Global benefit-risk analysis of adjunctive aripiprazole in the treatment of patients with major depressive disorder.

OBJECTIVE: This study quantified the overall merit of adjunctive aripiprazole in major depressive disorder (MDD). METHODS: Global benefit-risk (GBR) analysis quantified the benefit and risk differences between adjunctive aripiprazole and antidepressant (ADT) monotherapy. Three hundred and fifty six patients receiving ADT monotherapy and 366 patients receiving ADT and adjunctive aripiprazole (2-20 mg/day) were included. Efficacy measures included the Montgomery-Asberg depression rating scale (MADRS) Total score response (> or =50% reduction) and remission (response plus Total score < or = 10). Treatment-emergent adverse events were classified by severity. GBR ratio measures evaluated the relative benefit of adjunctive aripiprazole. Logistic regression models tested the effect of adjunctive aripiprazole on GBR and were used to identify predictors of net benefit and potential factors affecting the adjunctive aripiprazole treatment effect. RESULTS: For MADRS-defined response and remission, the relative gain of adjunctive aripiprazole versus ADT monotherapy was 1.46 (p = 0.044) and 1.43 (p = 0.085), respectively. Gender, current escitalopram, duration of current episode, and baseline body mass index are potential factors affecting the adjunctive aripiprazole treatment effect. CONCLUSIONS: Compared with ADT monotherapy, adjunctive aripiprazole was associated with an improved benefit-risk profile in MDD.

Comparative utility of aripiprazole and haloperidol in schizophrenia: post hoc analysis of two 52-week, randomized, controlled trials.

BACKGROUND: Since their introduction, second-generation antipsychotics (SGAs) have become the drugs of choice for the treatment of schizophrenia. However, recent findings have questioned the benefits of SGAs over first-generation antipsychotics (FGAs). OBJECTIVE: This post hoc analysis sought to compare the utility of the SGA aripiprazole with the FGA haloperidol in patients with early-phase schizophrenia (ES) or chronic schizophrenia (CS). METHOD: Data were pooled from two identical 52-week, randomized, active comparator trials (31-98-217 and 31-98-304) of aripiprazole 20-30 mg/day versus haloperidol 7-10 mg/day. Patients in the efficacy sample were classified as having ES if they were

A semiparametric transition model with latent traits for longitudinal multistate data.

SUMMARY: We propose a general multistate transition model. The model is developed for the analysis of repeated episodes of multiple states representing different health status. Transitions among multiple states are modeled jointly using multivariate latent traits with factor loadings. Different types of state transition are described by flexible transition-specific nonparametric baseline intensities. A state-specific latent trait is used to capture individual tendency of the sojourn in the state that cannot be explained by covariates and to account for correlation among repeated sojourns in the same state within an individual. Correlation among sojourns across different states within an individual is accounted for by the correlation between the different latent traits. The factor loadings for a latent trait accommodate the dependence of the transitions to different competing states from a same state. We obtain the semiparametric maximum likelihood estimates through an expectation-maximization (EM) algorithm. The method is illustrated by studying repeated transitions between independence and disability states of activities of daily living (ADL) with death as an absorbing state in a longitudinal aging study. The performance of the estimation procedure is assessed by simulation studies.

Explaining the effect of gender on functional transitions in older persons.

BACKGROUND: Women live longer but experience greater disability than men. The reasons for this gender difference in disability are not well understood. OBJECTIVE: Our objectives were to determine if the higher prevalence of disability in women is due to greater incidence of disability, longer duration of disability, or both, and to identify factors that potentially explain these gender differences. METHODS: 754 community-living persons aged 70 and older who were non-disabled (required no personal assistance) in four essential activities of daily living (ADLs) were assessed monthly for disability for up to 6 years. A multi-state extension of the proportional hazards model was used to determine the effects of gender on transitions between states of no disability, mild disability, severe disability, and death, and to evaluate potential mediators of these effects. RESULTS: Women were more likely to make the transition from no disability to mild disability and less likely to make the transitions from mild to no disability and from both mild and severe disability to death. The gender difference in the transitions between no disability and mild disability was largely explained by differences in gait speed and physical activity, but gender difference in transitions to death persisted despite adjustment for multiple potential mediators. CONCLUSION: The higher prevalence of disability in women versus men is due to a combination of higher incidence and longer duration, resulting from lower rates of recovery and mortality among disabled women.

Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort.

INTRODUCTION: To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA). METHODS: Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR-BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2-immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1-3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored. RESULTS: A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [-], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2- group. DXR-BMD was lower in the anti-CCP2+ vs. the anti-CCP2- groups (Gp1-3 vs. anti-CCP2-: P < 0.0001 for left and right hands). DXR-BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR-BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181). CONCLUSION: Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity. FUNDING: Bristol-Myers Squibb. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01793103.

Association of anti-cyclic citrullinated protein antibodies, erosions, and rheumatoid factor with disease activity and work productivity: A patient registry study.

OBJECTIVES: To evaluate associations between the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) and rheumatoid factor (RF) and other outcomes, including joint erosions and both clinical and economic endpoints, in patients with rheumatoid arthritis (RA). METHODS: Data from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective registry of adult RA patients with established or recent-onset RA, were analyzed. Logistic regression models were constructed to test associations between anti-CCP/RF seropositivity and erosive disease and the presence of anti-CCP/RF seropositivity plus erosive disease and (1) RA severity; (2) hospitalizations; (3) durable medical equipment (DME) use; and (4) worker productivity (e.g., employment status). Covariates in these models included patient age, gender, race, body mass index (BMI), number of comorbidities, and treatment. RESULTS: Among 1309 registrants, those who were positive (vs. negative) for anti-CCP were 2.72 times more likely to have erosions (OR = 2.72; 95% CI: 1.77-4.18; P < 0.001). Individuals positive (vs. negative) for RF were 36% more likely to have erosions (95% CI: 0.88-2.08; P = 0.162). Patients with anti-CCP seropositivity and erosions were significantly more likely to: (1) have higher disease activity as measured by the Disease Activity Score in 28 joints C-reactive protein (DAS28-CRP ≥ 2.6); (2) be hospitalized; (3) use DME; and (4) be unemployed, disabled, or long-term disabled. CONCLUSIONS: For the first time in a "real-world" setting including patients with both recent-onset and chronic RA, this study demonstrated that the combination of anti-CCP seropositivity and erosions were significantly associated with more adverse clinical and health-economic consequences, including a lower probability of low disease activity and higher health resource utilization, despite use of biologic disease-modifying antirheumatic drugs by many patients. This dual presentation may signal a need for more intensive therapies, even when observed in patients with chronic, as well as recent-onset, RA. Trial registration [Brigham and Women's Hospital (BWH) Rheumatoid Arthritis Sequential Study; Registry URL: https://clinicaltrials.gov/ct2/show/NCT01793103; ClinicalTrials.gov Identifier NCT01793103].

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.

Motor deficits and altered striatal gene expression in aphakia (ak) mice.

Like humans with Parkinson's disease (PD), the ak mouse lacks the majority of the substantia nigra pars compacta (SNc) and experiences striatal denervation. The purpose of this study was to test whether motor abnormalities in the ak mouse progress over time, and whether motor function could be associated with temporal alterations in the striatal transcriptome. Ak and wt mice (28 to 180 days old) were tested using paradigms sensitive to nigrostriatal dysfunction. Results were analyzed using a linear mixed model. Ak mice significantly underperformed wt controls in rotarod, balance beam, string test, pole test and cotton shred tests at all ages examined. Motor performance in ak mice remained constant over the first 6 months of life, with the exception of the cotton shred test, in which ak mice exhibited marginal decline in performance. Dorsal striatal semi-quantitative RT-PCR for 19 dopaminergic, cholinergic, glutaminergic and catabolic genes was performed in 1- and 6-month-old groups of ak and wt mice. Preproenkephalin levels in ak mice were elevated in both age groups. Drd1, 3 and 4 levels declined over time, in contrast to increasing Drd2 expression. Additional findings included decreased Chrnalpha6 expression and elevated VGluT1 expression at both time points in ak mice and elevated AchE expression in young ak mice only. Results confirm that motor ability does not decline significantly for the first 6 months of life in ak mice. Their striatal gene expression patterns are consistent with dopaminergic denervation, and change over time, despite relatively unaltered motor performance.

