Effect of Cranberry Capsules on Bacteriuria Plus Pyuria Among Older Women in Nursing Homes: A Randomized Clinical Trial.

Importance: Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective: To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015). Interventions: Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants. Main Outcomes and Measures: Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration. Results: Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25). Conclusions and Relevance: Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year. Trial Registration: clinicaltrials.gov Identifier: NCT01691430.

Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults.

We evaluated in vivo innate immune responses in monocyte populations from 67 young (aged 21-30 years) and older (aged ≥65 years) adults before and after influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after vaccination in both young and older adults. In classical CD14(+)CD16(-) and inflammatory monocytes, production of tumor necrosis factor α and interleukin 6, as measured by intracellular staining, was strongly induced after vaccination. Cytokine production was strongly associated with influenza vaccine antibody response; the highest levels were found as late as day 28 after vaccination in young subjects and were substantially diminished in older subjects. Notably, levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly elevated in monocytes from older subjects before and after vaccination. In purified monocytes, we found age-associated elevation in phosphorylated signal transducer and activator of transcription-3, and decreased serine 359 phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1. These findings for the first time implicate dysregulated IL-10 production in impaired vaccine responses in older adults.

Associations between provider designation and female-specific cancer screening in women Veterans.

BACKGROUND: In 2010, the Department of Veterans Affairs Healthcare System (VA) implemented policy to provide Comprehensive Primary Care (for acute, chronic, and female-specific care) from designated Women's Health providers (DWHPs) at all VA sites. However, since that time no comparisons of quality measures have been available to assess the level of care for women Veterans assigned to these providers. OBJECTIVES: To evaluate the associations between cervical and breast cancer screening rates among age-appropriate women Veterans and designation of primary-care provider (DWHP vs. non-DWHP). RESEARCH DESIGN: Cross-sectional analyses using the fiscal year 2012 data on VA women's health providers, administrative files, and patient-specific quality measures. SUBJECTS: The sample included 37,128 women Veterans aged 21 through 69 years. MEASURES: Variables included patient demographic and clinical factors (ie, age, race, ethnicity, mental health diagnoses, obesity, and site), and provider factors (ie, DWHP status, sex, and panel size). Screening measures were defined by age-appropriate subgroups using VA national guidelines. RESULTS: Female-specific cancer screening rates were higher among patients assigned to DWHPs (cervical cytology 94.4% vs. 91.9%, P<0.0001; mammography 86.3% vs. 83.3%, P<0.0001). In multivariable models with adjustment for patient and provider characteristics, patients assigned to DWHPs had higher odds of cervical cancer screening (odds ratio, 1.26; 95% confidence interval, 1.07-1.47; P<0.0001) and breast cancer screening (odds ratio, 1.24; 95% CI, 1.10-1.39; P<0.0001). CONCLUSIONS: As the proportion of women Veterans increases, assignment to DWHPs may raise rate of female-specific cancer screening within VA. Separate evaluation of sex neutral measures is needed to determine whether other measures accrue benefits for patients with DWHPs.

Baseline cluster membership demonstrates positive associations with first occurrence of multiple gerontologic outcomes over 10 years.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The potential of cluster analysis (CA) as a baseline predictor of multivariate gerontologic outcomes over a long period of time has not been previously demonstrated. METHODS: Restricting candidate variables to a small group of established predictors of deleterious gerontologic outcomes, various CA methods were applied to baseline values from 754 nondisabled, community-living persons, aged 70 years or older. The best cluster solution yielded at baseline was subsequently used as a fixed explanatory variable in time-to-event models of the first occurrence of the following outcomes: any disability in four activities of daily living, any disability in four mobility measures, and death. Each outcome was recorded through a maximum of 129 months or death. Associations between baseline ordinal cluster level and first occurrence of all three outcomes were modeled over a 10-year period with proportional hazards regression and compared with the associations yielded by the analogous latent class analysis (LCA) solution. RESULTS: The final cluster-defining variables were continuous measures of cognitive status and depressive symptoms, and dichotomous indicators of slow gait and exhaustion. The best solution yielded by baseline values of these variables was obtained with a K-means algorithm and cosine similarity and consisted of three clusters representing increasing levels of impairment. After adjustment for age, sex, ethnic group, and number of chronic conditions, baseline ordinal cluster level demonstrated significantly positive associations with all three outcomes over a 10-year period that were equivalent to those from the corresponding LCA solution. CONCLUSION: These findings suggest that baseline clusters based on previously established explanatory variables have potential to predict multivariate gerontologic outcomes over a long period of time.

