Search

Arguably, the most important parameter in treating cognitive decline associated with Alzheimer's disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy, resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvements in patients with cognitive decline, but long-term follow-up (>5 years) has not been reported previously. Therefore, here, we report sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol-something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

Gaining a systematic understanding of possible ways to increase the quality and lifespan of older adults experiencing self-neglect has unique challenges. These challenges include identifying self-neglect in the community and navigating levels of cognitive, physical, and/or psychological difficulties in this population that impact recruitment, consent, and accurate data collection. Conducting quality research under some of the environmental self-neglect conditions such as squalor, animal and insect infestations and no utilities can also challenge planned study protocols and study validity. This manuscript presents details of these overarching challenges and some of the workable solutions noted and implemented by research field-team members who have enrolled over 300 adults experiencing self-neglect for various studies. Usual research methodology must overcome these barriers to work to create consciousness about the self-neglect population. The classic series of cases is still a good alternative when describing self-neglect. Considerations for conducting future self-neglect research are presented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pickens, Burnett, Trail Ross, Jones and Jefferson.)

In emergencies like the COVID-19 pandemic, the reuse or reprocessing of filtering facepiece respirators (FFRs) may be required to mitigate exposure risk. Research gap: Only a few studies evaluated decontamination effectiveness against SARS-CoV-2 that are practical for low-resource settings. This study aimed to determine the effectiveness of a relatively inexpensive ultraviolet germicidal irradiation chamber to decontaminate FFRs contaminated with SARS-CoV-2. A custom-designed UVGI chamber was constructed to determine the ability to decontaminate seven FFR models including N95s, KN95, and FFP2s inoculated with SARS-CoV-2. Vflex was excluded due to design folds/pleats and UVGI shadowing inside the chamber. Structural and functional integrity tolerated by each FFR model on repeated decontamination cycles was assessed. Twenty-seven participants were fit-tested over 30 cycles for each model and passed if the fit factor was ≥100. Of the FFR models included for testing, only the KN95 model failed filtration. The 3M™ 3M 1860 and Halyard™ duckbill 46727 (formerly Kimberly Clark) models performed better on fit testing than other models for both pre-and-post decontaminations. Fewer participants (0.3 and 0.7%, respectively) passed fit testing for Makrite 9500 N95 and Greenline 5200 FFP2 and only two for the KN95 model post decontamination. Fit testing appeared to be more affected by donning & doffing, as some passed with adjustment and repeat fit testing. A ≥ 3 log reduction of SARS-CoV-2 was achieved for worn-in FFRs namely Greenline 5200 FFP2. Conclusion: The study showed that not all FFRs tested could withstand 30 cycles of UVGI decontamination without diminishing filtration efficiency or facial fit. In addition, SARS-CoV-2 log reduction varied across the FFRs, implying that the decontamination efficacy largely depends on the decontamination protocol and selection of FFRs. We demonstrated the effectiveness of a low-cost and scalable decontamination method for SARS-CoV-2 and the effect on fit testing using people instead of manikins. It is recognized that extensive experimental evidence for the reuse of decontaminated FFRs is lacking, and thus this study would be relevant and of interest in crisis-capacity settings, particularly in low-resource facilities.

Background: One of the most complicated medical needs of older adults is managing their complex medication regimens. However, the use of technology to aid older adults in this endeavor is impeded by the fact that their technological capabilities are lower than those of much of the rest of the population. What is needed to help manage medications is a technology that seamlessly integrates within their comfort levels, such as artificial intelligence agents., Objective: This study aimed to assess the benefits, barriers, and information needs that can be provided by an artificial intelligence-powered medication information voice chatbot for older adults., Methods: A total of 8 semistructured interviews were conducted with geriatrics experts. All interviews were audio-recorded and transcribed. Each interview was coded by 2 investigators (2 among ML, PR, METR, and KR) using a semiopen coding method for qualitative analysis, and reconciliation was performed by a third investigator. All codes were organized into the benefit/nonbenefit, barrier/nonbarrier, and need categories. Iterative recoding and member checking were performed until convergence was reached for all interviews., Results: The greatest benefits of a medication information voice-based chatbot would be helping to overcome the vision and dexterity hurdles experienced by most older adults, as it uses voice-based technology. It also helps to increase older adults' medication knowledge and adherence and supports their overall health. The main barriers were technology familiarity and cost, especially in lower socioeconomic older adults, as well as security and privacy concerns. It was noted however that technology familiarity was not an insurmountable barrier for older adults aged 65 to 75 years, who mostly owned smartphones, whereas older adults aged >75 years may have never been major users of technology in the first place. The most important needs were to be usable, to help patients with reminders, and to provide information on medication side effects and use instructions., Conclusions: Our needs analysis results derived from expert interviews clarify that a voice-based chatbot could be beneficial in improving adherence and overall health if it is built to serve the many medication information needs of older adults, such as reminders and instructions. However, the chatbot must be usable and affordable for its widespread use., (©Meghana Gudala, Mary Ellen Trail Ross, Sunitha Mogalla, Mandi Lyons, Padmavathy Ramaswamy, Kirk Roberts. Originally published in JMIR Aging (https://aging.jmir.org), 28.04.2022.)

