Upward feedback in nursing: A matter of giving, taking and asking.

The educational program for nurses takes place in school and at the workplace. At the workplace, student nurses and their supervisors work together while providing the best care for their patients. In this context, it is important that both, students and supervisors, provide feedback to each other. However, it can be difficult for nursing students to provide feedback to professionals who are higher up in the hierarchy. The goal of this study is to investigate the factors that facilitate nursing students to provide so-called upward feedback and nursing supervisors to receive it. Seven focus groups of nursing students (n = 40) and two focus groups of nursing supervisors (n = 12) were organized. The qualitative data analyses of the focus group interviews and a literature study show that a feedback-friendly culture is essential in enabling upward feedback. The following aspects contribute to a feedback-friendly culture: (1) the role of the feedback receiver, (2) the role of the feedback provider, (3) relations between feedback receivers and providers and (4) the context. This study shows that nursing students and supervisors are open to provide and receive upward feedback. However more attention is needed in nursing education for the factors that facilitate this process.

[Improving the quality of supervision of residents: an evaluation of supervisors using feedback by residents]. / Verbetering van begeleiding door supervisors; evaluatie met feedback van aiossen.

BACKGROUND: To evaluate the quality of the supervision of residents, questionnaires are frequently used.
AIM: Changes in resident ratings were assessed using the validated Evaluation and Feedback for Effective Clinical Teaching (effect) questionnaire.
METHOD: Supervisors (n=89) of nine medical specialities were evaluated using a validated instrument (effect). Mean overall scores (mos) and mean scale scores were compared using paired t-tests. Ten supervisors were interviewed to determine factors that stimulate or hinder improvement after an evaluation.
RESULTS: The strongest increase was seen in supervisors with an mos <4.0. Motivation to improve and dialogue about the feedback stimulated improvement. Lack of time and support hindered improvement.
CONCLUSION: Evaluating supervisors by providing feedback and a dialogue is suitable to improve their supervision of residents.

Teaching adjuvant endocrine breast cancer treatment to medical students.

BACKGROUND: In undergraduate medical education, students are supposed to acquire knowledge and understanding about the basic principles of adjuvant breast cancer treatment. The best education method in this context is unknown. In this randomised study we assessed the effect of designing a patient education poster on knowledge, perceived participation and students' satisfaction compared with case-oriented education concerning endocrine therapy for breast cancer patients. METHODS: This study was conducted in the Bachelor Oncology Course for undergraduate students in Medical Science of the Radboud University Nijmegen Medical Centre. In the experimental group, students designed and created a patient education poster in small groups. In the control group, students answered case-based questions in small groups. Knowledge was tested at different moments using multiple-choice questions. To assess perceived participation and satisfaction, students filled out questionnaires. RESULTS: 329 students participated in the study. No difference in knowledge was observed between the experimental and control group. However, students in the control group reported a higher perceived participation and satisfaction compared with the students in the experimental group (p<0.05). CONCLUSION: In this study, working on case-based questions was preferred compared with designing a patient education poster in terms of students' perceived participation and satisfaction. Working on case-based questions may be appreciated by medical students as most relevant for their future profession. We advocate more attention to the importance of patient education in the medical curriculum, to help students realise the relevance of this aspect of medical profession.

Efficacy of topically delivered moxifloxacin against wound infection by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus.

Wound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 10(5) CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.

Assessment of activity levels for CYP2D6*1, CYP2D6*2, and CYP2D6*41 genes by population pharmacokinetics of dextromethorphan.

