Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies.

CONTEXT: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction. OBJECTIVE: Assess tildacerfont safety and efficacy. DESIGN AND SETTING: Two Phase 2 open-label studies. PATIENTS: Adults with 21OHD. INTERVENTION: Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2). MAIN OUTCOME MEASURE: Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 > 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments. RESULTS: In Study 1, evaluable participants with baseline A4 > 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (-59.4% to -28.4%), 17-OHP (-38.3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%). CONCLUSIONS: For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal.

The Surprising Creativity of Digital Evolution: A Collection of Anecdotes from the Evolutionary Computation and Artificial Life Research Communities.

Evolution provides a creative fount of complex and subtle adaptations that often surprise the scientists who discover them. However, the creativity of evolution is not limited to the natural world: Artificial organisms evolving in computational environments have also elicited surprise and wonder from the researchers studying them. The process of evolution is an algorithmic process that transcends the substrate in which it occurs. Indeed, many researchers in the field of digital evolution can provide examples of how their evolving algorithms and organisms have creatively subverted their expectations or intentions, exposed unrecognized bugs in their code, produced unexpectedly adaptations, or engaged in behaviors and outcomes, uncannily convergent with ones found in nature. Such stories routinely reveal surprise and creativity by evolution in these digital worlds, but they rarely fit into the standard scientific narrative. Instead they are often treated as mere obstacles to be overcome, rather than results that warrant study in their own right. Bugs are fixed, experiments are refocused, and one-off surprises are collapsed into a single data point. The stories themselves are traded among researchers through oral tradition, but that mode of information transmission is inefficient and prone to error and outright loss. Moreover, the fact that these stories tend to be shared only among practitioners means that many natural scientists do not realize how interesting and lifelike digital organisms are and how natural their evolution can be. To our knowledge, no collection of such anecdotes has been published before. This article is the crowd-sourced product of researchers in the fields of artificial life and evolutionary computation who have provided first-hand accounts of such cases. It thus serves as a written, fact-checked collection of scientifically important and even entertaining stories. In doing so we also present here substantial evidence that the existence and importance of evolutionary surprises extends beyond the natural world, and may indeed be a universal property of all complex evolving systems.

Bite force in the horned frog (Ceratophrys cranwelli) with implications for extinct giant frogs.

Of the nearly 6,800 extant frog species, most have weak jaws that play only a minor role in prey capture. South American horned frogs (Ceratophrys) are a notable exception. Aggressive and able to consume vertebrates their own size, these "hopping heads" use a vice-like grip of their jaws to restrain and immobilize prey. Using a longitudinal experimental design, we quantified the ontogenetic profile of bite-force performance in post-metamorphic Ceratophrys cranwelli. Regression slopes indicate positive allometric scaling of bite force with reference to head and body size, results that concur with scaling patterns across a diversity of taxa, including fish and amniotes (lizards, tuatara, turtles, crocodylians, rodents). Our recovered scaling relationship suggests that exceptionally large individuals of a congener (C. aurita) and extinct giant frogs (Beelzebufo ampinga, Late Cretaceous of Madagascar) probably could bite with forces of 500 to 2200 N, comparable to medium to large-sized mammalian carnivores.

Predicting the EuroQol Group's EQ-5D index from CDC's "Healthy Days" in a US sample.

BACKGROUND: Obtaining reliable preference-based scores from the widely used Healthy Days measures would enable calculation of quality-adjusted life years (QALYs) and cost-utility analyses in many US community populations and over time. Previous studies translating the Healthy Days to the EQ-5D, a preference-based measure, relied on an indirect method because of a lack of population-based survey data that asked both sets of questions of the same respondents. METHOD: Data from the 2005-2006 National Health Measurement Study (NHMS; n = 3844 adults 35 years old or older) were used to develop regression-based models to estimate EQ-5D index scores from self-reported age, self-rated general health, and numbers of unhealthy days. RESULTS: The models explained up to 52% of the variance in the EQ-5D. Estimated EQ-5D scores matched well to the observed EQ-5D scores in mean scores overall and by age, gender, race/ethnicity, income, education, body mass index, smoking, and disease categories. The average absolute differences were 0.005 to 0.006 on a health utility scale. After estimating mean EQ-5D index scores overall and for various subgroups in a large representative US sample of Healthy Days respondents, the authors found that these mean scores also closely matched the corresponding mean scores of EQ-5D respondents obtained from another large US representative sample with an average absolute difference of 0.013 points. CONCLUSIONS: This study yielded a mapping algorithm to estimate EQ-5D index scores from the Healthy Days measures for populations of adults 35 years old and older. Such analysis confirms it is feasible to estimate mean EQ-5D index scores with acceptable validity for use in calculating QALYs and cost-utility analyses based on the overall model fit and relatively small differences between the observed and the estimated mean scores.

