Biomedical subjects

Heather G Allore

Publications and source records attributed to Heather G Allore.

12 recordsLinked to original sources

PubMed2007

Age-associated defect in human TLR-1/2 function.

The effects of aging on human TLR function remain incompletely understood. We assessed TLR function and expression in peripheral blood monocytes from 159 subjects in 2 age categories, 21-30 and >65 years of age, using a multivariable mixed effect model. Using flow cytometry to assess TLR-induced cytokine production, we observed a substantial, highly significant defect in TLR1/2-induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults compared with young controls. In contrast to findings in aged mice, other TLR (including TLR2/6)-induced cytokine production appeared largely intact. These differences were highly significant even after correcting for covariates including gender, race, medications, and comorbidities. This defect in TLR1/2 signaling may result from alterations in baseline TLR1 surface expression, which was decreased by 36% in older adults (p < 0.0001), whereas TLR2 surface expression was unaffected by aging. Production of IL-6 (p < 0.0001) and TNF-alpha (p = 0.003) after stimulation by N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-Cys-[S]-Ser1-[S]-Lys(4) trihydrochloride was strongly associated with TLR1 surface expression. Diminished TLR1/2 signaling may contribute to the increased infection-related morbidity and mortality and the impaired vaccine responses observed in aging humans.

Adult↗

PubMed2006

Improved self-confidence was a mechanism of action in two geriatric trials evaluating physical interventions.

OBJECTIVE: To evaluate the mechanisms of action in two successful geriatric clinical trials that tested multicomponent physical conditioning programs and to determine whether the pathways for overall benefit were through improvement in physical ability and/or self-confidence. STUDY DESIGN AND SETTING: PREHAB and DRIVER were conducted by the Yale Pepper Center. PREHAB participants received an individualized program that focused on the impairments present (standardly tailored design); DRIVER participants received the entire intervention (global design). PREHAB enrolled 188 community-living persons, aged 75 years or older, who were physically frail but ambulatory; DRIVER enrolled 178 drivers aged 70 years or older with physical impairments associated with poor driving performance. The primary outcome for PREHAB was a disability score and for DRIVER it was a driving score; potential mediators were measures of physical ability and self-confidence. RESULTS: In PREHAB, pathways for the intervention were established through improvement in physical ability and self-confidence. In DRIVER, there was some evidence for a pathway through improved driving self-confidence but not through physical ability; however, the intervention effect was largely unexplained. CONCLUSION: Multicomponent physical interventions may operate through psychological mechanisms, and these mechanisms should be anticipated in trial designs so that the component effects can be suitably evaluated.

Activities of Daily Living↗

PubMed2006

Potentially modifiable resident characteristics that are associated with physical or verbal aggression among nursing home residents with dementia.

BACKGROUND: Physical aggression by nursing home residents is a burden to residents and staff. The identification of modifiable correlates would facilitate developing preventive strategies. The objectives of the study were to determine potentially modifiable resident characteristics that are associated with physical aggression and to correlate these characteristics with verbal aggression. METHODS: This was a cross-sectional study of nursing home residents in 5 states who had at least 1 annual Minimum Data Set assessment completed during 2002. Case subjects were defined as nursing home residents 60 years and older with dementia who were reported to have been physically aggressive in the week before their assessment. Control subjects were all other residents 60 years and older with dementia. The main outcome measure was being physically aggressive during the past week. RESULTS: A total of 103 344 residents met study criteria, of whom 7120 (6.9%) had been physically aggressive in the week before their annual Minimum Data Set assessment. After adjustment for potential confounders, including age, sex, severity of cognitive impairment, and dependence in activities of daily living, physical aggression was associated with depressive symptoms (adjusted odds ratio [AOR], 3.3; 99% confidence interval [CI], 3.0-3.6), delusions (AOR, 2.0; 99% CI, 1.7-2.4), hallucinations (AOR, 1.4; 99% CI, 1.1-1.8), and constipation (AOR, 1.3; 99% CI, 1.2-1.5). Urinary tract infections, respiratory tract infections, fevers, reported pain, and participation in recreational activities were not significantly associated with physical aggression in multivariate analyses (P >.01 for all). Except for constipation, the correlates of verbal aggression were similar to those of physical aggression. CONCLUSION: If the associations we have estimated are causal, then treatment of depression, delusions, hallucinations, and constipation may reduce physical aggression among nursing home residents.

Aged, 80 and over↗

PubMed2006

Transitions between frailty states among community-living older persons.