The hypnotic induction profile and absorption.

This study examined the relationship between scores on the Hypnotic Induction Profile (HIP) and the trait of absorption in three different clinical groups: Smokers (n = 226), Phobics (n = 95), and patients with Chronic Pain (n = 65). Two hypotheses were investigated. The first predicted that both the Eye-Roll sign (ERS) and Induction Score (IND) of the HIP would correlate similarly (r = .30) with scores on the Tellegen Absorption Scale (TAS), as has been previously reported with other measures of hypnotic responsivity in student samples. The second was that using a combination of both ERS and IND scores to predict TAS scores would result in a significant increase in forecasting accuracy over using either HIP measure alone. Both hypotheses were supported in all three clinical groups. Correlations between HIP and Absorption scores ranged from .33 to .53. Clinical and theoretical implications of the findings are discussed.

Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease.

The pathogenesis of chronic obstructive pulmonary disease (COPD) remains poorly understood. Cellular senescence and apoptosis contribute to the development of COPD; however, crucial regulators of these underlying mechanisms remain unknown. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that antagonizes both apoptosis and premature senescence and may be important in the pathogenesis of COPD. This study examines the role of MIF in the pathogenesis of COPD. Mice deficient in MIF (Mif(-/-)) or the MIF receptor CD74 (Cd74(-/-)) and wild-type (WT) controls were aged for 6 mo. Both Mif(-/-) and Cd74(-/-) mice developed spontaneous emphysema by 6 mo of age compared with WT mice as measured by lung volume and chord length. This was associated with activation of the senescent pathway markers p53/21 and p16. Following exposure to cigarette smoke, Mif(-/-) mice were more susceptible to the development of COPD and apoptosis compared with WT mice. MIF plasma concentrations were measured in a cohort of 224 human participants. Within a subgroup of older current and former smokers (n = 72), MIF concentrations were significantly lower in those with COPD [8.8, 95%CI (6.7-11.0)] compared with those who did not exhibit COPD [12.7 ng/ml, 95%CI (10.6-14.8)]. Our results suggest that both MIF and the MIF receptor CD74 are required for maintenance of normal alveolar structure in mice and that decreases in MIF are associated with COPD in human subjects.

MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis-induced lung injury.

Sepsis is a systemic inflammatory response to infection and a major cause of death worldwide. Because specific therapies to treat sepsis are limited, and underlying pathogenesis is unclear, current medical care remains purely supportive. Therefore targeted therapies to treat sepsis need to be developed. Although an important mediator of sepsis is thought to be mitochondrial dysfunction, the underlying molecular mechanism is unclear. Modulation of mitochondrial processes may be an effective therapeutic strategy in sepsis. Here, we investigated the role of the kinase MKK3 in regulation of mitochondrial function in sepsis. Using clinically relevant animal models, we examined mitochondrial function in primary mouse lung endothelial cells exposed to LPS. MKK3 deficiency reduces lethality of sepsis in mice and by lowering levels of lung and mitochondrial injury as well as reactive oxygen species. Furthermore, MKK3 deficiency appeared to simultaneously increase mitochondrial biogenesis and mitophagy through the actions of Sirt1, Pink1, and Parkin. This led to a more robust mitochondrial network, which we propose provides protection against sepsis. We also detected higher MKK3 activation in isolated peripheral blood mononuclear cells from septic patients compared with nonseptic controls. Our findings demonstrate a critical role for mitochondria in the pathogenesis of sepsis that involves a previously unrecognized function of MKK3 in mitochondrial quality control. This mitochondrial pathway may help reveal new diagnostic markers and therapeutic targets against sepsis.