County-level social environment determinants of health-related quality of life among US adults: a multilevel analysis.

To show that an individual's health-related quality of life (HRQOL) is not determined only by their personal-level characteristics, but also is socially determined by both physical and social environmental characteristics of their communities. This analysis examined the association of selected county-level indicators on respondents' unhealthy days and assessed the utility of mean unhealthy days for US counties as community health indicators. Data came from the 1999-2001 Behavioral Risk Factor Surveillance System. We used multilevel models to calculate the proportion of between-county variation in HRQOL that was explained by county-level contextual variables and examine the causal heterogeneity of some personal-level factors modified by these contextual variables. Counties with worse socioeconomic indicators, high mortality rate, and low life expectancy were associated with higher numbers of unhealthy days. These indicators explained 13-22% variance of county-level physically unhealthy days and 4.5-9.5% variance of county-level mentally unhealthy days. The GINI index, suicide rate, percent uninsured, primary care facilities-to-population ratio, and most county-level demographic and housing indicators also had significant but smaller impact on respondents' unhealthy days. Also, the counties with poorer socioeconomic scores had additional negative HRQOL impact on older persons. This study provides important new empirical information on whether various commonly-measured characteristics of the social environment, which are believed to be social determinants of health, are in fact associated with the perceived physical and mental health of its residents. Our findings provide additional support for the construct validity of county-level HRQOL as a community health indicator.

Geographic patterns of frequent mental distress: U.S. adults, 1993-2001 and 2003-2006.

BACKGROUND: Mental illnesses and other mental health problems often lead to prolonged, disabling, and costly mental distress. Yet little is known about the geographic distribution of such mental distress in the U.S. METHODS: Since 1993, the CDC has tracked self-perceived mental distress through the Behavioral Risk Factor Surveillance System (BRFSS). In 2007 and 2008, analysis was performed on BRFSS data reported by 2.4 million adults from 1993-2001 and 2003-2006 to map and describe the prevalence of frequent mental distress (FMD)-defined as having >or=14 mentally unhealthy days during the previous 30 days-for all states and for counties with at least 30 respondents. RESULTS: The adult prevalence of FMD for the combined periods was 9.4% overall, ranging from 6.6% in Hawaii to 14.4% in Kentucky. From 1993-2001 to 2003-2006, the mean prevalence of FMD increased by at least 1 percentage point in 27 states and by more than 4 percentage points in Mississippi, Oklahoma, and West Virginia. Most states showed internal geographic variations in FMD prevalence. The Appalachian and the Mississippi Valley regions had high and increasing FMD prevalence, and the upper Midwest had low and decreasing FMD prevalence. CONCLUSIONS: Geographic areas were identified with consistently high and consistently low FMD prevalence, as well as areas in which FMD prevalence changed substantially. Further evaluation of the causes and implications of these patterns is warranted. Surveillance of mental distress may be useful in identifying unmet mental health needs and disparities and in guiding health-related policies and interventions.

Choline status is not a reliable indicator of moderate changes in dietary choline consumption in premenopausal women.

