The Overlap Syndrome of Depression and Delirium in Older Hospitalized Patients

OBJECTIVES: To measure the prevalence, predictors, and posthospitalization outcomes associated with the overlap syndrome of coexisting depression and incident delirium in older hospitalized patients. DESIGN: Secondary analysis of prospective cohort data from the control group of the Delirium Prevention Trial. SETTING: General medical service of an academic medical center. Follow-up interviews at 1 month and 1 year post-hospital discharge. PARTICIPANTS: Four hundred fifty-nine patients aged 70 and older who were not delirious at hospital admission. MEASUREMENTS: Depressive symptoms assessed at hospital admission using the 15-item Geriatric Depression Scale (cutoff score of 6 used to define depression), daily assessments of incident delirium from admission to discharge using the Confusion Assessment Method, activities of daily living at admission and 1 month postdischarge, and new nursing home placement and mortality determined at 1 year. RESULTS: Of 459 participants, 23 (5.0%) had the overlap syndrome, 39 (8.5%) delirium alone, 121 (26.3%) depression alone, and 276 (60.1%) neither condition. In adjusted analysis, patients with the overlap syndrome had higher odds of new nursing home placement or death at 1 year (adjusted odds ratio (AOR)=5.38, 95% confidence interval (CI)=1.57–18.38) and 1-month functional decline (AOR=3.30, 95% CI=1.14–9.56) than patients with neither condition. CONCLUSION: The overlap syndrome of depression and delirium is associated with significant risk of functional decline, institutionalization, and death. Efforts to identify, prevent, and treat this condition may reduce the risk of adverse outcomes in older hospitalized patients

Population Structure and Genetic Diversity of the Boll Weevil (Coleoptera: Curculionidae) on Gossypium in North America

Although the boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), is a devastating pest in the United States and Mexico, its population structure and genetic diversity in Mexico on wild and cultivated cotton hosts (genus Gossypium) is poorly understood. Past studies using morphology, host use, and distribution records suggest that A.grandis grandis comprises three forms with host-associated characteristics: the southeastern form (from domesticated Gossypium hirsutum L., southeastern United States and northeastern Mexico), the thurberia form (from Gossypium thurberi Todaro, Arizona and northwestern Mexico), and the Mexican form (from multiple Gossypium species and other malvaceous plant genera in the remainder of Mexico and Central America). However, the phylogenetic relationships, host preferences, and distributions of these forms are not completely understood. An alternative hypothesis of an eastern and western form of the boll weevil is suggested by the suspected phylogeographic range expansion from an ancestral distribution in the tropics northward along both Mexican coasts, culminating in the maximally contrasting phenotypes observed in the northeastern and northwestern arms of the current distribution. In this study, we sequenced one mitochondrial and four nuclear genes to gain insight into the evolutionary relationships among the putative forms and their distributions on wild and domesticated cotton hosts. Using models of evolution, we compared the three-form to the two-form classification and to two alternative classifications that incorporate geography and host use traits. The genetic data at most loci provide stronger support for the two-form than the three-form hypothesis, with an eastern and western group separated by the Sierra Madre Occidental mountain range. They do not support separate taxonomic status for boll weevils developing onG. thurberi

Energy dependence of {\rm K}S0^0_{\rm S} and hyperon production at CERN SPS

Recent results on K$^0_{\rm S}$ and hyperon production in Pb-Pb collisions at 40 and 158 $A$ GeV/$c$ beam momentum from the NA57 experiment at CERN SPS are presented. Yields and ratios are compared with those measured by the NA49 experiment, where available. The centrality dependence of the yields and a comparison with the higher collision energy data from RHIC are discussed.Comment: 4 pages, 3 figures, proceedings of QM2004 conferenc

Adjustment of nursing home quality indicators

Background: This manuscript describes a method for adjustment of nursing home quality indicators (QIs) defined using the Center for Medicaid & Medicare Services (CMS) nursing home resident assessment system, the Minimum Data Set (MDS). QIs are intended to characterize quality of care delivered in a facility. Threats to the validity of the measurement of presumed quality of care include baseline resident health and functional status, pattern of comorbidities, and facility case mix. The goal of obtaining a valid facility-level estimate of true quality of care should include adjustment for resident- and facility-level sources of variability. Methods: We present a practical and efficient method to achieve risk adjustment using restriction and indirect and direct standardization. We present information on validity by comparing QIs estimated with the new algorithm to one currently used by CMS. Results: More than half of the new QIs achieved a "Moderate" validation level. Conclusions: Given the comprehensive approach and the positive findings to date, research using the new quality indicators is warranted to provide further evidence of their validity and utility and to encourage their use in quality improvement activities

Environmental tipping points and food system dynamics: Main report

First paragraph: Environmental tipping points occur when there are step changes in the way the biophysical world works – whether loss of soil fertility, collapse of a fishing stock, or sudden changes in weather patterns, such as those that caused the grasslands in North Africa to become deserts, 6000 years ago. These non-linear shifts arise following a critical degree of change, resulting from either many small cumulative changes or one large shock, “tipping” the system over a threshold and into a new stable state. Entering an alternative stable state is associated with a change to system function, usually being difficult to reverse or “tip” back into the original state. Increasingly we recognise that human-environment interactions are affecting the likelihood that critical thresholds for tipping points will be crossed, leading to step-changes in the provision of environmental goods and services, and impacting upon food security

