Objectives
To explore the association between a newly developed cumulative laboratory‐based frailty index (FI) and intrinsic (personal) and extrinsic (social, environmental) characteristics.
Design
...Cross‐sectional longitudinal study.
Setting
The third and fourth waves of the community‐representative, five‐county, 10‐year Duke Established Populations for Epidemiologic Studies of the Elderly study, carried out in a health service‐rich area.
Participants
Cognitively intact survivors of the third wave (N = 1,740), who provided blood samples for standard laboratory work.
Measurements
Biomarkers (n = 28) were measured to develop a cumulative deficit laboratory test–based FI (Duke FI) derived from standard laboratory tests: SMAC‐24 chemistry panel, high‐density lipoprotein cholesterol panel, and complete blood count. Information was gathered on scales assessing intrinsic characteristics (personal locus of control, life satisfaction, self‐esteem, depressive symptomatology) and extrinsic characteristics (support received from and provided to family and friends, stressful life events, neighborhood disadvantage).
Results
The newly developed Duke FI had content, construct, concurrent, and predictive validity. In addition to sex, race, and income, the Duke FI was associated at the intrinsic level with locus of control, self‐esteem, life satisfaction, and depressive symptomatology (each P < .01) and at the extrinsic level with provision (P < .01) and with receipt of instrumental help (P < .10), social stressors (P < .03), and neighborhood disadvantage (P < .01) in unadjusted analysis; race fully explained neighborhood disadvantage.
Conclusion
Intrinsic (personality) characteristics and personally close extrinsic characteristics (contacts with family and friends, personal stressors) are associated with laboratory test–based frailty, as is neighborhood disadvantage, although in this accessible, health service–rich environment, race fully explained association with neighborhood disadvantage, suggesting that interventions to reduce frailty in residents in such an environment should pay particular attention to characteristics that immediately affect the individual.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the ...temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms.
Serum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice.
An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs.
Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and ...associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span.
The physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014.
Physical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function.
These results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline.
To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls.
English-speaking women age ≥ 60 years, newly ...diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect-lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results.
There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years; range, 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor-positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all
< .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls (
interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance (
controls), with significant interactions with CRP only for the Trails B test.
Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.
Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends ...and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non-small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 ( P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 95% CI, 0.00 to 0.06; EDR, 1.07 95% CI, 1.00 to 1.16). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non-small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of patients with lung cancer.
Intervention studies have found that psychotherapeutic interventions that explicitly integrate clients' spiritual and religious beliefs in therapy are as effective, if not more so, in reducing ...depression than those that do not for religious clients. However, few empirical studies have examined the effectiveness of religiously (vs. spiritually) integrated psychotherapy, and no manualized mental health intervention had been developed for the medically ill with religious beliefs. To address this gap, we developed and implemented a novel religiously integrated adaptation of cognitive-behavioral therapy (CBT) for the treatment of depression in individuals with chronic medical illness. This article describes the development and implementation of the intervention. First, we provide a brief overview of CBT. Next, we describe how religious beliefs and behaviors can be integrated into a CBT framework. Finally, we describe Religiously Integrated Cognitive Behavioral Therapy (RCBT), a manualized therapeutic approach designed to assist depressed individuals to develop depression-reducing thoughts and behaviors informed by their own religious beliefs, practices, and resources. This treatment approach has been developed for 5 major world religions (Christianity, Judaism, Islam, Buddhism, and Hinduism), increasing its potential to aid the depressed medically ill from a variety of religious backgrounds.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, is present in over 5% of adults aged 70 and older, a population with a high prevalence of multimorbidity. ...MGUS is often diagnosed incidentally when patients seek care for unrelated conditions. Our study sought to examine patterns of multimorbidity among MGUS patients, as overall health may impact patient care and the prioritization of MGUS surveillance. We examined patterns of comorbidities in 429 patients diagnosed with MGUS (2007‐2015) and 1287 matched controls. Twenty‐seven conditions were defined at diagnosis/index date using algorithms developed by the Centers for Medicare and Medicaid Chronic Conditions Warehouse. Patterns of common comorbidities were identified individually, in dyads and triads, and compared between MGUS cases and controls. We conducted a latent class analysis to identify comorbidity patterns among cases only. We also examined comorbidity patterns among a subset of 32 MGUS cases who progressed to cancer during the study period. The most common comorbidities among both MGUS cases and controls included hypertension and hyperlipidemia. Anemia (cases: 43%; controls: 16%) and chronic kidney disease (CKD; cases: 36%; controls: 18%), and dyads and triads containing those conditions, were more common among cases. Latent class analysis identified three classes of comorbidity among MGUS cases: hypertension‐hyperlipidemia plus anemia and CKD (31%); low comorbidity burden (17%); and hypertension‐hyperlipidemia alone (52%). The higher prevalence among cases of anemia and CKD, which may be involved in the pathogenesis of, or surveillance for, MGUS, warrants additional investigation.