Healthcare workers are under such a tremendous amount of pressure during the COVID-19 pandemic that many have become concerned about their jobs and even intend to leave them. It is paramount for healthcare workers to feel satisfied with their jobs and lives during a pandemic. This study aims to examine the predictors of job satisfaction, life satisfaction, and turnover intention of healthcare workers during the COVID-19 pandemic. Between 10 and 30 April 2020, 240 healthcare workers in Bolivia completed a cross-sectional online survey, which assessed their job satisfaction, life satisfaction, and turnover intention in the ongoing COVID-19 pandemic. The results revealed that their number of office days predicted job satisfaction, life satisfaction, and turnover intention, but the relationships varied by their age. For example, healthcare workers' office days negatively predicted job satisfaction for the young (e.g., at 25 years old: b  = - 0.21; 95% CI: - 0.36 to - 0.60) but positively predicted job satisfaction for the old (e.g., at 65 years old: b  = 0.25; 95% CI: 0.06 to 0.44). These findings provide evidence to enable healthcare organizations to identify staff concerned about job satisfaction, life satisfaction, and turnover intention to enable early actions so that these staffs can remain motivated to fight the prolonged COVID-19 pandemic., Competing Interests: Conflict of InterestThe authors declare that there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Introduction: There is an urgent need to develop effective interventional treatments for people with Alzheimer's disease (AD). AD results from a complex multi-decade interplay of multiple interacting dysfunctional biological systems that have not yet been fully elucidated. Epidemiological studies have linked several modifiable lifestyle factors with increased incidence for AD. Because monotherapies have failed to prevent or ameliorate AD, interventional studies should deploy multiple, targeted interventions that address the dysfunctional systems that give rise to AD., Methods: This randomized controlled trial (RCT) will examine the efficacy of a 12-month personalized, multimodal, lifestyle intervention in 60 mild cognitive impairment (MCI) and early stage AD patients (aged 50+, amyloid positivity). Both groups receive data-driven, lifestyle recommendations designed to target multiple systemic pathways implicated in AD. One group receives these personalized recommendations without coaching. The other group receives personalized recommendations with health coaching, dietary counseling, exercise training, cognitive stimulation, and nutritional supplements. We collect clinical, proteomic, metabolomic, neuroimaging, and genetic data to fuel systems-biology analyses. We will examine effects on cognition and hippocampal volume. The overarching goal of the study is to longitudinally track biological systems implicated in AD to reveal the dynamics between these systems during the intervention to understand differences in treatment response., Results: We have developed and implemented a protocol for a personalized, multimodal intervention program for early AD patients. We began enrollment in September 2019; we have enrolled a third of our target (20 of 60) with a 95% retention and 86% compliance rate., Discussion: This study presents a paradigm shift in designing multimodal, lifestyle interventions to reduce cognitive decline, and how to elucidate the biological systems being targeted. Analytical efforts to explain mechanistic or causal underpinnings of individual trajectories and the interplay between multi-omic variables will inform the design of future hypotheses and development of effective precision medicine trials., Competing Interests: None., (© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Abstract: Scombrotoxin fish poisoning (SFP) is caused by the ingestion of certain fish species with elevated concentrations of histamine due to decomposition. In fall 2019, the U.S. Food and Drug Administration (FDA) was notified of 51 SFP cases including two hospitalizations from 11 states through the FDA consumer complaint system or directly from state partners. A case patient was defined as an individual who experienced a histamine-type reaction after consumption of tuna imported from Vietnam and an illness onset between 14 August and 24 November 2019. A traceback investigation was initiated at 19 points of service to identify a common tuna source. The FDA and state partners collected 34 product samples throughout the distribution chain, including from a case patient's home, points of service, distributors, and the port of entry. Samples were analyzed for histamine by sensory evaluation and/or chemical testing. Case patients reported exposure to tuna imported from Vietnam. The traceback investigation identified two Vietnamese manufacturers as the sources of the tuna. Twenty-nine samples were confirmed as decomposed by sensory evaluation and/or were positive for elevated histamine concentrations by chemical testing. Both Vietnamese companies were placed on an import alert. Seven U.S. companies and one Vietnamese company initiated voluntary recalls. The FDA released public communication naming the U.S. importers to help suppliers and distributors identify the product and effectuate the foreign company's recall. This SFP outbreak investigation highlights the complexities of the federal outbreak response, specifically related to imported food. Cultural considerations regarding imported foods should be addressed during outbreak responses when timing is critical. Collaboration with countries where confidentiality agreements are not in place can limit information sharing and the speed of public health responses., (Published 2021 by the International Association for Food Protection Not subject to U.S. Copyright.)

We report a case of a patient with mixed dementia successfully treated with a personalized multimodal therapy. Monotherapeutics are inadequate for the treatment of Alzheimer's disease (AD) and mixed dementia; therefore, we approach treatment through an adaptive personalized multimodal program. Many multimodal programs are pre-determined, and thus may not address the underlying contributors to cognitive decline in each particular individual. The combination of a targeted, personalized, precision medicine approach using a multimodal program promises advantages over monotherapies and untargeted multimodal therapies for multifactorial dementia. In this case study, we describe successful treatment for a patient diagnosed with AD, using a multimodal, programmatic, precision medicine intervention encompassing therapies targeting multiple dementia diastheses. We describe specific interventions used in this case that are derived from a comprehensive protocol for AD precision medicine. After treatment, our patient demonstrated improvements in quantitative neuropsychological testing, volumetric neuroimaging, PET scans, and serum chemistries, accompanied by symptomatic improvement over a 3.5-year period. This case outcome supports the need for rigorous trials of comprehensive, targeted combination therapies to stabilize, restore, and prevent cognitive decline in individuals with potentially many underlying causes of such decline and dementia. Our multimodal therapy included personalized treatments to address each potential perturbation to neuroplasticity. In particular, neuroinflammation and metabolic subsystems influence cognitive function and hippocampal volume. In this patient with a primary biliary cholangitis (PBC) multimorbidity component, we introduced a personalized diet that helped reduce liver inflammation. Together, all these components of multimodal therapy showed a sustained functional and cognitive benefit. Multimodal therapies may have systemwide benefits on all dementias, particularly in the context of multimorbidity. Furthermore, these therapies provide generalized health benefits, as many of the factors - such as inflammation - that impact cognitive function also impact other systems., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare.

Risks of pediatric tracheostomy are well known. The objectives of this quality improvement study were to organize tracheostomy supplies into a comprehensive care kit and demonstrate that the kits improved nursing and parental comfort in providing tracheostomy care routinely and emergently. Kits were assembled using roll-up toiletry style bags and organized in a uniform fashion with necessary supplies. Nurses and parents were surveyed using a 5-point Likert-type. Feedback was overall very positive; the kits were found to ease the transition of caring for a child with a new tracheostomy from hospital to home. This intervention can easily be adapted at other pediatric institutions., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

