diabetes risk reduction., Method: People at risk for diabetes enrolled in a program combining digital health with human coaching. Participation and health outcomes were examined at 16 weeks and 6 and 12 months., Results: A total of 501 participants enrolled; 92% completed at least nine of 16 core lessons. Participants averaged 19 of 31 possible opportunities for weekly program engagement. At 12 months, participants lost 7.5% ( SD = 7.8%) of initial body weight; among participants with clinical data, glucose control improved (glycosylated hemoglobin [HbA1c] change = -0.14%, p = .001) and total cholesterol decreased (-7.08 mg/dL, p = .008). Self-reported well-being, depression, and self-care improved ( p < .0001)., Discussion: This Medicare population demonstrated sustained program engagement and improved weight, health, and well-being. The findings support digital programs with human coaching for reducing chronic disease risk among older adults.

Objective: Readmission is costly among patients with type 2 diabetes (T2DM) in Medicare Advantage Prescription Drug Plans; identifying high-risk patients is necessary for targeting reduction programs. The objective of this study was to develop a claims-based algorithm to predict all-cause 30 day readmission among patients with T2DM., Methods: This study used administrative data from 1 January 2012 through 31 January 2014. The cohort included hospitalized T2DM patients, aged 18-90 with ≥12 months' continuous enrollment before an unplanned hospital admission and ≥1 month of enrollment post-discharge, excluding patients in long-term care >30 days pre-index. Multivariate logistic regression predicted the likelihood of readmission following hospitalization in 2013. The analytic file was randomly split into training and test datasets to build and validate the model. Candidate variables included physician and patient demographics, baseline clinical conditions, and healthcare utilization metrics. Clinical conditions were classified using the Healthcare Cost and Utilization Project clinical classification system for ICD-9-CM., Results: Of 63,237 individuals, 17.1% experienced a readmission. Of nearly 200 candidate variables, 14 were predictors of readmission, including total cumulative number of days for inpatient stays and the number of emergency department visits in the baseline period. Male gender, older age, and certain comorbidities were associated with higher likelihood of readmission. The final model demonstrated good discriminant ability (c-statistic = 0.82)., Conclusions: This study provided evidence that certain patient characteristics and healthcare utilization are predictive of readmission. An algorithm with good discriminant ability was developed which could be used to target readmission reduction programs. Physician gender, specialty, and ownership status did not appear to influence the likelihood of readmission.

Introduction: Arthritis is related to poor health-related quality of life (HRQoL) in adults aged 18 years or older. We sought to determine whether this relationship persisted in an older population using claims-based arthritis diagnoses and whether people who also had arthritis and at least 1 of 5 other chronic conditions had lower HRQoL., Methods: We identified adults aged 65 years or older with Medicare Advantage coverage in November or December 2014 who responded to an HRQoL survey (Healthy Days). For respondents with and without arthritis, we used linear regression to compare mean physically, mentally, and total unhealthy days, overall and in 5 comorbidity subgroups (coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, and hypertension), accounting for age, sex, dual Medicaid/Medicare eligibility, rural/urban commuting area, and Charlson Comorbidity Index., Results: Of the 58,975 survey respondents, 44% had arthritis diagnosed through claims. Respondents with arthritis reported significantly more adjusted mean physically, mentally, and total unhealthy days than those without arthritis (P < .001). Older adults with arthritis and either congestive heart failure, chronic obstructive pulmonary disease, diabetes, or hypertension reported significantly more adjusted physically, mentally, and total unhealthy days than older adults without arthritis but with the same chronic conditions., Conclusions: In older adults, having arthritis is associated with lower HRQoL and even lower HRQoL among those with at least 1 of 5 other common chronic conditions. Because arthritis is so common among older adults, improving HRQoL depends on managing both underlying chronic conditions and any accompanying arthritis.