For the prevention of liver dysfunction in women, a choline adequate intake of 425 mg/day was established. To date, the relationship between dietary choline intake and plasma concentrations of choline moieties remains relatively unexplored. As an extension of our previous work, this 14-week controlled feeding study investigated the relationship between moderate changes in dietary choline intake and blood indicators of status. The influences of folate intake and the methylenetetrahydrofolate reductase (MTHFR) C677T genotype were also considered. Healthy premenopausal women (n=45, 18-46 years) with the MTHFR 677CC (n=28) or TT (n=17) genotype consumed a folate-restricted diet for 2 weeks followed by randomization to one of four dietary treatments (n=6-9/group) differing in total choline (344-486 mg/day), betaine (122-349 mg/day) and/or folate (400-800 microg dietary folate equivalents/day) content for 12 weeks. Responses to treatment were assessed as changes in the plasma levels of choline moieties (i.e., betaine, choline, phosphatidylcholine and sphingomyelin) and/or leukocyte global DNA methylation between pretreatment (Week 2) and posttreatment (Week 14) values. No significant changes were detected in the measured variables in response to dietary increases in choline (i.e., 41% increase) or betaine (i.e., 286% increase) intake. However, the MTHFR C677T genotype, alone or together with a diet, influenced betaine (P=.03) and phosphatidylcholine (P=.03). These data suggest that choline status is not a reliable indicator of moderate changes in dietary choline intake possibly due to the engagement of compensatory mechanisms. In addition, the MTHFR C677T genotype appears to influence the direction and use of choline moieties in this group of women.

Ethnicity and folate influence choline status in young women consuming controlled nutrient intakes.

OBJECTIVE: We previously demonstrated that choline and folate are interrelated and that African American women have lower folate nutriture than Caucasian and Mexican American women under conditions of controlled folate intake. The present study sought to examine the influences of ethnicity and controlled folate intake on choline status. METHODS: Forty-two women of Mexican American (n = 14), African American (n = 14), and Caucasian American (n = 14) descent consumed a folate restricted diet (135 microg DFE/d) for 7 weeks, followed by 7 weeks of folate treatment with either 400 or 800 microg DFE/d. Total choline intake remained unchanged throughout the study at approximately 350 mg/d. Plasma choline and its derivatives were measured by LC-MS/MS at weeks 0, 7, and 14. RESULTS: Plasma phosphatidylcholine declined during folate restriction (P < 0.001) and tended to increase in response to 800 microg DFE/d (week x folate, P = 0.099) in Mexican American and Caucasian women. For African American women, however, phosphatidylcholine continued to decline (week x race, P = 0.056). Plasma betaine was modified by ethnicity and level of folate intake (week x race x folate, P = 0.039) however no clear patterns emerged. CONCLUSIONS: The phosphatidylcholine data suggest that the lower folate status observed in African American women may also be associated with lower choline status. In turn, diseases linked to folate may also be linked to choline.

Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype.

Since the establishment of the 1998 folate recommended dietary allowance (RDA), the methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant has emerged as a strong modifier of folate status. This controlled feeding study investigated the adequacy of the RDA, 400 microg/d as dietary folate equivalents (DFE), for Mexican American men with the MTHFR 677CC or TT genotype. Because of the interdependency between folate and choline, the influence of choline intake on folate status was also assessed. Mexican American men (n = 60; 18-55 y) with the MTHFR 677CC (n = 31) or TT (n = 29) genotype consumed 438 microg DFE/d and total choline intakes of 300, 550 (choline adequate intake), 1100, or 2200 mg/d for 12 wk. Folate status response was assessed via serum folate (SF), RBC folate, plasma total homocysteine (tHcy), and urinary folate. SF decreased (P < 0.001) 66% to 7.9 +/- 0.7 nmol/L (means +/- SEM) in men with the 677TT genotype and 62% to 11.3 +/- 0.9 nmol/L in the 677CC genotype. Plasma tHcy increased (P < 0.0001) 170% to 31 +/- 3 micromol/L in men with the 677TT genotype and 18% to 11.6 +/- 0.3 micromol/L in the 677CC genotype. At the end of the study, 34% (677TT) and 16% (677CC) had SF concentrations <6.8 nmol/L and 79% (677TT) and 7% (677CC) had tHcy concentrations >14 micromol/L. Choline intake did not influence the response of the measured variables. These data showed that the folate RDA is not adequate for men of Mexican descent, particularly for those with the MTHFR 677TT genotype, and demonstrated a lack of influence of choline intake on the folate status variables measured in this study.

