Health-related quality of life in patients with human immunodeficiency virus infection in the United States: results from the HIV Cost and Services Utilization Study

PURPOSE: To measure health-related quality of life among adult patients with human immunodeficiency virus (HIV) disease; to compare the health-related quality of life of adults with HIV with that of the general population and with patients with other chronic conditions; and to determine the associations of demographic variables and disease severity with health-related quality of life. SUBJECTS AND METHODS: We studied 2,864 HIV-infected adults participating in the HIV Cost and Services Utilization Study, a probability sample of adults with HIV receiving health care in the contiguous United States (excluding military hospitals, prisons, or emergency rooms). A battery of 28 items covering eight domains of health (physical functioning, emotional well-being, role functioning, pain, general health perceptions, social functioning, energy, disability days) was administered. The eight domains were combined into physical and mental health summary scores. SF-36 physical functioning and emotional well-being scales were compared with the US general population and patients with other chronic diseases on a 0 to 100 scale. RESULTS: Physical functioning was about the same for adults with asymptomatic HIV disease as for the US population [mean (+/- SD) of 92+/-16 versus 90+/-17) but was much worse for those with symptomatic HIV disease (76+/-28) or who met criteria for the acquired immunodeficiency syndrome (AIDS; 58+/-31). Patients with AIDS had worse physical functioning than those with other chronic diseases (epilepsy, gastroesophageal reflux disease, clinically localized prostate cancer, clinical depression, diabetes) for which comparable data were available. Emotional well-being was comparable among patients with various stages of HIV disease (asymptomatic, 62+/-9; symptomatic, 59+/-11; AIDS, 59+/-11), but was significantly worse than the general population and patients with other chronic diseases except depression. In multivariate analyses, HIV-related symptoms were strongly associated with physical and mental health, whereas race, sex, health insurance status, disease stage, and CD4 count were at most weakly associated with physical and mental health. CONCLUSIONS: There is substantial morbidity associated with HIV disease in adults. The variability in health-related quality of life according to disease progression is relevant for health policy and allocation of resources, and merits the attention of clinicians who treat patients with HIV disease.     

Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Wnt8a and Wnt3a cooperate in the axial stem cell niche to promote mammalian body axis extension

Background: Vertebrate body axis extension occurs in a head‐to‐tail direction from a caudal progenitor zone that responds to interacting signals. Wnt/β‐catenin signaling is critical for generation of paraxial mesoderm, somite formation, and maintenance of the axial stem cell pool. Body axis extension requires Wnt8a in lower vertebrates, but in mammals Wnt3a is required, although the anterior trunk develops in the absence of Wnt3a. Results: We examined mouse Wnt8a^–/– and Wnt3a^–/– single and double mutants to explore whether mammalian Wnt8a contributes to body axis extension and to determine whether a posterior growth function for Wnt8a is conserved throughout the vertebrate lineage. We find that caudal Wnt8a is expressed only during early somite stages and is required for normal development of the anterior trunk in the absence of Wnt3a. During this time, we show that Wnt8a and Wnt3a cooperate to maintain Fgf8 expression and prevent premature Sox2 up‐regulation in the axial stem cell niche, critical for posterior growth. Similar to Fgf8, Wnt8a requires retinoic acid (RA) signaling to restrict its caudal expression boundary and possesses an upstream RA response element that binds RA receptors. Conclusions: These findings provide new insight into interaction of caudal Wnt‐FGF‐RA signals required for body axis extension. Developmental Dynamics 244:797–807, 2015. © 2015 Wiley Periodicals, Inc.     

Impact of Critical Illness Polyneuromyopathy in Rehabilitation: A Prospective Observational Study

Background

Critical illness polyneuromyopathy (CIPNM) increasingly is recognized as a source of disability in patients requiring intensive care unit (ICU) admission. The prevalence and impact of CIPNM on patients in the rehabilitation setting has not been established.

Considerations for Incorporating “Well-Being” in Public Policy for Workers and Workplaces

Action to address workforce functioning and productivity requires a broader approach than the traditional scope of occupational safety and health. Focus on “well-being” may be one way to develop a more encompassing objective. Well-being is widely cited in public policy pronouncements, but often as “. . . and well-being” (e.g., health and well-being). It is generally not defined in policy and rarely operationalized for functional use. Many definitions of well-being exist in the occupational realm. Generally, it is a synonym for health and a summative term to describe a flourishing worker who benefits from a safe, supportive workplace, engages in satisfying work, and enjoys a fulfilling work life. We identified issues for considering well-being in public policy related to workers and the workplace.Major changes in population demographics and the world of work have significant implications for the workforce, business, and the nation.1–8 New patterns of hazards, resulting from the interaction of work and nonwork factors, are affecting the workforce.1,2,8–11 As a consequence, there is a need for an overarching or unifying concept that can be operationalized to optimize the benefits of work and simultaneously address these overlapping hazards. Traditionally, the distinct disciplines of occupational safety and health, human resources, health promotion, economics, and law have addressed work and nonwork factors from specialized perspectives, but today changes in the world of work require a holistic view.There are numerous definitions of well-being within and between disciplines, with subjective and objective orientations addressing such conceptualizations as happiness, flourishing, income, health, autonomy, and capability.12–22 Well-being is widely cited in public policy pronouncements, but often in the conjunctive form of “. . . and well-being” (as in health and well-being). It is rarely defined or operationalized in policy.In this article, we consider if the concept of “well-being” is useful in addressing contemporary issues related to work and the workforce and, if so, whether it can be operationalized for public policy and what the implications are of doing so. We discuss the need to evaluate a broad range of work and nonwork variables related to worker health and safety and to develop a unified approach to this evaluation. We discuss the potential of well-being to serve as a unifying concept, with focus on the definitions and determinants of well-being. Within this part of the discussion, we touch on topics of responsibility for well-being. We also explore issues of importance when one is incorporating well-being into public policy. We present examples of the incorporation of the principles of well-being into public policy, and the results thus far of the implementation of such guidance. We describe research needs for assessing well-being, particularly the need to operationalize this construct for empirical analysis. We aim to contribute to the ongoing efforts of occupational safety and health and public health researchers, practitioners, and policymakers to protect working populations.     

Role of clinical suspicion in pediatric blunt trauma patients with severe mechanisms of injury

Objectives

In adult patients with blunt trauma, severe mechanism of injury leads to routine pan-computed tomography (CT). Due to concerns about the risk of radiation, we sought to determine whether clinical suspicion could identify children requiring radiographic imaging.

Moving research tools into practice: the successes and challenges in promoting uptake of classification tools

Purpose: In this paper, we present our experiences – both successes and challenges – in implementing evidence-based classification tools into clinical practice. We also make recommendations for others wanting to promote the uptake and application of new research-based assessment tools.

Method: We first describe classification systems and the benefits of using them in both research and practice. We then present a theoretical framework from Implementation Science to report strategies we have used to implement two research-based classification tools into practice. We also illustrate some of the challenges we have encountered by reporting results from an online survey investigating 58 Speech-language Pathologists’ knowledge and use of the Communication Function Classification System (CFCS), a new tool to classify children’s functional communication skills.

Result and conclusions: We offer recommendations for researchers wanting to promote the uptake of new tools in clinical practice. Specifically, we identify structural, organizational, innovation, practitioner, and patient-related factors that we recommend researchers address in the design of implementation interventions. Roles and responsibilities of both researchers and clinicians in making implementations science a success are presented.

• Implications for rehabilitation

• Promoting uptake of new and evidence-based tools into clinical practice is challenging.

• Implementation science can help researchers to close the knowledge-to-practice gap.

• Using concrete examples, we discuss our experiences in implementing evidence-based classification tools into practice within a theoretical framework.

• Recommendations are provided for researchers wanting to implement new tools in clinical practice. Implications for researchers and clinicians are presented.

     

Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System

Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT_2AR receptor (5-HT_2AR) promote and 5-HT_2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT_2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT_2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT_2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT_2AR binding density in frontal cortex ([³H]-ketanserin radioligand binding). Elevated mPFC 5-HT_2AR protein expression concomitant with augmented association of the 5-HT_2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT_2AR ligands and associated distinct 5-HT_2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT_2AR system.