BACKGROUND: Little is known about the natural course of frailty. We performed a prospective study to determine the transition rates between frailty states and to evaluate the effect of the preceding frailty state on subsequent frailty transitions. METHODS: We studied 754 community-living persons, aged 70 years or older, who were nondisabled in 4 essential activities of daily living. Frailty, assessed every 18 months for 54 months, was defined on the basis of weight loss, exhaustion, low physical activity, muscle weakness, and slow walking speed. Participants were classified as frail if they met 3 or more of these criteria, as prefrail if they met 1 or 2 of the criteria, and as nonfrail if they met none of the criteria. RESULTS: Of the 754 participants, 434 (57.6%) had at least 1 transition between any 2 of the 3 frailty states during 54 months. The rates were 36.8%, 21.5%, and 9.2% for 1, 2, and 3 transitions, respectively. During the 18-month intervals, transitions to states of greater frailty were more common (rates up to 43.3%) than transitions to states of lesser frailty (rates up to 23.0%), and the probability of transitioning from being frail to nonfrail was very low (rates, 0%-0.9%), even during an extended period. The likelihood of transitioning between frailty states was highly dependent on one's preceding frailty state. CONCLUSIONS: Frailty among older persons is a dynamic process, characterized by frequent transitions between frailty states over time. Our findings suggest ample opportunity for the prevention and remediation of frailty.

Aged↗

PubMed2006

The effect of prior disability history on subsequent functional transitions.

BACKGROUND: Many older persons experience multiple transitions between states of disability and independence, but little is known about the effect of prior disability history on subsequent functional transitions. Our objective was to determine the effect of prior disability on subsequent transitions between no disability, mild disability, severe disability, and death. METHODS: For 60 months, 754 persons aged 70 or older underwent monthly assessments of disability in basic activities of daily living. We used a multistate extension of the proportional hazards model to determine the effects of amount, defined as cumulative duration, and distribution, defined as number of episodes, of prior disability on subsequent functional transitions, adjusted for age, gender, cognitive status, timed gait, and habitual physical activity. RESULTS: For each additional month of prior disability, participants were more likely to make transitions representing new or worsening disability and were less likely to make transitions from disability to independence or from severe disability to death. Adjusting for the cumulative duration of prior disability, more episodes of prior disability were associated with a higher likelihood of most transitions, representing both increasing and decreasing disability, but had no effect on transitions to death. CONCLUSIONS: Both the amount and distribution of prior disability are important determinants of the likelihood of subsequent functional transitions. Analytic methods that account for prior disability history should be used in studies of functional transitions, and new measures of disability burden are needed that incorporate distribution as well as amount of disability.

Activities of Daily Living↗

PubMed2006

Bathing disability and the risk of long-term admission to a nursing home.

BACKGROUND: The prevalence of disability in bathing and the likelihood of a long-term nursing home admission increase substantially with age. We performed a prospective study to determine whether the occurrence of persistent disability in bathing is associated with the risk of a long-term nursing home admission, independent of potential confounders, including persistent disability in other essential activities of daily living. METHODS: We studied 754 community-living persons, 70 years old or older, who were nondisabled in four essential activities of daily living. Participants were followed with monthly telephone interviews for a median of 75 months to determine the occurrence of persistent (i.e., present for at least 2 consecutive months) disability in bathing and the time to the first long-term nursing home admission, defined as longer than 3 months. RESULTS: One hundred thirteen (15.0%) participants had a long-term nursing home admission. At least one episode of persistent bathing disability occurred among 59 (52.2%) participants with a long-term nursing home admission and 210 (32.8%) without a long-term admission (p <.001). In a proportional hazards model that was fully adjusted for potential confounders, the occurrence of persistent bathing disability increased the risk of a long-term nursing home admission by 77% (hazard ratio 1.77, 95% confidence interval 1.05 to 2.98), but had no effect on the risk of a short-term nursing home admission (hazard ratio 0.87, 95% confidence interval 0.51 to 1.49). CONCLUSIONS: Among community-living older persons, the occurrence of persistent disability in bathing is independently associated with the risk of a long-term nursing home admission, but has no effect on short-term admissions. Interventions directed at the prevention and remediation of bathing disability have the potential to reduce the burden and expense of long-term care services.

Activities of Daily Living↗

PubMed2006

The dynamic nature of mobility disability in older persons.

OBJECTIVES: To determine the rates of clinically meaningful transitions in mobility disability; evaluate how these transitions differ according to age, sex, and physical frailty; and depict the duration of the resulting episodes of mobility disability. DESIGN: Prospective cohort study. SETTING: General community in greater New Haven, Connecticut, from March 1998 to October 2004. PARTICIPANTS: Seven hundred fifty-four community-living older persons, aged 70 and older, who were nondisabled (i.e., required no personal assistance) in four activities of daily living. MEASUREMENTS: Mobility disability, defined as the inability to walk one quarter of a mile and to climb a flight of stairs, respectively without personal assistance, was assessed every month for up to 5 years. RESULTS: For both mobility tasks, rates per 1,000 person-months were higher for transitions from no disability to intermittent disability (34.7 for walking one quarter of a mile and 17.4 for climbing a flight of stairs), intermittent to continuous disability (52.0 and 42.5), continuous to intermittent disability (35.4 and 31.5), and intermittent to no disability (68.6 and 85.4) than for other transitions. Older age, female sex, and physical frailty were associated with greater likelihood of transition to states of greater disability and lower likelihood of regaining independent mobility. CONCLUSION: Mobility disability in older persons is a highly dynamic process, characterized by frequent transitions between states of independence and disability. Programs designed to enhance independent mobility should focus not only on the prevention of mobility disability but also on the restoration and maintenance of independent mobility in older persons who become disabled.

