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].

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.

Diagnoses associated with use of atypical antipsychotics in a commercial health plan: a claims database analysis.

BACKGROUND: Atypical antipsychotics are indicated for specific psychiatric conditions; however, they are frequently used for US Food and Drug Administration-nonapproved indications. OBJECTIVE: This study assessed the types of medical diagnoses associated with atypical antipsychotic prescriptions in commercial health care plans. METHODS: This retrospective cohort study used the OptumInsight commercial data set from January 2008 to June 2011. The index date was defined as the earliest date of prescription for the atypical antipsychotics aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009, through June 30, 2010. Medical claims during a 2-year period (12 months before and 12 months after the index date) were used to identify relevant diagnostic codes from the International Classification of Diseases, Ninth Edition, Clinical Modification associated with the antipsychotic prescription. A logistic regression analysis was conducted to examine the predictors of use of atypical antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or major depressive disorder (MDD). RESULTS: Of 18,352 patients included in the analysis, 3593 (19.5%) who filled a prescription for atypical antipsychotics did not have an approved diagnosis. Off-label utilization varied, with approximately a quarter of patients with prescriptions for quetiapine (24.1%), risperidone (23.1%), or olanzapine (21.8%) being without a relevant diagnostic code, whereas proportions were lower for patients prescribed aripiprazole (14.0%) or ziprasidone (13.1%). Of those with a psychiatric disorder other than schizophrenia, bipolar disorder, or MDD, approximately a third of prescriptions were for anxiety disorders, with similar proportions across all atypical antipsychotics. Patients were often prescribed quetiapine for substance abuse (22.7%), whereas patients with "other psychiatric conditions" were prescribed risperidone (26.3%) or ziprasidone (25.0%). The logistic regression analysis indicated that patients prescribed olanzapine, quetiapine, or risperidone were significantly more likely to have no diagnostic code for schizophrenia, bipolar disorder, or MDD compared with patients prescribed aripiprazole. CONCLUSION: Nearly a fifth of commercially insured patients were prescribed atypical antipsychotics, in particular, olanzapine, quetiapine, or risperidone, for diagnoses that were not aligned with US Food and Drug Administration-approved indications.

Screening for predementia AD: time-dependent operating characteristics of episodic memory tests.

OBJECTIVE: Data from the Einstein Aging Study (EAS) were used to prospectively evaluate the free recall score from the free and cued selective reminding test (FCSRT-FR) and logical memory I immediate recall (LM-IR) subtest of the Wechsler memory scale-revised for prediction of incident Alzheimer disease (AD) dementia among individuals from a community-based cohort with memory complaints. METHODS: Analyses included 854 participants, age ≥70 years, who initially had no dementia, and had memory complaints. Clinic evaluations were completed annually and AD dementia was diagnosed using standard criteria (n = 86 cases; average follow-up 4.1 years). Time-dependent receiver operating characteristic analysis was used to evaluate the prognostic ability of FCSRT-FR and LM-IR for incident AD over various durations of follow-up. RESULTS: For identifying those with memory complaints who will develop incident AD dementia over 2-4 years, the FCSRT-FR had better operating characteristics than LM-IR. APOE ε4 status, age, and education did not affect cut points; however, positive predictive values were higher among APOE ε4-positive individuals. CONCLUSIONS: For follow-up intervals of 2-4 years, the FCSRT-FR is more predictive than the LM-IR for identifying individuals with memory complaints who will develop incident AD. APOE ε4 status improves positive predictive value, but does not affect the choice of optimal cuts.

Dosing patterns of aripiprazole and quetiapine for adjunctive treatment of major depressive disorder (2006-2010).

