Pharmacist Prescribing in Pediatric and Neonatal Acute Care: An Observational Study.

OBJECTIVE: The intent of this project was to objectively describe the frequency of pharmacist prescribing in acute care pediatrics and neonatology and to determine the medications most often prescribed by pharmacists practicing in a jurisdiction that permits pharmacists' prescribing. METHODS: This was a subgroup analysis of a retrospective observational study using prescribing data from an electronic medical record system used in 5 acute care hospitals (1 pediatric, 4 primarily adult but with pediatric and neonatal units) within Calgary, Alberta, Canada. RESULTS: Considering orders for pediatric or neonatal patients only, there was a mean (SD) of 126 (226) prescriptions per pharmacist per year, with a wide range (1-1101 per year). Considering only the 9 clinical pharmacist full-time equivalents (FTEs) assigned to pediatrics and/or neonatology (i.e., not including dispensary pharmacist FTE), this represents 572 prescriptions per clinical pharmacist FTE per year (726 in pediatrics and 380 in neonatology). The most common medication classes on pediatric units included anti-infective agents, central nervous system agents, and gastrointestinal agents. In NICUs, blood formation, coagulation and thrombosis agents (mainly iron), electrolytes, caloric and water balance agents (primarily sodium supplements), and vitamins were also commonly prescribed by pharmacists. CONCLUSIONS: As the scope of pharmacy practice expands to include prescribing, health team leadership can use these data to support incorporation of this role into practice. Prescribing pharmacists can ensure appropriate use of many medications used in acutely ill infants and children, potentially improving efficiency and quality of care.

Transabdominal ultrasound to assess pelvic floor muscle performance during abdominal curl in exercising women.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess pelvic floor muscle (PFM) function using transabdominal ultrasound (TAUS) in women attending group exercise classes. Specific aims were to: (1) identify the ability to perform a correct elevating PFM contraction and (2) assess bladder-base movement during an abdominal curl exercise. METHODS: Ninety women participating in group exercise were recruited to complete a survey and TAUS assessment performed by two qualified Continence and Women's Health physiotherapists with clinical experience in ultrasound scanning. The assessment comprised three attempts of a PFM contraction and an abdominal curl exercise in crook lying. Bladder-base displacement was measured to determine correct or incorrect activation patterns. RESULTS: Twenty-five percent (n = 23) of women were unable to demonstrate an elevating PFM contraction, and all women displayed bladder-base depression on abdominal curl (range 0.33-31.2 mm). Parous women displayed, on average, significantly more bladder-base depression than did nulliparous women [15.5 (7.3) mm vs 11.4 (5.8) mm, p < 0.009). Sixty percent (n = 54) reported stress urinary incontinence (SUI). There was no association between SUI and the inability to perform an elevating PFM contraction (p = 0.278) or the amount of bladder-base depression with abdominal curl [14.1 (7.6) mm SUI vs 14.2 (6.7) mm non-SUI]. CONCLUSIONS: TAUS identified that 25 % of women who participated in group exercise were unable to perform a correctly elevating PFM contraction, and all depressed the bladder-base on abdominal curl. Therefore, exercising women may be at risk of PFM dysfunction when performing abdominal curl activities.

Comparison of the effects of estradiol and progesterone on serotonergic function.

