Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period.

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage.

Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in older adults may be due to a strong IL-10 response to influenza following vaccination, and persistent CMV infection.

Cytomegalovirus Seropositivity Predicts a Decline in the T Cell But Not the Antibody Response to Influenza in Vaccinated Older Adults Independent of Type 2 Diabetes Status.

Type 2 diabetes mellitus (T2DM) and persistent cytomegalovirus (CMV) infection are postulated contributors to inflammatory processes that impact on the age-related decline in T-cell responses to influenza vaccination. Older subjects with T2DM (n = 30) and healthy aged controls (n = 40) were enrolled and received influenza vaccination in this study. Serum inflammatory markers and CMV serostatus were measured. Pre- to post-vaccination changes in serum antibody titers to the A/H3N2 strain, and levels of granzyme B (GrB, cytotoxic T lymphocytes) in lysates and cytokines in supernatants from influenza A/H3N2-challenged peripheral blood mononuclear cells were measured. We found no difference between the T2DM and healthy groups in the immune responses measured. However, CMV serostatus was a key determinant of the GrB response to influenza challenge; CMV+ subjects had low levels of inducible GrB (iGrB) activity in response to influenza challenge. In contrast, the serum antibody response to the A/H3N2 vaccine strain did not differ with CMV serostatus, and serum levels of the inflammatory marker, ß2-microglobulin, were positively correlated with age, T2DM, and serum IL-10 levels. In conclusion, CMV seropositivity associated with a decline in GrB responses to influenza may predict increased susceptibility to influenza in older adults.

Connecticut's 'Money Follows The Person' Yields Positive Results For Transitioning People Out Of Institutions.

A centerpiece of federal and state efforts to rebalance long-term services and supports to enhance consumer choice and contain costs, the federal Money Follows the Person Rebalancing Demonstration helps qualified individuals living in institutions make the transition to life in the community. The Connecticut Money Follows the Person program is an unusually rich source of data, with information on the 2,262 people who transitioned to the community under that state's program during 2008-14. Responses to participant surveys completed before and six, twelve, and twenty-four months after transition indicate that, for the majority of respondents who remained in the community, quality of life and life satisfaction improved significantly after transition, and they stayed high. About half of the participants visited hospitals or emergency departments after transition; however, only 14 percent had returned to an institution one year after transition. Predictors of reinstitutionalization included some not previously observed: mental health disability, difficulties with family members before transition, and not exercising choice and control in daily life. These and other findings suggest multiple ways in which policy makers can target efforts to strengthen transition programs that can meaningfully improve people's lives while containing costs.

The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults.

CONTEXT: It has been assumed that the increase in urine calcium (Ca) that accompanies an increase in dietary protein was due to increased bone resorption. However, studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption. OBJECTIVE: The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density (BMD). DESIGN: This was a randomized, double-blind, placebo-controlled trial of protein supplementation daily for 18 months. SETTING: The study was conducted at two institutional research centers. PARTICIPANTS: Two hundred eight older women and men with a body mass index between 19 and 32 kg/m(2) and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study. INTERVENTION: Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months. MAIN OUTCOME MEASURE: BMD by dual-energy x-ray absorptiometry, body composition, and markers of skeletal and mineral metabolism were measured at baseline and at 9 and 18 months. RESULTS: There were no significant differences between groups for changes in L-spine BMD (primary outcome) or the other skeletal sites of interest. Truncal lean mass was significantly higher in the protein group at 18 months (P = .048). C-terminal telopeptide (P = .0414), IGF-1 (P = .0054), and urinary urea (P < .001) were also higher in the protein group at the end of the study period. There was no difference in estimated glomerular filtration rate at 18 months. CONCLUSION: Our data suggest that protein supplementation above the recommended dietary allowance (0.8 g/kg) may preserve fat-free mass without adversely affecting skeletal health or renal function in healthy older adults.

Genetic determinants of amidating enzyme activity and its relationship with metal cofactors in human serum.