During the COVID-19 pandemic, healthcare workers are facing high workloads with resource constraints and risk of virus exposure, and healthcare organizations need to support their healthcare workers to reduce their anxiety. Based on a recent 8-point framework of COVID-19 specific organization support, we devised a measure of COVID-19 Organizational Support (COVID-OS). We tested the new measure with 712 healthcare workers in Bolivia, Ecuador, and Peru and found the new measure formed three factors to predict healthcare workers' anxiety and life satisfaction during the COVID-19 pandemic. We call for further studies to test COVID-OS in other countries and settings., Competing Interests: Declaration of Competing Interests The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: With more than 1 million older adults being abused each year, it is imperative for nurses to be knowledgeable about signs and symptoms of elder abuse, assessment, and interventions. This article describes a three-part learning strategy consisting of lecture, simulation using standardized patients (SPs), and debriefing to educate prelicensure nursing students about how to identify, assess, and report elder abuse. Furthermore, the effects of the teaching strategies were assessed., Method: Students received a lecture on elder abuse, followed by a simulation with an SP and debriefing. Pre- and posttests were used to assess knowledge, skills, and attitudes about elder abuse., Results: Significant differences were found in pre- and posttest results for knowledge and skills. There were no significant differences in attitude. Teaching strategies affected learning, and students reported increased knowledge and skills in identifying abuse and advocating for vulnerable older adults., Conclusion: Lecture and SP simulation followed by debriefing was an effective approach to educate prelicensure nursing students about elder abuse. [J Nurs Educ. 2020;59(6):331-335.]., (Copyright 2020, SLACK Incorporated.)

We evaluated a full-face snorkel mask with an airway circuit filter to protect health care providers against airborne pathogens. First, a quantified N95 fit test was performed using aerosolized saline. Second, cardiorespiratory variables (heart rate, peripheral oxygen saturation, end-tidal carbon dioxide tension, and inspired fraction of carbon dioxide) were measured at rest and during moderate exercise. The modified mask passed the United States Occupational Safety and Health Administration (OSHA) N95 respirator (N95) fit test requirements with a fit factor of 142. Neither hypercapnia nor hypoxemia occurred. This modified mask has the potential to protect providers who care for patients with coronavirus disease 2019 (COVID-19).

To inform regulatory decisions on the risk due to exposure to ambient air pollution, consistent and transparent communication of the scientific evidence is essential. The United States Environmental Protection Agency (U.S. EPA) develops the Integrated Science Assessment (ISA), which contains evaluations of the policy-relevant science on the effects of criteria air pollutants and conveys critical science judgments to inform decisions on the National Ambient Air Quality Standards. This article discusses the approach and causal framework used in the ISAs to evaluate and integrate various lines of scientific evidence and draw conclusions about the causal nature of air pollution-induced health effects. The framework has been applied to diverse pollutants and cancer and noncancer effects. To demonstrate its flexibility, we provide examples of causality judgments on relationships between health effects and pollutant exposures, drawing from recent ISAs for ozone, lead, carbon monoxide, and oxides of nitrogen. U.S. EPA's causal framework has increased transparency by establishing a structured process for evaluating and integrating various lines of evidence and uniform approach for determining causality. The framework brings consistency and specificity to the conclusions in the ISA, and the flexibility of the framework makes it relevant for evaluations of evidence across media and health effects., (Published by Elsevier Inc.)

The use of simulation is an innovative teaching strategy that has proven to be valuable in nursing education. This article describes the benefits of a simulation lab involving faculty role-play to teach baccalaureate nursing students how to properly assess the functional status of older adults. Details about the simulation lab, which involved functional assessments of two elderly community-dwelling residents, are presented, along with student and faculty evaluations of this teaching modality.

BI 1002494 [(R)-4-{(R)-1-[7-(3,4,5-trimethoxy-phenyl)-[1,6]napthyridin-5-yloxy]-ethyl}pyrrolidin-2-one] is a novel, potent, and selective spleen tyrosine kinase (SYK) inhibitor with sustained plasma exposure after oral administration in rats, which qualifies this molecule as a good in vitro and in vivo tool compound. BI 1002494 exhibits higher potency in inhibiting high-affinity IgE receptor-mediated mast cell and basophil degranulation (IC50 = 115 nM) compared with B-cell receptor-mediated activation of B cells (IC50 = 810 nM). This may be explained by lower kinase potency when the physiologic ligand B-cell linker was used, suggesting that SYK inhibitors may exhibit differential potency depending on the cell type and the respective signal transduction ligand. A 3-fold decrease in potency was observed in rat basophils (IC50 = 323 nM) compared with human basophils, but a similar species potency shift was not observed in B cells. The lower potency in rat basophils was confirmed in both ex vivo inhibition of bronchoconstriction in precision-cut rat lung slices and in reversal of anaphylaxis-driven airway resistance in rats. The different cellular potencies translated into different in vivo efficacy; full efficacy in a rat ovalbumin model (that contains an element of mast cell dependence) was achieved with a trough plasma concentration of 340 nM, whereas full efficacy in a rat collagen-induced arthritis model (that contains an element of B-cell dependence) was achieved with a trough plasma concentration of 1400 nM. Taken together, these data provide a platform from which different estimates of human efficacious exposures can be made according to the relevant cell type for the indication intended to be treated., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Sphingosine kinase 1 (SphK1) is a lipid kinase that phosphorylates sphingosine to produce the bioactive sphingolipid, sphingosine-1-phosphate (S1P), and therefore represents a potential drug target for a variety of pathological processes such as fibrosis, inflammation, and cancer. We developed two assays compatible with high-throughput screening to identify small-molecule inhibitors of SphK1: a purified component enzyme assay and a genetic complementation assay in yeast cells. The biochemical enzyme assay measures the phosphorylation of sphingosine-fluorescein to S1P-fluorescein by recombinant human full-length SphK1 using an immobilized metal affinity for phosphochemicals (IMAP) time-resolved fluorescence resonance energy transfer format. The yeast assay employs an engineered strain of Saccharomyces cerevisiae, in which the human gene encoding SphK1 replaced the yeast ortholog and quantitates cell viability by measuring intracellular adenosine 5'-triphosphate (ATP) using a luciferase-based luminescent readout. In this assay, expression of human SphK1 was toxic, and the resulting yeast cell death was prevented by SphK1 inhibitors. We optimized both assays in a 384-well format and screened ∼10(6) compounds selected from the Boehringer Ingelheim library. The biochemical IMAP high-throughput screen identified 5,561 concentration-responsive hits, most of which were ATP competitive and not selective over sphingosine kinase 2 (SphK2). The yeast screen identified 205 concentration-responsive hits, including several distinct compound series that were selective against SphK2 and were not ATP competitive.