The aim of this study was to investigate the dosing patterns of adjunctive quetiapine or adjunctive aripiprazole in the treatment of major depressive disorder from 2006 to 2010, and to evaluate the impact of Food and Drug Administration (FDA) approval on these dosing patterns. Patients included in the study were adults diagnosed with major depressive disorder, and treated with adjunctive aripiprazole or quetiapine between the years 2006 and 2010. The average daily dose and dose distribution were calculated and assessed statistically over the same time period. The mean daily dose for patients treated with adjunctive aripiprazole decreased from 13.5 mg/day in 2006 to 6.9 mg/day in 2010, whereas the mean daily dose for patients treated with quetiapine increased from 129 mg/day in 2006 to 139 mg/day in 2007, decreasing to 123 mg/day in 2010. The proportion of patients receiving FDA-recommended doses increased significantly for aripiprazole (86.3% in 2006 to 94.5% in 2010; P<0.001) and remained relatively stable for quetiapine (21.3% in 2006 to 24.0% in 2010; NS). The majority of patients treated with quetiapine received doses below those recommended by the FDA throughout the study period. Aripiprazole was mostly prescribed at therapeutic doses (pre-FDA and post-FDA approval), although the mean dose decreased significantly over time.

Incidence of urinary tract infection among patients with type 2 diabetes in the UK General Practice Research Database (GPRD).

The objective of this observational study was to quantify the incidence of urinary tract infections (UTI) among diabetes patients and compare this risk to patients without diabetes. Type 2 diabetes patients and a matched sample of patients without diabetes were identified from GPRD. Patients were followed for 1-year from their study index date until the first record of a UTI or a censored event. The incidence of UTI was 46.9 per 1000 person-years (95% confidence interval (CI) 45.8-48.1) among diabetes patients and 29.9 (95% CI 28.9-30.8) for patients without diabetes. Compared to the non-diabetes patients, the risk of UTI was 1.53 (95% CI 1.46-1.59) for all diabetes patients; and 2.08 (95% CI 1.93-2.24) for patients with previously diagnosed diabetes. In general practice, across gender and age, the risk of developing a UTI is higher for patients with type 2 diabetes compared to patients without diabetes.

Incidence of genital infection among patients with type 2 diabetes in the UK General Practice Research Database.

The objective of this population-based study was to evaluate the incidence of vaginitis (females) and balanitis (males) among a cohort of type 2 diabetes patients and compare this risk to patients without diabetes. The study population included 125,237 female patients and 146,603 males identified from GPRD. All patients were followed for 1-year from their study index date for the first record of an infection or a censored event. Among patients with diabetes the incidence of vaginitis was 21.0/1000PY (95% CI 19.8-22.1) with the risk being 1.81 (95% CI 1.64-2.00) greater that patients without diabetes. The incidence of balanitis among diabetes patients was 8.4/1000PY (95% CI 7.8-9.1) with a relative risk of 2.85 (2.39-3.39) compared to patients without diabetes. Additional analyses were performed by HbA1c level. Results from this large population-based study indicate that patients with diabetes are at an increased risk of being diagnosed with infections of the genital tract and patients with poorly controlled diabetes have higher risks.

Trends in combination antipsychotic use among persons with commercial insurance: a data snapshot.

In this data snapshot, the IMS PharMetrics Database was examined to assess the prevalence of combination antipsychotic therapy for the years 2003 through 2009 among 122,349 commercially insured adult individuals with bipolar disorder, depression, or schizophrenia. Although all three diagnostic groups were associated with varying amounts of combination antipsychotic use that included aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone, persons with schizophrenia exhibited the highest rates. These findings indicate that from the perspective of "practice-based evidence," providers see value in combination therapy.

Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials.