The associations between life satisfaction and health-related quality of life, chronic illness, and health behaviors among U.S. community-dwelling adults.

The primary purpose of this article was to examine the associations between life satisfaction level and health-related quality of life (HRQOL), chronic illness, and adverse health behaviors among adults in the U.S. and its territories. Data were obtained from the 2005 Behavioral Risk Factor Surveillance System, an ongoing, state-based, random-digit telephone survey of the noninstitutionalized U.S. population aged >or=18 years. An estimated 5.6% of U.S. adults (about 12 million) reported that they were dissatisfied/very dissatisfied with their lives. As the level of life satisfaction decreased, the prevalence of fair/poor general health, disability, and infrequent social support increased as did the mean number of days in the past 30 days of physical distress, mental distress, activity limitation, depressive symptoms, anxiety symptoms, sleep insufficiency, and pain. The prevalence of smoking, obesity, physical inactivity, and heavy drinking also increased with decreasing level of life satisfaction. Moreover, adults with chronic illnesses were significantly more likely than those without to report life dissatisfaction. Notably, all of these associations remained significant after adjusting for sociodemographic characteristics. Our findings showed that HRQOL and health risk behaviors varied with level of life satisfaction. As life satisfaction appears to encompass many individual life domains, it may be an important concept for public health research.

Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women.

Numerous studies have reported a relationship between folate status, the methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant and disease risk. Although folate and choline metabolism are inter-related, only limited data are available on the relationship between choline and folate status in humans. This study sought to examine the influences of folate intake and the MTHFR 677C-->T variant on choline status. Mexican-American women (n=43; 14 CC, 12 CT and 17 TT) consumed 135 microg/day as dietary folate equivalents (DFE) for 7 weeks followed by randomization to 400 or 800 microg DFE/day for 7 weeks. Throughout the study, total choline intake remained unchanged at approximately 350 mg/day. Plasma concentrations of betaine, choline, glycerophosphocholine, phosphatidylcholine and sphingomyelin were measured via LC-MS/MS for Weeks 0, 7 and 14. Phosphatidylcholine and sphingomyelin declined (P=.001, P=.009, respectively) in response to folate restriction and increased (P=.08, P=.029, respectively) in response to folate treatment. The increase in phosphatidylcholine occurred in response to 800 (P=.03) not 400 (P=.85) microg DFE/day (week x folate interaction, P=.017). The response of phosphatidylcholine to folate intake appeared to be influenced by MTHFR C677T genotype. The decline in phosphatidylcholine during folate restriction occurred primarily in women with the CC or CT genotype and not in the TT genotype (week x genotype interaction, P=.089). Moreover, when examined independent of folate status, phosphatidylcholine was higher (P<.05) in the TT genotype relative to the CT genotype. These data suggest that folate intake and the MTHFR C677T genotype influence choline status in humans.

Global leukocyte DNA methylation is similar in African American and Caucasian women under conditions of controlled folate intake.

DNA methylation is an epigenetic feature that may modify disease risk, and can be influenced by folate status as well as by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. The aim of this study was to investigate the influence of ethnicity/race on global leukocyte DNA methylation under conditions of controlled folate intake. Caucasian (n = 14) and African American (n = 14) women (18 - 45 y) possessing the MTHFR 677CC genotype consumed a folate restricted diet (135 mug/d as dietary folate equivalents, DFE) for 7 week followed by folate treatment with 400 or 800 microg DFE/d for 7 week. Global leukocyte DNA methylation was assessed via the cytosine extension assay at baseline (wk 0), after folate restriction (wk 7) and after folate treatment (wk 14). Ethnicity/race was not a determinant of global leukocyte DNA methylation. No differences (p > 0.05) were detected in DNA methylation between African American and Caucasian women at baseline or any other study time point. In addition, folate intake did not modify global leukocyte DNA methylation. These data suggest that global leukocyte DNA methylation does not differ between Caucasian and African American women and that short-term folate restriction is not sufficient to modify methylation content in young women with the MTHFR 677CC genotype.