Universal screening for maternal group B Streptococcus (GBS) in the prenatal period has led to administration of intrapartum antibiotic prophylaxis (IAP). Although IAP decreased the rate of early neonatal GBS disease, exposure of childbearing women to penicillin and other beta-lactam antibiotics has increased. Beta-lactam-induced anaphylaxis in the breastfeeding woman during the postpartum period illustrates risk factors for beta-lactam allergy and anaphylaxis. Treatment and nursing implications for this adverse reaction are suggested., (© 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.)

There is abundant literature finding that susceptibility factors, including race and ethnicity, age, and housing, directly influence blood lead levels. No study has explored how susceptibility factors influence the blood lead-air lead relationship nationally. The objective is to evaluate whether susceptibility factors act as effect measure modifiers on the blood lead-air lead relationship. Participant level blood lead data from the 1999 to 2008 National Health and Nutrition Examination Survey were merged with air lead data from the US Environmental Protection Agency. Linear mixed effects models were run with and without an air lead interaction term for age group, sex, housing age, or race/ethnicity to determine whether these factors are effect measure modifiers for all ages combined and for five age brackets. Age group and race/ethnicity were determined to be effect measure modifiers in the all-age model and for some age groups. Being a child (1-5, 6-11, and 12-19 years) or of Mexican-American ethnicity increased the effect estimate. Living in older housing (built before 1950) decreased the effect estimate for all models except for the 1-5-year group, where older housing was an effect measure modifier. These results are consistent with the peer-reviewed literature of time-activity patterns, ventilation, and toxicokinetics.

Background: In the weeks following the first imported case of Ebola in the U. S. on September 29, 2014, coverage of the very limited outbreak dominated the news media, in a manner quite disproportionate to the actual threat to national public health; by the end of October, 2014, there were only four laboratory confirmed cases of Ebola in the entire nation. Public interest in these events was high, as reflected in the millions of Ebola-related Internet searches and tweets performed in the month following the first confirmed case. Use of trending Internet searches and tweets has been proposed in the past for real-time prediction of outbreaks (a field referred to as "digital epidemiology"), but accounting for the biases of public panic has been problematic. In the case of the limited U. S. Ebola outbreak, we know that the Ebola-related searches and tweets originating the U. S. during the outbreak were due only to public interest or panic, providing an unprecedented means to determine how these dynamics affect such data, and how news media may be driving these trends., Methodology: We examine daily Ebola-related Internet search and Twitter data in the U. S. during the six week period ending Oct 31, 2014. TV news coverage data were obtained from the daily number of Ebola-related news videos appearing on two major news networks. We fit the parameters of a mathematical contagion model to the data to determine if the news coverage was a significant factor in the temporal patterns in Ebola-related Internet and Twitter data., Conclusions: We find significant evidence of contagion, with each Ebola-related news video inspiring tens of thousands of Ebola-related tweets and Internet searches. Between 65% to 76% of the variance in all samples is described by the news media contagion model.

Background: Epidemiologic and experimental studies have reported a variety of health effects in response to ozone (O3) exposure, and some have indicated that certain populations may be at increased or decreased risk of O3-related health effects., Objectives: We sought to identify potential response-modifying factors to determine whether specific groups of the population or life stages are at increased or decreased risk of O3-related health effects using a weight-of-evidence approach., Methods: Epidemiologic, experimental, and exposure science studies of potential factors that may modify the relationship between O3 and health effects were identified in U.S. Environmental Protection Agency's 2013 Integrated Science Assessment for Ozone and Related Photochemical Oxidants. Scientific evidence from studies that examined factors that may influence risk were integrated across disciplines to evaluate consistency, coherence, and biological plausibility of effects. The factors identified were then classified using a weight-of-evidence approach to conclude whether a specific factor modified the response of a population or life stage, resulting in an increased or decreased risk of O3-related health effects., Discussion: We found "adequate" evidence that populations with certain genotypes, preexisting asthma, or reduced intake of certain nutrients, as well as different life stages or outdoor workers, are at increased risk of O3-related health effects. In addition, we identified other factors (i.e., sex, socioeconomic status, and obesity) for which there was "suggestive" evidence that they may increase the risk of O3-related health effects., Conclusions: Using a weight-of-evidence approach, we identified a diverse group of factors that should be considered when characterizing the overall risk of health effects associated with exposures to ambient O3.

Background: It is difficult to discern the proportion of blood lead (PbB) attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources and pathways of exposure. The PbB-PbA relationship has previously been evaluated across populations. This relationship was a central consideration in the 2008 review of the Pb national ambient air quality standards., Objectives: The objectives of this study were to evaluate the relationship between PbB and PbA concentrations among children nationwide for recent years and to compare the relationship with those obtained from other studies in the literature., Methods: We merged participant-level data for PbB from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 9908 (1999-2008) with PbA data from the U.S. Environmental Protection Agency. We applied mixed-effects models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit change in PbA, from the model results to assess the relationship between PbB and PbA., Results: Comparing the NHANES regression results with those from the literature shows that slope factor increased with decreasing PbA among children 0-11 years of age., Conclusion: These findings suggest that a larger relative public health benefit may be derived among children from decreases in PbA at low PbA exposures. Simultaneous declines in Pb from other sources, changes in PbA sampling uncertainties over time largely related to changes in the size distribution of Pb-bearing particulate matter, and limitations regarding sampling size and exposure error may contribute to the variability in slope factor observed across peer-reviewed studies.

The emergence of sphingosine-1-phosphate lyase (SPL) as a promising therapeutic target for inflammatory diseases has heightened interest in the identification of small molecules that modulate its activity. The enzymatic activity of SPL is typically measured using radiometric or fluorescence-based assays that require a lipid extraction step, or by direct quantitation of reaction products using mass spectrometry (MS). To facilitate testing large numbers of compounds to identify SPL modulators, we developed a robust scintillation proximity assay (SPA) that is compatible with high-throughput screening (HTS). This assay employs recombinant human full-length SPL in insect cell membrane preparations to catalyze the conversion of biotinylated aminosphingosine-1-[(33)P]phosphate (S1(33)P-biotin) to trans-2-hexadecenal-biotin and ethanolamine [(33)P]phosphate. To validate the SPA and confirm the fidelity of its measurement of SPL enzyme activity, we developed a Rapid-Fire MS method that quantitates nonradiolabeled S1P-biotin. In addition, we developed a simple, scalable method to produce S1(33)P-biotin in quantities sufficient for HTS. The optimized SPA screen in 384-well microplates produced a mean plate-wise Z'-statistic of 0.58 across approximately 3,000 plates and identified several distinct structural classes of SPL inhibitor. Among the inhibitors that the screen identified was one compound with an IC50 of 1.6 μM in the SPA that induced dose-dependent lymphopenia in mice.

