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.

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.

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.

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.

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.

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.

Dementia care consultation for family caregivers: collaborative model linking an Alzheimer's association chapter with primary care physicians.

OBJECTIVE: The primary objective is to report on the efficacy of an individualized dementia care consultation intervention for family caregivers of patients with diagnosed dementia living in the community. The secondary objective is to present evidence on the intervention process to inform the feasibility and sustainability of the model featuring collaboration between primary care physicians and a voluntary sector organization. METHOD: Randomization was based on primary care physician practice site. In the intervention group, dementia care consultants located at an Alzheimer's association chapter provided individualized counseling and support over a 12-month period, and sent copies of care plans developed with family caregivers to referring primary care physicians. In the control group, family caregivers received educational and community resource information but no care consultation. Nursing home admission of patients during the 12-month study period was the primary outcome; secondary outcomes included measures of caregiver self-efficacy for managing dementia, caregiver depressive symptoms, and caregiver burden. RESULTS: A total of 84 family caregivers participated. After adjusting for baseline characteristics, patients whose family caregivers were in the intervention group were less likely than their control group counterparts to be admitted to a nursing home (Adjusted odds ratio = 0.40; 95% C.I. = 0.14-1.18; p = 0.10). No other outcomes were significantly different between treatment groups; however, intervention group caregivers reporting greater satisfaction with the intervention showed improved self-efficacy for managing dementia compared to their less satisfied counterparts. Medical record reviews found that care plans were found in most patient records, but that only 27% of intervention group caregivers reported discussing these care plans with physicians. Three different individuals occupied the dementia care consultant position during the study period, and this turnover led to family caregiver dissatisfaction. CONCLUSION: The dementia care consultation intervention showed favorable effects on nursing home admission and on caregiver outcomes among intervention group caregivers more satisfied with the intervention, but there are important barriers to sustaining this collaboration between primary care physicians and a voluntary sector organization such as an Alzheimer's association chapter.

Factors associated with skilled nursing facility transfers in dementia-specific assisted living.

BACKGROUND: Medical, functional, and behavioral problems are associated with transitions from assisted living (AL), but limited information is available on those at highest risk for transition. METHODS: We conducted a multidisciplinary geriatric team assessment of individuals newly admitted to 2 dementia-specific AL communities from January 2000 to March 2002. Transitions of individuals to permanent skilled nursing facilities (SNF) was assessed for 9 months. Multidisciplinary assessment on admission included medical and cognitive evaluations, physical function, nutritional status, and psychosocial adjustment. RESULTS: Twenty-four men and 24 women with a mean age of 83+/-6 years were assessed. Mental status score was 15+/-6. Residents had 2.1+/-1.7 comorbidities and were prescribed 1.7+/-1.2 medications. During follow-up, 23 (47.9%) transitioned to SNF and 9 (18.8%) individuals died (censored events). Significant predictors of transfer to nursing home from AL by one-predictor Cox proportional hazards model included depression score [hazard ratio (HR) 1.19; P=0.008], dependent activities of daily living (HR 1.18; P=0.014), gait speed (HR 1.15; P=0.004), modified Berg Balance Score (HR 0.88; P=0.004), and mental status score (HR 0.924, P=0.034). Our multivariate model selected by the forward procedure indicates that the modified Berg Balance Scale score predicted transfer to permanent nursing home with a interquartile HR of 0.91 (95% CI 0.8264, 0.989). CONCLUSIONS: A significant number of new residents of dementia-specific AL transitioned to SNF over 9 months. In univariate analysis, depression score, walking speed, balance, and mental status score were significantly associated with transition and in multivariate analysis, balance performance predicted transfer. These results suggest that fall risk should receive attention on admission to AL to potentially mitigate the high transfer rate.

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.

The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women.