Black-white differences in health-related quality of life among older adults.

Very little information exists on racial differences in quality of life among older adults. In this paper, we examine black-white differences in health-related quality of life (HRQOL) and identify factors that may account for these differences. The participants were 5,986 community-dwelling persons age 65+ (62% black at baseline) from the Chicago Health and Aging Project. Poor HRQOL was defined as having 14 or more self-reported physically or mentally unhealthy days over the past 30 days. A higher proportion of blacks (11.0%) than whites (9.7%) reported poor HRQOL. After adjusting for age and sex, blacks had increased odds of reporting poor HRQOL compared with whites (odds ratio [OR] = 1.72; 95% CI: 1.50-1.98). The black-white differences in HRQOL tended to increase with age (p < 0.05) and were greater among females (p < 0.05). Lifetime socioeconomic status, summary measures of medical conditions, and cognitive function accounted for most of the black-white difference (OR = 1.06; 95% CI: 0.89-1.27). Our results suggest that racial differences in HRQOL are associated with the combined effects of social disadvantage, poor physical health, and lower cognitive function.

The MTHFR 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American women.

DNA methylation is an epigenetic feature that is associated with X chromosome inactivation, genomic imprinting, transcriptional silencing of genes and genomic stability. Folate provides a labile source of methyl groups which may be used for cellular methylation reactions including DNA methylation. The methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant is an important determinant of folate nutriture and may influence DNA methylation. This study sought to assess the influence of the MTHFR C677T genotype on global leukocyte DNA methylation in young (18-45y) Mexican American women (n=43; 14 CC, 12 CT and 17 TT). Subjects consumed a folate restricted diet (135 mug DFE/d) for 7 wk followed by folate treatment with 400 or 800 mug DFE/d for 7 wk. Global leukocyte DNA methylation was assessed via the cytosine extension assay at week 0, week 7 (after folate restriction) and week 14 (after folate treatment). No main effects of MTHFR C677T genotype or folate intake were detected at any time point during the study. However, at the end of folate treatment (wk 14), DNA methylation was lower (P<0.05) in women with the MTHFR 677TT genotype relative to the CT or CC genotype. Because it is unlikely that folate treatment would result in methyl group loss, we suggest that there was a delay in DNA methylation response to folate intake. Overall, these data suggest that the MTHFR 677TT genotype and folate interact to lower global leukocyte DNA methylation patterns in young Mexican American women.

Additional food folate derived exclusively from natural sources improves folate status in young women with the MTHFR 677 CC or TT genotype.

The effectiveness of additional food folate in improving folate status in humans is uncertain particularly in people with the common genetic variant (677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene. To examine the effect of a doubling of food folate consumption on folate status response variables, women (n=32; 18-46 years) with the MTHFR 677 CC or TT genotype consumed either 400 (n=15; 7 CC and 8 TT) or 800 (n=17; 8 CC and 9 TT) microg/day of dietary folate equivalents (DFE) derived exclusively from naturally occurring food folate for 12 weeks. A repeated measures two-factor ANOVA was used to examine the effect of the dietary treatment, the MTHFR C677T genotype and their interactions on serum folate, RBC folate and plasma total homocysteine (tHcy) during the last 3 weeks of the study. Consumption of 800 microg DFE/day resulted in serum folate concentrations that were 67% (P=.005) higher than consumption of 400 microg DFE/day (18.6+/-2.9 vs. 31.0+/-2.7 nmol/L, respectively) and RBC folate concentrations that were 33% (P=.001) higher (1172+/-75 vs. 1559+/-70 nmol/L, respectively). Serum folate (P=.065) and RBC folate (P=.022) concentrations were lower and plasma tHcy was higher (P=.039) in women with the MTHFR 677 TT genotype relative to the CC genotype. However, no genotype by dietary treatment interaction was detected. These data suggest that a doubling of food folate intake will lead to marked improvements in folate status in women with the MTHFR 677 CC or TT genotype.

Relationships Between Engaging in Recommended Levels of Physical Activity and Health-Related Quality of Life Among Hypertensive Adults.