Paclitaxel-Loaded Magnetic Nanoparticles: Synthesis, Characterization, and Application in Targeting.

Iron oxide magnetic nanoparticles (MNPs) are good candidates to implement fluid therapy in critical patients in clinic integrated system. Herein, we synthesized paclitaxel (PTX)-loaded MNPs modified with methoxy polyethylene glycol (PEG)-lysine-oleic acid2 (PTX-MNPs-PLO), which is expected to act as a magnetic resonance imaging (MRI) contrast agent and meanwhile for cancer therapy. MNPs were synthesized by thermal decomposition. Dialysis method was applied to prepare PTX-MNPs-PLO with 3 different PEG molecular weights (1000, 2000, and 4000 Da), which were subsequently freeze-dried into powders. PTX-MNPs-PLO was characterized by transmission electron microscope, scanning electron microscope, thermogravimetric analysis, vibrating sample magnetometer, and MRI. What is more is that pharmacokinetics and distribution in vivo were processed, the results of which exhibited that PTX-MNPs-PLO2000 had the longer circulation lifetime compared with Taxol, PTX-MNPs-PLO1000, and PTX-MNPs-PLO4000. Results of magnetic targeting in kidneys suggested that deep buried or ultrasmall magnet is likely to be more preferable. PTX-MNPs-PLO2000 holds great promise in the application of magnetic accumulation, target drug delivery, and thermal therapy.

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.

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.

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.

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.

Light to moderate alcohol consumption is associated with better cognitive function among older male veterans receiving primary care.

Among older persons, the effects of light to moderate alcohol consumption on cognitive function remain inadequately defined. The authors sought to determine whether light to moderate drinking is associated with better cognitive function among older men. Participants included men aged 65 years or older enrolled in a Veteran's Administration (VA) primary care clinic. Current (past 1 year) and lifetime use, cognitive functioning (as determined by the Trail Making Part B, Symbol Digit, FAS, and Hopkins Verbal Learning tests), and demographic, psychosocial, and medical status were obtained using standardized methods. Participants (N = 760) had a mean age of 74 (range, 65-89) years. Current drinkers (n = 509) as compared with never (n = 31) and former (n = 220) drinkers demonstrated significantly better cognitive performance on 3 (Trails B, Symbol Digit, and Hopkins Verbal Learning) of the 4 tests (P < .01 for all comparisons). In multiple linear regression models, current light to moderate drinking (ie, 7 or fewer drinks per week), as compared to a reference group of never and former drinkers, was associated with better performance on the Trails B, Symbol Digit, and Hopkins Verbal Learning tests (P < .01 for all comparisons). The number of years drinking 7 or fewer drinks per week also was independently associated with better cognitive performance. Current consumption of 7 or fewer drinks per week and the number of years drinking at this level are both associated with better cognitive performance in older male veterans receiving primary care. These findings are consistent with the hypothesis that light to moderate drinking confers cognitive benefits to older persons.

Restricted activity and functional decline among community-living older persons.