BACKGROUND: Ovarian hormones may contribute to the vulnerability to depression, as well as to the response to antidepressants (ADs). Previously, we reported that acute systemic treatment with estradiol or progesterone blocked the ability of the selective serotonin reuptake inhibitor, fluvoxamine, to inhibit serotonin transporter function in ovariectomized rats. In this study, behavioral consequences, as well as receptor mechanisms underlying these hormonal effects, were investigated. METHODS: Using the forced swimming test, the acute effect of estradiol and/or progesterone on fluvoxamine's AD-like effects was investigated. Using in vivo chronoamperometry, the effect of local application of estradiol or progesterone into the hippocampus of ovariectomized rats on serotonin (5-HT) clearance, as well as on the ability of fluvoxamine to slow 5-HT clearance, were investigated. RESULTS: The decreased immobility and increased swimming caused by fluvoxamine in the forced swimming test was blocked in rats treated with estradiol and/or progesterone. Local application of estradiol, but not progesterone, slowed 5-HT clearance and both hormones blocked the ability of fluvoxamine to slow 5-HT clearance. Use of hormone receptor agonists and antagonists, revealed that the effects of estradiol are mediated by activation of membrane, as well as nuclear estrogen receptors (ER). The AD-like effect of estradiol involved ER beta and G-protein coupled receptor 30, whereas its blockade of fluvoxamine's effects was ER alpha-mediated. The effects of progesterone occurred solely by activation of intracellular progesterone receptors. CONCLUSIONS: Targeting of ER beta or G-protein coupled receptor 30 might reveal a strategy to permit beneficial effects of estrogen without its deleterious effect on selective serotonin reuptake inhibitor efficacy.

The α7 nicotinic acetylcholine receptor and the acute stress response: maternal genotype determines offspring phenotype.

α7 Nicotinic acetylcholine receptors (α7nAchRs) modulate immune activation by suppressing production of pro-inflammatory cytokines in peripheral immune cells. α7nAchRs also modulate inhibitory output in the hippocampus, which provides input to key circuits of the HPA axis. Therefore, the α7 nicotinic acetylcholine receptor gene (CHRNA7) may be associated with cortisol stress response. Polymorphisms in the CHRNA7 promoter decrease its expression and may dampen the cholinergic response, leading to an increase in inflammation. Increased inflammation may change the intrauterine environment, altering neuroendocrine development in the offspring. Maternal CHRNA7 genotype could affect an offspring's HPA regulation via reprogramming in utero. Patients with allergic disorders have a differential cortisol response to stress. This study utilized samples collected from a cohort of 198 adolescents in a previous study of atopic disorders, who demonstrated a disturbance in HPA response associated with atopy. Salivary cortisol samples collected from the adolescents after a series of laboratory procedures and DNA samples collected from the adolescents and their parents were used for further analysis. DNA samples were genotyped for allelic variation in the CHRNA7 promoter. Genetic association analyses with the cortisol levels were performed in the adolescents. Maternal genotype influences were investigated for the CHRNA7 gene. We also included maternal and child atopy diagnosis as covariates in determining cortisol levels and tested for association of CHRNA7 to atopy. Polymorphisms in the CHRNA7 promoter were associated with lower cortisol levels after a small laboratory stress. Our findings also show that although the child's CHRNA7 genotype affects stress response, the maternal genotype has a stronger influence on cortisol release after stress in male offspring. These effects were independent of atopy status.

Validation of a new micro-manometer pressure sensor for cardiovascular measurements in mice.

Abstract The Scisense (London, ON, Canada) micro-manometer pressure sensor is currently being used by investigators to evaluate cardiovascular physiology in mice, but has not been validated to date. The purpose of the current study is to compare the 1.2 F Scisense pressure sensor to the current gold standard produced by Millar Instruments (Houston, TX) (1.4 F). In vitro comparisons were preformed including temperature drift, frequency response analysis up to 250 Hz, and damping coefficient and natural frequency determined via a pop test. The authors also performed in vivo comparisons including pressure drift, dose-response studies to IV isoproterenol, maximum adrenergic stimulation with IV dobutamine, and simultaneous placement of both micro-manometer pressure sensors in the same intact murine hearts. The authors conclude that both sensors are equivalent, and that the Scisense pressure sensor represents an alternative to the current gold standard, the Millar micro-manometer pressure sensor for in vivo pressure measurements in the mouse.

Creating diversity in a baccalaureate nursing program: a case study.

Minority groups in the United States experience disparity in the health care services they receive and in their health related outcomes. Minority healthcare providers are more likely to serve minority under-served populations, thus addressing this healthcare disparity in an effective culturally competent manner (Robert Wood Johnson 2005; Sullivan, 2004). The purpose of the project was to increase the number of racial and ethnic minority students who are successfully recruited and admitted to the nursing program at Hope College in Holland, Michigan. The project involved the identification of perceived barriers to increased minority participation in nursing at the college, review of the literature to identify evidence-based interventions, and implementation of selected interventions to overcome the identified barriers. Implementation and evaluation are still on-going but showing early success.

