"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Social isolation-induced changes in the hypothalamic-pituitary-adrenal axis in the rat

Social isolation of rats both reduces the cerebrocortical and plasma concentrations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) and 3 alpha,5 alpha-tetrahydrodeoxycorticosterone and potentiates the positive effects of acute stress and ethanol on the concentrations of these neuroactive steroids. We now show that social isolation decreased the plasma level of adrenocorticotropin ( ACTH), moreover, intracerebroventricular administration of corticotropin releasing factor (CRF) induced a marked increase in the plasma corticosterone level in both isolated and group-housed rats, but this effect was significantly greater in the isolated rats (+121%) than in the group-housed rats (+/- 86%). In addition, in isolated rats, a low dose of dexamethasone had no effect on the plasma corticosterone concentration, whereas, a high dose significantly reduced it; both doses of dexamethasone reduced plasma corticosterone in group-housed rats. Furthermore, the corticosterone level after injection of dexamethasone at the high dose was significantly greater in the isolated animals than in the group-housed rats. These results suggest that social isolation increased sensitivity of the pituitary to CRF and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis

Anticipation and consumption of food each increase the concentration of neuroactive steroids in rat brain and plasma

Stressful stimuli and anxiogenic drugs increase the plasma and brain concentrations of neuroactive steroids. Moreover, in rats trained to consume their daily meal during a fixed period, the anticipation of food is associated with changes in the function of various neurotransmitter systems. We have now evaluated the effects of anticipation and consumption of food in such trained rats on the plasma and brain concentrations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH DOC), two potent endogenous positive modulators of type A receptors for gamma-aminobutyric acid (GABA). The abundance of these neuroactive steroids was increased in both the cerebral cortex and plasma of the rats during both food anticipation and consumption. In contrast, the concentration of their precursor, progesterone, was increased in the brain only during food consumption, whereas it was increased in plasma only during food anticipation. Intraperitoneal administration of the selective agonist abecarnil (0.1 mg/kg) 40 min before food presentation prevented the increase in the brain levels of 3 alpha,5 alpha-TH PROG and 3 alpha,5 alpha-TH DOC during food anticipation but not that associated with consumption. The change in emotional state associated with food anticipation may thus result in an increase in the plasma and brain levels of 3 alpha,5 alpha-TH PROG and 3 alpha,5 alpha-TH DOC in a manner sensitive to the activation of GABA(A) receptor-mediated neurotransmission. A different mechanism, insensitive to activation of such transmission, may underlie the changes in the concentrations of these neuroactive steroids during food consumption. (c) 2006 Published by Elsevier Inc

Household-Based Costs and Benefits of Vaccinating Healthy Children in Daycare Against Influenza Virus: Results from a Pilot Study

Background: Vaccinating children against influenza virus may reduce infections in immunised children and household contacts, thereby reducing the household-based cost associated with respiratory illnesses. Objective: To evaluate the impact of influenza virus vaccination of daycare children on costs of respiratory illnesses of the children and their household contacts from the household and societal perspective. Study design: Cost analysis of data from a randomised controlled trial covering the period November to April of 1996-7 and 1998-9. Children (127 in 1996-7 and 133 in 1998-9) from daycare centres in Californian (USA) naval bases received influenza virus vaccine (inactivated) or hepatitis A virus vaccination. Outcome measures: Direct and indirect costs (1997 and 1999 US dollars) of respiratory illnesses in households of vaccinated and not vaccinated daycare children, excluding the cost of vaccination. Results: There were no statistically significant differences in household costs of respiratory illness between households with or without influenza virus-vaccinated children ($US635 vs$US492: p = 0.98 [1996-7]; $US412.70 vs$US499.50: p = 0.42 [1998-9]). In 1996-7, adult and 5- to 17-year-old contacts of vaccinated children had lower household costs than contacts of unvaccinated children ($US58.50 vs$US83.20, p = 0.01 and $US32.80 vs$US59.50, p = 0.04, respectively), while vaccinated children 0-4 years old had higher household costs than unvaccinated children in the same age group ($US383 vs$US236, p = 0.05). In 1998-9, there were no differences within individual age groups. Results from societal perspective were similar. Conclusions: Overall, from both the household and societal perspectives, there were no economic benefits to households from vaccinating daycare children against influenza virus. However, we found some over-time inconsistency in results; this should be considered if changing recommendations about routine influenza virus vaccination of healthy children. Our study size may limit the generalisability of the results.Children, Cost-analysis, Influenza-virus-infections, Influenza-virus-vaccine

Pharmaceuticals companies\u27 medication assistance programs: potentially useful but too burdensome to use

