Improving age-friendly advance care planning in primary care: Outcomes from a Pacific Northwest learning collaborative.

BACKGROUND: Advance care planning (ACP) is the process of having conversations with patients to ensure preferences are known and support patient healthcare goals. ACP and the Age-Friendly Health Systems (AFHS) Initiative's, "What Matters," are synergistic approaches to patient-centered conversations. Implementation and measurement of ACP in primary care (PC) are variables in quality and consistency. We examined whether participation in an ACP learning collaborative (LC) would improve knowledge and ability to conduct ACP discussions and increase the frequency of documented ACP in participating practices. METHODS: The WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network (WPRN) and the Northwest Geriatrics Workforce Enhancement Center collaboratively organized a 9-month virtual LC. It consisted of 4 synchronous, 1.5-h sessions, technical support, and a panel of ACP experts. A Wilcoxon rank sum test assessed differences in knowledge from a pre-post survey. Documentation of ACP in the EHR was collected after at least one plan-do-study-act cycle. RESULTS: We enrolled 17 participants from 6 PC practices (3 hospital-affiliated; 3 Federally Qualified Health Centers) from the WPRN. Two practices did not complete all LC activities. There was a trend toward increased ACP knowledge and skills overall especially in having discussions patients and families (pre-mean 2.9 [SD = 0.7]/post-mean 4.0[SD = 1.1], p < 0.05). 4/6 practices observed an increase in EHR documentation post-collaborative (median 16.3%, IQR 1.3%-36.9%). CONCLUSIONS: The LC increased PC providers knowledge and skills of ACP and AFHS's What Matters, reported ACP EHR documentation, and contributed to practice change.

Self-efficacy in nurse entrepreneurs: A concept analysis.

BACKGROUND: Nursing entrepreneurship represents an important opportunity for the nursing profession to address population health challenges and improve health care access. Although nurse entrepreneurs can be agents of change, the role of self-efficacy, as a determinant of nurses' success in business, is under-studied conceptually and in research. PURPOSE: This paper presents an in-depth concept analysis and model of self-efficacy within the context of the nurse entrepreneur role. METHODS: We used Walker and Avant's concept analysis methodology. DISCUSSION: A systematic understanding of self-efficacy in nurse entrepreneurs provides insights into how it may influence their judgments and actions. Our analysis sets the stage for research on how self-efficacy in nurse entrepreneurs impacts success in the nursing business. CONCLUSION: A conceptual model of self-efficacy in nurse entrepreneurs can guide their development through education and networking activities that incorporate experiential components to improve leadership and managerial skills for success in the health care business.

Risk factors and early prevention of skin cancer in rural older outdoor workers: A scoping review.

Skin cancer risk increases with age and prolonged exposure to ultraviolet radiation (UVR), particularly in rural geographical locations and for individuals with light skin complexions. However, the impact of UVR-induced skin cancer risk and sun-protective behaviors in rural older populations working outdoors has yet to be explored. A scoping review was conducted to fill this gap, with 12 articles meeting the inclusion criteria of aged 50 years and older among rural outdoor workers. Skin cancer risk factors, prevention strategies, and barriers to sun-protective behaviors were summarized for each study. The scoping review addressed some key differences in age-related effects of UVR among rural older outdoor workers compared to studies among adults in general. Findings have policy and research implications that highlight the need to design feasible preventive strategies to reduce rural disparities in cancer care and enhance access to preventive services for this high-risk population.

Mediterranean Diet and Fatigue among Community-Dwelling Postmenopausal Women.

We investigated cross-sectional relationships between the Mediterranean diet and overall fatigue, energy, and weariness scores among 4,563 women aged 65+ from the Women's Health Initiative study. We also used the Isocaloric Substitution approach to explore whether the substitution of fish for red and processed meat, whole for non-whole grains, and whole fruit for fruit juice relate to RAND-36 measured overall fatigue and its subdomains. The alternate Mediterranean Diet (aMED) Index quintiles (Q1-Q5) and selected Mediterranean foods available on a Food Frequency Questionnaire were exposure measures. Results showed aMED Q5 was associated with 2.99 (95% CI: 0.88, 5.11), 4.01 (95% CI: 1.51, 6.53), and 2.47 (95% CI: 0.24, 4.70) point improvements in fatigue, energy, and weariness scores, respectively, compared with aMED Q1. Substituting fish for red and processed meat and whole for non-whole grains was associated with more favorable fatigue scores, whereas substituting whole fruit for juice was not.