BACKGROUND: α-amidation is a final, essential step in the biosynthesis of about half of all peptide hormones and neurotransmitters. Peptidylglycine α-amidating monooxygenase (PAM), with enzymatic domains that utilize Cu and Zn, is the only enzyme that catalyzes this reaction. PAM activity is detected in serum, but its significance and utility as a clinical biomarker remain unexplored. METHODS: We used well-established enzymatic assays specific for the peptidylglycine-α -hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL) domains of PAM to quantify amidating activity in the sera of 144 elderly men. Relationships between PHM and PAL activity and serum levels of their respective active-site metals, Cu and Zn, were analyzed. Study participants were also genotyped for eight non-coding single nucleotide polymorphisms (SNPs) in PAM, and relationships between genotype and serum enzyme activity and metal levels were analyzed. RESULTS: Serum PHM and PAL activities were normally distributed and correlated linearly with each other. Serum PAL activity, but not serum PHM activity, correlated with serum Cu; neither activity correlated with serum Zn. Study subjects possessing the minor alleles for rs32680 had lower PHM and PAL activities, and subjects with minor alleles for rs11952361 and rs10515341 had lower PHM activities. CONCLUSIONS: Our results characterize large variation in serum amidating activity and provide unique insight into its potential origin and determinants. Common non-coding polymorphisms affect serum amidating activity and Cu levels. Serum amidating activity should be explored as a biomarker for functionality in the elderly and in additional study groups.

Risk factors for hospitalization in a national sample of medicare home health care patients.

Acute care hospitalization during or immediately following a Medicare home health care (HHC) episode is a major adverse outcome, but little has been published about HHC patient-level risk factors for hospitalization. The authors determined risk factors at HHC admission associated with subsequent acute care hospitalization in a nationally representative Medicare patient sample (N = 374,123). Hospitalization was measured using Medicare claims data; risk factors were measured using Outcome Assessment and Information Set data. Seventeen percent of sample members were hospitalized. Multivariate logistic regression analysis found that the most influential risk factors (all p < .001) were skin wound as primary HHC diagnosis, clinician-judged guarded rehabilitation prognosis, congestive heart failure as primary HHC diagnosis, presence of depressive symptoms, dyspnea severity, and Black, compared to White. HHC initiatives that minimize chronic condition exacerbations and actively treat depressive symptoms might help reduce Medicare patient hospitalizations. Unmeasured reasons for higher hospitalization rates among Black HHC patients deserve further investigation.

Effects of varenicline, nicotine or placebo on depressive symptoms in postmenopausal smokers.

BACKGROUND: Varenicline carries a black box warning for neuropsychiatric adverse events. OBJECTIVE: We examined varenicline use and past history of major depressive disorder (MDD) on depressive symptoms during smoking cessation. METHOD: This is a secondary analysis of two smoking cessation studies in 152 postmenopausal women who received placebo or nicotine patch, or 78 women who received varenicline with relaxation. Lifetime history of MDD (LH-MDD) was assessed at baseline and women with current MDD were excluded. Center for Epidemiologic Study Depression scale (CESD) measured depressive symptoms at baseline, 6 and 12 weeks. RESULTS: Baseline CESD scores were 5.3 + 4.4. Those with a LH-MDD reported higher CESD scores (p > .001). Those taking varenicline reported lower scores over all time periods compared to nicotine or placebo (p < .01). The differences between varenicline and the other treatments remained when controlling for LH-MDD, indicating an independent effect. CESD scores were associated with concurrent smoking status (p < .001), and with withdrawal symptoms (p < .001). CONCLUSION: CESD score were lower in those receiving varenicline, whether this is due to an anti-depressant effect, subject selection, use of relaxation or another cause is unknown. Varenicline does not increase depressive symptoms during smoking cessation in postmenopausal women without current MDD. Subjects with a LH-MDD are susceptible to developing depressive symptoms during smoking cessation, regardless of pharmacologic aid. SCIENTIFIC SIGNIFICANCE: Pharmacologic aids did not increase depression symptoms in this select population of postmenopausal women without current depression. Smoking cessation does increase depressive symptoms in those with LH-MDD, though the degree of increase was not clinically meaningful.

Results and lessons learned from a nurse practitioner-guided dementia care intervention for primary care patients and their family caregivers.