The objective of this work is to examine associations between blood lead (PbB) and air lead (PbA) in particulate matter measured at different size cuts by use of PbB concentrations from the National Health and Nutrition Examination Survey and PbA concentrations from the U.S. Environmental Protection Agency for 1999-2008. Three size fractions of particle-bound PbA (TSP, PM10, and PM2.5) data with different averaging times (current and past 90-day average) were utilized. A multilevel linear mixed effect model was used to characterize the PbB-PbA relationship. At 0.15 μg/m(3), a unit decrease in PbA in PM10 was significantly associated with a decrease in PbB of 0.3-2.2 μg/dL across age groups and averaging times. For PbA in PM2.5 and TSP, slopes were generally positive but not significant. PbB levels were more sensitive to the change in PbA concentrations for children (1-5 and 6-11 years) and older adults (≥ 60 years) than teenagers (12-19 years) and adults (20-59 years). For the years following the phase-out of Pb in gasoline and a resulting upward shift in the PbA particle size distribution, PbA in PM10 was a statistically significant predictor of PbB. The results also suggest that age could affect the PbB-PbA association, with children having higher sensitivity than adults.

Context: Scientists are now finding that light acts on individuals through multiple pathways, most notably the optic nerve that links to the brain's visual cortex, providing a pathway for the visual effects of light. The optic nerve also links to the more recently discovered retinohypothalamic tract, providing a pathway for the nonvisual effects of light. However, specific effects have not yet been widely evaluated clinically, especially in relationship to chromotherapy (ie, therapy based on colored light)., Objective: The purpose of this study was to evaluate the impact of modulated-light projections, perceived through the eyes, on the autonomic nervous system (ANS)., Design: The research team designed a randomized, controlled, partially blinded study with three intervention groups and one control group., Setting: The study took place in two locations: (1) Midwestern State University, Wichita Falls, Texas, USA (40 participants) and Centre de Santé Satori, Québec, Canada (77 participants)., Participants: The research team recruited 117 individuals, 89 women and 28 men, to participate in the study. Participants were normal healthy individuals who were 19 to 72 y old (average age = 43 y)., Intervention: Three types of light projections, each containing both specific colors and specific modulations in the frequency range of brainwaves, were tested, in addition to a placebo projection consisting of nonmodulated white light., Outcome Measures: Evaluation was done using a combination of physiological measures-heart rate (HR), heart rate variability (HRV), and skin conductance (SC)- and psychological tests: the Profile of Mood States (POMS) and a subjective evaluation questionnaire., Results: The research team observed significant differences in the effects of light-modulation projections from baseline to postsession as compared with an equivalent intensity of white light, including decreased HR, increased HRV standard deviations of normalized NN (beat-to-beat) intervals (SDNN), very low (VLF) and low frequency (LF) levels, and decreased POMS total mood disturbance (TMD). Also, the different colors of modulated light were found to result in different ANS effects., Conclusions: Interest is growing in the therapeutic potential of light. The effects demonstrated in the current study indicate that colored light could significantly enrich the therapeutic potential of light, and further research into chromotherapy is warranted.

National and local declines in lead (Pb) in blood (PbB) over the past several years coincide with the decline in ambient air Pb (PbA) concentrations. The objective of this work is to evaluate how the relationship between PbB levels and PbA levels has changed following the phase out of leaded gasoline and tightened controls on industrial Pb emissions over the past 30 years among a national population sample. Participant-level data from the National Health and Nutrition Examination Survey (NHANES) were employed for two time periods (1988-1994 and 1999-2008), and the model was corrected for housing, demographic, socioeconomic, and other covariates present in NHANES. NHANES data for PbB and covariates were merged with PbA data from the U.S. Environmental Protection Agency. Linear mixed effects models (LMEs) were run to assess the relationship of PbB with PbA; sample weights were omitted, given biases encountered with the use of sample weights in LMEs. The 1988-1994 age-stratified results found that ln(PbB) was statistically significantly associated with ln(PbA) for all age groups. The consistent influence of PbA on PbB across age groups for the years 1988-1994 suggests a ubiquitous exposure unrelated to age of the sample population. The comparison of effect estimates for ln(PbA) shows a statistically significant effect estimate and ANOVA results for ln(PbB) for the 6- to 11-year and 12- to 19-year age groups during 1999-2008. The more recent finding suggests that PbA has less consistent influence on PbB compared with other factors., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The purpose of this longitudinal study was to improve nurse medication management skills during home care (HC) visits, and thus improve care quality and the related patient ratings of nurse performance. Nurses completed presurveys asking how often they asked to see, taught about, and explained side effects of patient medications. Two focus groups were held with HC nurses to determine barriers to provision of such medication interventions, followed by presentation of a series of 5 medication-related educational sessions. HC nurse's surveys 6 months later reveal an increased frequency of medication skill performance, and patient ratings in these same areas improved statistically significantly, nearing or surpassing national benchmarks.

Methods are needed for helping researchers and farmers to interactively describe and analyze local practices in search of opportunities for improving health, environment, and economy. The authors worked with smallholder family farmers in five Andean villages in Ecuador to apply participatory four-cell analysis (PFCA) in characterizing agrobiodiversity. Margelef and Shannon indices examined ecological richness and evenness, and a simplified 24-hour dietary recall characterized food consumption. Cross-analysis tested interactions among agrobiodiversity, farm size, and diet. Overall trends appeared to work against sustainable intensification, with notable heterogeneity and positive deviance found in the practices of relatively smaller enterprises, representing a potential resource for sustainable intensification. The suite of methods was determined useful for initiating researcher-farmer explorations of promising innovation pathways.