The pharmacokinetics of dextromethorphan (DM) is markedly influenced by cytochrome P450 2D6 (CYP2D6) enzyme polymorphisms. The aim of this study was to quantify the effects of the CYP2D6*1, *2, and *41 variants on DM metabolism in vivo and to identify other sources of pharmacokinetic variability. Concentrations of DM and dextrorphan (DO) in plasma and urine were evaluated in 36 healthy Caucasian men. These volunteers participated in three clinical studies and received a single oral dose of 30 mg DM-HBr. Data were modeled simultaneously using the population pharmacokinetics NONMEM software. A five-compartment model adequately described the data. The activity levels of the alleles assessed differed significantly. The clearance attributable to an individual CYP2D6*1 copy was 2.5-fold higher as compared with CYP2D6*2 (5,010 vs. 2,020 l/h), whereas the metabolic activity of CYP2D6*41 was very low (85 l/h). Urinary pH was confirmed as a significant covariate for DM renal clearance. These results refine genotype-based predictions of pharmacokinetics for DM and presumably for other CYP2D6 substrates as well.

Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients.

This study aimed to quantify the inhibition of cytochrome P450 (CYP3A), CYP2D6, and P-glycoprotein in human immunodeficiency virus (HIV)-infected patients receiving an antiretroviral therapy (ART) containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pharmacokinetics. We measured activities of CYP3A, CYP2D6, and P-glycoprotein in 28 patients before and during ART using a cocktail phenotyping approach. Activities, demographics, and genetic polymorphisms in CYP3A, CYP2D6, and P-glycoprotein were tested as covariates. Oral midazolam clearance (overall CYP3A activity) decreased to 0.19-fold (90% confidence interval (CI), 0.15-0.23), hepatic midazolam clearance and intestinal midazolam availability changed to 0.24-fold (0.20-0.29) and 1.12-fold (1.00-1.26), respectively. In CYP2D6 extensive metabolizers, the plasma ratio AUC(dextromethorphan)/AUC(dextrorphan) increased to 2.92-fold (2.31-3.69). Digoxin area under the curve (AUC)(0-12) (P-glycoprotein activity) increased to 1.81-fold (1.56-2.09). Covariates had no major influence on lopinavir and ritonavir pharmacokinetics. In conclusion, CYP3A, CYP2D6, and P-glycoprotein are profoundly inhibited in patients receiving ritonavir boosted lopinavir. The covariates investigated are not useful for a priori dose selection.

Antenna model for wire lasers.

An antenna model is proposed for long (L >> A) lasers with subwavelength cross sections (wire lasers). It is shown that the far-field pattern of the wire lasers is determined by the ratio of the wavelength to the length. The radiation of the wire laser is predicted to be concentrated in a narrow beam theta approximately radical(2lambda/L) for laser modes where the longitudinal phase velocity is in synchronism with the velocity of light in air. Experimental results obtained using a terahertz quantum cascade wire laser are in agreement with the model.

Stimulated terahertz stokes emission of silicon crystals doped with antimony donors.

Stimulated Stokes emission has been observed from silicon crystals doped by antimony donors when optically excited by radiation from a tunable infrared free electron laser. The photon energy of the emission is equal to the pump photon energy reduced by the energy of the intervalley transverse acoustic (TA) g phonon in silicon (approximately 2.92 THz). The emission frequency covers the range of 4.6-5.8 THz. The laser process occurs due to a resonant coupling of the 1s(E) and 1s(A1) donor states (separation approximately 2.97 THz) via the g-TA phonon, which conserves momentum and energy within a single impurity center.

Effect of propiverine on cytochrome P450 enzymes: a cocktail interaction study in healthy volunteers.