Older adults with dementia care needs often visit primary care physicians (PCPs), but PCP dementia care limitations are widely documented. This study tested the value of employing a nurse practitioner (NP) with geropsychiatric expertise to augment PCP care for newly and recently diagnosed patients and family caregivers. Twenty-one dyads received the NP intervention; 10 dyads were controls. Outcomes included patient neuropsychiatric symptom and quality of life changes, and caregiver depression, burden, and self-efficacy changes. Intervention acceptability by patients, caregivers, and PCPs was determined. No outcome differences were found; however, the NP intervention was deemed highly satisfactory by all stakeholders. Patients experienced no significant cognitive decline during the 12-month study period, helping explain why outcomes did not change. Given widespread acceptability, future tests of this PCP-enhancing intervention should include patients with more progressive cognitive decline at study entry. NPs with geropsychiatric expertise are ideal interventionists for this rapidly growing target population.

Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Bone Turnover in Older Women.

Animal and human studies indicate that omega (n)-3 polyunsaturated fatty acids (PUFA) can influence bone health. We conducted a randomized, double-blind, placebo-controlled trial of the effects of n-3 long chain (LC) PUFA supplementation (N-3 LCPUFA) on red blood cell (RBC) fatty acid levels and bone turnover markers in older postmenopausal women. One hundred and twenty-six postmenopausal women (mean age 75±7 years) were treated with n-3 LCPUFA (1.2 g eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]/day, n=85) or placebo (olive oil, n=41) for 6 months. All women received 315 mg calcium citrate and 1000 IU cholecalciferol. RBC DHA (weight %) increased in the n-3 LCPUFA group, compared to no change in the placebo group (P<0.001). The ratio of DHA+EPA:arachidonic acid (AA) increased by 42 % in the n-3 LCPUFA group and by 5% in the placebo group (P<0.001). Bone-specific alkaline phosphatase and osteocalcin decreased in the n-3 LCPUFA group (P<0.05) with no between-group difference. Short-term n-3 LCPUFA supplementation increased RBC concentrations of DHA and n-3:n-6 ratios. Bone turnover decreased with n-3 LCPUF, but not statistically compared to placebo. The results point to the need for investigations with greater dosages of n-3 LCPUFA for a longer duration to understand the contribution to bone metabolism in postmenopausal women.

Effect of nicotine patch on energy intake and weight gain in postmenopausal women during smoking cessation.

INTRODUCTION: Post-cessation weight gain is a commonly cited barrier to smoking cessation. Some evidence suggests that nicotine replacement therapy may limit post-cessation weight gain by reducing energy intake. This project aims to assess differential changes in energy intake and body weight during smoking cessation in a sample of postmenopausal women randomized to receive 21 mg nicotine or placebo patch for 12 weeks. METHODS: Postmenopausal women who smoked ≥10 cigarettes/day were enrolled in this double-blind randomized placebo-controlled study. Total energy intake (via four-day food diaries), body mass index (BMI; kg/m(2)), cigarettes/day and smoking status (self-report verified by exhaled carbon monoxide) were assessed at three time points: 2 weeks prior to quit date, 12 weeks after quit date, and 12 months after smoking cessation treatment. RESULTS: Participants (n = 119) were, on average, 55.8 ± 6.7 years old with a baseline BMI of 27.0 ± 5.2 and average cigarette/day was 21.1 ± 8.6. At Week 12, participants randomized to nicotine patch increased their mean caloric intake by 146.4 ± 547.7 kcal/day whereas those on placebo patch decreased their caloric intake by 175.3 ± 463.2 (f-value = 10.1, p-value = 0.002). Despite the differences in caloric intake, body weight remained similar between groups. CONCLUSIONS: The results of this study indicate that nicotine patch may increase energy intake during treatment, and does not prevent post-cessation weight gain in postmenopausal smokers. Additional research is needed to replicate these findings and assess whether different forms of nicotine replacement therapy influence caloric intake and post-cessation weight gain in postmenopausal smokers.

Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial.