BACKGROUND: Restricted activity is common among community-living older persons, but its prognostic significance is not known. We performed a prospective cohort study to evaluate the association between the occurrence of restricted activity and functional decline over an 18-month period. METHODS: We studied 680 community-living persons, 70 years or older, who were categorized into 3 groups according to their risk for disability (low, intermediate, or high) in activities of daily living (ADL). Participants were subsequently followed up with monthly telephone interviews to ascertain the occurrence of restricted activity, defined as having stayed in bed for at least half a day and/or having cut down on their usual activities due to an illness, injury, or other problem in the past month. Functional decline was defined as an increase in ADL disability scores between the baseline and 18-month follow-up assessments, which were completed in the home. RESULTS: After adjusting for the baseline risk of disability and other covariates, the disability score at 18 months increased (ie, worsened) by 11.2% (95% confidence interval [CI], 7.0%-15.6%) for each additional month with restricted activity. The association between restricted activity and functional decline differed significantly by risk group (P<.001). For the low- and intermediate-risk groups, the adjusted disability scores increased by 18.7% (95% CI, 10.3%-27.8%) and 7.5% (95% CI, 2.7%-12.5%), respectively, for each additional month with restricted activity. There was no association between restricted activity and functional decline in the high-risk group, as evidenced by a nonsignificant increase in the adjusted disability score of 2.7% (95% CI, -6.6% to 12.9%). CONCLUSION: For older persons who are not otherwise at high risk for ADL disability, restricted activity is an important predictor of functional decline and not just a benign feature of old age.

Timing in the communication of pain among nursing home residents, nursing staff, and clinicians.

BACKGROUND: The management of nursing home (NH) residents' pain requires adequate nursing assessment and clinician knowledge of pain therapies. However, the timely communication of pain from residents to nurses and from nurses to clinicians is equally necessary. Using a 4-step model (nursing assessment of pain, notification of clinicians regarding pain assessment, clinicians' assessment of pain and intervention), and nursing reassessment following an intervention, we describe the timing with which each of these steps occur. METHODS: In a telephone survey of directors of nursing from 63 of the 68 nursing homes in New Haven County, Connecticut, we determined (1) how often nurses assess pain in residents, (2) when nurses notify clinicians about residents' pain, (3) how often clinicians assess pain, and (4) when nurses reassess pain after a clinician's intervention. RESULTS: Whereas in 76% of NHs nurses assessed pain in residents without pain at least "quarterly," only in 46% of NHs was pain assessed in residents with pain at least "every shift." In 42% of NHs nurses notified clinicians at least when the regimen was "ineffective." Only 55% of directors of nursing reported that clinicians assessed pain at least every 30 to 60 days. Finally, in 73% of NHs nursing reassessment occurred at least 1 hour after intervention. CONCLUSIONS: There is considerable variability in how frequently nurses and clinicians assess pain, when clinicians are notified about pain, and how frequently nurses reassess pain. Studies are needed to determine optimal timing in the communication process of pain to allow better pain management outcomes and quality of care for NH residents.

Functional self-efficacy and pain-related disability among older veterans with chronic pain in a primary care setting.

We examined the relationship between functional self-efficacy and pain-related disability in a sample of older veterans with chronic pain. A total of 1045 veterans aged 65 years or older who received primary care at the VA Connecticut Healthcare System in West Haven, CT, were assessed for the presence of chronic pain (i.e. pain due to a non-cancer cause for >/=3 consecutive months in the past 12 months); 303 (26%) screened positive; and 245 (81%) participated. Using a ten-item functional self-efficacy questionnaire (scale: 0-40), participants were categorized into three functional self-efficacy groups: low, score

The development of insidious disability in activities of daily living among community-living older persons.

PURPOSE: To determine how often disability in essential activities of daily living develops insidiously, and to evaluate whether the likelihood of insidious disability differs on the basis of physical frailty. METHODS: We conducted a prospective study of 754 nondisabled, community-living persons aged 70 years or older. Participants were categorized according to the presence or absence of physical frailty, which was defined on the basis of gait speed. Participants were subsequently followed with monthly telephone interviews for 3 years to determine the occurrence of disability in bathing, dressing, walking, or transferring, and to ascertain exposure to precipitating events, which included acute hospital admissions and other illnesses, injuries, or problems leading to restricted activity. RESULTS: For first episodes of disability, 73 (36%) of 203 developed insidiously among the 322 participants who were physically frail and 26 (18%) of 141 developed insidiously among the 432 participants who were not physically frail (P <0.001). Physical frailty was the only factor that was associated significantly with the development of insidious disability, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.4 to 4.1). The likelihood that an episode of disability was insidious increased progressively, from 29% of the 344 first episodes to 65% of the 155 fourth or higher episodes (P for trend <0.001). CONCLUSION: Disability in essential activities of daily living often occurs insidiously, particularly among older persons who are physically frail or who have had prior episodes of disability.