Measuring population health with morbidity and mortality data, often collected at the site of care, fails to capture the individual's perspective on health and well-being. Because health happens outside the walls of medical facilities, a holistic and singular measure of health that can easily be captured for an entire population could aid in understanding the well-being of communities. This paper postulates that Healthy Days, a health-related quality of life measure developed and validated by the Centers for Disease Control and Prevention, is an ideal survey instrument to advance population health. A systematic literature review was conducted and revealed a strong evidence base using Healthy Days with significant correlations to chronic disease conditions. Building on the literature base and experience, methods for analyzing Healthy Days data are discussed, including stratified sampling techniques, statistical measures to account for variance, and modeling techniques for skewed distributions. Using such analytic techniques, Healthy Days has been used extensively in national health surveillance. As the health care system faces increasing costs and constrained resources, the Healthy Days survey instrument can be used to inform public policies and allocate health service resources. Because Healthy Days captures broad dimensions of health from the individual's perspective, it is a simple way to holistically measure the health and well-being of a population and its trend over time. Expanded use of Healthy Days can aid population health managers and contribute to the understanding of the broader determinants of the nation's and individual community's health and aid in evaluating progress toward health goals., Competing Interests: Author Disclosure Statement The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs. Davidson, Happe, Miao, Prewitt, and Slabaugh, Mr. Cordier and Mr. Havens are employees of Humana Inc. Drs. Happe and Slabaugh own Humana stock. No external financial support was provided to Humana for this research. Dr. Jia received compensation from Humana for his contributions. Drs. Shah and Zack report no conflict of interest. The investigators retained full independence in the conduct of this research. The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

The Paris Hospital in Paris, Arkansas, provided high quality care during its existence from 1910 to 1971, offering a prepaid health care plan from 1920 to 1971. Three generations of Smith doctors were its nucleus, subsidizing the annual losses of the hospital and providing care to all, regardless of ability to pay. The hospital was a community unto itself for the nurses who lived, trained, and worked there. A unique family in the history of medicine in Arkansas, the Smith physicians were well trained, altruistic, compassionate, and conscientious, exemplifying the traditional values of twentieth century medical practice.

Dr. J. G. Eberle's efforts to pave the streets of Fort Smith are illustrative of the challenges facing Arkansas in the nineteenth century. Development of sewers, drains, and a safe water supply helped control epidemics of malaria, yellow fever, cholera, and other forms of dysentery. During this time the medical profession struggled to establish professional standards before the great reforms of medical education took hold in the twentieth century. The military hospital of the Civil War was a precursor of the role hospitals would play in bringing higher standards of care to their communities.

Medical practice in the late nineteenth and early twentieth centuries consisted largely of kitchen surgery and house calls. The practices of Dr. St. Cloud Cooper and other Fort Smith doctors reflected the standards of practice in Arkansas and the nation as the principles of aseptic surgery gradually gained acceptance. The doctor's black bag used on house calls still lacked the effective agents which became available during the mid-twentieth century, leaving the physician to rely on personal inner resources in order to perform a useful service.

Selenium has been shown to prevent cancer in a variety of animal model systems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresses tumor development remains unknown. Selenium is present in known human selenoproteins as the amino acid selenocysteine (Sec). Sec is inserted cotranslationally in response to UGA codons within selenoprotein mRNAs in a process requiring a sequence within the 3'-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human Mr 15,000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon and a SECIS element in the 3'-UTR. Examination of the available cDNA sequences for this protein revealed two polymorphisms located at position 811 (C/T) and at position 1125 (G/A) located within the 3'-UTR. Here, we demonstrate significant differences in Sep15 allele frequencies by ethnicity and that the identity of the nucleotides at the polymorphic sites influences SECIS function in a selenium-dependent manner. This, together with genetic data indicating loss of heterozygosity at the Sep15 locus in certain human tumor types, suggests that Sep15 may be involved in cancer development, risk, or both.

Background: Prevention efforts to reduce the morbidity and mortality disparity between blacks and whites in the United States present a national health priority. However, participation of blacks in prevention trials has been low. The present study reports successful recruitment processes from two economically diverse black populations., Methods: The two studies were independent projects, but both were part of a nationally funded collaboration on cardiovascular health. "Hip Hop to Health" is a 4-year randomized controlled trial aimed at dietary fat reduction and increased exercise among inner-city black families. The Fat Reduction Intervention Trial in African-Americans project is a 5-year trial to reduce total fat, saturated fat, and cholesterol intake among black families from a working class community., Results: The two populations differed on demographic characteristics. Direct presentation was the most effective recruitment strategy in the "Hip Hop to Health" program. In contrast, telephone recruitment and neighborhood canvassing were the more successful strategies for FRITAA., Conclusions: Although both populations were black and at comparable cardiovascular disease risk, the differing demographics between the groups made different recruitment strategies necessary. This study documented the labor-intensive quality of successful recruitment, and results suggest that successful recruitment requires strategies tailored to the needs, experiences, and environment of the target group.