Soy foods contain several components, notably, isoflavones and amino acids, that may improve cardiovascular health. We evaluated the long-term effect of soy protein and/or soy isoflavones supplementation on serum lipids and inflammatory markers using a 1-year randomized, double-blind, placebo-control, clinical trial in 131 healthy ambulatory women older than 60 years. We hypothesized that soy protein, in combination with isoflavones, would have the largest positive effect on coronary heart disease risk factors (serum lipids and inflammatory markers) compared with either intervention alone and that, within groups receiving isoflavones, equol producers would have more positive effects on coronary heart disease risk factors than nonequol producers. After a 1-month baseline period, participants were randomized into 1 of 4 intervention groups: soy protein (18 g/d) and isoflavone tablets (105 mg/d isoflavone aglycone equivalents), soy protein and placebo tablets, control protein and isoflavone tablets, or control protein and placebo tablets. T Tests were used to assess differences between equol and nonequol producers. Ninety-seven women completed the trial. Consumption of protein powder and isoflavone tablets did not differ among groups, and compliance with study powder and tablets was 79% and 90%, respectively. After 1 year, in the entire population, there were either no or little effects on serum lipids and inflammatory markers, regardless of treatment group. Equol producers, when analyzed separately, had significant improvements in total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios (-5.9%, P = .02; -7.2%, P = .04 respectively). Soy protein and isoflavone (either alone or together) did not impact serum lipids or inflammatory markers. Therefore, they should not be considered an effective intervention to prevent cardiovascular disease because of lipid modification in healthy late postmenopausal women lacking the ability to produce equol.

Gender differences in anthropometric predictors of physical performance in older adults.

BACKGROUND: Both high body fat and low muscle mass have been associated with physical disability in older adults. However, men and women differ markedly in body composition; men generally have more absolute and relative lean muscle mass and less fat mass than women. It is not known how these anthropometric differences differentially affect physical ability in men and women. OBJECTIVES: This study examines differences in anthropometric predictors of physical performance in older women and men. METHODS: Participants were 470 older women and men 72.9 (7.9) years of age. Body composition was measured using dual-energy x-ray absorptiometry. Maximum leg strength and power were measured using a leg press. Muscle quality (MQ) was calculated as relative strength (leg press strength per kilogram of leg muscle mass). Gait speed and chair rise were used to assess mobility performance and functional strength. RESULTS: Body mass index (BMI), age, and MQ emerged as predictors (P < 0.05) of functional strength and mobility in men and women somewhat differently. After accounting for age and sample, leg MQ was related to chair rise time and gait speed in men but not women. BMI was related to gait speed in both men and women, but BMI was related to chair rise time only in women. CONCLUSION: Results implicate the prioritized importance of healthy weight and muscle maintenance in older women and men for maintained physical functioning with aging.

High serum Cu and Cu/Zn ratios correlate with impairments in bone density, physical performance and overall health in a population of elderly men with frailty characteristics.

Serum Cu levels rise with age and high Cu/Zn ratios are linked with multiple-cause mortality in the elderly. The relationships of these parameters to measures of musculoskeletal health and frailty have not yet been analyzed. We used inductively coupled mass spectrometry to assess serum levels of Cu and Zn and probed for relationships between serum Cu levels and the Cu/Zn ratio with specific measures of bone, physical and overall health in a cohort of 144 frail elderly men. Subjects were divided into quintiles based on serum metal levels and comparisons for functional measures were made between the reference (middle) group and the low and high groups. Subjects' serum metal values were normally distributed. We found significant correlations between high Cu/Zn ratios and deficits in femoral bone mineral density, measures of speed and strength, muscle mass and hematocrit. High Cu/Zn ratios were also correlated with decreased triglycerides and increased reliance on ADL assistance. This study identifies specific deficits associated with high Cu/Zn ratios that span multiple organ systems and supports earlier studies indicating that serum Cu levels and the Cu/Zn ratio may serve as useful predictive biomarkers for poor health in the elderly.

Are baby boomers who care for their older parents planning for their own future long-term care needs?

A rapidly expanding number of baby boomers provide care to aging parents. This study examines associations between caregiver status and outcomes related to awareness and anticipation of future long-term care (LTC) needs using 2007 Connecticut Long-Term Care Needs Assessment survey data. Baby boomers who were adult child caregivers (n = 353) versus baby boomers who were not (n = 1242) were more likely to anticipate some future LTC needs and to have considered certain financing strategies. Although baby boomer adult child caregivers more readily anticipate some future LTC needs, they are not taking specific actions. It is important to address the need for public education directed toward those who are currently (or have recently completed) caring for aging parents.

