Publications

CONTEXT

Older adults with type 2 diabetes are at higher risk for fracture compared with nondiabetic adults after adjustment for their higher bone mineral density. Infiltration of muscle by fat predicts increased risk of hip fracture.

OBJECTIVE

We investigated whether fat infiltration of muscle, which is greater in diabetic adults, is associated with all clinical fracture and whether it accounts for the increased fracture risk in those with diabetes.

DESIGN, SETTING, AND PARTICIPANTS

Data were analyzed from the Health, Aging, and Body Composition Study, a cohort of community-dwelling adults aged 70-79 yr. Glucose metabolism status and x-ray attenuation of thigh muscle were determined at baseline for 2762 participants.

MAIN OUTCOME MEASURES

During a mean 8.2 ± 2.3 yr follow-up, 331 participants reported at least one clinical fracture.

RESULTS

Fat infiltration of muscle was higher in those with diabetes or impaired glucose metabolism than in those with normal glucose metabolism (P < 0.001). Fat infiltration of muscle was independently associated with a 19% increased risk of incident clinical fracture (multivariate hazard ratio = 1.19; 95% confidence interval = 1.04-1.36); this association did not differ across glucose metabolism groups (P for interaction = 0.65). As previously reported, diabetes was associated with a greater fracture risk compared with normal glucose metabolism (hazard ratio = 1.42; 95% confidence interval = 1.07-1.89) after adjustment for bone mineral density, but further adjustment for fat infiltration of muscle did not attenuate this association.

CONCLUSIONS

Fat infiltration of muscle predicts clinical fracture in older adults. Although fat infiltration of muscle is higher among those with diabetes, it does not account for their increased fracture risk.

Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0.5 μg/min), or a combination. The right (noninfused) kidney served as a control. Intrarenal NONOate had no effect on mean arterial pressure (MAP); however, SILD reduced MAP in virgin rats, and the combination of NONOate+SILD reduced MAP in both virgin and pregnant rats. Neither NONOate nor SILD altered glomerular filtration rate. NONOate and SILD each stimulated sodium excretion (U(Na)V) and fractional excretion of sodium (FE(Na)) in virgin rats, but the combination did not result in an additional natriuretic response. However, NONOate infusion did not increase U(Na)V or FE(Na) in pregnant rats, but the natriuretic response to NONOate was restored with SILD, and SILD alone produced a natriuresis during pregnancy. Sodium nitroprusside (10(-4) mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10(-7) mol/l). Therefore, increased intrarenal PDE5 mediates the blunted natriuretic response to NO, and loss of responsiveness to the cGMP-dependent, natriuretic agents may contribute to volume expansion during pregnancy.

Previous studies have suggested that polyfunctional mucosal CD8(+) T-cell responses may be a correlate of protection in HIV controllers. Mucosal T-cell breadth and/or specificity may also contribute to defining protective responses. In this study, rectal CD8(+) T-cell responses to HIV Gag, Env, and Nef were mapped at the peptide level in four subject groups: elite controllers (n = 16; viral load [VL], <75 copies/ml), viremic controllers (n = 14; VL, 75 to 2,000 copies/ml), noncontrollers (n = 14; VL, >10,000 copies/ml), and antiretroviral-drug-treated subjects (n = 8; VL, <75 copies/ml). In all subject groups, immunodominant CD8(+) T-cell responses were generally shared by blood and mucosa, although there were exceptions. In HIV controllers, responses to HLA-B27- and HLA-B57-restricted epitopes were common to both tissues, and their magnitude (in spot-forming cells [SFC] per million) was significantly greater than those of responses restricted by other alleles. Furthermore, peptides recognized by T cells in both blood and rectal mucosa, termed "concordant," elicited higher median numbers of SFC than discordant responses. In magnitude as well as breadth, HIV Gag-specific responses, particularly those targeting p24 and p7, dominated in controllers. Responses in noncontrollers were more evenly distributed among epitopes in Gag, Env, and Nef. Viremic controllers showed significantly broader mucosal Gag-specific responses than other groups. Taken together, these findings demonstrate that (i) Gag-specific responses dominate in mucosal tissues of HIV controllers; (ii) there is extensive overlap between CD8(+) T cells in blood and mucosal tissues, with responses to immunodominant epitopes generally shared by both sites; and (iii) mucosal T-cell response breadth alone cannot account for immune control.