Selecting Optimal Screening Items for Delirium: An Application of Item Response Theory

Background: Delirium (acute confusion), is a common, morbid, and costly complication of acute illness in older adults. Yet, researchers and clinicians lack short, efficient, and sensitive case identification tools for delirium. Though the Confusion Assessment Method (CAM) is the most widely used algorithm for delirium, the existing assessments that operationalize the CAM algorithm may be too long or complicated for routine clinical use. Item response theory (IRT) models help facilitate the development of short screening tools for use in clinical applications or research studies. This study utilizes IRT to identify a reduced set of optimally performing screening indicators for the four CAM features of delirium. Methods: Older adults were screened for enrollment in a large scale delirium study conducted in Boston-area post-acute facilities (n = 4,598). Trained interviewers conducted a structured delirium assessment that culminated in rating the presence or absence of four features of delirium based on the CAM. A pool of 135 indicators from established cognitive testing and delirium assessment tools were assigned by an expert panel into two indicator sets per CAM feature representing (a) direct interview questions, including cognitive testing, and (b) interviewer observations. We used IRT models to identify the best items to screen for each feature of delirium. Results: We identified 10 dimensions and chose up to five indicators per dimension. Preference was given to items with peak psychometric information in the latent trait region relevant for screening for delirium. The final set of 48 indicators, derived from 39 items, maintains fidelity to clinical constructs of delirium and maximizes psychometric information relevant for screening. Conclusions: We identified optimal indicators from a large item pool to screen for delirium. The selected indicators maintain fidelity to clinical constructs of delirium while maximizing psychometric information important for screening. This reduced item set facilitates development of short screening tools suitable for use in clinical applications or research studies. This study represents the first step in the establishment of an item bank for delirium screening with potential questions for clinical researchers to select from and tailor according to their research objectives

Protocol for the Metformin Aneurysm Trial (MAT): A placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm

Background: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. Methods: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). Discussion: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design

Protease-activated receptor 4 variant p.Tyr157Cys reduces platelet functional responses and alters receptor trafficking

OBJECTIVE—: Protease-activated receptor 4 (PAR4) is a key regulator of platelet reactivity and is encoded by F2RL3, which has abundant rare missense variants. We aimed to provide proof of principle that rare F2LR3 variants potentially affect on platelet reactivity and responsiveness to PAR1 antagonist drugs and to explore underlying molecular mechanisms. APPROACH AND RESULTS—: We identified 6 rare F2RL3 missense variants in 236 cardiac patients, of which the variant causing a tyrosine 157 to cysteine substitution (Y157C) was predicted computationally to affect most on PAR4 structure. Y157C platelets from 3 cases showed reduced responses to PAR4-activating peptide and to α-thrombin compared with controls, but no reduction in responses to PAR1-activating peptide. Pretreatment with the PAR1 antagonist vorapaxar caused lower residual α-thrombin responses in Y157C platelets than in controls, indicating greater platelet inhibition. HEK293 cells transfected with a PAR4 Y157C expression construct had reduced PAR4 functional responses, unchanged total PAR4 expression but reduced surface expression. PAR4 Y157C was partially retained in the endoplasmic reticulum and displayed an expression pattern consistent with defective N-glycosylation. Mutagenesis of Y322, which is the putative hydrogen bond partner of Y157, also reduced PAR4 surface expression in HEK293 cells. CONCLUSIONS—: Reduced PAR4 responses associated with Y157C result from aberrant anterograde surface receptor trafficking, in part, because of disrupted intramolecular hydrogen bonding. Characterization of PAR4 Y157C establishes that rare F2RL3 variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists

Calibration and Validation of an Innovative Approach for Estimating General Cognitive Performance

Objective: To evaluate a new approach for creating a composite measure of cognitive function, we calibrated a measure of general cognitive performance from existing neuropsychological batteries. Methods: We applied our approach in an epidemiological study and scaled the composite to a nationally representative sample of older adults. Criterion validity was evaluated against standard clinical diagnoses. Convergent validity was evaluated against the Mini-Mental State Examination (MMSE). Results: The general cognitive performance factor was scaled to have a mean of 50 and standard deviation of 10 in a nationally representative sample of older adults. A cutoff point of approximately 45, corresponding to an MMSE of 23/24, optimally discriminated participants with and without dementia (sensitivity = 0.94, specificity = 0.90, area under the curve = 0.97). The general cognitive performance factor was internally consistent (Cronbach's α = 0.91) and provided reliable measures of functional ability across a wide range of cognitive functioning. It demonstrated minimal floor and ceiling effects, which is an improvement over most individual cognitive tests. Conclusions: The cognitive composite is a highly reliable measure, with minimal floor and ceiling effects. We calibrated it using a nationally representative sample of adults over the age of 70 in the USA and established diagnostically relevant cutoff points. Our methods can be used to harmonize neuropsychological test results across diverse settings and studies