BACKGROUND: There are limited published data on the impact of treatment on the health-related quality of life (HRQOL) in individuals with autistic disorder. OBJECTIVE: The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder. METHODS: This post hoc analysis assessed data from two 8-week, double-blind, randomized, placebo-controlled studies that compared the efficacy of aripiprazole (fixed-dose study, 5, 10, and 15 mg/d; flexible-dose study, 2-15 mg/d) with placebo in the treatment of irritability associated with autistic disorder. HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory (PedsQL™) scales. Clinically relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 standard error of measurement. RESULTS: In total, 316 patients were randomly assigned to receive treatment with aripiprazole (fixed-dose study, 166; flexible-dose study, 47) or placebo (fixed-dose study, 52; flexible-dose study, 51). Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score (difference, 7.8; 95% CI, 3.8-11.8; P < 0.001) and in 3 PedsQL scale scores (differences [95% CI]: Emotional Functioning, 7.8 [3.4-12.2]; Social Functioning, 6.2 [0.7-11.8]; Cognitive Functioning, 9.3 [3.8-14.9]; all, P < 0.05). Patients who received aripiprazole were significantly more likely than those who received placebo to have a clinically meaningful improvement on the combined-scales total score (odds ratio [OR] = 1.9; 95% CI, 1.0-3.3; P < 0.05), Emotional Functioning scale (OR = 2.2; 95% CI, 1.2-4.0; P < 0.05) and Social Functioning scale (OR = 2.2; 95% CI, 1.2-4.1; P < 0.05), and were significantly less likely to experience deterioration (OR: 0.3, 95% CI: 0.1-0.8; P < 0.05) when "Stable" was used as the reference group. CONCLUSIONS: The findings from the present post hoc analysis suggest that aripiprazole was associated with improved HRQOL, as assessed using 3 PedsQL scales, in pediatric patients with irritability associated with autistic disorder.

Impact of early intervention and disease modification in patients with predementia Alzheimer's disease: a Markov model simulation.

BACKGROUND: Early screenings involving biomarkers and use of potential disease-modifying therapies (DMTs) may have significant humanistic implications for treatment strategies in Alzheimer's disease. METHODS: Markov models simulated transitions of patient cohorts beginning in predementia, a hypothetical early stage of Alzheimer's disease marked by objective cognitive impairment/memory complaints without functional impairment, and followed for 10 years. Hypothetical cohorts of 10,000 patients included those who were treated with standard of care (donepezil) upon reaching mild-moderate Alzheimer's disease, a DMT in predementia, and a DMT in mild-moderate Alzheimer's disease. Transition probabilities were based on data from the Alzheimer's Disease Neuroimaging Initiative and published clinical data, and estimated for the hypothetical DMT. In each disease stage (predementia, mild, moderate, or severe), time was computed and costs were estimated using literature review and published data, and published data provided mortality rates. The impact of screening was evaluated using positive predictive value (patients identified as predementia truly at risk for transition to dementia). RESULTS: Earlier treatment yielded modest gains in total life-years; however, the distribution was skewed towards milder disease. Assuming a 25% reduction in the annual risk of progression, treating predementia patients with DMT increased life-years in predementia to mild states on average from 3.2 to 4.2, while life-years spent in moderate-to-severe Alzheimer's disease decreased from 2.6 to 2.2. Average time in the community increased from 4.4 to 5.4 years, while time in long-term care declined from 1.3 to 0.9 years. This impact grows as the advantage of the novel agent increases. Screening accuracy had significant implications for cost-effectiveness. CONCLUSION: If screening can accurately identify predementia patients at risk for progression, earlier treatment with DMTs has the potential benefit to patients of prolonging time in milder disease, reducing time spent with more severe disease, increasing time in the community, and reducing time in long-term care.

Incidence of serious upper and lower gastrointestinal events in older adults with and without Alzheimer's disease.