The present study was conducted to assess a possible in vivo effect of propiverine, an anticholinergic drug to treat urinary incontinence and related disorders, on the activity of intestinal CYP3A4 and of hepatic CYP3A4, CYP2C9, CYP2C19, and CYP1A2. The activity of the respective cytochromes P450 was measured using the following metrics of selective substrates given as a tailored low-dose phenotyping cocktail: intestinal availability of midazolam (2 mg orally), clearance of midazolam (1 mg i.v.), apparent clearance of tolbutamide (125 mg orally), urinary excretion of 4'-hydroxymephenytoin 0 to 8 h postdose (50 mg of mephenytoin orally), and the paraxanthine/caffeine plasma ratio 6 h postdose (150 mg of caffeine orally). These metrics were determined in 16 healthy young men at the end of 7 days of treatment with 15 mg of propiverine (test) or placebo (reference) twice daily. All phenotyping drugs were quantified by liquid chromatography-tandem mass spectrometry. Chronic propiverine treatment reduced hepatic and intestinal CYP3A4 activity slightly to 0.89-fold and 0.80-fold, respectively [90% confidence interval (CI) for test/reference ratios 0.85-0.93 and 0.72-0.89], with the combined effect resulting in a 1.46-fold increase in area under the curve of oral midazolam (90% CI 1.36-1.57). Propiverine had no relevant effect on CYP2C9, CYP2C19, and CYP1A2 (90% CI for test/reference ratios 0.93-1.00, 0.84-0.96, and 0.97-1.07, respectively). All study drugs were well tolerated. In conclusion, propiverine has a minor potential to cause drug-drug interactions.

Mood congruent memory bias induced by tryptophan depletion.

BACKGROUND: Mood congruent memory bias predicts a more superior recall memory of learnt material congruent with the mood state at the time of learning. The present study is the first report of an experimental study in which a biological mood induction was used to test this hypothesis. The influence of acute tryptophan (TRP) depletion, inducing low serotonin neurotransmission and a depression of mood, on memory bias was evaluated in healthy volunteers (16 with and 11 without a family history of major affective disorder). METHODS: Twenty-seven subjects received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind, balanced, cross-over design. An affective memory test consisting of a 30-word list with words of positive, neutral, and negative affective valence and a mood questionnaire were assessed at 6 and 24 h following treatment administration. RESULTS: TRP depletion impaired delayed recall of neutral and positive words, but not of negative words. There was no interaction of family history and treatment and there was no post hoc association between the influence of TRP-depletion on mood and on affective memory bias. CONCLUSION: Experimentally induced serotonergic depletion in normal individuals shifts affective memory bias towards negative affective valent verbal stimuli.

Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood.

Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.

Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients.

Results of an earlier study in healthy volunteers suggest that the serotonergic system is involved in anxiety-related mechanisms. We studied the influence of tryptophan depletion on the response to a 35% carbon dioxide challenge. Twenty-four panic disorder patients received a mixture of amino acids, either with or without tryptophan, under double-blind conditions. There was a significant increase in anxiety as well as in neurovegetative symptoms in the depletion group, compared to the placebo condition. Furthermore, when we compare the results of the placebo group with earlier panic provocation studies, it also seems that a balanced amino acid mixture might have a protective effect against a panic provocation. We conclude that the panic-enhancing effect of tryptophan depletion as well as the potential protective effect of tryptophan administration in panic disorder patients can be explained by the Deakin-Graeff theory of anxiety.

Mood effects of 24-hour tryptophan depletion in healthy first-degree relatives of patients with affective disorders.

BACKGROUND: Acute tryptophan (TRP) depletion was evaluated in healthy volunteers with or without a family history of major affective disorder (FH+ versus FH-). METHODS: Twenty-seven subjects (16 FH+, 11 FH-) received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind cross-over design and a diet devoid of TRP for the next 24 hours. RESULTS: The ratio TRP/large neutral amino acids declined to 22% of baseline values after 6 hours, and increased during the night reaching 85% of baseline after 24 hours. Overall, after 6 hours, TRP depletion lead to a lowering of mood, but after 24 hours, these changes were no longer detected. Mood changes and gastrointestinal side effects were significantly more evident in FH+ subjects than in FH- subjects. CONCLUSIONS: Our data support the hypothesis that subjects with a positive family history for depression are predisposed to increased vulnerability to the adverse consequences of serotonergic imbalance.

Duchenne and Becker muscular dystrophies: an Estonian experience.

The clinical and molecular features of 25 Duchenne (DMD), two intermediate (D/BMD) and three Becker (BMD) muscular dystrophy patients from 26 unrelated families were evaluated. Early psychomotor development was normal in patients with D/BMD and BMD. Learning to walk independently after 15 months of age was a risk sign of DMD in nine (36%) patients. Abnormality in crawling was seen in 13 (54%) patients with DMD. These boys demonstrated initial symptoms earlier than those who learned to crawl normally. Mental retardation was established in five (20%) patients with DMD. Deletions in the dystrophin gene were found in 11 families (48%). They were accumulated (9/11, 82%) in the distal region of the gene.

Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation.

Serotonin (5-hydroxytryptamine; 5-HT) circuits may play a role in cognitive performance, particularly in learning and memory. Cognitive impairment is often seen in depressed patients, in whom 5-HT turnover in the brain is thought to be lowered. A possible human pharmacological model to study the involvement of the serotonergic system in cognitive impairment is to reduce central 5-HT synthesis through L-tryptophan depletion in healthy subjects. In this study, the cognitive effects of tryptophan depletion were assessed and whether genetically or developmentally determined vulnerability factors were predictive of the cognitive impairment induced by tryptophan depletion. Sixteen healthy volunteers with a positive family history of depression and 11 without were given 100 g of an amino acid mixture with or without tryptophan, according to a double-blind, cross-over design. Tryptophan depletion specifically impaired long-term memory performance in all subjects: delayed recall performance, recognition sensitivity, and recognition reaction times were significantly impaired after tryptophan depletion relative to placebo. Short-term memory and perceptual and psychomotor functions were unchanged. There were no differences between groups with a positive and a negative family history for depression. On the basis of these results, it is concluded that tryptophan depletion specifically impairs long-term memory formation, presumably as a result of an acute decrease in 5-HT turnover in the brain.

Specificity of the tryptophan depletion method.

Thirteen healthy subjects were subjected to tryptophan (TRP) depletion, lysine (LYS) depletion, and a placebo condition in a double blind cross-over study. The aim of the study was to test the specificity of psychological effects induced by TRP depletion. Subjects ingested a 100 g amino acid mixture with or without TRP or LYS. Six hours later, plasma TRP levels had decreased by 77% in the TRP depletion test and LYS levels by 51% in the LYS depletion condition. After 6 h of TRP depletion, subjects reported significantly more tiredness and lowering of mood, compared to subjects in the placebo group, and memory performance declined. After 6 h of LYS depletion, no significant differences in mood and memory compared to placebo were found. We conclude that the effects of TRP depletion on mood and memory are specific for the depletion of TRP and are not caused by the depletion of an amino acid per se. This supports the hypothesis that TRP depletion affects brain serotonin metabolism and not only brain protein metabolism in general.

Serotonin syndrome after challenge with the 5-HT agonist meta-chlorophenylpiperazine.

meta-Chlorophenylpiperazine (mCPP) is a non-selective 5-HT-receptor agonist/antagonist that is used extensively in psychiatry to assess central serotonergic function. We report on three patients who developed symptoms of the serotonin syndrome when they participated in an mCPP (0.5 mg/kg body weight p.o.) challenge test as part of a research protocol. They had relatively high plasma mCPP concentrations. The syndrome did not occur in normal volunteers who had comparable plasma concentrations of mCPP. Investigators should be aware of the possible occurrence of the serotonin syndrome after a single oral dose of mCPP.

Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge.

Results of several studies suggest that anxiety is under serotonergic control. We studied the influence of tryptophan depletion on generalized anxiety and on the response to a 35% carbon dioxide (CO2) challenge. Fifteen healthy male volunteers received both a mixture of amino acids without tryptophan and a placebo mixture under double-blind conditions. The tryptophan-free mixture led to an 80% decrease in blood tryptophan levels compared to the placebo. There was a significant increase in anxiety on the Spielberger Anxiety Inventory and a trend towards more tension on the Profile of Mood States-'tension' items, both of which were interpreted as increased nervousness. Furthermore, a significant increase in neurovegetative panic symptoms occurred after the CO2 challenge. We conclude that the serotonergic system is causally involved in anxiety-related mechanisms and that it may be worth pursuing the role of tryptophan depletion on CO2-induced panic in patients with anxiety disorders.