The use of intranasal sufentanil and/or s-ketamine for treatment of procedural pain in children in an ambulatory setting: A retrospective observational study.

BACKGROUND: Minor but painful medical procedures are often handled at the operating room. If safe and effective treatment options are available many procedures may be performed outside of the operating room. OBJECTIVE(S): The objective of this study is to assess the adverse events of intranasal s-ketamine and/or sufentanil alone or as part of a multimodal analgesic regime for medical procedures outside of the operating room. Secondary outcomes included analgesic effect, doses and indications for use. DESIGN: Retrospective observational study. SETTING: Tertiary care paediatric hospital. PATIENTS: Children 1 year up till 18 years. INTERVENTION(S): Intranasal (IN) sufentanil (S), intranasal s-ketamine (K) or the free combination of the two drugs (SK). MAIN OUTCOME MEASURE(S): The frequency of adverse events including serious adverse events reported by intervention. RESULTS: Between 2004 and 2014, 2185 medical procedures were registered, including 652 procedures with IN SK, 1469 procedures with IN S and 64 procedures with IN K. The children's median age was 5.6 years (range 1.0-17.9). Medical procedures with at least one adverse event were 18% with IN SK, 25% with IN K and 18% with IN S. Common adverse events included episodes of vomiting (9%), nausea (8%) and dizziness (3%). In two patients receiving IN S, serious adverse events occurred. One patient had respiratory depression and bronchospasm and another patient with cerebral palsy had a seizure. Both were handled immediately and did not result in any sequelae. The median doses of intranasal sufentanil were 38% lower when combined with s-ketamine (IN SK free combination: sufentanil dose 0.5 µg/kg (range 0.2-1.3) and s-ketamine dose 0.5 mg/kg (range 0.2-1.5). IN S monotherapy, sufentanil dose 0.8 µg/kg (range 0.2-2.7)). Similar analgesic effect was reported for S and SK. CONCLUSIONS: Intranasal sufentanil and/or s-ketamine are feasible for the treatment of procedural pain in an ambulatory setting with appropriate per- and post-procedural observations and trained staff.

Clonidine for preventing emergence agitation in infants (PREVENT AGITATION II): Protocol and statistical analysis plan.

BACKGROUND: Emergence agitation is a common clinical condition in children. Symptoms pertaining to the spectrum of early postoperative negative behavior typically occur upon emergence from anesthesia. Clonidine is an effective adjunctive agent for the prevention of emergence agitation in children, but evidence in the smallest age groups is sparse We aim to investigate the efficacy and safety of an intraoperative bolus of intravenous clonidine for preventing emergence agitation in children 3-12 months of age. METHODS: This is a randomized, placebo-controlled, double-blind trial. We will enroll 320 patients aged 3-12 months who have been scheduled for general anesthesia maintained with sevoflurane and opioid. The randomization is parallel and stratified by age group, sex, and site. The investigational medicinal product will be administered intravenously ~20 min before the anticipated end of the surgical procedure. The intervention is clonidine 3 µg/kg and placebo is isotonic saline in a corresponding volume. RESULTS: The primary outcome is the incidence of emergence agitation as assessed on the Watcha scale, that is, any Watcha score >2 during participants' stay in the postanesthetic care unit. Secondary outcomes are the proportion of participants with postoperative pain, with postoperative nausea and vomiting, and a composite safety outcome. Statistical analysis will be conducted according to the Statistical Analysis Plan with the intention-to-treat population for our primary analyses. CONCLUSION: The PREVENT AGITATION II trial will contribute valuable knowledge on efficacy for the prevention of emergence agitation and safety in infants.

Evaluation of topical morphine for treatment of oral mucositis in cancer patients.