Activities of Daily Living↗

PubMed2006

The epidemiology of bathing disability in older persons.

OBJECTIVES: To quantify the burden of bathing disability over time; to determine whether the burden of bathing disability differs according to age, sex, and physical frailty; and to evaluate the relationship between disability in bathing and disability in other essential activities of daily living (ADLs). DESIGN: Prospective cohort study. SETTING: General community in greater New Haven, Connecticut. PARTICIPANTS: Seven hundred fifty-four community-living older persons aged 70 and older who were nondisabled (required no personal assistance) in four essential ADLs: bathing, dressing, transferring from a chair, and walking inside the house. MEASUREMENTS: Bathing disability, defined as the inability to wash and dry one's whole body without personal assistance, was assessed every month for up to 6 years, along with disability in dressing, transferring, and walking. RESULTS: Over the course of 6 years, 440 participants (58.4%) had at least one episode of bathing disability, and 266 (34.0%) had multiple episodes, with the duration of each episode averaging about 6 months. Whether assessed as number of episodes, duration of episodes, incidence rates, or number of months per 100 months, the burden of bathing disability was greatest in participants who were physically frail and was consistently higher in women than men and in participants who were aged 80 and older than those who were aged 70 to 79. Most episodes of bathing disability (86.1%) were not preceded in the prior month by disability in dressing, transferring, or walking, and nearly half (48.3%) were not accompanied at onset by disability in one or more of these other ADLs. In a multivariable model that included age, sex, and physical frailty, the onset of bathing disability increased the likelihood of developing disability in the other essential ADLs the following month fivefold (hazard ratio=5.1, 95% confidence interval=4.1-6.4). CONCLUSION: Disability in bathing may serve as a sentinel event in the disabling process. Given the recurrent nature of bathing disability, programs designed to enhance independent bathing will need to focus not only on the prevention of bathing disability, but also on the restoration and maintenance of independent bathing in older persons who become disabled.

Activities of Daily Living↗

PubMed2006

Multimorbidity and survival in older persons with colorectal cancer.

OBJECTIVES: To ascertain the effect of common chronic conditions on mortality in older persons with colorectal cancer. DESIGN: Retrospective cohort study. SETTING: Population-based cancer registry. PARTICIPANTS: Patients in the Surveillance Epidemiology and End Results-Medicare linked database who were aged 67 and older and had a primary diagnosis of Stage 1 to 3 colorectal cancer during 1993 through 1999. MEASUREMENTS: Chronic conditions were identified using claims data, and vital status was determined from the Medicare enrollment files. After estimating the adjusted hazard ratios for mortality associated with each condition using a Cox model, the population attributable risk (PAR) was calculated for the full sample and by age subgroup. RESULTS: The study sample consisted of 29,733 patients, 88% of whom were white and 55% were female. Approximately 9% of deaths were attributable to congestive heart failure (CHF; PAR = 9.4%, 95% confidence interval (CI) = 8.4-10.5%), more than 5% were attributable to chronic obstructive pulmonary disease (COPD; PAR = 5.3%, 95% CI = 4.7-6.6%), and nearly 4% were attributable to diabetes mellitus (PAR = 3.9%, 95% CI = 3.1-4.8%). The PAR associated with CHF increased with age, from 6.3% (95% CI = 4.4-8.8%) in patients aged 67 to 70 to 14.5% (95% CI = 12.0-17.5%) in patients aged 81 to 85. Multiple conditions were common. More than half of the patients who had CHF also had diabetes mellitus or COPD. The PAR associated with CHF alone (4.29%, 95% CI = 3.68-4.94%) was similar to the PAR for CHF in combination with diabetes mellitus (3.08, 95% CI = 2.60-3.61%) or COPD (3.93, 95% CI = 3.41-4.54%). CONCLUSION: A substantial proportion of deaths in older persons with colorectal cancer can be attributed to CHF, diabetes mellitus, and COPD. Multimorbidity is common and exerts a substantial effect on colorectal cancer survival.

Aged↗

PubMed2005

CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina.