Fatigue in community-dwelling older adults: A review of definitions, measures, and related factors.

Fatigue is a common age-related symptom among community-dwelling adults aged 65 years and older. Yet, a systematic approach has rarely been applied to review definitions, measures, related factors, and consequences of fatigue in this population. A scoping review was conducted in December 2020 to fill the gap, and 36 articles met the inclusion criteria. Definitions, albeit diverse, included at least one of the following attributes: an early indicator of disablement, subjective, a lack of energy, multidimensional, impaired daily activities, and temporal. A summary of fatigue measures used in this population was provided, including a brief overview, number of items, reliability, and validity. In general, different measures were used with considerable variability in the content. Additionally, most measures had limited information on test-retest reliability and validity. Fatigue-related factors mapped into biological, psychological, social, and behavioral factors. Fatigue consequences were primarily declines in physical and cognitive functions. (100-150 words).

A Feasibility Study of Primary Care Liaisons: Linking Older Adults to Community Resources.

INTRODUCTION: Programs and services available through the aging services network can help community-dwelling older adults to age in place but are often not discussed in routine primary care. The primary care liaison was developed as a novel integration intervention to address this disconnect. METHODS: Employed by an Area Agency on Aging, primary care liaisons performed outreach to primary care with the goal of raising awareness of community-based programs, resources, and services available to older adults and their caregivers and facilitating referrals. The evaluation of the primary care liaison model, conducted from December 2015 to February 2019, used the Reach, Effectiveness, Adoption, Implementation, Maintenance framework and assessed reach (number of clinics contacted), adoption (number of referrals to the Area Agency on Aging), implementation (number of follow-up contacts with a practice), and effectiveness (proportion of referrals reached and provided relevant resources). RESULTS: The primary care liaisons contacted a median of 18.5 clinics per month (IQR=15-31). Primary care referrals averaged >100 per month, and referrals increased over time. Successful follow-up outreach visits had a median of 3 (IQR=2-10), and follow-up contacts had a median of 3 (IQR=1-7) per practice. Three quarters of caregivers for people with dementia reached by Area Agency on Aging staff were provided with information about relevant resources. CONCLUSIONS: The primary care liaison model is feasible, fosters ongoing interactions between primary care and Area Agencies on Aging, and connects older adults and their caregivers to relevant programs and services. Adoption of the primary care liaison model by other Area Agencies on Aging across the U.S. may help further the vision of optimized health and well-being of older adults.

Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival.

BACKGROUND: Leukocyte telomere length has been associated with risk of subsequent pancreatic cancer. Few prospective studies have evaluated the association of prediagnostic leukocyte telomere length with pancreatic cancer survival. METHODS: We prospectively examined the association of prediagnostic leukocyte telomere length with overall survival (OS) time among 423 participants diagnosed with pancreatic adenocarcinoma between 1984 and 2008 within the Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, and Women's Health Initiative. We measured prediagnostic leukocyte telomere length in banked blood samples using quantitative PCR. Cox proportional hazards models were used to estimate HRs for OS with adjustment for potential confounders. We also evaluated 10 SNPs at the telomerase reverse transcriptase locus. RESULTS: Shorter prediagnostic leukocyte telomere length was associated with reduced OS among patients with pancreatic cancer (P trend = 0.04). The multivariable-adjusted HR for OS comparing the lowest with highest quintiles of leukocyte telomere length was 1.39 (95% confidence interval, 1.01-1.93), corresponding to a 3-month difference in median OS time. In an analysis excluding cases with blood collected within 2 years of cancer diagnosis, the association was moderately stronger (HR, 1.55; 95% confidence interval, 1.09-2.21; comparing the lowest with highest quintiles; P trend = 0.01). No prognostic association or effect modification for the prognostic association of prediagnostic leukocyte telomere length was noted in relation to the studied SNPs. CONCLUSIONS: Prediagnostic leukocyte telomere length was associated with pancreatic cancer survival. IMPACT: Prediagnostic leukocyte telomere length can be a prognostic biomarker in pancreatic cancer.

Falls and Social Isolation of Older Adults in the National Health and Aging Trends Study.