OBJECTIVES: To evaluate the effect of ultra-low-dose (0.25 mg/d) micronized 17beta-estradiol on cognitive function in older postmenopausal women. DESIGN: Randomized, placebo-controlled trial conducted for 3 years. SETTING: Academic health center in greater Hartford, Connecticut. PARTICIPANTS: Fifty-seven healthy, community-dwelling, older postmenopausal women. INTERVENTION: Women received 0.25 mg/d of micronized 17beta-estradiol (estrogen therapy (ET), n=32) or placebo (n=25); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MEASUREMENTS: Neuropsychological measures of memory, language, mood, and executive function were collected at baseline, 3 months, and 36 months. Measures of executive function included the Controlled Oral Word Association Test, the Trail Making Test, and the Wisconsin Card Sorting Test. The Boston Naming Test was used to measure language skills. The Symbol Digit Modalities Test was used as a measure of sustained attention. Measures of memory included the Complex Figure Test, Fuld Object Memory Test, and a selected subtest from the Wechsler Memory Scale. Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression. RESULTS: No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments, nor were there any differences when the groups were stratified according to age. CONCLUSION: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials.

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.

Impact of smoking cessation on bone mineral density in postmenopausal women.

BACKGROUND: Although clinical guidelines recommend smoking cessation to improve bone health, the impact of short-term smoking cessation (i.e., 1 year) on bone mineral density (BMD) is not known. We examined the effects of smoking cessation on BMD measurements, markers of bone turnover, and hormone profiles in postmenopausal women. METHODS: Postmenopausal women (n = 152) who smoked at least 10 cigarettes per day were randomly assigned to behavioral counseling and either nicotine or placebo patch for smoking cessation (3-month treatment with a 1-month taper) and followed for an additional year. The BMD at various sites (hip, spine, wrist, and total body), serum and urine biochemical markers of bone turnover, and sex hormones were measured at baseline and again 1 year after smoking treatment. Women who continuously abstained from smoking between the end of treatment and 1 year later (quitters) (n = 42) were compared with women who completed the study and continued to smoke (n = 77). RESULTS: Femoral trochanter BMD increased by 2.9% among quitters vs. 0.6% among continued smokers (p = 0.02). Total hip BMD increased by 1.52% among quitters vs. 0.43% among continued smokers (p = 0.03). Changes in BMD at the femoral neck, radius, spine, and total body did not significantly differ between groups. The effects of smoking cessation on bone were mediated in part by weight gain. Smoking cessation was also associated with an increase in bone alkaline phosphatase. CONCLUSIONS: Smoking cessation, relative to continued smoking, increases BMD at the femoral trochanter and total hip in postmenopausal women.

Association between level of frailty and bone mineral density in community-dwelling men.

The goal of this study is to determine the associations between the components of a frailty definition and bone mineral density (BMD) in older men. A total of 392 community dwelling men (age range: 58-95 yr) with a mean age of 73+/-8 yr were evaluated. Femoral neck BMD T-scores ranged from -5.78 to +2.50, with 48.7% who had T-scores between -1 and -2.5 (low bone mass) and 8.7% who had T scores < or = -2.5 (osteoporosis). Participants were characterized as normal (39%), intermediate (55%), or frail (6%). Hand grip strength was 31.5+/-9.1 kg in those with normal BMD compared with 26.5+/-7.9 kg in those with osteoporotic BMD (p=0.0026). Walk speed (8 ft) was 2.32+/-0.49 s in those with normal BMD compared with 2.87+/-1.30 s with osteoporotic BMD (p=0.0015). Femoral neck T-score declined significantly with increasing level of frailty (p=0.014), but significance of decline was lost when corrected for age. Increasing frailty was associated with lower femoral neck BMD, although the association was not independent of age. Two components of the frailty model (i.e., hand grip strength and walking speed) were independently associated with lower femoral neck BMD, a finding that has not previously been reported in men.

Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women.

OBJECTIVES: To determine the effects of ultra-low-dose hormone therapy on muscle mass and physical function in community-dwelling women. DESIGN: Double-blind, placebo-controlled trial. SETTING: Clinical research center in Connecticut. PARTICIPANTS: Healthy, community-dwelling women aged 65 and older (n=167). INTERVENTION: Eligible women were randomly assigned to treatment with 0.25 mg 17-beta estradiol or placebo for 36 months. All women (estradiol or placebo) with an intact uterus received micronized progesterone 100 mg/d for 2 weeks every 6 months. All participants received 1,300 mg elemental calcium with 1,000 IU vitamin D per day. MEASUREMENTS: Appendicular skeletal muscle mass (ASM), lean body mass (LBM), and percentage body fat were measured using dual x-ray absorptiometry. Sarcopenia was defined as skeletal muscle mass (ASM/height2) 2 standard deviations or less than young, healthy reference population mean. Physical activity (Physical Activity Scale in the Elderly (PASE)) and performance were measured. Serum estrone, estradiol, and sex hormone-binding globulin were measured. RESULTS: The prevalence of sarcopenia at baseline was 13%. There were no baseline differences between groups except for PASE score and chair rise time, in which the estrogen group had better performance. No changes in ASM, LBM, percentage of body fat, or physical performance were found after 3 years of estrogen therapy. CONCLUSION: Sarcopenia was present in 13% of this group of community-dwelling, postmenopausal older women. Ultra-low-dose estrogen therapy neither improves nor harms ASM. Similarly, no changes in body fat or physical performance were detected.