Racial and ethnic group variations in service use in a national sample of Medicare home health care patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus is known to affect adults in racial and ethnic minority groups disproportionately. When diabetes mellitus-related symptoms lead to the need for skilled care in the community-dwelling Medicare population, physicians can order the Medicare home health care (HHC) benefit, and Medicare-certified home health agencies can deliver it. Little is known about the extent to which racial and ethnic disparities exist in types and patterns of HHC services delivered to Medicare beneficiaries with diabetes mellitus when they are approved for the Medicare HHC benefit. This was examined by comparing racial and ethnic groups in terms of measures of HHC service use in a nationally representative sample of Medicare HHC beneficiaries with a primary diagnosis of type 2 diabetes mellitus. Uniform clinical data from the Outcome and Assessment Information Set were linked with Medicare HHC claims for beneficiaries who received a complete episode of HHC in 2002. In the study sample (n=9,838), 62% of participants self-identified as white, 22% African American, 12% Hispanic, and 3% Asian. Nearly all (99%) participants in all racial and ethnic groups received skilled nursing services. Controlling for numerous sociodemographic and health-related covariates and geographic region of the country, African-American participants received fewer nurse visits per week and fewer visits per week from all clinical disciplines combined than whites (both P<.001), and Hispanic participants were less likely than whites to receive physical therapy (adjusted odds ratio (AOR)=0.640, 95% confidence interval (CI)=0.543-0.754, P<.001) or home health aide (AOR=0.716, 95% CI=0.582-0.880, P=.002) services. Lower use of skilled nursing and rehabilitation services by African Americans and of rehabilitation services by Hispanics warrant further clinical and research attention.

Predictors of compliance with free endoscopic colorectal cancer screening in uninsured adults.

BACKGROUND: National guidelines endorse colonoscopy as the only colorectal cancer (CRC) screening test which prevents CRC and evaluates the entire large bowel. However, little is known regarding patient compliance with a screening program that exclusively uses colonoscopy, particularly in an underserved population. The Connecticut Department of Public Health provided funds for the total cost of colonoscopies, patient navigators and education of staff and primary care providers. With cost and provider barriers removed, we were able to examine patient related factors influencing compliance with colonoscopy in an ethnically diverse sample of underinsured adults. OBJECTIVE: To determine what patient related factors are predictors of compliance with screening colonoscopy. DESIGN: Cross sectional retrospective study. PARTICIPANTS: Underinsured patients (50-64 years) visiting nine Connecticut community health centers (CHCs) were evaluated for medical eligibility for screening; eligible patients were offered a free colonoscopy. MAIN MEASURES: Patients were deemed non-compliant if they refused, canceled or did not show for the colonoscopy. Obesity (Body Mass Index ≥ 30), educational attainment, gender, race, ethnicity, previous screening and social ties were examined as primary risk factors for compliance. KEY RESULTS: Of 424 uninsured patients (62% female, 21% White, 26% Black, 53% Hispanic), 354 were eligible for colonoscopy. Among eligible patients, 263 (74.3%) were compliant. Obese patients were more likely than non-obese patients to be non-compliant with colonoscopy (adjusted odds ratio = 2.16; 95% Confidence interval = 1.20-3.89). A high school education was positively correlated with increased compliance social ties such as having a spouse, significant other, family or friend also increased compliance. CONCLUSIONS: In an ethnically diverse, uninsured population, obese patients and patients with lower educational attainment were less likely to comply with free colonoscopy. These patients require special attention in colonoscopy-based CRC screening efforts.

The 6-minute walk is associated with frailty and predicts mortality in older adults with heart failure.