Boehringer Ingelheim's Automated Liquids Processing System (ALPS) in Ridgefield, Connecticut, was built to accommodate all compound solution-based operations following dissolution in neat DMSO. Process analysis resulted in the design of two nearly identical conveyor-based subsystems, each capable of executing 1400 × 384-well plate or punch tube replicates per batch. Two parallel-positioned subsystems are capable of independent execution or alternatively executed as a unified system for more complex or higher throughput processes. Primary ALPS functions include creation of high-throughput screening plates, concentration-response plates, and reformatted master stock plates (e.g., 384-well plates from 96-well plates). Integrated operations included centrifugation, unsealing/piercing, broadcast diluent addition, barcode print/application, compound transfer/mix via disposable pipette tips, and plate sealing. ALPS key features included instrument pooling for increased capacity or fail-over situations, programming constructs to associate one source plate to an array of replicate plates, and stacked collation of completed plates. Due to the hygroscopic nature of DMSO, ALPS was designed to operate within a 10% relativity humidity environment. The activities described are the collaborative efforts that contributed to the specification, build, delivery, and acceptance testing between Boehringer Ingelheim Pharmaceuticals, Inc. and the automation integration vendor, Thermo Scientific Laboratory Automation (Burlington, ON, Canada).

Plant cellulosic biomass is an abundant, low-cost feedstock for producing biofuels and chemicals. Expressing cell wall-degrading (CWD) enzymes (e.g. xylanases) in plant feedstocks could reduce the amount of enzymes required for feedstock pretreatment and hydrolysis during bioprocessing to release soluble sugars. However, in planta expression of xylanases can reduce biomass yield and plant fertility. To overcome this problem, we engineered a thermostable xylanase (XynB) with a thermostable self-splicing bacterial intein to control the xylanase activity. Intein-modified XynB (iXynB) variants were selected that have <10% wild-type enzymatic activity but recover >60% enzymatic activity upon intein self-splicing at temperatures >59 °C. Greenhouse-grown xynB maize expressing XynB has shriveled seeds and low fertility, but ixynB maize had normal seeds and fertility. Processing dried ixynB maize stover by temperature-regulated xylanase activation and hydrolysis in a cocktail of commercial CWD enzymes produced >90% theoretical glucose and >63% theoretical xylose yields.

Investigators examined 5,654 children enrolled in the El Paso, Texas, public school district by questionnaire in 2001. Exposure measurements were first collected in the late fall of 1999. School-level and residence-level exposures to traffic-related air pollutants were estimated using a land use regression model. For 1,529 children with spirometry, overall geographic information system (GIS)-modeled residential levels of traffic-related ambient air pollution (calibrated to a 10-ppb increment in nitrogen dioxide levels) were associated with a 2.4% decrement in forced vital capacity (95% confidence interval (CI): -4.0, -0.7) after adjustment for demographic, anthropomorphic, and socioeconomic factors and spirometer/technician effects. After adjustment for these potential covariates, overall GIS-modeled residential levels of traffic-related ambient air pollution (calibrated to a 10-ppb increment in nitrogen dioxide levels) were associated with pulmonary function levels below 85% of those predicted for both forced vital capacity (odds ratio (OR) = 3.10, 95% CI: 1.65, 5.78) and forced expiratory volume in 1 second (OR = 2.35, 95% CI: 1.38, 4.01). For children attending schools at elevations above 1,170 m, a 10-ppb increment in modeled nitrogen dioxide levels was associated with current asthma (OR = 1.56, 95% CI: 1.08, 2.50) after adjustment for demographic, socioeconomic, and parental factors and random school effects. These results are consistent with previous studies in Europe and California that found adverse health outcomes in children associated with modeled traffic-related air pollutants.

Objectives: The U.S. Environmental Protection Agency is working toward gaining a better understanding of the human health impacts of exposure to complex air pollutant mixtures and the key features that drive the toxicity of these mixtures, which can then be used for future scientific and risk assessments., Data Sources: A public workshop was held in Chapel Hill, North Carolina, 22-24 February 2011, to discuss scientific issues and data gaps related to adopting multipollutant science and risk assessment approaches, with a particular focus on the criteria air pollutants. Expert panelists in the fields of epidemiology, toxicology, and atmospheric and exposure sciences led open discussions to encourage workshop participants to think broadly about available and emerging scientific evidence related to multipollutant approaches to evaluating the health effects of air pollution., Synthesis: Although there is clearly a need for novel research and analytical approaches to better characterize the health effects of multipollutant exposures, much progress can be made by using existing scientific information and statistical methods to evaluate the effects of single pollutants in a multipollutant context. This work will have a direct impact on the development of a multipollutant science assessment and a conceptual framework for conducting multipollutant risk assessments., Conclusions: Transitioning to a multipollutant paradigm can be aided through the adoption of a framework for multipollutant science and risk assessment that encompasses well-studied and ubiquitous air pollutants. Successfully advancing methods for conducting these assessments will require collaborative and parallel efforts between the scientific and environmental regulatory and policy communities.

Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch.

Service learning is valued as a means of providing education to students and service to the community. The purpose of this article is to describe the incorporation of service learning in an undergraduate baccalaureate level Gerontology nursing course. Details of the service learning experience, community agency partnership, the students' reflections, evaluations from both the students and community agency staff, and faculty challenges are presented. This information may be useful to others who are considering service learning as a strategy for educating students while providing service to the community.

Background: Epidemiological, controlled human exposure, and toxicological studies have demonstrated a variety of health effects in response to particulate matter (PM) exposure with some of these studies indicating that populations with certain characteristics may be disproportionately affected., Objective: To identify populations potentially at greatest risk for PM-related health effects, we evaluated epidemiological studies that examined various characteristics that may influence susceptibility, while using results from controlled human exposure and toxicological studies as supporting evidence. Additionally, we formulated a definition of susceptibility, building from the varied and inconsistent definitions of susceptibility and vulnerability used throughout the literature., Data Synthesis: We evaluated recent epidemiological studies to identify characteristics of populations potentially susceptible to PM-related health effects. Additionally, we evaluated controlled human exposure and toxicological studies to provide supporting evidence. We conducted a comprehensive review of epidemiological studies that presented stratified results (e.g., < 65 vs. ≥ 65 years of age), controlled human exposure studies that examined individuals with underlying disease, and toxicological studies that used animal models of disease. We evaluated results for consistency across studies, coherence across disciplines, and biological plausibility to assess the potential for increased susceptibility to PM-related health effects in a specific population or life stage., Conclusions: We identified a diverse group of characteristics that can lead to increased risk of PM-related health effects, including life stage (i.e., children and older adults), preexisting cardiovascular or respiratory diseases, genetic polymorphisms, and low-socioeconomic status. In addition, we crafted a comprehensive definition of susceptibility that can be used to encompass all populations potentially at increased risk of adverse health effects as a consequence of exposure to an air pollutant.