Although US Food and Drug Administration (FDA)-approved Biopharmaceutics Classification System (BCS) class 1 drugs are designated as high-permeability drugs, in fact, the criterion utilized is high extent of absorption. This ambiguity should be eliminated, and the FDA criterion should explicitly be stated as > or =90% absorption based on absolute bioavailability or mass balance. Maintaining confidentiality regarding the drugs for which the FDA has approved BCS waivers of in vivo bioequivalence studies is not good public policy and should be reversed.

BACKGROUND

The Internet is widely used for health information, yet little is known about the online activity of family caregivers of elders, a rapidly growing group. In order to better understand the online information-seeking activity of "e-caregivers" and other visitors at a caregiving website, we undertook a qualitative analysis of survey data from a website marketed as a comprehensive resource for adults caring for aging parents.

OBJECTIVE

The objectives were to better understand what types of information are sought by those visiting a website focused on elder-care issues and to identify overarching themes that might inform future development of Internet resources related to caregiving and aging.

METHODS

From March 2008 to March 2009, a 5-question pop-up survey was offered 9662 times and completed 2161 times. For 1838 respondents, included was a free text answer to the question "What were you looking for?" and 1467 offered relevant and detailed responses. The survey also asked about satisfaction with the site, gender of the respondent, and relationship to the individual being cared for. Content analysis was used to develop a coding dictionary, to code responses into information-seeking categories, and to identify overarching themes.

RESULTS

Of the respondents (76% of whom were female), 50% indicated they were caring for parents, 17% for themselves only, and 31% for others. Over half (57%) reported finding what they were looking for, and 46% stated they were extremely likely to recommend the website. Frequently mentioned information-seeking categories included "health information," "practical caregiving," and "support." Respondents also requested information related to housing, legal, insurance, and financial issues. Many responses referred to multiple comorbid conditions and complex caregiving situations. Overarching themes included (1) a desire for assistance with a wide range of practical skills and information and (2) help interpreting symptoms and behavior, such as knowing what life impacts to expect over the course of a health condition or treatment.

CONCLUSION

Visitors to a website targeting adults caring for aging parents reported seeking both general information on caregiving and specific assistance with the complex custodial, medical, emotional, and financial aspects of caregiving. Visitors requested both information to build caregiving skills as well as assistance in interpreting and knowing what to expect from symptoms, health conditions, and changes in behavior and relationships. Many desired communication with and support from other caregivers. Health care providers and eHealth developers should expect that many caregivers of elders are using the Internet as a resource. Further research and development is needed to fully realize the Internet's potential for education and support of caregivers.

BACKGROUND

National-level data are needed on predictors of mild physical impairment among older adults to assist policy makers with resource allocation.

METHOD

We analyzed data on adults above age 64 from the Medicare Current Beneficiary Survey (MCBS) with no activity of daily living (ADL) difficulties at baseline ( n = 14,226). Five ADLs were measured annually and recovery was defined as regaining complete ADL function at follow-up.

RESULTS

The strongest correlates of ADL difficulty were use of antipsychotic medications (adjusted odds ratio [AOR] = 1.93, 95% confidence interval [CI] = 1.44 to 2.58), instrumental ADL difficulty (AOR = 1.90, 95% CI = 1.74 to 2.07), and fair-poor general health (AOR = 1.59, 95% CI = 1.42 to 1.78). Only the number of incident ADL difficulties was associated with recovery (AOR = 0.02, 95% CI = 0.01 to 0.02).

CONCLUSION

Identifying factors associated with development of mild physical impairment could help direct patients toward preventive care programs to preempt decline in physical function.