BACKGROUND: Hypertension (HTN), which affects more than 65 million Americans, is associated with poor health-related quality of life (HRQOL). Regular physical activity (PA) has been shown to reduce blood pressure and is associated with higher levels of HRQOL. METHODS: Using self-reports from 60,321 hypertensive adults age 18 y or older who participated in the 2003 Behavioral Risk Factor Surveillance Survey, we examined the independent relationship between engaging in recommended levels of moderate or vigorous PA and four measures of HRQOL developed by the Centers for Disease Control and Prevention. RESULTS: For all age and racial/ethnic groups and both sexes, the proportion of hypertensive adults with 14 or more unhealthy days (physical or mental) in the past month was significantly lower among those who attained recommended levels of PA than among physically inactive adults. CONCLUSIONS: Participation in regular PA is one of several lifestyle strategies available to control and prevent HTN. These results suggest that PA is associated with higher levels of HRQOL among adults with HTN and highlight the importance of health programs that promote participation in regular PA.

The glycine N-methyltransferase (GNMT) 1289 C->T variant influences plasma total homocysteine concentrations in young women after restricting folate intake.

Glycine N-methyltransferase (GNMT) is a key regulatory protein in folate metabolism, methionine availability, and transmethylation reactions. Perturbations in GNMT may lead to aberrations in homocysteine metabolism, a marker of numerous pathologies. The primary objective of this study was to examine the influence of the GNMT 1289 C-->T alone, and in combination with the methylenetetrahydrofolate reductase (MTHFR) 677 C-->T variant, on plasma total homocysteine concentrations in healthy young women (n = 114). Plasma total homocysteine was measured at baseline (wk 0) and after 2 wk of controlled folate restriction (135 microg/d as dietary folate equivalents). Plasma homocysteine concentrations did not differ among the GNMT C1289T genotypes at baseline. However, after folate restriction, women with the GNMT 1289 TT genotype (n = 16) had higher (P = 0.019) homocysteine concentrations than women with the CT (n = 51) or CC (n = 47) genotype. The influence of the GNMT 1289 C-->T variant on homocysteine was dependent on the MTHFR C677T genotype. In subjects with the MTHFR 677 CC genotype, homocysteine was greater (P < or = 0.05) for GNMT 1289 TT subjects relative to 1289 CT or CC subjects. However, in subjects with the MTHFR 677 TT genotype, plasma homocysteine concentrations did not differ among the GNMT C1289T genotypes. Overall, these data suggest that the GNMT 1289 C-->T polymorphism influences plasma homocysteine and is responsive to folate intake.

Health-related quality of life surveillance--United States, 1993-2002.