Developmental stability (the precision with which genotypes are translated into phenotypes under physically stressful developmental conditions), is a major source of phenotypic and behavioural variation, yet researchers have largely ignored its potential role in the ontogeny of individual propensities toward human aggression and violence. In this study, we measured fluctuating asymmetry of the body and administered aggression and fighting history questionnaires to 229 college students (139 female and 90 male undergraduates). Among males, but not females, fluctuating asymmetry correlated negatively and significantly with the participants' number of fights and propensity to escalate agonistic encounters to physical violence. Principal components analyses and scree tests suggested that two psychometric factors underlie observed correlations between self-report measures of aggressive tendencies. The first factor, 'aggressive negative affect', reflected verbal aggression and hostility toward others, while the second factor, 'self-assessed fighting ability', reflected physical violence and a tendency to win fights. The two factors correlated minimally. For both males and females, the second factor correlated with number of fights while the first factor did not. Fluctuating asymmetry did not significantly correlate with either factor for either sex, but for both sexes, psychometric intelligence (IQ) correlated positively with the first factor.

Little is known about the genetic nature of human psychometric intelligence (IQ), but it is widely assumed that IQ's heritability is at loci for intelligence per se. We present evidence consistent with a hypothesis that interindividual IQ differences are partly due to heritable vulnerabilities to environmental sources of developmental stress, an indirect genetic mechanism for the heritability of IQ. Using fluctuating asymmetry (FA) of the body (the asymmetry resulting from errors in the development of normally symmetrical bilateral traits under stressful conditions), we estimated the relative developmental instability of 112 undergraduates and administered to them Cattell's culture fair intelligence test (CFIT). A subsequent replication on 128 students was performed. In both samples, FA correlated negatively and significantly with CFIT scores. We propose two non-mutually exclusive physiological explanations for this correlation. First, external body FA may correlate negatively with the developmental integrity of the brain. Second, individual energy budget allocations and/or low metabolic efficiency in high-FA individuals may lower IQ scores. We review the data on IQ in light of our findings and conclude that improving developmental quality may increase average IQ in future generations.

The management of high-grade extremity sarcomas typically combines local surgical excision with some form of adjuvant therapy. However, some patients with large proximal lesions present with no local resection options, and high radical amputation is often the only way to accomplish complete tumour excision. A retrospective review was made of the clinical courses of 53 patients with high-grade sarcomas of the lower extremity who underwent hemipelvectomy with curative intent at the National Institutes of Health between 1975 and 1989. Hemipelvectomy provided excellent local control, with no local recurrences. Although 60% of the patients experienced post-operative complications, the operative mortality was zero. Ten years after hemipelvectomy, the actuarial disease-free rate was 25% and the survival rate was 35%. There were no statistically significant survival differences when patients were stratified according to tumour size, perioperative blood transfusion requirements or the use of adjuvant chemotherapy. We conclude that hemipelvectomy provides excellent local control and a reasonable cure rate for patients with locally unresectable soft tissue sarcomas of the lower extremity.

We periodically obtained blood samples from mildly hypercholesterolemic, but otherwise healthy, premenopausal women who were recruited to participate in a study of a long-term, cholesterol-lowering diet. All meals were prepared and most meals were consumed in the study center dining facility. Tests performed on blood samples included fibrinogen, cholesterol, factor VII coagulant activity (VIIc), and other measures of factor VII. We found that when women switched from a typical American diet (37% fat, polyunsaturated fatty acid to saturated fatty acid [P/S] ratio 0.5, 300 mg cholesterol/d) to a diet lower in fat and cholesterol (American Heart Association phase 2 diet: 30% fat, P/S ratio of 1, 150 to 200 mg cholesterol/d) and maintained that diet for 20 weeks, their plasma cholesterol levels decreased by approximately 6% after 4 weeks and remained at that level until study termination. Likewise, VIIc decreased by approximately 11% while factor VII antigen, total factor VII activity, and fibrinogen concentration did not change appreciably from baseline values. Our results show that premenopausal women benefit from a diet lower in total and saturated fat by a reduction in blood cholesterol and VIIc. Extrapolation from data on men in the Northwick Park Heart Study indicates that the 11% decrease in VIIc activity would correspond to an approximately 30% decrease in risk of mortality from coronary heart disease.

Tumor necrosis factor can alter the cell cycle of tumor cells and protect hematopoietic stem cells from cell cycle-specific chemotherapy, but the ability of tumor necrosis factor to protect cancer cells from chemotherapy by manipulation of the cell cycle is unknown. Twenty-four-hour exposure of A549 human lung cancer cells to tumor necrosis factor shifted cells from S phase to G0/G1 phase as determined by analysis of isolated cell nuclei with an FACScan Cell Sorter. This effect was not seen in cells exposed to interleukin-1 or interleukin-6. Growth assays demonstrated that tumor necrosis factor slowed the doubling time of A549 cells, confirming that tumor necrosis factor caused G0/G1 arrest in these cells. Pretreatment with tumor necrosis factor rendered cells resistant to subsequent 1-hour exposure to doxorubicin, a chemotherapeutic agent active against S phase cells. Tumor necrosis factor did not protect cells against either cisplatin or mitomycin C, drugs not specific for S phase. Measurement of intracellular drug levels indicated that pretreatment with tumor necrosis factor did not affect doxorubicin uptake or efflux. These findings suggest that cells producing tumor necrosis factor within a tumor may render surrounding malignant cells resistant to cell cycle-specific chemotherapy, and this mechanism may explain failure of sequential immunotherapy-chemotherapy protocols.