OBJECTIVES: To estimate and compare the incidence of serious upper and lower gastrointestinal (GI) events in individuals aged 65 and older with and without Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: PharMetrics, a large population-based health insurance claims database was used for the study. PARTICIPANTS: Individuals aged 65 and older with a diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification Code 331.0) were identified between January 1, 2003, and December 31, 2006, using the PharMetrics database. The control cohort consisted of a random sample of health plan enrollees matched to the AD cohort according to age, sex, location, and index year in a 1:1 ratio. MEASURES: The outcomes of interest were serious GI events, including ulceration, perforation, and bleeding in the upper or lower GI tract. RESULTS: Twenty-seven thousand seventy-six individuals with AD were identified. Approximately 66% of them were age 80 and older, and 65% were female. Participants with AD had higher incidence of serious GI events (upper GI: AD vs non-AD: 27.4 vs 17.1/1000 person-years, HR = 1.49, 95%CI = 1.34-1.65; lower GI: AD vs non-AD: 9.4 vs 6.9/1000 person-years, HR = 1.26, 95%CI = 1.06-1.48). The association was also present in participants without a history of GI bleeding (upper GI: HR = 1.54, 95%CI = 1.37-1.73; lower GI: HR = 1.37, 95%CI = 1.14-1.64). CONCLUSION: Participants with AD had higher incidence of serious upper and lower GI events, compared to those without AD. Physicians should recognize the high risk of serious GI events that exists in individuals with AD.

A real-world data analysis of dose effect of second-generation antipsychotic therapy on hemoglobin A1C level.

Previous studies have demonstrated an association between certain second-generation antipsychotics (SGAs) and diabetes mellitus. The study assessed the impact of SGA dose on hemoglobin A1C (HbA(1c) >6.0) levels in a real-world setting. Patients aged ≥ 18 years during 2002-2006 in Ingenix LabRx claims database were included. The database collects medical and prescription claims and a subset of laboratory results for an employed, commercially insured population distributed throughout the United States. Patients with previously diagnosed diabetes, identified by the ICD-9-CM code of 250.x or use of antidiabetic agents, were excluded. The main exposure measure was the cumulative dose over a 30 day period before the HbA(1c) test, calculated as [sum of (number of pills per day×strength)]/100. A logistic regression was used to examine the relation with HbA(1c) >6.0 by tertile of the cumulative dose and average daily dose, adjusted for the covariates. The study included 391 patients on olanzapine, 467 on quetiapine, and 262 on risperidone. Patients treated with aripiprazole or ziprasidone (n=212) were included as a secondary reference because of their minimal metabolic risk. Compared to lower (Tertiles 1 and 2) cumulative doses of risperidone, patients with a high cumulative dose of risperidone (Tertile 3) had a significantly higher odds ratio (OR) for HbA(1c) >6.0 (adjusted OR=2.45; 95% confidence interval=1.13-5.32; P=0.023). A similar increase in OR was seen in patients with high cumulative dose of olanzapine (2.41; 1.19-4.89; P=0.015). Analyses of average daily dose revealed that quetiapine ≥ 400 mg/day and risperidone ≥ 2 mg/day had an OR of 2.29 (1.04-5.06; P=0.041) and 2.28 (1.08-4.83; P=0.032), respectively, compared to aripiprazole/ziprasidone. Both olanzapine groups (≥ 10 and <10mg/day) were associated with a significantly increased OR. All results remained similar after further adjustment for the predicated probability of having an HbA(1c) test and additional medication covariates. In this claims data study, use of olanzapine was associated with elevated HbA(1c) and risperidone and quetiapine appeared to have dose-related association with elevated HbA(1c). One of the limitations of a claims data analysis is the lack of information on potential confounders such as ethnicity and weight.

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

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.

Remission, response without remission, and nonresponse in major depressive disorder: impact on functioning.

Major depressive disorder (MDD) is associated with significant functional impairment. This post-hoc analysis of data from two randomized trials assessed the impact of response status on functioning in MDD. Patients with at least one historical treatment failure followed by an inadequate response after 8 weeks of prospective open-label treatment with escitalopram, fluoxetine, paroxetine-CR, sertraline, or venlafaxine-XR plus single-blind placebo were randomized to 6 weeks of double-blind treatment with adjunctive placebo or adjunctive aripiprazole. At the end of double-blind treatment, patients were defined as: in remission [>or=50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score with MADRS or=50% reduction in MADRS with MADRS >10); or with a nonresponse (all others). Functional status was assessed with the Sheehan Disability Scale. Of the 679 patients, 144 were in remission, 44 had a response without remission, and 491 had a nonresponse. Mean improvements in the Sheehan Disability Scale total and item scores were significantly greater in patients in remission versus those with a response without remission (P<0.02) as well as nonresponse (P<0.001). Structural Equation Modeling found that efficacy (Hamilton Rating Scale for Depression scores) did not significantly correlate with functioning in this study. In conclusion, MDD patients achieving symptomatic remission experience greater functional improvements than those respond without remission. Functioning may be a distinctly different outcome from symptom reduction. Treatments focused on producing high remission rates may improve patient functioning over and above that seen with patients who only achieve response.