Comparing modalities of opioid education in patients undergoing total knee arthroplasty: a randomized pilot trial.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) experience significant postoperative pain and routinely require opioids, yet they often lack knowledge regarding appropriate use and handling of these medications. Evidence suggests that educational interventions in various formats may help reinforce proper usage and improve postoperative pain control. The aim of this study is to compare the institution standard of care (webinar) with two novel educational interventions-one in-person and the other a video recording-that focus specifically on the use of opioids and pain control. METHODS: This prospective, randomized pilot study included 42 patients undergoing TKA. Patients were randomized into one of three groups: (1) webinar: 50 min virtual session standard of care at Hospital for Special Surgery (HSS), (2) in-person education, or (3) video education. The primary outcomes of this study were the number of opioid refill requests through postoperative day (POD) 30 and POD 60. The secondary outcomes evaluated Numerical Rating Scale (NRS) pain scores, opioid consumption in oral morphine equivalents (OME), surveys on medication usage and opioid knowledge, reported medication storage and disposal. We hypothesize that the novel educational interventions, presented either in-person or by video, will lead to a decrease in opioid refills within 60 days compared with current education delivered through virtual webinar. RESULTS: No significant differences were found among groups in the number of opioid refill requests, average NRS pain score, or OME consumption at any time point. Opioid refill requests ranged from 0% to 16.7% at POD 30 (Fisher's exact test, p=0.625) and from 0% to 8.3% at POD 60 (p=1.000). The median opioid refill request was zero requests per group from POD 21 to 60 (webinar 0 (0.0, 0.0), in-person 0 (0.0, 0.0), video 0 (0.0, 0.0), Kruskal-Wallis test, p=0.381). Average NRS pain scores were 5 or below for all groups on POD 1, 7 and 14. By POD 7, all groups had an average daily intake OME of 14 or below. CONCLUSIONS: Overall, patients in each group did well with postoperative pain management after TKA and had minimal opioid refill requests. There were no statistically significant differences in outcomes of NRS pain scores or opioid usage among groups suggesting that educational interventions were similarly effective. As a pilot trial, study demonstrated successful recruitment and retention of participants, and important feedback was elicited from patients regarding education, as well. Of note, this was a pilot study and was likely underpowered to detect a difference. TRIAL REGISTRATION NUMBER: NCT05593341.

Analgesic prescribing trends in a national sample of older veterans with osteoarthritis: 2012-2017.

Few investigations examine patterns of opioid and nonopioid analgesic prescribing and concurrent pain intensity ratings before and after institution of safer prescribing programs such as the October 2013 Veterans Health Administration system-wide Opioid Safety Initiative (OSI) implementation. We conducted a quasi-experimental pre-post observational study of all older U.S. veterans (≥50 years old) with osteoarthritis of the knee or hip. All associated outpatient analgesic prescriptions and outpatient pain intensity ratings from January 1, 2012 to December 31, 2016, were analyzed with segmented regression of interrupted time series. Standardized monthly rates for each analgesic class (total, opioid, nonsteroidal anti-inflammatory drug, acetaminophen, and other study analgesics) were analyzed with segmented negative binomial regression models with overall slope, step, and slope change. Similarly, segmented linear regression was used to analyze pain intensity ratings and percentage of those reporting pain. All models were additionally adjusted for age, sex, and race. Before OSI implementation, total analgesic prescriptions showed a steady rise, abruptly decreasing to a flat trajectory after OSI implementation. This trend was primarily due to a decrease in opioid prescribing after OSI. Total prescribing after OSI implementation was partially compensated by continuing increased prescribing of other study analgesics as well as a significant rise in acetaminophen prescriptions (post-OSI). No changes in nonsteroidal anti-inflammatory drug prescribing were seen. A small rise in the percentage of those reporting pain but not mean pain intensity ratings continued over the study period with no changes associated with OSI. Changes in analgesic prescribing trends were not paralleled by changes in reported pain intensity for older veterans with osteoarthritis.

Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial.

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age.

Serious adverse events of older adults in nursing home and community intervention trials.

BACKGROUND/AIMS: Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based. METHODS: We performed a secondary data analysis from two randomized clinical trials at one academic health center and 21 nursing homes involving 200 sedentary community dwellers aged 70-89 years and 185 female nursing home residents aged 65 years or older. Interventions included structured physical activity to reduce mobility disability in the Lifestyle Interventions and Independence for Elders (LIFE) study and oral cranberry capsules to reduce bacteriuria plus pyuria in nursing home residents (CRANNY) trial. We measured SAE incidence per 100 person-years and incidence of protocol-related unanticipated SAE per 100 person-years in LIFE and CRANNY trials. RESULTS: Mean age and proportion of patients with dementia in LIFE and CRANNY trials were 79.3 years and 86.4 years and 0% and 78%, respectively. There were 179 total SAE in LIFE including 8 (4%) deaths, and 116 total SAE in CRANNY including 33 (28%) deaths. SAE incidence was 33.7 (95% CI 27.2, 41.8) events per 100 person-years in LIFE and 69.4 (95% CI 49.1, 98.1) events per 100 person-years in CRANNY. No protocol-related unanticipated SAE occurred in either trial. CONCLUSIONS: The frequency and severity of SAE vary in older adults. While SAE are common in nursing home residents, protocol-related, unanticipated SAE are rare in nursing home residents and community dwellers. This finding can inform trial monitoring protocols. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT01072500 and NCT01691430.