Heart failure (HF) may contribute to the development of functional decline and frailty in older adults. Sixty HF patients with an ejection fraction ≤ 40% evaluated in 2004 and 2005 were reevaluated in 2008. Six-minute walk distance (6MW), frailty score, and biomarkers (25-hydroxyvitamin D, C-reactive protein, and interleukin-6 [IL-6]) were measured. Participants were categorized at baseline and follow-up into 3 groups: nonfrail/normal endurance (NF/NE), nonfrail/low endurance (NF/LE) and frail/low endurance (F/LE). Survival time was assessed according to frailty/endurance status and associated predictors of mortality. Forty-three men, 17 women (mean age, 78 ± 12 years) were contacted. At follow-up, 20 had died, 20 participated, and 20 did not participate. There were no changes in frailty/endurance status over time (McNemar;P=.19). Deaths occurred in 18% of NF/NE, 45% of NF/LE, and 60% of F/LE persons. The NF/NE group had greater survival rates than the NF/LE (  P=.032) and F/LE (  P=.014) groups. The 6MW and frailty score were independently predictive of mortality, with hazard ratios of 0.82 (95% confidence interval, 0.72-0.94) and 1.64 (95% confidence interval, 1.19-2.26), respectively, as was New York Heart Association class and IL-6. Backward stepwise Cox regression revealed that 6MW and frailty each were associated with mortality (P=.005) and highly correlated. Physical function is an important predictor of mortality in older adults with HF. The 6MW may be useful as a measure of frailty.

Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women.

OBJECTIVES: To investigate the effects of dehydroepiandrosterone (DHEA) combined with exercise on bone mass, strength, and physical function in older, frail women. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A major medical institution. PARTICIPANTS: Ninety-nine women (mean age 76.6 ± 6.0) with low sulfated DHEA (DHEAS) levels, low bone mass, and frailty. INTERVENTION: Participants received 50 mg/d DHEA or placebo for 6 months; all received calcium and cholecalciferol. Women participated in 90-minute twice-weekly exercise regimens. MEASUREMENTS: Hormone levels, bone mineral density (BMD), bone turnover markers, body composition, upper and lower extremity strength, physical performance. RESULTS: Eighty-seven women (88%) completed 6 months. There were no significant changes in BMD or bone turnover markers. DHEA supplementation resulted in gains in lower extremity strength (from 459 ± 121 N to 484 ± 147 N; P=.01). There was also improvement in Short Physical Performance Battery score, a composite score that focuses on lower extremity function, in those taking DHEA (from 10.1 ± 1.8 to 10.7 ± 1.9; P=.02). There were significant changes in all hormone levels, including DHEAS, estradiol, estrone, and testosterone, and a decline in sex hormone-binding globulin levels in those taking DHEA. CONCLUSION: DHEA supplementation improved lower extremity strength and function in older, frail women involved in a gentle exercise program of chair aerobics or yoga. No changes were found in BMD either due to small sample size, short duration of study or no effect. The physical function findings are promising and require further evaluation as frail women are at high risk for falls and fracture.

Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty.

OBJECTIVES: To investigate the effects of testosterone supplementation on bone, body composition, muscle, physical function, and safety in older men. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A major medical institution. PARTICIPANTS: One hundred thirty-one men (mean age 77.1 +/- 7.6) with low testosterone, history of fracture, or bone mineral density (BMD) T-score less than -2.0 and frailty. INTERVENTION: Participants received 5 mg/d of testosterone or placebo for 12 to 24 months; all received calcium (1500 mg/d diet and supplement) and cholecalciferol (1,000 IU/d). MEASUREMENTS: BMD of hip, lumbar spine, and mid-radius; body composition; sex hormones, calcium-regulating hormones; bone turnover markers; strength; physical performance; and safety parameters. RESULTS: Ninety-nine men (75.6%) completed 12 months, and 62 (47.3%) completed end therapy (mean 23 months; range 16-24 months for 62 who completed therapy). Study adherence was 54%, with 40% of subjects maintaining 70% or greater adherence. Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL, respectively, in the treatment group. BMD on testosterone increased 1.4% at the femoral neck and 3.2% at the lumbar spine (P=.005) and decreased 1.3% at the mid-radius (P<.001). There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance. There were no differences in safety parameters. CONCLUSION: Older, frail men receiving testosterone replacement increased testosterone levels and had favorable changes in body composition, modest changes in axial BMD, and no substantial changes in physical function.