PROBLEM/CONDITION: Population-based surveillance of health-related quality of life (HRQOL) is needed to promote the health and quality of life of U.S. residents and to monitor progress in achieving the two overall Healthy People 2010 goals: 1) increase the quality and years of healthy life and 2) eliminate health disparities. REPORTING PERIOD: This report examines surveillance-based HRQOL data from 1993 through 2002. DESCRIPTION OF SYSTEM: Survey data from a validated set of HRQOL measures (CDC HRQOL-4) were analyzed for 1993-2001 from the Behavioral Risk Factor Surveillance System (BRFSS) surveys for the 50 states and the District of Columbia (DC) and for 2001-2002 from the National Health and Nutrition Examination Survey (NHANES). These measures assessed self-rated health; physically unhealthy days (i.e., the number of days during the preceding 30 days for which physical health, including physical illness and injury, was not good); mentally unhealthy days (i.e., the number of days during the preceding 30 days for which mental health, including stress, depression, and problems with emotions, was not good); and days with activity limitation (i.e., number of days during the preceding 30 days that poor physical or mental health prevented normal daily activities). A summary measure of overall unhealthy days also was computed from the sum of a respondent's physically unhealthy and mentally unhealthy days, with a maximum of 30 days. RESULTS AND INTERPRETATION: During 1993-2001, the mean number of physically unhealthy days, mentally unhealthy days, overall unhealthy days, and activity limitation days was higher after 1997 than before 1997. During 1993-1997, the percentage of respondents with zero overall unhealthy days was stable (51%-53%) but declined to 48% by 2001. The percentage of respondents with >/=14 overall unhealthy days increased from 15%-16% during 1993-1997 to 18% by 2001. Adults increasingly rated their health as fair or poor and decreasingly rated it as excellent or very good. Women, American Indians/Alaska Natives, persons of "other races," separated or divorced persons, unmarried couples, unemployed persons, those unable to work, those with a <$15,000 annual household income, and those with less than a high school education reported worse HRQOL (i.e., physically unhealthy days, mentally unhealthy days, overall unhealthy days, and activity limitation days). Older adults reported more physically unhealthy days and activity limitation days, whereas younger adults reported more mentally unhealthy days. A seasonal pattern was observed in physically unhealthy days and overall unhealthy days. During 1993-2001, BRFSS respondents in 13 states reported increasing physically unhealthy days; respondents in 13 states and DC reported increasing mentally unhealthy days; respondents in Alabama, Connecticut, Maine, New Jersey, New Mexico, North Carolina, and Oregon reported both increasing physically and mentally unhealthy days; and respondents in 16 states and DC reported increasing activity limitation days. During 2001-2002, NHANES respondents with one or more medical conditions (e.g., arthritis or stroke) reported worse HRQOL than those without such conditions, and those with an increasing number of medical conditions reported increasingly worse HRQOL. PUBLIC HEALTH ACTION: Policy makers and researchers should continue to monitor HRQOL and its correlates in the U.S. population. In addition, public health professionals should expand monitoring to populations currently missed by existing surveys, including institutionalized and homeless persons, adolescents, and children. A key aspect is to study and identify the personal and community determinants of HRQOL in prevention research and population studies, to understand how to improve HRQOL, and to reduce HRQOL disparities. In addition, population health assessment professionals should continue to refine and validate HRQOL, functional status, and self-reported health measures.

Tracking Healthy Days -- a window on the health of older adults.

In collaboration with its partners in the public health and aging services communities, the Centers for Disease Control and Prevention (CDC) Health Care and Aging Studies Branch has developed and validated a brief set of health-related quality of life (CDC HRQOL) measures for tracking the perceived physical and mental health of adults over time. For the past 12 years, these measures -- also called the Healthy Days measures -- have been used in an expanding set of population health surveys, surveillance systems, performance report cards, and evaluation studies, and they have provided useful disease and disability burden data to inform decision making and provide new insights for prevention research. Although now used continuously to assess health-related quality of life for Americans aged 12 years and older, the measures and population data have been especially valuable in applications affecting older adults, for which health-related quality of life is an outcome of primary importance. The CDC HRQOL measures are recommended to public health and social service professionals as a feasible way to assess perceived physical and mental health needs of older adults and to document the effects of policies and interventions.

Physical activity and health related quality of life among people with arthritis.

STUDY OBJECTIVE: To assess the association between physical activity and health related quality of life (HRQOL) among persons with arthritis or chronic joint symptoms (CJS). DESIGN: Cross sectional survey investigating the relation between physical activity level and HRQOL. HRQOL was estimated using the number of physically or mentally unhealthy days during the past 30 days. Physical activity was categorised as recommended, insufficient, or inactive according to federal activity recommendations. Persons with arthritis were defined as those with either self reported CJS or doctor diagnosed arthritis. SETTING: Community dwelling, US adults residing in all 50 states and the District of Columbia. PARTICIPANTS: Respondents (n = 212 000) in the 2001 behavioral risk factor surveillance system (BRFSS), an annual population based, telephone survey. MAIN RESULTS: The 33% of BRFSS respondents with arthritis had a mean of 6.7 physically and 4.9 mentally unhealthy days during the past 30 days, compared with 1.8 and 2.7 among those without arthritis. Inactive men and women were 1.2-2.4 times more likely to report impaired HRQOL compared with those who met physical activity recommendations. Men and women who engage in insufficient physical activity also report variably reduced HRQOL. CONCLUSIONS: Among people with arthritis, recommended levels of physical activity were associated with fewer mean physically and mentally unhealthy days and a decreased probability of having severely impaired physical or mental HRQOL.