Association of the 5'-upstream regulatory region of the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7) with schizophrenia.

BACKGROUND: The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) is localized in a chromosomal region (15q14) linked to schizophrenia in multiple independent studies. CHRNA7 was selected as the best candidate gene in the region for a well-documented endophenotype of schizophrenia, the P50 sensory processing deficit, by genetic linkage and biochemical studies. METHODS: Subjects included Caucasian-Non Hispanic and African-American case-control subjects collected in Denver, and schizophrenic subjects from families in the NIMH Genetics Initiative on Schizophrenia. Thirty-five single nucleotide polymorphisms (SNPs) in the 5'-upstream regulatory region of CHRNA7 were genotyped for association with schizophrenia, and for smoking in schizophrenia. RESULTS: The rs3087454 SNP, located at position -1831 bp in the upstream regulatory region of CHRNA7, was significantly associated with schizophrenia in the case-control samples after multiple-testing correction (P=0.0009, African American; P=0.013, Caucasian-Non Hispanic); the association was supported in family members. There was nominal association of this SNP with smoking in schizophrenia. CONCLUSIONS: The data support association of regulatory region polymorphisms in the CHRNA7 gene with schizophrenia.

Regulation of a novel alphaN-catenin splice variant in schizophrenic smokers.

The alphaN-catenin (CTNNA2) gene represents a promising candidate gene for schizophrenia based upon previous genetic linkage, expression, and mouse knockout studies. CTNNA2 is differentially regulated by smoking in schizophrenic patients. In this report, the genomic structure of a primate-specific alphaN-catenin splice variant (alphaN-catenin III) is described. A comparison of alphaN-catenin III mRNA expression across postmortem hippocampi from schizophrenic and non-mentally ill smokers and non-smokers revealed a significant decrease in expression among patient non-smokers compared to all other groups. The recent evolutionary divergence of this gene, as well as the differences in gene expression in postmortem brain of schizophrenic non-smokers, supports the role of alphaN-catenin III as a novel disease susceptibility gene.

Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.

Interleukin (IL)-18 is a cardiotropic proinflammatory cytokine chronically elevated in the serum of patients with cardiac hypertrophy (LVH). The purpose of this study was to examine the role of IL-18 in pressure-overload hypertrophy using wild type (WT) and IL-18 -/- (null) mice. Adult male C57Bl/6 mice underwent transaortic constriction (TAC) for 7days or sham surgery. Heart weight/body weight ratios showed blunted hypertrophy in IL-18 null TAC mice compared to WT TAC animals. Microarray analyses indicated differential expression of hypertrophy-related genes in WT versus IL-18 nulls. Northern, Western, and EMSA analyses showed Akt and GATA4 were increased in WT but unchanged in IL-18 null mice. Our results demonstrate blunted hypertrophy with reduced expression of contractile-, hypertrophy-, and remodeling-associated genes following pressure overload in IL-18 null mice, and suggest that IL-18 plays a critical role in the hypertrophic response.

Cloning and functional expression of a human orthologue of rat vanilloid receptor-1.

Capsaicin, resiniferatoxin, protons or heat have been shown to activate an ion channel, termed the rat vanilloid receptor-1 (rVR1), originally isolated by expression cloning for a capsaicin sensitive phenotype. Here we describe the cloning of a human vanilloid receptor-1 (hVR1) cDNA containing a 2517 bp open reading frame that encodes a protein with 92% homology to the rat vanilloid receptor-1. Oocytes or mammalian cells expressing this cDNA respond to capsaicin, pH and temperature by generating inward membrane currents. Mammalian cells transfected with human VR1 respond to capsaicin with an increase in intracellular calcium. The human VR1 has a chromosomal location of 17p13 and is expressed in human dorsal root ganglia and also at low levels throughout a wide range of CNS and peripheral tissues. Together the sequence homology, similar expression profile and functional properties confirm that the cloned cDNA represents the human orthologue of rat VR1.