What's new?
Although monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, is often diagnosed incidentally, the distribution of comorbid conditions at MGUS diagnosis has not been well studied. In our study, the most common comorbid conditions among all participants included hypertension, hyperlipidemia, and arthritis. Hypertension and arthritis were however more prevalent among MGUS cases than matched controls. Notably, anemia and chronic kidney disease, and combinations of conditions including these diagnoses, were significantly more prevalent among patients with MGUS. In the clinic, multimorbidity may influence how MGUS patients are followed, and whether surveillance for MGUS progression is a priority.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite greatly improved survival in pediatric patients with end-stage heart failure through the use of ventricular assist devices (VADs), heart failure ultimately remains a life-threatening disease ...with a significant symptom burden. With increased demand for donor organs, liberalizing the boundaries of case complexity, and the introduction of destination therapy in children, more children can be expected to die while on mechanical support. Despite this trend, guidelines on the ethical and pragmatic issues of compassionate deactivation of VAD support in children are strikingly absent. As VAD support for pediatric patients increases in frequency, the pediatric heart failure and palliative care communities must work toward establishing guidelines to clarify the complex issues surrounding compassionate deactivation. Patient, family and clinician attitudes must be ascertained and education regarding the psychological, legal and ethical issues should be provided. Furthermore, pediatric-specific planning documents for use before VAD implantation as well as deactivation checklists should be developed to assist with decision-making at critical points during the illness trajectory. Herein we review the relevant literature regarding compassionate deactivation with a specific focus on issues related to children.
Abstract
Context
Testosterone treatment of hypogonadal men improves their hemoglobin, but the mechanism is not understood.
Objective
To investigate possible mechanisms by which testosterone ...stimulates erythropoiesis in hypogonadal older men with unexplained or iron-deficiency anemia.
Design
The Anemia Trial of The Testosterone Trials, a placebo-controlled study in older, hypogonadal men.
Setting
Twelve academic medical centers.
Participants
A total of 95 hypogonadal men (testosterone < 275 ng/mL) ≥65 years with anemia (hemoglobin < 12.7 g/dL). They were classified as having unexplained (n = 58) or iron deficiency anemia (n = 37).
Intervention
Testosterone or placebo gel for 1 year.
Main Outcome Measures
Markers of iron metabolism during the first 3 months of treatment.
Results
Testosterone replacement significantly (P < 0.001) increased hemoglobin in the 58 men who had unexplained anemia (adjusted mean difference 0.58 g/dL; 95% confidence interval, 0.31-0.85). Testosterone replacement tended to increase hemoglobin in the 37 men who had iron deficiency (0.38 g/dL; −0.19, 0.95), but the response was more variable and not statistically significant (P = 0.19). In men with unexplained anemia, testosterone replacement suppressed hepcidin (−8.2 ng/mL; −13.7, −2.7; P = 0.004) and ferritin (−19.6 µg/L; −32.8, −6.3; P = 0.004), but in men with iron deficiency, testosterone replacement did not. The decrease in hepcidin was moderately correlated with the increase in hemoglobin in the men with unexplained anemia (correlation coefficient −0.35, P = 0.01) but not in those with iron deficiency anemia (correlation coefficient −0.07, P = 0.73).
Conclusions
Testosterone replacement of older hypogonadal men with unexplained anemia stimulates erythropoiesis associated with increased iron mobilization. This effect appears to be attenuated by iron deficiency.
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