Ciliary neurotrophic factor (CNTF) provides morphologic preservation of rods in several animal models of retinitis pigmentosa (RP). However, CNTF may alter photoreceptor morphology and rod photoreceptor differentiation in vitro, as well as affecting normal retinal electrophysiology. In addition, the capacity of CNTF to support other cell types affected secondarily in RP (cones and ganglion cells) is unclear. The purposes of this study were to examine the effects of CNTF upon a canine model of RP, the rod-cone degeneration (rcd-1) dog. Archival tissue from a previous study assessing the capacity of CNTF to rescue photoreceptors in rcd-1 dogs was used. One eye was treated for 7 weeks before being explanted. The contralateral eye was untreated. A total of 23 rcd-1 dogs and seven control dogs (four untreated and three CNTF-treated) were used. Morphometric data describing outer and inner nuclear layer thickness, inner retinal thickness, cones and ganglion cells were collected at nine evenly spaced points along each retina and analysed using a mixed effects model. Immunohistochemistry was performed on a subset of 11 dogs for expression of rhodopsin, human cone arrestin (hCAR) and recoverin. CNTF protected the outer nuclear layer and increased inner retinal thickness in a dose-dependent manner (both were maximal at CNTF doses of 1-6 ng day-1). Significant cone loss or reduction of inner nuclear layer width in rcd-1 did not occur in this model, therefore we were unable to assess the protective effect of CNTF upon these parameters. CNTF did not afford significant ganglion cell protection. CNTF induced morphologic changes in rods and ganglion cells, as well as reducing expression of hCAR and rhodopsin, but not recoverin. The dose of CNTF which provided optimal outer nuclear layer protection also resulted in several other effects, including altered ganglion cell morphology, increased thickness of the entire retina, and reduced expression of some phototransduction proteins. These changes were more marked in rcd-1 retinas than in wild-type retinas. This implies that the consequences of CNTF treatment may be substantially influenced by the cellular context into which it is introduced.

Animals↗

PubMed2005

Experimental designs for multicomponent interventions among persons with multifactorial geriatric syndromes.

This paper discusses issues about the design of clinical trials to test multicomponent interventions for multifactorial health conditions, such as geriatric syndromes in which more than one risk factor is related to the outcome. The issues covered include: identification and selection of modifiable risk factors related to the outcome of interest, selection of intervention components to reduce the deleterious effects of the modifiable risk factors, assignment of components of the intervention, blinding, sample size requirements and estimation of component effects. Each of these issues is explored using examples from nine illustrative multicomponent intervention trials. Statistical and clinical concerns regarding the design of multicomponent interventions are addressed. We also propose elements of multicomponent interventions for multifactorial health conditions that should be reported in publications and areas where future research is needed.

Accidental Falls↗

PubMed2004

Hospitalization, restricted activity, and the development of disability among older persons.

CONTEXT: Preventing the development of disability in activities of daily living is an important goal in older adults, yet relatively little is known about the disabling process. OBJECTIVES: To evaluate the relationship between 2 types of intervening events (hospitalization and restricted activity) and the development of disability and to determine whether this relationship is modified by the presence of physical frailty. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study, conducted in the general community in greater New Haven, Conn, from March 1998 to March 2003, of 754 persons aged 70 years or older, who were not disabled (ie, required no personal assistance) in 4 essential activities of daily living: bathing, dressing, walking inside the house, and transferring from a chair. Participants were categorized into 2 groups according to the presence of physical frailty (defined on the basis of slow gait speed) and were followed up with monthly telephone interviews for up to 5 years to ascertain exposure to intervening events and determine the occurrence of disability. MAIN OUTCOME MEASURE: Disability, defined as the need for personal assistance in bathing, dressing, walking inside the house, or transferring from a chair. RESULTS: During the 5-year follow-up period, disability developed among 417 (55.3%) participants, 372 (49.3%) were hospitalized and 600 (79.6%) had at least 1 episode of restricted activity. The multivariable hazard ratios for the development of disability were 61.8 (95% confidence interval [CI], 49.0-78.0) within a month of hospitalization and 5.54 (95% CI, 4.27-7.19) within a month of restricted activity. Strong associations were observed for participants who were physically frail and those who were not physically frail. Hospital admissions for falls were most likely to lead to disability. Intervening events occurring more than a month prior to disability onset were not associated with the development of disability. The population-attributable fractions associated with new exposure to hospitalization and restricted activity, respectively, were 0.48 and 0.19; 0.40 and 0.20, respectively, for frail participants and 0.61 and 0.16, respectively, for nonfrail participants. CONCLUSIONS: Illnesses and injuries leading to either hospitalization or restricted activity represent important sources of disability for older persons living in the community, regardless of the presence of physical frailty. These intervening events may be suitable targets for the prevention of disability.

Activities of Daily Living↗