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.

Higher burden of depression among older women: the effect of onset, persistence, and mortality over time.

CONTEXT: The prevalence of depression is disproportionately higher in older women than men, yet the reasons for this sex difference are not clear. OBJECTIVE: To determine whether the higher burden of depression among older women than men might be attributable to sex differences in the onset (ie, first or recurrent episodes) or persistence of depression and/or to differential mortality among those who are depressed. DESIGN: Prospective cohort study. SETTING: General community in greater New Haven, Connecticut, from March 23, 1998, to August 31, 2005. PARTICIPANTS: A total of 754 persons, 70 years or older, who were evaluated at 18-month intervals for 72 months. MAIN OUTCOME MEASURES: The 3 outcome states were depressed, nondepressed, and death, with scores of 20 or more and less than 20 on the Center for Epidemiological Studies Depression Scale denoting depressed and nondepressed, respectively. The association between sex and the likelihood of 6 possible transitions (namely, from nondepressed or depressed to nondepressed, depressed, or death) was evaluated over time. RESULTS: The prevalence of depression was substantially higher among women than men at each of the 5 time points (P < .001). In most cases, transitions between the nondepressed and depressed states were characterized by moderate to large absolute changes in depression scores (ie, > or = 10 points). Adjusting for other demographic characteristics, women had a higher likelihood of transitioning from nondepressed to depressed (odds ratio, 2.02; 95% confidence interval, 1.39-2.94) and a lower likelihood of transitioning from depressed to nondepressed (odds ratio, 0.27; 95% confidence interval, 0.13-0.56) or death (odds ratio, 0.24; 95% confidence interval, 0.09-0.60). CONCLUSION: Among older persons, the higher burden of depression in women than men seems to be attributable to a greater susceptibility to depression and, once depressed, to more persistent depression and a lower probability of death.

Subtypes of disability in older persons over the course of nearly 8 years.

OBJECTIVES: To characterize distinct and clinically meaningful subtypes of disability, defined based on the number and duration of disability episodes, and to determine whether the incidence of these disability subtypes differ according to age, sex, or physical frailty. DESIGN: Prospective cohort study. SETTING: Greater New Haven, Connecticut. PARTICIPANTS: Seven hundred fifty-four community-living residents aged 70 and older and initially nondisabled in four essential activities of daily living. MEASUREMENTS: Disability was assessed during monthly telephone interviews for nearly 8 years; physical frailty was assessed during comprehensive home-based assessments at 18-month intervals. The incidence of five disability subtypes was determined within the context of the 18-month intervals in participants who were nondisabled at the start of the interval: transient, short-term, long-term, recurrent, and unstable. RESULTS: Incident disability was observed in 29.8% of the 18-month intervals. The most common subtypes were transient disability (9.7% of all intervals), defined as a single disability episode lasting only 1 month, and long-term disability (6.9%), defined as one or more disability episodes, with at least one lasting 6 or more months. Approximately one-quarter (24.7%) of all participants had two or more intervals with an incident disability subtype. Although there were no sex differences in the incidence rates for any of the subtypes, differences in rates were observed for each subtype according to age and physical frailty, with only one exception, and were especially large for long-term disability. CONCLUSION: The mechanisms underlying the different disability subtypes may differ. Additional research is warranted to evaluate the natural history, risk factors, and prognosis of the five disability subtypes.