INTRODUCTION: Oral mucositis is a painful side effect to chemotherapy. Orally applied opioids may offer analgesia with fewer side effects than systemic opioids. METHODS: A randomized trial comparing the analgesic effect of a morphine oromucosal solution (OM) to placebo and a positive control group receiving intravenous (IV) morphine as an add-on treatment to morphine patient-controlled analgesia (PCA) in a mixed population of paediatric and adult haematology patients. All patients in the study were equipped with a morphine PCA pump and the participating patients were instructed to use this pump as an escape. Primary outcome was morphine consumption (mg/kg/hour) on the PCA pump. Secondary outcomes included pain intensity difference at rest and when performing oral hygiene, time to first PCA bolus, nutrition intake and adverse events. FINDINGS: A total of 60 patients (38 children <18 years) were randomized. Thirty patients were allocated to morphine OM/placebo IV (group MO), 15 patients to placebo OM/morphine IV (group MI) and 15 patients to placebo OM/placebo IV (group P). The median morphine consumption in the MO group (22.7 mcg/kg/hour 95% confidence interval (CI) 19.4-29.4 mcg/kg/hour, p = 0.38) was not significantly different from the placebo group (24.6 mcg/kg/hour 95% CI 16.8-34.4 mcg/kg/hour, p = 0.44) or the MI group (13.7 mcg/kg/hour 95% CI 9.7-37.8 mcg/kg/hour). For the secondary outcomes, the analysis of summed pain intensity difference after the first, third and fourth administrations of study medication indicated a reduction in pain for the MI group compared to the P and MO groups. No serious adverse events were reported. CONCLUSION: The findings indicate that the analgesic effect of peripherally applied morphine is not significantly different from placebo, and parenteral opioids should continue to be the standard of care.

Pharmacokinetics of an intravenous bolus dose of clonidine in children undergoing surgery.

BACKGROUND: Clonidine is used off-label in children but only limited pediatric pharmacokinetic data are available for intravenously administered clonidine. OBJECTIVES: To determine pharmacokinetic parameter estimates of clonidine in healthy children undergoing surgery and to investigate age-related differences. Furthermore, to investigate possible pharmacokinetic differences of clonidine between this group of children and a cohort with cardiac diseases. METHODS: In a randomized placebo-controlled trial (The PREVENT AGITATION trial), blood samples for clonidine pharmacokinetic analysis were collected in a proportion of the enrolled patients. Healthy children with ASA score 1-2 in the age-groups 1 to <2 years and 2-5 years were randomized for blood sampling. Clonidine was administered as a single intravenous bolus of 3 µg/kg intraoperatively. Blood samples were drawn at baseline, 5, 10, 15, 30, 60 minutes after dosing and additionally every hour until discharge from the PACU. Clonidine analysis was performed on liquid chromatography-mass spectrometry. RESULTS: Data form eighteen children were available for pharmacokinetic analysis (ASA I; male/female: 17/1; age: 1-5 years; weight 8.7-24 kg). Population parameter estimates for the 2-compartment model were similar to previous published data for children who underwent cardiac surgery. A pooled analysis including data from 59 children indicated clearance of 14.4 L h-1  70 kg-1 and volume of distribution of 192.6 L 70 kg-1 . No age-related pharmacokinetic differences and no difference in time from administration of study medication to awakening were found. Children 1 to <2 years had a shorter PACU stay than children 2-5 years (mean difference 17% 95% CI:3%-34%, P = .02). CONCLUSION: Pharmacokinetic parameter estimates were similar for children undergoing general surgery and cardiac surgery given a single dose of intravenous clonidine. These results indicated that no dose reduction is needed in children aged 1 to <2 years compared with those 2-5 years, which was supported by pharmacodynamic observations.

Morphine consumption is associated with systemic inflammation in children undergoing allogeneic hematopoietic stem cell transplantation.

Background: The majority of children undergoing allogenic hematopoietic stem cell transplantation (HSCT) experience severe pain due to chemotherapy-induced gastrointestinal toxicity. Inter-individual differences in pain perceived and opioid consumption remain unexplained, limiting the possibility for individualized pain control. The aim of this study was to investigate the associations between opioid consumption and markers of gastrointestinal toxicity (plasma citrulline) and systemic inflammation (plasma CRP and IL-6) in these patients. Methods: We retrospectively included 38 children undergoing HSCT in Denmark in 2010-2012. Opioids doses on days 0-21 post-HSCT were registered as intravenous morphine equivalents (MEs). CRP was measured daily on days 0-21. IL-6 was measured on day 7. Citrulline was measured before conditioning, on days 7 and 21. Results: Out of 38 children, 37 (97%) received opioids during days 0-21. CRP level and ME dose peaked on days 9-10 while citrulline level reached a nadir on day 7 indicating maximum enterocyte loss. CRP was associated with ME dose, with an estimated increase of 0.030 mg/kg (95% CI 0.024-0.035) in ME for a 50% increase in CRP level on the same day (p < .001). IL-6 was correlated with ME on day 7 (rho = 0.55, p = .002). Citrulline did not correlate with ME. Conclusions: Opioid consumption in the early post-HSCT period is associated with the degree of chemotherapy-induced systemic inflammation and not with the extent of enterocyte loss. These findings contribute to our understanding of mucositis-related pain and may be of interest for future studies on therapeutic strategies.

Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial.

BACKGROUND: Postoperative agitation is a frequent and stressful condition for a child, their family, and their health-care providers, and prevention would be of benefit. We aimed to assess the effects of intravenous clonidine administered intraoperatively on the incidence of postoperative agitation, pain, and adverse events. METHODS: We did this randomised, placebo-controlled, double-blind trial (PREVENT AGITATION) at one tertiary-level hospital and two urban-district hospitals in Denmark. Children aged 1-5 years, with an American Society of Anesthesiologists physical classification score of 1-2, who were scheduled for anaesthesia with sevoflurane and fentanyl were randomly assigned (1:1) in blocks of ten by computer-generated centralised randomisation, stratified by age (<2 years or ≥2 years) and site, to receive either intravenous clonidine 3 µg/kg or an equal quantity of isotonic saline in identical vials, administered around 20 min before the completion of surgery. Data were collected from the postoperative care unit (24 h) and at follow-up (30 days). Our primary outcome was the proportion of patients with one or more episodes of postoperative agitation, measured every 15 min in the postoperative care unit (POCU) with the four-point Watcha scale (ie, Watcha >2). We analysed by intention to treat. The trial is registered with ClinicalTrials.gov (number NCT02361476). FINDINGS: Between January and December, 2015, of the 379 eligible children, we randomly assigned 191 to receive clonidine treatment and 188 to receive placebo; 75 were girls (20%). Nine were excluded from the primary outcome analysis because of missing data points. 46 (25%) of 187 clonidine participants compared with 86 (47%) of 183 placebo participants had one or more episodes of postoperative agitation (Watcha score >2; relative risk 0·56, 95% CI 0·43-0·73; p<0·0001). 30 (20%) of 150 boys in the clonidine group were agitated compared with 69 (47%) of 147 boys in the placebo group (0·43, 0·30-0·61; p<0·0001). The observed effect was not significant in girls. Incidence of adverse events was similar in the clonidine and placebo groups. INTERPRETATION: On the basis of our results, clonidine might be used to safely prevent postoperative agitation in boys anaesthetised with sevoflurane. FUNDING: Danish Society of Anaesthesia and Intensive Care.

Identification of Implementation Strategies Used for the Circle of Security-Virginia Family Model Intervention: Concept Mapping Study.

BACKGROUND: A reoccurring finding from health and clinical services is the failure to implement theory and research into practice and policy in appropriate and efficient ways, which is why it is essential to develop and identify implementation strategies, as they constitute the how-to component of translating and changing health practices. OBJECTIVE: The aim of this study was to provide a systematic and comprehensive review of the implementation strategies that have been applied for the Circle of Security-Virginia Family (COS-VF) model by developing an implementation protocol. METHODS: First, informal interviews and documents were analyzed using concept mapping to identify implementation strategies. All documentation from the Network for Infant Mental Health's work with COS-VF was made available and included for analysis, and the participants were interviewed to validate the findings and add information not present in the archives. To avoid lack of clarity, an existing taxonomy of implementation strategies, the Expert Recommendations for Implementing Change, was used to conceptualize (ie, name and define) strategies. Second, the identified strategies were specified according to Proctor and colleagues' recommendations for reporting in terms of seven dimensions: actor, the action, action targets, temporality, dose, implementation outcomes, and theoretical justification. This ensures a full description of the implementation strategies and how these should be used in practice. RESULTS: Ten implementation strategies were identified: (1) develop educational materials, (2) conduct ongoing training, (3) audit and feedback, (4) make training dynamic, (5) distribute educational materials, (6) mandate change, (7) obtain formal commitments, (8) centralize technical assistance, (9) create or change credentialing and licensure standards, and (10) organize clinician implementation team meetings. CONCLUSIONS: This protocol provides a systematic and comprehensive overview of the implementation of the COS-VF in health services. It constitutes a blueprint for the implementation of COS-VF that supports the interpretation of subsequent evaluation studies, facilitates knowledge transfer and reproducibility of research results in practice, and eases the replication and comparison of implementation strategies in COS-VF and other interventions.

Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial.

INTRODUCTION: Post-operative agitation (PA) is a common problem (20-70%) in children anaesthetised with sevoflur-ane. Clonidine is widely used off-label in children for several indications, including PA, but the current level of evidence is limited. Our aim is to investigate the impact of prophylactic intravenous (IV) clonidine administered at the end of surgery on the incidence and degree of PA. Furthermore, the pharmacokinetic profile of IV clonidine in children is not well established and our aim is to obtain pharmacokinetic data relating hereto. METHODS: This is a multicentre, randomised and blinded clinical trial in which we will be enrolling 380 children aged 1-5 years who are planned for anaesthesia with sevoflurane and fentanyl. Inclusion is based on computer-generated randomisation (1:1) and stratified by age and site. The study drug is administered IV approximately 20 min. before the expected completion of surgery (intervention: clonidine 3 µg per kg; placebo: equal quantity of saline). CONCLUSION: The primary outcome is PA measured on the Watcha scale. The secondary outcomes include post-operative pain relief and adverse effects, including a 30-day follow-up. In total, 40 children will be allocated to drug assay sampling, enabling a compartmental pharmacokinetic analysis. FUNDING: Funded by the participating departments and by two unrestricted scientific grants from the Danish Society of Anaesthesia and Intensive. TRIAL REGISTRATION: This study was approved by the Danish Health and Medicines Authority (EudraCT number 2014-001466-10), the Ethics Committee of the Capital Region of Denmark (H-2-2014-072) and registered with Clinicaltrials.gov (NCT02361476).

Intranasal sufentanil/ketamine analgesia in children.

BACKGROUND: The management of procedural pain in children ranges from physical restraint to pharmacological interventions. Pediatric formulations that permit accurate dosing, are accepted by children and a have a rapid onset of analgesia are lacking. OBJECTIVES: To investigate a pediatric formulation of intranasal sufentanil 0.5 mcg·kg(-1) and ketamine 0.5 mg·kg(-1) for procedural pain and to characterize the pharmacokinetic (PK) profile. METHODS: Fifty children (≥10 kg) scheduled for a painful procedure were included in this prospective nonrandomized open-label clinical trial. Thirteen of these children had central venous access for drug assay sampling; enabling a compartmental PK analysis using nonlinear mixed-effects models. Pain intensity before and during the procedure was measured using age-appropriate pain scales. Heart rate, oxygen saturation and sedation were recorded. RESULTS: Children had a mean age of 8.8 (sd 4.9) years and weight 35.2 (sd 20.1) kg. Sufentanil/ketamine nasal spray was effective (procedural pain intensity scores ≤5 (0-10)) in 78% of the painful procedures. The spray was well accepted by 94% of the children. Oxygen saturation and heart rate remained stable, and sedation was minimal. The bioavailability of sufentanil and ketamine was 24.6% and 35.8%, respectively. Maximum plasma concentration (Cmax) of sufentanil was 0.042 mcg·l(-1) (coefficient of variation (CV) 12.9%) at 13.8 min (CV 12.4%) (Tmax). Cmax for ketamine was 0.102 mg·l(-1) (CV 10.8%), and Tmax was 8.5 min (CV 17.3%). CONCLUSION: Sufentanil/ketamine nasal spray provided rapid onset of analgesia for a variety of painful procedures with few adverse effects and has promising features for use in pediatric procedural pain management.

Topical morphine for oral mucositis in children: dose finding and absorption.