A longitudinal secondary analysis of 2 years of data from the National Health and Aging Trends Study was undertaken to determine the extent to which social isolation predicts falls in older adults. Social isolation during Year 1 (baseline) was operationalized as a multiple-indicator measure based on Social Network Index participation domains. Falling during the previous year was self-reported using Year 2 data. Logistic regression models revealed social isolation significantly predicted falls (odds ratio [OR] = 1.11; 95% confidence interval [CI] [1.05, 1.17]). The relationship remained significant after adjusting for age, gender, and education (OR = 1.08; 95% CI [1.02, 1.14]). The relationship weakened after adjusting for self-reported general health, depression risk, and worry about falling (OR = 1.02; 95% CI [0.96, 1.08]). Adjusting for Short Physical Performance Battery (SPPB), assistive mobility device, and activities of daily living further weakened the relationship (OR = 0.99; 95% CI [0.94, 1.04]). SPPB demonstrated the strongest correlation with social isolation (r = -0.42; p < 0.01). Fall prevention intervention studies specifically targeting social isolation may incorporate physical performance as a shorter-term and cost-effective proxy outcome for falls. [Res Gerontol Nurs. 2018; 11(2):61-70.].

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

BACKGROUND & AIMS: Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. METHODS: We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). RESULTS: In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; Ptrend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). CONCLUSIONS: Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies.

Measuring Social Isolation in the National Health and Aging Trends Study.

The objectives of the current study were to describe the development of a social isolation measure based on Berkman and Syme's Social Network Index domains with data from the National Health and Aging Trends Study. A descriptive correlational design was used, establishing convergent and divergent validity of the measure with depression risk and well-being. Depression risk was measured with the Patient Health Questionnaire-2 and an ordinal well-being measure was developed based on measures in MIDUS-Midlife in the U.S.-A Study of National Health and Well-Being. Participants who scored ≥4 (cutoff point) on the social isolation measure represented 21.9% (N = 7,609) of the sample (95% confidence interval [20.6, 23.3]). Spearman's correlation with depression was 0.23 (p < 0.001) and -0.24 (p ≤ 0.001) with well-being. The weighted data complex samples general linear model with depression (R = 0.22, p ≤ 0.001) and well-being (R = -0.26, p ≤ 0.001) confirm the relationships. This measure offers conceptual clarity and measurement consistency for developing the components and targets for future social isolation intervention research. [Res Gerontol Nurs. 2017; 10(6):277-287.].

Comparison of the Simplified sWHI and the Standard CHS Frailty Phenotypes for Prediction of Mortality, Incident Falls, and Hip Fractures in Older Women.

BACKGROUND: We compared the simplified Women's Health Initiative (sWHI) and the standard Cardiovascular Health Study (CHS) frailty phenotypes in predicting falls, hip fracture, and death in older women. METHODS: Participants are from the WHI Clinical Trial. CHS frailty criteria included weight loss, exhaustion, weakness, slowness, and low physical activity. The sWHI frailty score used two items from the RAND-36 physical function and vitality subscales, one item from the WHI physical activity scale plus the CHS weight loss criteria. Specifically, level of physical function was the capacity to walk one block and scored as severe (2-points), moderate (1-point), or no limitation (0). Vitality was based on feeling tired most or all of the time (1-point) versus less often (0). Low physical activity was walking outside less than twice a week (1-point) versus more often (0). A total score of 3 resulted in a frailty classification, a score of 1 or 2 defined pre-frailty, and 0 indicated nonfrailty. Outcomes were modeled using Cox regression and Harrell C-statistics were used for comparisons. RESULTS: Approximately 5% of the participants were frail based on the CHS or sWHI phenotype. The sWHI frailty phenotype was associated with higher rates of mortality (hazard ratio [HR] = 2.36, p ≤ .001) and falls (HR = 1.45, p = .005). Comparable HRs in CHS-phenotype were 1.97 (p < .001) and 1.36 (p = .03), respectively. Neither phenotype predicted hip fracture. Harrell C-statistics revealed nonsignificant differences in HRs between the CHS and sWHI frailty phenotypes. CONCLUSION: The sWHI phenotype, which is self-reported and brief, might be practical in settings with limited resources.

Cigarette Smoking and Pancreatic Cancer Survival.