Long-Term Clinical Outcomes in Diabetic Rhesus Macaques (Macaca mulatta) Treated with Medroxyprogesterone Acetate for Endometriosis.

Depot medroxyprogesterone acetate (DMPA) is a common medical treatment for endometriosis in NHP. Because DMPA reportedly impairs glucoregulatory function in humans and rhesus macaques, as well as predisposes humans to diabetes mellitus (DM), we performed a retrospective study to further investigate its potential long-term clinical effects in animals with and without DM. Using a cohort of 29 rhesus macaques, we explored the hypotheses that DMPA treatment accelerates the onset of DM and that its use in rhesus macaques with endometriosis worsens clinical outcome measures (lifespan, body weight and body condition score). For both body weight and body condition score, a declining and statistically significant trend in mean values was evident as macaques developed either DM, or endometriosis or both. The addition of DMPA did not significantly alter this pattern. The presence of DM, endometriosis, or DMPA treatment statistically but not clinically significantly increased risk of death. Similarly, the presence of the 2 highly correlated variables endometriosis and DMPA treatment statistically but not clinically significantly increased the risk of incident DM. These results indicate that DMPA treatment was associated with worsening trends in lifespan and incident DM, however these trends did not achieve clinical significance in this cohort.

Coordinated expression of tyro3, axl, and mer receptors in macrophage ontogeny.

The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor-tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream pathways and restore homeostasis. TAM triple mutant mice (Tyro3-/-, Axl-/-, Mer-/-) have elevated levels of pro-inflammatory cytokines and are prone to developing lymphoproliferative disorders and autoimmunity. Understanding differential expression of TAM receptors among human subjects is critical to harnessing this pathway for therapeutic interventions. We have quantified changes in TAM expression during the ontogeny of human macrophages using paired samples of monocytes and macrophages to take advantage of characteristic expression within an individual. No significant differences in levels of Tyro3 were found between monocytes and macrophages (flow cytometry: p=0.652, immunoblot: p=0.231, qPCR: p=0.389). Protein levels of Axl were reduced (flow cytometry: p=0.049, immunoblot: p<0.001) when monocytes matured to macrophages. No significant differences in the levels of Axl mRNA transcripts were found (qPCR: p=0.082), however, Tyro3 and Axl were proportionate. The most striking difference was upregulation of expression of Mer with both protein and mRNA being significantly increased when monocytes developed into macrophages (flow cytometry: p<0.001, immunoblot: p<0.001, qPCR: p=0.004). A fuller characterization of TAM receptor expression in macrophage ontogeny informs our understanding of their function and potential therapeutic interventions.

Methodology to Estimate the Longitudinal Average Attributable Fraction of Guideline-recommended Medications for Death in Older Adults With Multiple Chronic Conditions.

BACKGROUND: Persons with multiple chronic conditions receive multiple guideline-recommended medications to improve outcomes such as mortality. Our objective was to estimate the longitudinal average attributable fraction for 3-year survival of medications for cardiovascular conditions in persons with multiple chronic conditions and to determine whether heterogeneity occurred by age. METHODS: Medicare Current Beneficiary Survey participants (N = 8,578) with two or more chronic conditions, enrolled from 2005 to 2009 with follow-up through 2011, were analyzed. We calculated the longitudinal extension of the average attributable fraction for oral medications (beta blockers, renin-angiotensin system blockers, and thiazide diuretics) indicated for cardiovascular conditions (atrial fibrillation, coronary artery disease, heart failure, and hypertension), on survival adjusted for 18 participant characteristics. Models stratified by age (≤80 and >80 years) were analyzed to determine heterogeneity of both cardiovascular conditions and medications. RESULTS: Heart failure had the greatest average attributable fraction (39%) for mortality. The fractional contributions of beta blockers, renin-angiotensin system blockers, and thiazides to improve survival were 10.4%, 9.3%, and 7.2% respectively. In age-stratified models, of these medications thiazides had a significant contribution to survival only for those aged 80 years or younger. The effects of the remaining medications were similar in both age strata. CONCLUSIONS: Most cardiovascular medications were attributed independently to survival. The two cardiovascular conditions contributing independently to death were heart failure and atrial fibrillation. The medication effects were similar by age except for thiazides that had a significant contribution to survival in persons younger than 80 years.

Patient Perception of Enough Time Spent With Provider Is a Mechanism for Improving Women Veterans' Experiences With VA Outpatient Health Care.