Identification of strategies used to cope with chronic pain in older persons receiving primary care from a Veterans Affairs Medical Center.

OBJECTIVES: To identify the strategies used by older persons to cope with chronic noncancer pain, determine the perceived effectiveness of the strategies, and ascertain factors associated with their use. DESIGN: Cross-sectional telephone survey. SETTING: Primary care practice located at a Veterans Affairs Medical Center in New England. PARTICIPANTS: Two hundred forty-five patients (aged 65-90) with chronic pain. MEASUREMENTS: Qualitative methods were used to ascertain participants' coping strategies, and their effectiveness was determined using a five-category response scale (1=not at all effective to 5=extremely effective). In multivariate analyses, associations between participants' demographic, medical, psychosocial, and pain characteristics and prevalent coping strategies were assessed. RESULTS: Participants had a mean age+/-standard deviation of 75+/-5.1; 84% were male. Overall, 240 (98%) participants had employed at least one coping strategy in the previous month; the mean number used per participant was 2.8+/-1.4. Prevalent coping strategies included analgesic medications (used by 187/240=78% participants), exercise (35%), cognitive methods (37%), religious activities (21%), and activity restriction (20%). The proportion of participants who used a given strategy and rated it quite a bit or extremely effective exceeded 50% for only five of the 15 identified strategies. Women were more likely than men to use cognitive coping methods (odds ratio (OR)=3.2, 95% confidence interval (CI)=1.5-6.8) and religious activities (OR=2.6, 95% CI=1.2-5.7). Participants with chronic pain due to a musculoskeletal cause were more likely to use analgesic medications than those with pain due to all other causes (OR=3.2, 95% CI=1.6-6.4), whereas those with trauma-related pain were less likely to use exercise than those with pain due to all other causes (OR=0.2, 95% CI=0.1-0.7). CONCLUSION: Older primary care patients use a broad variety of coping strategies to cope with chronic pain. Studies are needed to confirm these findings in other older populations and to characterize the longitudinal effects of the coping strategies. Given the finding that the perceived effectiveness of most coping strategies was modest, efforts to increase their effectiveness in older persons are indicated.

The deleterious effects of bed rest among community-living older persons.

BACKGROUND: Older persons often "take to bed" while they are ill or injured, but relatively little is known about the functional consequences of bed rest among community-living older persons. In this prospective cohort study, the association between episodes of bed rest and functional decline was evaluated during an 18-month period. METHODS: Participants included 680 nondisabled, community-living persons aged 70 years or older. They were separated into 2 groups according to the presence or absence of physical frailty, which was defined based on slow gait speed. Episodes of bed rest were ascertained each month in a telephone interview for a median of 18 months. The completion rate was 99.1%. Functional decline was defined as a worsening in scores between the baseline and 18-month follow-up assessments in 1 or more of the following measures: instrumental activities of daily living, mobility, physical activity, and social activity. RESULTS: Among the 404 (59.4%) participants who had at least 1 episode of bed rest, the mean number of months with bed rest was 2.8 (standard deviation, 2.4). After adjustments were made for several potential confounders, the number of months with bed rest was significantly associated with decline in each of the functional measures. Significant associations were also observed for each of the functional outcomes among participants who were not physically frail, but they were observed only for instrumental activities of daily living disability among participants who were physically frail. CONCLUSIONS: These findings indicate that episodes of bed rest among community-living older persons are associated with decline in several important indicators of function.