Purpose: The intensity and selection of therapy for the treatment of type 2 diabetes mellitus in elderly patients are discussed., Summary: Glycemic control is fundamental in diabetes care; however, as glycemic goals are approached, the risk of hypoglycemia increases. This risk is even greater in the elderly due to many predisposing factors, including renal insufficiency, polypharmacy, drug-drug interactions, comorbidities, irregular meal patterns, and infrequent self-monitoring of blood glucose. When deciding on the desired intensity of diabetes treatment, the risk of hypoglycemic complications must be weighed against the potential benefit of reducing microvascular and macrovascular complications. Three large-scale, randomized controlled trials examining the effects of intensive versus standard glycemic control on microvascular and macrovascular outcomes in patients with type 2 diabetes have been published in recent years. In general, a glycosylated hemoglobin (HbA(1c)) goal of <7% is reasonable for most patients. A less-aggressive goal may be considered for patients at high risk of hypoglycemia or high risk of complications from hypoglycemia, as long as acutely symptomatic hyperglycemia is avoided. Chlorpropamide, glyburide, and rosiglitazone, which pose a great risk for hypoglycemia, should be avoided in the elderly., Conclusion: In the absence of clear evidence advocating strict glycemic targets goal of <7% is for elderly patients, an HbA(1c) reasonable for most patients; however, the risk of hypoglycemic complications must be weighed against the potential benefit of reducing microvascular and macrovascular disease. Metformin may be used as first-line therapy, but chlorpropamide and glyburide, which pose a great risk for hypoglycemia, should be avoided in the elderly. Due to increased cardiovascular risk, use of rosiglitazone in the elderly should also be avoided.

We present a 9-month-old male with mosaic trisomy 18 with a right hepatic lobe mass. The tumor was completely resected and identified as pure fetal histology hepatoblastoma but contained increased mitotic activity. Adjuvant chemotherapy consisted of cisplatin, vincristine, and 5-fluorouracil. After the first and fourth cycles of chemotherapy, recurrent tumor developed. The patient underwent rescue orthotopic liver transplantation, and is currently alive without evidence of hepatoblastoma 28 months after transplantation. This report demonstrates the use of orthotopic liver transplantation in a child with mosaic trisomy 18 and hepatoblastoma., (© 2010 Wiley-Liss, Inc.)

Purpose: The most recent large-scale studies evaluating the effects of calcium supplementation for prevention of osteoporosis-related fractures in postmenopausal women are reviewed., Summary: Osteoporosis is a very common disease associated with significant morbidity and mortality. For many years, use of a calcium supplement (preferably in combination with vitamin D to optimize calcium absorption) has been recommended for postmenopausal women to decrease fracture risk. However, five large-scale, randomized, controlled trials have called into question the benefits of calcium in reducing fracture risk, and four of the studies indicated that calcium users may be at increased risk for renal stones and gastrointestinal problems. However, all five studies had one or more important limitations, including possible selection bias and study participants' relatively high baseline calcium intake and generally low adherence to treatment regimens. Moreover, in some of the studies, vitamin D was not included in the treatment protocol or was not used at levels sufficient to optimize calcium absorption. In three of the five trials, subgroup analysis of the most treatment-adherent participants indicated significant reductions in osteoporotic fracture risk with calcium supplement use., Conclusion: Results of recent clinical trials indicate that calcium supplementation does not significantly reduce fracture risk in postmenopausal women. However, evidence from the same studies suggests that beneficial effects on fracture risk may be seen in women who are adherent to therapy. Postmenopausal women should continue calcium supplementation to reduce osteoporosis risk.

Purpose: The risks and benefits of long-term bisphosphonate therapy were reviewed., Summary: Bisphosphonates are used first line in the treatment of osteoporosis due to their demonstrated ability to reduce the risk of fracture. Benefits on bone mineral density (BMD) and fracture prevention appear to be sustained for 7-10 years; however, the lack of clinical trials extending beyond this treatment period has raised the question of how long therapy should be continued. Furthermore, some reports have suggested the potential for an increased risk of fragility fractures due to oversuppression of bone turnover with long-term bisphosphonate use. Though rare, these fragility fractures appear to have a specific fracture pattern and tend to occur after 3-8 years of bisphosphonate therapy. The use of a drug holiday has been considered as an option to avoid this risk. Data suggest that bisphosphonates have a residual therapeutic effect after being stopped and that fracture benefit appears to be sustained 2-5 years after discontinuation. This sustained benefit, however, was observed only in women with good adherence who were treated with bisphosphonate therapy for at least 2 years and whose BMD was not in the osteoporotic range before discontinuation., Conclusion: The benefits of long-term bisphosphonate therapy in patients at high risk of fracture likely outweigh the risks. In lower risk patients, such as those with a BMD in the osteopenic or normal range after two to five years of treatment and no history of fracture, consideration could be given to stopping therapy for two to five years.

Competencies for military nurses are much broader in scope than their civilian counterparts. Not only must they be proficient at basic nursing skills, but they must also quickly master such military skills as protecting themselves and others during attack or threat of attack, caring for major trauma victims under austere conditions, and preparing such patients for transport through the military system of evacuation. This requires consistent and specialized training. This article describes the competencies necessary for practice by military nurses., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: We evaluated the impact of migration to the USA-Mexico border city of El Paso, Texas (USA), parental language preference, and Hispanic ethnicity on childhood asthma to differentiate between its social and environmental determinants., Methods: Allergy and asthma prevalence was surveyed among 9797 fourth and fifth grade children enrolled in the El Paso Independent School District. Parents completed a respiratory health questionnaire, in either English or Spanish, and a sub-sample of children received spirometry testing at their school. Here we report asthma and allergy outcomes across ethnicity and El Paso residency duration., Results: Asthma and allergy prevalence increased with longer duration of El Paso residency independent of ethnicity and preferred language. Compared with immigrants who arrived in El Paso after entering first grade (18%), lifelong El Paso residents (68%) had more prevalent allergy (OR, 1.72; 95% CI, 1.32 - 2.24), prevalent asthma (OR, 1.75; 95% CI, 1.24 - 2.46), and current asthma (OR, 2.01; 95% CI, 1.37 - 2.95). Spirometric measurements (FEV1/FVC and FEF25-75) also declined with increasing duration of El Paso residency (0.16% and 0.35% annual reduction, respectively)., Conclusion: These findings suggest that a community-wide environmental exposure in El Paso, delayed pulmonary development, or increased health of immigrants may be associated with allergy and asthma development in children raised there.

Purpose: The relationship among metformin use, plasma lactate levels, and lactic acidosis in patients with type 2 diabetes mellitus and the appropriateness of metformin use in patients with renal dysfunction are discussed., Summary: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus. Despite this recommendation, metformin may be underutilized due to the fear of metformin-associated lactic acidosis and because its use is contraindicated in patients with renal dysfunction. Several studies have attempted to characterize the relationship among plasma metformin levels, plasma lactate levels, and lactic acidosis. However, a causal relationship between metformin and lactic acidosis has not been definitively established. In the United States, the estimated rate of lactic acidosis among diabetic patients treated with metformin is similar to that of diabetic patients not taking metformin. Despite specific guidelines advising against prescribing metformin in renal dysfunction, published reports indicate that metformin is continued in 25% of patients after the contraindication is discovered. Individual studies point to a possible correlation between metformin levels and plasma lactate levels, but mortality does not appear to correlate with plasma metformin levels. These results indicate that there may not be a direct relationship between plasma lactate and metformin levels., Conclusion: Current studies point to a weak causal relationship between metformin and lactic acidosis. In patients without comorbid conditions that would predispose them to lactic acidosis, elevated serum creatinine levels should be considered a risk factor for the development of lactic acidosis but not an absolute contraindication.

Purpose: This phase II study was conducted to determine the efficacy and safety of capecitabine and bevacizumab in untreated elderly metastatic colorectal cancer patients., Methods: Patients received 1500 mg/m(2)/dose of capecitabine twice daily x 7 days and bevacizumab at 5mg/kg on day 1, in 2 week-cycles., Results: The study was closed early, due to poor accrual, after a total of 16 patients enrolled. Four patients had an objective response and 11 patients had stable disease. The median time to progression and overall survival were 9.5 and 21.2 months, respectively. The most common grade >or= 3 toxicities included diarrhea (13%) and hand and foot syndrome (25%). Three patients had an arterial thrombotic event and one patient developed a bowel perforation., Conclusions: In this underpowered phase II study in elderly patients with metastatic colorectal cancer, capecitabine plus bevacizumab was associated with considerable clinical activity but at an increased risk of hand and foot syndrome and arterial thrombotic events.

Purpose: We conducted a phase I study to determine the maximum tolerated dose of vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin, and oxaliplatin (FOLFOX)., Experimental Design: Vorinostat was given orally twice daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg twice daily. Escalation occurred in cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and oxaliplatin were studied., Results: Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable patients at dose level 4 (vorinostat 400 mg orally twice daily) developed dose-limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and the area under the curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with day 1. The median C(max) of FU at each dose level increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was not consistent; only two of six patients had a decrease in intratumoral TS expression by reverse transcription-PCR., Conclusions: The maximum tolerated dose of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of TS expression.

Introduction: Patient falls are the most common adverse events reported in hospitals. There is a growing body of literature on inpatient falls but a lack of data on ED falls. We applied the Hendrich II Fall Risk Model to patients who fell during their ED stays and provided a description of the patients and their injuries., Methods: We retrospectively reviewed the medical records of all patients who fell in the emergency department during a 2-year period. We collected the 8 assessment parameters for high-risk fall identification in the Hendrich II Fall Risk Model. We also collected subject characteristics, circumstances surrounding the falls, fall-related injuries, and ED disposition., Results: Fifty-seven falls were recorded, representing a rate of 0.288 falls per 1000 patient visits. The average age was 50 years, and a median of 48. 67% were men. Twenty-one subjects had a Hendrich II Model score of 5 of greater, which represents a sensitivity of 37.5%. Eleven subjects (19.6%) were intoxicated with alcohol. Eleven subjects (19.6%) received a potentially sedating medication prior to the fall. Thirty-six subjects (64.3%) fell in their ED rooms. Six subjects (10.7%) fell in the restroom. Three falls (5.4%) resulted in lacerations and 2 falls (3.6%) resulted in hematomas., Discussion: The Hendrich II Fall Risk Model may not reliably identify patients at high risk of falling in the ED setting. It may be necessary to develop an emergency department-specific fall model considering additional factors, such as intoxication and receipt of potentially sedating medications.

Background: There is a wealth of first- (type or extent) and second- (causes) generation health disparities research. Literature on health disparities interventions (third-generation research) is emerging. In this study, we compiled and qualitatively evaluated interventions to eliminate health disparities in cardiovascular disease (CVD) among African Americans., Methods: We reviewed articles published from 1996 through 2006. Inclusion criteria were focus on CVD, African American participants, and intervention, including evaluation data. Two readers evaluated each abstract for including in the full review, and a third reader resolved incongruence. Articles with abstracts that received at least 2 votes for inclusion were reviewed in their entirety by 2 readers. Data were recorded in a Microsoft Access database., Results: Of 524 abstracts identified, 111 were selected for full review. Only 33 articles were considered third-generation health disparities research by 2 readers and 23 by 1 reader. Approximately half of the interventions were in high-risk populations (low income, low education, urban) and hypertension and nutrition and physical activity were the most common focuses. Of the 33 that received 2 votes, the interventions that received the most enthusiasm from the reviewers used community-based clinics with lay health volunteers. The intensity of the intervention was not correlated with outcome., Conclusions: While not widely published, third-generation health disparities research demonstrates interventions to reduce CVD among African Americans. More of this type of research is necessary, and those results must be disseminated.

One hundred twenty one opiate-dependent individuals in methadone maintenance treatment at an urban university medical center in the U.S. were administered the Inventory of Drug Use Consequences (InDUC), and 68 subjects provided follow-up assessments at two to six weeks. The sample included 61 (50.4%) women; 86 (71.1%) of the subjects reported that they were White, 29 (24.0%) Black, and six (5.0%) other race. The mean age was 41.9 (SD = 9.7) years. Ninety-nine (81.8%) of participants had used opiates intravenously. INDUC total scores and a short form showed high internal consistency (alpha) and test-retest reliability (ICC) across gender, race, ethnicity, and education, supporting their use as global measures of drug use consequences. The interpersonal scale was also reliable across strata whereas the physical and intrapersonal scales were not reliable. The impulse control and social responsibility scales were stable but not internally consistent.