We postulated that associations between two specific provider characteristics, class (nurse practitioner relative to physician) and primary care providers who are proficient and interested in women's health (designated women's provider relative to nondesignated) and overall satisfaction with provider, were mediated through women veterans' perception of enough time spent with the provider. A national patient experience survey was administered to 7,620 women veterans. Multivariable models of overall patient satisfaction with provider were compared with and without the proposed mediator. A structural equation model (SEM) of the mediation of the two provider characteristics was also evaluated. Without the mediator, associations of provider class and designation with overall patient satisfaction were significant. With the proposed mediator, these associations became nonsignificant. An SEM showed that the majority (>80%) of the positive associations between provider class and designation and the outcome were exerted through patient perception of enough time spent with provider. Higher ratings of overall satisfaction with provider exhibited by nurse practitioners and designated women's health providers were exerted through patient perception of enough time spent with provider. Future research should examine what elements of provider training can be developed to improve provider-patient communication and patient satisfaction with their health care.

Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease.

Influenza A virus (IAV) causes up to half a million deaths worldwide annually, 90% of which occur in older adults. We show that IAV-infected monocytes from older humans have impaired antiviral interferon production but retain intact inflammasome responses. To understand the in vivo consequence, we used mice expressing a functional Mx gene encoding a major interferon-induced effector against IAV in humans. In Mx1-intact mice with weakened resistance due to deficiencies in Mavs and Tlr7, we found an elevated respiratory bacterial burden. Notably, mortality in the absence of Mavs and Tlr7 was independent of viral load or MyD88-dependent signaling but dependent on bacterial burden, caspase-1/11, and neutrophil-dependent tissue damage. Therefore, in the context of weakened antiviral resistance, vulnerability to IAV disease is a function of caspase-dependent pathology.

Longitudinal average attributable fraction as a method for studying time-varying conditions and treatments on recurrent self-rated health: the case of medications in older adults with multiple chronic conditions.

PURPOSE: The objective is to modify the longitudinal extension of the average attributable fraction (LE-AAF) for recurrent outcomes with time-varying exposures and control for covariates. METHODS: We included Medicare Current Beneficiary Survey participants with two or more chronic conditions enrolled from 2005 to 2009 with follow-up through 2011. Nine time-varying medications indicated for nine time-varying common chronic conditions and 14 of 18 forward-selected participant characteristics were used as control variables in the generalized estimating equations step of the LE-AAF to estimate associations with the recurrent universal health outcome self-rated health (SRH). Modifications of the LE-AAF were made to accommodate these indicated medication-condition interactions and covariates. Variability was empirically estimated by bias-corrected and accelerated bootstrapping. RESULTS: In the adjusted LE-AAF, thiazide, warfarin, and clopidogrel had significant contributions of 1.2%, 0.4%, 0.2%, respectively, to low (poor or fair) SRH; whereas there were no significant contributions of the other medications to SRH. Hyperlipidemia significantly contributed 4.6% to high SRH. All the other conditions except atrial fibrillation contributed significantly to low SRH. CONCLUSIONS: Our modifications to the LE-AAF method apply to a recurrent binary outcome with time-varying factors accounting for covariates.

Increasing negativity of age stereotypes across 200 years: evidence from a database of 400 million words.

Scholars argue about whether age stereotypes (beliefs about old people) are becoming more negative or positive over time. No previous study has systematically tested the trend of age stereotypes over more than 20 years, due to lack of suitable data. Our aim was to fill this gap by investigating whether age stereotypes have changed over the last two centuries and, if so, what may be associated with this change. We hypothesized that age stereotypes have increased in negativity due, in part, to the increasing medicalization of aging. This study applied computational linguistics to the recently compiled Corpus of Historical American English (COHA), a database of 400 million words that includes a range of printed sources from 1810 to 2009. After generating a comprehensive list of synonyms for the term elderly for these years from two historical thesauri, we identified 100 collocates (words that co-occurred most frequently with these synonyms) for each of the 20 decades. Inclusion criteria for the collocates were: (1) appeared within four words of the elderly synonym, (2) referred to an old person, and (3) had a stronger association with the elderly synonym than other words appearing in the database for that decade. This yielded 13,100 collocates that were rated for negativity and medicalization. We found that age stereotypes have become more negative in a linear way over 200 years. In 1880, age stereotypes switched from being positive to being negative. In addition, support was found for two potential explanations. Medicalization of aging and the growing proportion of the population over the age of 65 were both significantly associated with the increase in negative age stereotypes. The upward trajectory of age-stereotype negativity makes a case for remedial action on a societal level.