Purpose Cigarette smoking is associated with increased incidence of pancreatic cancer. However, few studies have prospectively evaluated the association of smoking with patient survival. Patients and Methods We analyzed survival by smoking status among 1,037 patients from two large US prospective cohort studies diagnosed from 1986 to 2013. Among 485 patients from four prospective US cohorts, we also evaluated survival by prediagnostic circulating levels of cotinine, a metabolite of nicotine that is proportional to tobacco smoke exposure. On the basis of prediagnosis cotinine levels, we classified patients as nonsmokers (< 3.1 ng/mL), light smokers (3.1-20.9 ng/mL), or heavy smokers (≥ 21.0 ng/mL). We estimated hazard ratios (HRs) for death by using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, body mass index, diabetes status, diagnosis year, and cancer stage. Results The multivariable-adjusted HR for death was 1.37 (95% CI, 1.11 to 1.69) comparing current smokers with never smokers ( P = .003). A statistically significant negative trend in survival was observed for increasing pack-years of smoking ( Ptrend = .008), with HR for death of 1.49 (95% CI, 1.05 to 2.10) for > 60 pack-years of smoking versus never smoking. Survival among former smokers was similar to that for never smokers, regardless of time since quitting. Heavy smokers defined by prediagnostic circulating cotinine levels had a multivariable-adjusted HR for death of 1.76 (95% CI, 1.23 to 2.51) compared with nonsmokers. Among patients with circulating cotinine levels measured within 5 years before diagnosis, heavy smokers had a multivariable-adjusted HR for death of 2.47 (95% CI, 1.24 to 4.92) compared with nonsmokers. Conclusion Cigarette smoking was associated with a reduction in survival among patients with pancreatic cancer.

Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer.

OBJECTIVE: Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase (TERT) gene region have been associated with pancreatic cancer risk. However, it is unknown whether prediagnostic leucocyte telomere length is associated with subsequent risk of pancreatic cancer. DESIGN: We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the TERT region in relation to pancreatic cancer risk and leucocyte telomere length using logistic and linear regression, respectively. RESULTS: Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; ptrend=0.048). Results remained unchanged after adjustment for diabetes, body mass index and physical activity. Three SNPs at TERT (linkage disequilibrium r2<0.25) were associated with pancreatic cancer risk, including rs401681 (per minor allele OR 1.33; 95% CI 1.12 to 1.59; p=0.002), rs2736100 (per minor allele OR 1.36; 95% CI 1.13 to 1.63; p=0.001) and rs2736098 (per minor allele OR 0.75; 95% CI 0.63 to 0.90; p=0.002). The minor allele for rs401681 was associated with shorter telomere length (p=0.023). CONCLUSIONS: Prediagnostic leucocyte telomere length and genetic variants at the TERT gene region were associated with risk of pancreatic cancer.

Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms.

Leptin is an adipokine involved in regulating energy balance, which has been identified as a potential biologic link in the development of obesity-associated cancers, such as pancreatic cancer. In this prospective, nested case-control study of 470 cases and 1,094 controls from five U.S. cohorts, we used conditional logistic regression to evaluate pancreatic cancer risk by prediagnostic plasma leptin, adjusting for race/ethnicity, diabetes, body mass index, physical activity, plasma C-peptide, adiponectin, and 25-hydroxyvitamin D. Because of known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging SNPs in the leptin receptor (LEPR) gene and pancreatic cancer risk. Leptin levels were higher in female versus male control participants (median, 20.8 vs. 6.7 ng/mL; P < 0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk and those in the top quintile had a multivariable-adjusted OR of 3.02 [95% confidence interval (CI), 1.27-7.16; Ptrend = 0.02] compared with men in the bottom quintile. Among women, circulating leptin was not associated with pancreatic cancer risk (Ptrend = 0.21). Results were similar across cohorts (Pheterogeneity = 0.88 for two male cohorts and 0.35 for three female cohorts). In genetic analyses, rs10493380 in LEPR was associated with increased pancreatic cancer risk among women, with an OR per minor allele of 1.54 (95% CI, 1.18-2.02; multiple hypothesis-corrected P = 0.03). No SNPs were significantly associated with risk in men. In conclusion, higher prediagnostic levels of plasma leptin were associated with an elevated risk of pancreatic cancer among men, but not among women. Cancer Res; 76(24); 7160-7. ©2016 AACR.

Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival.