CONTEXT: Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors are upregulated during inflammation, for example, in oral mucositis. OBJECTIVES: The aims of this study were to investigate the dose-response relationship (n=7) and the potential absorption of topical morphine (n=5) across oral mucosa in children with oral mucositis. METHODS: The dose-response study was conducted according to a sequential study design (Dixon's Up-and-Down method) for topical morphine doses of 0.025-0.400mg/kg, with the decrease in oral pain score as the primary outcome. To assess potential absorption across oral mucosa after a single dose of topical morphine of 0.050mg/kg, blood samples were drawn and the plasma concentrations of morphine and metabolites were determined by high-pressure liquid chromatography. RESULTS: A decrease in oral pain score of ≥36% was achieved in six of seven patients in the dose-response part of the study. Plasma concentrations of morphine and metabolites were well below effective analgesic levels. CONCLUSION: No obvious dose-response effect was found for topical morphine doses of 0.025-0.400mg/kg, and topically applied morphine was not absorbed in clinically relevant doses. However, this study was limited by the small number of patients and the allowance of a systemic opioid as rescue medication. Thus, randomized controlled studies are needed to further investigate the analgesic properties of topical morphine.

Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers.

OBJECTIVE: The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only. METHODS: Twenty-three healthy male volunteers aged 21-40 years received 0.6 mg buprenorphine by means of an i.v. infusion over a 150-min period. The plasma concentration-time profiles up to 24 h post-administration of the infusion were subjected to population pharmacokinetic modelling using NONMEM: software. RESULTS: A three-compartment model best described the plasma concentration-time course. Body weight was found to be a significant covariate for elimination clearance in a linear fashion. Inter-individual variability (coefficient of variation) was estimable for apparent clearance (CL, 23.5%), central distribution volume (V(1), 81.8%), peripheral distribution volume 1 (V(2), 23.7%) and inter-compartmental clearances between V(1) and V(2) (Q(2), 34.8%). Models using parameters derived from previous published data obtained after an i.v. bolus of buprenorphine were found to overestimate the measured buprenorphine concentrations during the course of the i.v. infusion and to underpredict those following the end of the infusion. CONCLUSION: Most parameters describing the disposition of buprenorphine in the volunteers showed only moderate inter-subject variability. However, the parameters differed from those previously reported for i.v. bolus administration. We conclude that pharmacokinetic parameter estimates obtained from the appropriate study in accordance to the mode of administration should be used in the design of dose regimens of buprenorphine.

Nursing documentation audit--the effect of a VIPS implementation programme in Denmark.

AIM AND OBJECTIVES: The aim of this paper is to present a study describing nurses' adherence to the VIPS model by evaluating the quality of nursing assessment, and the quantity of completed nursing care plans. BACKGROUND: Numerous efforts have been made over the years to improve nursing documentation in Denmark. Hospitals have traditionally based nurses' charting on a rudimentary version of the nursing process and on Virginia Henderson's theory of human needs. In 2002-2004 the Copenhagen University Hospital, Rigshospitalet, introduced the Swedish VIPS model for nursing documentation. VIPS is an acronym for well being, integrity, prevention and safety, all of which are seen as major goals for nursing care. The model organizes nursing data according to a system of keywords, which facilitates storage and retrieval of data. DESIGN AND METHODS: The design in this part of the study was retrospective, wherein 50 journals from each of the departments of cardiology, neurology, oncology and urology were audited annually for three years using the Cat-ch-Ing instrument (n=600). All nursing journals were randomly selected by including the first 50 journals at each site given a specific date. RESULTS: The nursing documentation significantly improved during the course of the study. After the second year the participants used the keywords appropriately and correctly according to the VIPS model. Application of primary nursing increased during the study. Initial, ongoing and discharge patient status improved. The nurses' familiarity with nursing diagnoses, goals and interventions increased. CONCLUSIONS: The structured implementation programme significantly improved nursing documentation, and the simultaneous training of the entire nursing staff shows promise. The VIPS model has prepared the nurses for more complex computerized taxonomies and classification systems in the future by improving the nurses' analytical skills. Relevance to clinical practice. New strategies for improving nursing documentation have been demonstrated.

Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP.

The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.

Crystal structure of a partly self-complementary peptide nucleic acid (PNA) oligomer showing a duplex-triplex network.