OBJECTIVES: This study examined how physicians perceive pharmaceutical companies\u27 medication assistance programs (MAPs). METHODS: The study was conducted using a survey of 373 primary care physicians from four southern states; they were surveyed within the formative evaluation phase of a larger study (MI-Plus). Respondents were queried about use and usefulness of MAPs for patients who cannot afford drugs, and barriers to using them. Bivariate associations between physician-level variables (patients without drug coverage) and usefulness and barriers to using MAPs were assessed using Chi square tests. Independence of associations was assessed using multiple logistic regressions. RESULTS: Of the 364 (97.6%) respondents who used MAPs, 70% used them regularly, the rest occasionally; 63% found MAPs very useful in caring for patients who could not afford drugs. About 89% reported one or more barriers to using MAPs; 47% saw inability of patients to apply directly; and 57% saw enrollment process being time-consuming for staff as barriers. Compared to physicians with fewer elderly patients without drug coverage, those with more of these patients were less likely to find MAPs very useful; less likely to report no barriers to using MAPs; and more likely to see low income thresholds and inability of patients to apply directly as barriers. CONCLUSION: While MAPs are considered useful in caring for patients in need of assistance, there are many barriers to their use. Pharmaceutical companies should address these barriers. Limitations include a low response rate (about 10%)

Increased expression of the gene for the Y-1 receptor of neuropeptide Y in the amygdala and paraventricular nucleus of Y1R/LacZ transgenic mice in response to restraint stress

A sustained increase in the brain concentrations of neuroactive steroids was previously shown to induce Y-1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice which harbour a construct comprising the murine Y-1 receptor gene promoter and the lacZ reporter gene. We now investigated the effects of restraint stress on both the cerebrocortical concentrations of neuroactive steroids and Y-1 receptor gene expression in the amygdala and hypothalamic paraventricular nucleus (PVN) of Y1R/LacZ transgenic mice. The cerebrocortical concentrations of allopregnanolone and allotetrahydrodeoxycorticosterone were significantly increased immediately after a 1-h exposure to restraint stress and had returned to control values within 30 min. Expression of Y1R/LacZ was increased in the amygdala and PVN 6 h after restraint. The 5alpha-reductase inhibitor finasteride, that prevented the increase in neuroactive steroid concentrations, did not block that in transgene expression induced by 1-h restraint. Daily exposure to restraint for 10 days also increased the cerebrocortical concentrations of neuroactive steroids but failed to affect transgene expression. Acute but not repeated restraint thus increases Y-1 receptor gene expression in the amygdala and PVN, suggesting that tolerance develops towards this stressor. The effect of acute restraint is not mediated by the increase in the brain concentrations of neuroactive steroids but may rather reflect a ligand-induced increase in Y-1 receptor gene transcription. Data support a role of Y-1 receptors in the behavioural and neuroendocrine responses to stress

Social isolation-induced increase in the sensitivity of rats to the steroidogenic effect of ethanol

Social isolation of rats for 30 days immediately after weaning results in marked decreases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, 3a-hydroxy-5apregnan-20-one (3a,5a-TH PROG), and 3a,5a-tetrahydrodeoxycorticosterone (3a,5a-TH DOC), as well as a moderate increase in the plasma concentration of corticosterone. This mildly stressful condition has now been shown to increase the sensitivity of rats to the effect of acute ethanol administration on the cerebrocortical and plasma concentrations of neuroactive steroids. The percentage increases in the brain and plasma concentrations of pregnenolone, progesterone, 3a,5a-TH PROG, and 3a,5a-TH DOC, apparent 20 min after a single intraperitoneal injection of ethanol (1 g/kg), were thus markedlygreater in isolated rats than in group-housed animals. A subcutaneous injection of isoniazid (300 mg/kg) also induced greater percentage increases in the concentrations of these steroids in isolated rats than in group-housed animals. These results suggest that mild chronic stress, such as that induced by social isolation, enhances the steroidogenic effect of ethanol, a drug abused by humans under stress or affected by neuropsychiatric disorders. Social isolation also induced hyperresponsiveness of the hypothalamic–pituitary–adrenal (HPA) axis, as was apparent after reduction of GABA-mediated inhibitory tone by isoniazid administratio

Development of a novel technique for the measurement of neuromuscular junction functionality in isotonic conditions

Introduction: The neuromuscular junction (NMJ) is a chemical synapse responsible for converting electrical pulses generated by the motor neuron into electrical activity in muscle fibers, and is severely impaired in various diseases, such as Amyotrophic Lateral Sclerosis (ALS). Here, we proposed a novel technique to measure, for the first time, NMJ functionality in isotonic conditions, which better reflect muscle physiological activity. Methods: We employed the in-situ testing technique, studied a proper placing of two pairs of wire electrodes for nerve and muscle stimulation, developed an extensive testing protocol, and proposed a novel parameter, the Isotonic Neurotransmission Failure (INF), to properly capture the impairments in neurotransmission during isotonic fatigue. We employed wild-type mice to assess the feasibility of the proposed technique, and the ALS model SOD1G93A mice to demonstrate the validity of the INF. Results: Results confirmed the measurement accuracy in term of average value and coefficient of variation of the parameters measured through nerve stimulation in comparison with the corresponding values obtained for membrane stimulation. The INF values computed for the SOD1G93A tibialis anterior muscles pointed out an impairment of ALS mice during the isotonic fatigue test, whereas, as expected, their resistance to fatigue was higher. Conclusions: In this work we devised a novel technique and a new parameter for a deep assessment of NMJ functionality in isotonic conditions, including fatigue, which is the most crucial condition for the neuronal signal transmission. This technique may be applied to other animal models, to unravel the mechanisms behind muscle-nerve impairments in other neurodegenerative pathologies