PURPOSE: Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored. PATIENTS AND METHODS: We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; sufficient ≥ 30 ng/mL) by using Cox proportional hazards regression models adjusted for age, cohort, race and ethnicity, smoking, diagnosis year, stage, and blood collection month. We also evaluated 30 tagging single-nucleotide polymorphisms in the vitamin D receptor gene, requiring P < .002 (0.05 divided by 30 genotyped variants) for statistical significance. RESULTS: Mean prediagnostic plasma level of 25(OH)D was 24.6 ng/mL, and 165 patients (33%) were vitamin D insufficient. Compared with patients with insufficient levels, multivariable-adjusted HRs for death were 0.79 (95% CI, 0.48 to 1.29) for patients with relative insufficiency and 0.66 (95% CI, 0.49 to 0.90) for patients with sufficient levels (P trend = .01). These results were unchanged after further adjustment for body mass index and history of diabetes (P trend = .02). The association was strongest among patients with blood collected within 5 years of diagnosis, with an HR of 0.58 (95% CI, 0.35 to 0.98) comparing patients with sufficient to patients with insufficient 25(OH)D levels. No single-nucleotide polymorphism at the vitamin D receptor gene met our corrected significance threshold of P < .002; rs7299460 was most strongly associated with survival (HR per minor allele, 0.80; 95% CI, 0.68 to 0.95; P = .01). CONCLUSION: We observed longer overall survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25(OH)D.

Identification of Risk Factors for Mortality and Poor-Quality-of-Life Survival in Frail Older Women Participating in the Women's Health Initiative Observational Study.

OBJECTIVES: To identify potentially modifiable factors associated with overall and poor-quality-of-life (QoL) survival in physically frail older women. DESIGN: Prospective study with 7 years of follow-up to examine mortality and, in survivors with a QoL measurement within the next 3 years, to examine poor- versus good-QoL patterns of survival. SETTING: Women's Health Initiative Observational Study (WHI OS). PARTICIPANTS: Frail older women (N = 11,070; average age 72.6, range 65-82). MEASUREMENTS: Frailty was defined using the modified Fried criteria. Study outcomes were overall survival and global QoL. Risk factors were measured at the first follow-up clinic visit for WHI OS participants between 1997 and 2001. RESULTS: Of 11,070 frail women, 1,487 (13%) died. After 2,677 survivors with poor or unknown QoL were excluded at study baseline, 3,153 (46%) reported good QoL, and 1,263 (18%) reported poor QoL at the end of study follow-up; QoL measures for 2,490 (38%) were unavailable. Older age, history of cardiovascular disease, diabetes mellitus, poor self-rated health, body mass index less than 25.0 kg/m(2) , waist circumference greater than 88 cm, systolic blood pressure greater than 140 mmHg, high number and severity of somatic symptoms, smoking, and low education were associated with greater likelihood of poor-QoL survival. Cumulative baseline risk scores demonstrated an approximately linear increase in probability of poor-QoL survival with an increase in risk factors. The probability of poor-QoL survival was 0.19 (95% confidence interval (CI) = 0.15-0.22) in those with zero to two risk factors and 0.40 (95% CI = 0.35-0.44) in those with six or more risk factors. CONCLUSION: Several potentially important risk factors for aging well that can be monitored in clinical and research settings, some of which are modifiable, were identified in a large group of frail old women.

Aging Well: Observations From the Women's Health Initiative Study.

BACKGROUND: As the proportion of the population aged 80 and over accelerates, so does the value of understanding the processes of aging well. The purposes of this article are to: (a) review contemporary theoretical and conceptual perspectives on aging well, (b) describe indicators of aging well that reflect key concepts and perspectives as assessed in the Women's Health Initiative (WHI) and (c) characterize the status of aging among women aged 80 and older using data obtained from WHI participants at the WHI Extension 2 follow-up. METHODS: Data from the Lifestyle Questionnaire, which was administered from 2011 to 2012 during the WHI Follow-up Study (Extension 2), were analyzed to provide a profile of the WHI cohort with respect to aging well. RESULTS: Data revealed substantial diversity in the cohort with respect to the various measures of aging well. Although many reported physical functioning levels consistent with disability, most rated their health as good or better. Most reported moderately high levels of resilience, self-control, and self-mastery but lower levels of environmental mastery. Finally, the cohort reported high levels of optimal aging as reflected by their high levels of emotional well-being and moderately high levels of life satisfaction and social support, but more modest levels of personal growth and purpose in life. CONCLUSIONS: The wide range of some dimensions of aging well suggest that further examination of predictors of positive coping and resilience in the face of aging-related disability could identify opportunities to support and facilitate aging well among U.S. women.

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80.

BACKGROUND: We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65-80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. METHODS: Women's Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). RESULTS: Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. CONCLUSIONS: Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late-life (after age 80) functional independence.

Circulating Metabolites and Survival Among Patients With Pancreatic Cancer.

BACKGROUND: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. METHODS: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. RESULTS: Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. CONCLUSIONS: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer.