Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039)

Group II metabotropic glutamate (mGlu) receptor agonists, including (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), have demonstrated efficacy in animal models of anxiety and schizophrenia, and LY354740 decreased anxiety in human subjects. Herein, we report the in vitro pharmacological profile and pharmacokinetic properties of another potent, selective, and structurally novel mGlu2/3 receptor agonist, (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039) and provide comparisons with LY354740. Similar to LY354740, LY404039 is a nanomolar potent agonist at recombinant human mGlu2 and mGlu3 receptors (K(i) = 149 and 92, respectively) and in rat neurons expressing native mGlu2/3 receptors (Ki = 88). LY404039 is highly selective for mGlu2/3 receptors, showing more than 100-fold selectivity for these receptors, versus ionotropic glutamate receptors, glutamate transporters, and other receptors targeted by known anxiolytic and antipsychotic medications. Functionally, LY404039 potently inhibited forskolin-stimulated cAMP formation in cells expressing human mGlu2 and mGlu3 receptors. Electrophysiological studies indicated that LY404039 suppressed electrically evoked excitatory activity in the striatum, and serotonin-induced l-glutamate release in the prefrontal cortex; effects reversed by LY341495. These characteristics suggest LY404039 modulates glutamatergic activity in limbic and forebrain areas relevant to psychiatric disorders; and that, similar to LY354740, it works through a mechanism that may be devoid of negative side effects associated with current antipsychotics and anxiolytics. Interestingly, despite the slightly lower potency (approximately 2-5-fold) of LY404039 versus LY354740 in binding, functional, and electrophysiological assays, LY404039 demonstrated higher plasma exposure and better oral bioavailability in pharmacokinetic experiments. Collectively, the current data indicate that LY404039 may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis.     

A single-item approach to screening elders for oral health assessment

BACKGROUND: Oral health contributes significantly to overall health. Finding a single item that can be used by primary care providers to screen elders who are in need of oral care is important. OBJECTIVES: The objective of this article was to evaluate usefulness of the item: "Do you have regular dental checkups?" as a means to decide whether an oral health assessment or further referral is indicated. Answering no is postulated as a positive predictor of poor oral health and need for care. METHODS: This study was a secondary analysis of a nutritional survey of 240 community-dwelling elders. Examiner-rated Kayser-Jones Brief Oral Health Status Examination; self-reported General Oral Health Assessment Index; number of remaining teeth; and pattern of checkups (regular vs. irregular) were evaluated by a trained gerontological nurse practitioner during an in-home assessment. RESULTS: A dental visit within the past year for any reason was reported by 132 subjects (55.0%), but only 81 (33.8%) reported some sort of regular dental checkups. For dentate elders (n = 147), an irregular checkup was associated with lower educational level, Protestant faith, and Black race. People with irregular checkups scored significantly lower on all three oral indices. The negative predictive values and likelihood ratio negative values ranged 98.7-100.0% and 0.00-0.98, respectively, indicating that this item of interest is valid for ruling-out dentate subjects with good oral health. For edentulous elders (n = 93), the item was less effective. DISCUSSION: A single item, "Do you have regular dental checkups?" can be used effectively to rule out dentate elders with good oral health and identify those who are in need of further oral health assessment or referrals.     

Visual graphical analysis: a technique to investigate symptom trajectories over time

BACKGROUND: Research to address clinical symptoms and the way they change over time in an individual is of paramount importance to healthcare researchers who are interested in improving the quality of life for ill patients. However, typical statistical methods that rely on means can obscure individual trajectories of change. Visual graphical analysis (VGA) is a technique that can provide researchers with an alternative method of quantitative statistical analysis that is more sensitive to individual change and variation. OBJECTIVES: To (a) describe the use of VGA as a method to evaluate longitudinal data, (b) discuss challenges to using this method, and (c) offer recommendations for future research in which the method could be implemented. APPROACH: This methodological article uses data collected from a primary study to present the method of VGA. Daily self-reported sore mouth severity scores from patients receiving outpatient chemotherapy were used in this VGA. The steps of VGA include (a) determining inclusion criteria, (b) managing missing data, (c) creating visual graphs, (d) identifying specific patterns, and (e) performing validation and verification. DISCUSSION: Because symptoms occur differently for each patient, this method allows researchers to see symptom trajectories on an individual basis. Creation and analysis of longitudinal graphs could be used also to inspect other symptoms or clinical problems such as headaches, fatigue, constipation, nausea and vomiting, and psychological difficulties. The value of VGA is that it allows a researcher to study the patterns of an individual's experience, as opposed to averaging all individuals' responses over time. Although graphical analysis is exploratory in nature, it may lead to enhanced longitudinal recognition of symptoms that might not be identified otherwise by quantitative data analysis using summary statistics.     

Nursing home residents in emergency departments: a Foucauldian analysis

AIM: This paper is a critical review of current knowledge about use of emergency departments by nursing home residents. BACKGROUND: A great deal of literature focuses on the challenges presented by older adults in acute care environments. Nursing home residents who transfer to emergency departments have been identified as being particularly problematic because they use considerable resources and their needs are not always amenable to acute interventions. METHOD: A literature search was conducted in May 2006 using the CINAHL, Medline and Cochrane databases and Google Scholar with the keywords 'nursing home resident', 'long-term care resident', 'hospital transfer', and 'acute illness and emergency room'. No date restrictions were imposed. Foucault's concept of subjectivity was used to demonstrate how power derived from medical knowledge is used by emergency department personnel to construct nursing home residents as problematic. FINDINGS: Knowledge about the use of emergency departments by nursing home residents has been derived mainly from retrospective record reviews, while the events in nursing homes that lead to transfers have been virtually ignored. Moreover, the primary focus of these investigations has been the effect of residents on emergency departments, rather than how residents themselves were affected. CONCLUSION: Current understanding of the care of nursing home residents in emergency departments is embedded in a complex web of social, historical and political factors. Research is needed that considers multiple perspectives, including those of both emergency department and nursing home staff, residents and ambulance personnel who act as mediators between the two settings.     

Informal stroke rehabilitation: what are the main reasons of Thai caregivers?

The aim of this study was to identify the reasons for the provision of informal rehabilitation services at home to stroke relatives by Thai caregivers. Twenty primary informal caregivers were individually interviewed at their homes by using semistructured questions elaborated by the researchers. All interviews were recorded on audiotape. Content analysis was used to determine the reasons for performing informal rehabilitation. Four major reasons, (i) biological, (ii) psychological, (iii) social, and (iv) spiritual, emerged from our content analysis to maintain for the stroke victims the highest possible quality of life. Improvement and prevention of further deterioration were the two main concepts in the biological and psychological reasons expressed by these Thai caregivers, whereas maintaining human relations and usual social activities were the two main considerations in the social reason. The main concepts in the spiritual reason were respecting the religious beliefs, superstitions, and culture of the caregivers or patients, improving patients' empowerment, and improving caregivers' satisfaction. These four reasons encompassed the biological, psychological, social, and spiritual aspects of a holistic approach to the definition of health. The health professional in Thailand should encourage stroke caregivers to continue providing informal rehabilitation services for their stroke relatives, as it might sustain the well being of stroke survivors during their stay at home.     

The impact of organizational culture on clinical managers' organizational commitment and turnover intentions

OBJECTIVES: The purpose was to investigate managers' perceptions of organizational culture and attitudinal and behavioral reactions during and after restructuring, and to test a model linking culture to outcome. BACKGROUND: Healthcare reform has altered the work environment, but few studies have documented the impact of system changes on managers responsible for clinical services. METHODS: Survey data were collected from clinical managers (N = 104; 99) employed by 3 institutional boards in Newfoundland and Labrador in 2000 and 2002. Response rates were 57.6% and 47.7%, respectively. RESULTS: For both periods, most variable ratings were in the low range and depicted moderately, positive intercorrelations. Select culture variables, trust, and job satisfaction emerged as significant predictors of commitment. Although culture and trust exerted inconsistent effects on intent, satisfaction remained a predictor over time. CONCLUSION: The findings support the negative impact of reform on clinical managers, and the strong link between positive ratings of culture, trust, and satisfaction, and greater commitment and intent to stay. Greater attention should focus on promoting more positive cultures and work-related attitudes, and less turnover intentions.     

The abused female oral and maxillofacial surgery patient: treatment approaches for identification and management

Violence and abuse affect one in four women during their lifetime. Specifically, a woman seeking treatment of a facial injury has a one in three chance of being a victim of violence and abuse. Many dental professionals, however, are uncomfortable discussing these issues with potential victims. The oral and maxillofacial surgeon is in a unique position to approach the topic of violence and abuse. This article discusses violence and abuse as it pertains to the female patient and family members. Suggestions for screening and evaluation of patients are discussed. The overall importance of timely identification for stopping this cycle of violence and abuse and the obligations of health care providers are also addressed.     

Headache associated with miller fisher syndrome

Miller Fisher syndrome, a variant of Guillain-Barre syndrome, is composed of the clinical triad of ophthalmoplegia, ataxia, and areflexia. A variety of other symptoms and signs have been reported in this syndrome, but headache is not a commonly reported symptom. We report a 35-year-old man with anti-GQ(1b) antibody-confirmed Miller Fisher syndrome presenting with severe and persistent headache, and we propose that the headache is caused by antibody-mediated effects on the trigeminovascular pain pathway.     

Management of access to branded psychotropic medications in private health plans

BACKGROUND: In the past decade, health insurers have increased their reliance on cost control policies such as prior authorization and 3-tier formularies. Little is known about how these policies are being applied to psychotropic medications, many of which have low rates of patient adherence. OBJECTIVE: This study reports on plans' cost-sharing tier placement and authorization policies for 12 brand only psychotropic medications in 3 classes: antidepressants, anti-psychotics, and medications for attention deficit/hyperactivity disorder (ADFID). METHODS: Data were from a nationally representative survey of private health plans regarding mental health and substance-abuse services in 2003; 368 plans responded (83% response rate). Results were weighted and represent national estimates of health-plan characteristics. RESULTS: The majority of insurance products provided unrestricted placement on Tier 2 (medium copayment) for at least 2 brand-only antidepressants and at least 2 brand-only antipsychotics. This approach allows clinicians some limited leeway in initial medication selection. However, most patients who did not respond to the Tier-2 options typically faced a substantial escalation in copayment (Tier 3), possibly leading to premature medication discontinuation. For ADHI)5 the options were considerably more limited, with 22.1% of products applying some restriction to all 3 medications and only 15.9% of products leaving all 3 medications unrestricted. Plans with specialty contracts for mental health were considerably more likely to use Tier 3 (highest copayment) as their only restriction approach. CONCLUSIONS: Based on the results of this analysis,private plans were managing psychotropic costs using copayment incentives rather than administrative controls. This approach was less intrusive for clinicians, but resulting higher copayments could worsen already high rates of nonadherence; future research should examine this issue.