The X-ray structure of a partly self-complementary peptide nucleic acid (PNA) decamer (H-GTAGATCACT-l-Lys-NH(2)) to 2.60 A resolution is reported. The structure is mainly controlled by the canonical Watson-Crick base pairs formed by the self-complementary stretch of four bases in the middle of the decamer (G(4)A(5)T(6)C(7)). One right- and one left-handed Watson-Crick duplex are formed. The two PNA units C(9)T(10) change helical handedness, so that each PNA strand contains both a right- and a left-handed section. The changed handedness in C(9)T(10) allows formation of Hoogsteen hydrogen bonding between C(9)T(10) and G(4)A(5) of a PNA strand in an adjacent Watson-Crick double helix of the same handedness. Thereby, a PNA-PNA-PNA triplex is formed. The PNA unit A(3) forms a noncanonical base pair with A(8) in a symmetry-related strand of opposite handedness; the base pair is of the A-A reverse Hoogsteen type. The structural diversity of this PNA demonstrates how the PNA backbone is able to adapt to structures governed by the stacking and hydrogen-bonding interactions between the nucleobases. The crystal structure further shows how PNA oligomers containing limited sequence complementarity may form complex hydrogen-bonding networks.

Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2.

Ionotropic glutamate receptors mediate most rapid excitatory synaptic transmission in the mammalian central nervous system, and their involvement in neurological diseases has stimulated widespread interest in their structure and function. Despite a large number of agonists developed so far, few display selectivity among (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA)-receptor subtypes. The present study provides X-ray structures of the glutamate receptor 2 (GluR2)-selective partial agonist (S)-2-amino-3-(1,3,5,6,7-pentahydro-2,4-dioxocyclopenta[e] pyrimidin-1-yl) propanoic acid [(S)-CPW399] in complex with the ligand-binding core of GluR2 (GluR2-S1S2J) and with a (Y702F)GluR2-S1S2J mutant. In addition, the structure of the nonselective partial agonist kainate in complex with (Y702F)GluR2-S1S2J was determined. The results show that the selectivity of (S)-CPW399 toward full-length GluR2 relative to GluR3 is reflected in the binding data on the two soluble constructs, allowing the use of (Y702F)GluR2-S1S2J as a model system for studying GluR2/GluR3 selectivity. Structural comparisons suggest that selectivity arises from disruption of a water-mediated network between ligand and receptor. A D1-D2 domain closure occurs upon agonist binding. (S)-CPW399 and kainate induce greater domain closure in the Y702F mutant, indicating that these partial agonists here act in a manner more reminiscent of full agonists. Both kainate and (S)-CPW399 exhibited higher efficacy at (Y702F)GluR2(Q)i than at wild-type GluR2(Q)i. Whereas an excellent correlation exists between domain closure and efficacy of a range of agonists at full-length GluR2 determined by electrophysiology in Xenopus laevis oocytes, a direct correlation between agonist induced domain closure of (Y702F)GluR2-S1S2J and efficacy at the GluR3 receptor is not observed. Although it clearly controls selectivity, mutation of this residue alone is insufficient to explain agonist-induced conformational rearrangements occurring in this variant.

The effect of a VIPS implementation programme on nurses' knowledge and attitudes towards documentation.

The Copenhagen University Hospital decided to adhere to the standards of the Joint Commission of International Accreditation in 2000. These standards require systematic assessment of patient care needs and include the use of written nursing care plans. In order to meet these standards, the hospital management decided to introduce the Swedish VIPS model, which is a model designed to structure nursing documentation (VIPS is an acronym for well-being, integrity, prevention and safety). The present study explores the nurses' knowledge and attitudes towards documentation and addresses the research questions: (a) what are the nurses' attitudes towards documentation of nursing care? and (b) do nurses have sufficient knowledge of the documentation system to systematically document their patient assessment and clinical decisions? The research design was prospective, comparative, and quasi-experimental (nonrandomized), including a study group (n=72) and a control group (n=57). A questionnaire was used to compare nurses' self-evaluated attitudes towards documentation, and a multiple-choice test was given in order to assess nurses' knowledge of the documentation system. The study group participated in a special implementation programme (response rate 82%), while the control group attended the regular 3-day documentation course at the hospital (response rate 79%). The study showed that the two groups responded similarly, but the nurses in the study group were significantly stronger in their conviction that they had the knowledge to make care plans and that they routinely made them. The study group demonstrated slightly less motivation than the control group, while the two groups shared a positive attitude towards nursing documentation. The study group did consistently better on the knowledge tests. The findings show that the implementation programme had a positive impact on nursing documentation, and that the VIPS model increased the nurses' understanding of the nursing process.