Competition between the (n - 3) and (n - 6) types of highly unsaturated fatty acids can diminish the abundance of (n - 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by (n - 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18:2 (n - 6) and 18:3 (n - 3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505-516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of (n - 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic or other disorders that are mediated by (n - 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated (n - 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon (n - 3) fatty acids compared to that for the 18-carbon (n - 3) fatty acid in decreasing the ability of dietary 18:2 (n - 6) to maintain 20:4 (n - 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n - 3 fatty acids in the elongation/desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n - 6 vs. the n - 3 type indicated a greater competitive effectiveness of 20:4 (n - 6) relative to 20:5 (n - 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the (n - 3) and (n - 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids.

Selected immunotherapies (tumor necrosis factor, interleukin-1, interleukin-2, and gamma interferon), chemotherapeutic agents (mitomycin, platinum, doxorubicin [Adriamycin], and bleomycin), and radiation therapy have been described to exert cytotoxicity through the generation of reactive oxygen species, including superoxide and hydrogen peroxide. Tumor necrosis factor, however, has been shown to impart increased resistance in vitro and in vivo against reactive oxygen species stress, including radiation therapy and oxygen toxicity, possibly because of the induction of increased cellular buffering capacities. It is unknown whether the sensitivity of a lung cancer cell to reactive oxygen species therapy is altered by tumor necrosis factor through the induction of free radical scavenging enzymes such as manganese superoxide dismutase. This question was investigated as follows: A549 lung adenocarcinoma cells, exposed for 24 hours to 0, 0.1, 1.0, or 10 micrograms/ml concentrations of tumor necrosis factor, were exposed to hypoxanthine plus xanthine oxidase, a superoxide generating system, for varying intervals. The number of cells surviving 5 days after the stress was determined, and cells exposed to tumor necrosis factor were examined by Northern Blot analysis for induction of the manganese superoxide dismutase gene. The hypoxanthine-xanthine oxidase stress alone caused a time-dependent decrease in survival; however, pretreatment with tumor necrosis factor increased cell survival significantly. Moreover, the cells exposed to tumor necrosis factor had a fivefold increase in the number of manganese superoxide dismutase transcripts. These findings suggest that tumor necrosis factor may confer resistance of lung cancer cells to subsequent reactive oxygen species-based therapies, and the resistance of these cells may be due to increased expression of manganese superoxide dismutase. Clinical treatment failures may result, especially if tumor necrosis factor is given concurrently with other therapies.

Our specific aim was to assess differences in nutrient intake and in lipids and lipoprotein cholesterols between blacks and whites in 259 black children (129 boys, 130 girls) and in 811 white children (424 boys, 387 girls) ages 5-19. The nutrient intake data were obtained by 24-hr recall from the Houston and Cincinnati Lipid Research Clinics. The fundamental nutrient differences between blacks and whites were in total calories and in calories per kilogram of body weight, both of which were uniformly and significantly lower among black than white boys and generally, but less consistently and significantly, lower among black than white girls. No racial differences in total cholesterol or cholesterol intake per kilogram body weight were observed. After statistically controlling for education of the head of household, there were no consistent significant racial differences in Quetelet index. There was no significant independent effect of education of head of household on the children's caloric intake and racial differences in socioeconomic status did not appear to systematically account for differences in total energy intake. In aggregate, black children had lower triglyceride and very-low-density lipoprotein cholesterol levels, and higher levels of high-density lipoprotein cholesterol than whites; there were no significant differences by race in low-density lipoprotein cholesterol levels. Race was a significant independent explanatory variable for high-density lipoprotein cholesterol levels (higher in blacks) and for very-low-density lipoprotein and triglyceride levels (higher in whites) (P less than 0.005), after covariance adjusting for education of head of household, sex, age, Quetelet index, calories, saturated fat (g/day/kg body wt), and clinic. Lower caloric intake among blacks compared with whites, the major nutrient difference in the current study, did not account for differences in lipoprotein cholesterol levels between the two groups.