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.

Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy.

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. We have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen. The objective of this study was to determine the prevalence of sarcopenia in a population of older, nonobese, community-dwelling women who had been long-term users of estrogen replacement therapy (ERT). METHODS: We measured appendicular skeletal muscle mass by dual x-ray absorptiometry (DXA) in 189 women aged 59 to 78 years old who had been using ERT for at least 2 years (mean +/- SD duration, 12.7 +/- 8.2 years). We defined sarcopenia as an adjusted appendicular skeletal muscle mass (ASM) (mass divided by height squared) more than 2 SDs below the mean for a young healthy reference population. Health and menopause history were obtained. Body mass index (BMI) was calculated, and physical activity and performance were measured using the Physical Activity Scale in the Elderly, the chair rise time, the 6-minute walk, and measures of lower extremity strength and power. Serum estrone, estradiol, testosterone, and sex hormone binding globulin were measured. RESULTS: The prevalence of sarcopenia in nonobese, community-dwelling women who were long-term ERT users was 23.8%. Skeletal muscle mass correlated significantly with BMI, age at the time of starting ERT, hand grip strength, lower extremity strength and power, and testosterone level, but not with estradiol level. In linear regression analysis, BMI, leg press strength, and testosterone level contributed to adjusted ASM, accounting for 48.7% of the variance (p <.001). CONCLUSIONS: Sarcopenia is as common in nonobese women who are long-term ERT users as in community-dwelling women not using ERT, suggesting that ERT does not protect against the muscle loss of aging. BMI, strength, and testosterone level contributed to appendicular skeletal mass in women. These data suggest that interventions to target nutrition, strength training, and testosterone replacement should be further investigated for their role in preventing muscle loss with age.

Retrospective evaluation and adjustment of dual energy X-ray absorptiometry measurements for bone mineral density research studies.

Dual-energy X-ray absorptiometry (DXA) is widely used for bone mineral density (BMD) measurements. Prospective daily quality control procedures such as cumulative sum (CUSUM) plots and Shewhart charts are very important and commonly used for routine monitoring of DXA measurements. These procedures are less suitable for post hoc adjustment of DXA measurements for clinical research studies, if and when that is needed. Extending previous methods, we propose and illustrate a simple statistical method for retrospective quality evaluation that may be used to adjust BMD measurements before they are analyzed in clinical research studies. Using multivariate regression, this method allows for simultaneous adjustment of different types of temporal variation such as sudden jumps, simple linear trends, changes in the slope of these trends, quadratic terms, and seasonal fluctuations. Adjusting the measurements to account for different types of temporal trends decreases the variance of bone mass density measurements and is an inexpensive way to increase the power of a study without increasing the sample size. The method is illustrated with measurements of two different phantoms used on the same DXA, with 2 and 3 yr of data, respectively. Results were consistent for both phantoms, with a gradual trend and a sudden jump, as well as a seasonal fluctuation term.

Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial.

CONTEXT: Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. OBJECTIVE: To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. INTERVENTION: Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MAIN OUTCOME MEASURES: The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. RESULTS: Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo. Estradiol, estrone, and sex hormone-binding globulin levels increased in the estrogen-treated group compared with placebo. The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups. The number of abnormal mammograms over 3 years was 15 for the low-dose estrogen group and 10 for the placebo group (8 occurred at baseline) (P =.26). There were no reports of breast cancer during the study. CONCLUSIONS: In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects. Future studies evaluating the effect of low-dose estrogen on fractures are indicated.

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.