Can we rely on simulated patients' satisfaction with their consultation for assessing medical students' communication skills? A cross-sectional study.

BACKGROUND: In medical education, teaching methods offering intensive practice without high utilization of faculty resources are needed. We investigated whether simulated patients' (SPs') satisfaction with a consultation could predict professional observers' assessment of young doctors' communication skills. METHODS: This was a comparative cross-sectional study of 62 videotaped consultations in a general practice setting with young doctors who were finishing their internship. The SPs played a female patient who had observed blood when using the toilet, which had prompted a fear of cancer. Immediately afterwards, the SP rated her level of satisfaction with the consultation, and the scores were dichotomized into satisfaction or dissatisfaction. Professional observers viewed the videotapes and assessed the doctors' communication skills using the Arizona Communication Interview Rating Scale (ACIR). Their ratings of communication skills were dichotomized into acceptable versus unacceptable levels of competence. RESULTS: The SPs' satisfaction showed a predictive power of 0.74 for the observers' assessment of the young doctors and whether they reached an acceptable level of communication skills. The SPs' dissatisfaction had a predictive power of 0.71 for the observers' assessment of an unacceptable communication level. The two assessment methods differed in 26% of the consultations. When SPs felt relief about their cancer concern after the consultation, they assessed the doctors' skills as satisfactory independent of the observers' assessment. CONCLUSIONS: Accordance between the dichotomized SPs' satisfaction score and communication skills assessed by observers (using the ACIR) was in the acceptable range. These findings suggest that SPs' satisfaction scores may provide a reliable source for assessing communication skills in educational programs for medical trainees (students and young doctors). Awareness of the patient's concerns seems to be of vital importance to patient satisfaction.

Risk of depression in diabetes is highest for young persons using oral anti-diabetic agents.

AIMS: Previous studies report an increased risk of depression in patients with diabetes, but there is little knowledge about if or how the risk varies according to sex, groups of age and different type of treatments for the diabetes. We therefore aimed to investigate the risk of depression in different types of treatment for diabetes and in subgroups of age and sex. METHODS: Data on the Norwegian population from 20 years of age being prescribed antidepressants (n = 253 668) and anti-diabetic agents (n = 121 392) in 2006 was obtained from the National Register of Prescriptions and analysed in a cross-sectional design. RESULTS: Individuals using insulin in monotherapy (n = 29 611) had an age- and sex-adjusted odds ratio of 1.47 (95% CI 1.42-1.53) for receiving antidepressants. Corresponding odds ratios for individuals receiving oral anti-diabetic agents in monotherapy (n = 76 387) and for those who received both insulin and oral anti-diabetic agents (n = 15 394) were 1.44 (95% CI 1.41-1.47) and 1.82 (95% CI 1.80-1.97), respectively. No major differences in risk according to age were found for persons receiving insulin in monotherapy, while a marked and inverse association between age and risk of receiving antidepressants was found for those receiving oral anti-diabetic agents. Highest risk of antidepressant treatment [odds ratio 4.15 (95% CI 3.12-5.52)] was found for patients receiving both oral anti-diabetic agents and insulin at 30-39 years. The risk was equally increased among men and women. CONCLUSIONS: The risk of depression among patients with diabetes varies strongly according to age and type of treatment for diabetes.

Meta-analysis of brain-derived neurotrophic factor p.Val66Met in adult ADHD in four European populations.

Attention-deficit hyperactivity disorder (ADHD) is a multifactorial, neurodevelopmental disorder that often persists into adolescence and adulthood and is characterized by inattention, hyperactivity and impulsiveness. Before the advent of the first genome-wide association studies in ADHD, genetic research had mainly focused on candidate genes related to the dopaminergic and serotoninergic systems, although several other genes had also been assessed. Pharmacological data, analysis of animal models and association studies suggest that Brain-Derived Neurotrophic Factor (BDNF) is also a strong candidate gene for ADHD. Several polymorphisms in BDNF have been reported and studied in psychiatric disorders but the most frequent is the p.Val66Met (rs6265G > A) single nucleotide polymorphism (SNP), with functional effects on the intracellular trafficking and secretion of the protein. To deal with the inconsistency raised among different case-control and family-based association studies regarding the p.Val66Met contribution to ADHD, we performed a meta-analysis of published as well as unpublished data from four different centers that are part of the International Multicentre Persistent ADHD CollaboraTion (IMpACT). A total of 1,445 adulthood ADHD patients and 2,247 sex-matched controls were available for the study. No association between the p.Val66Met polymorphism and ADHD was found in any of the four populations or in the pooled sample. The meta-analysis also showed that the overall gene effect for ADHD was not statistically significant when gender or comorbidity with mood disorders were considered. Despite the potential role of BDNF in ADHD, our data do not support the involvement of p.Val66Met in the pathogenesis of this neuropsychiatric disorder.

A psychophysiological investigation of the interplay between orienting and executive control during stimulus conflict: A heart rate variability study.

BACKGROUND: It has been hypothesized that resting state cardiac vagal activity (CVA) - an indicator of parasympathetic nervous system activity - is a specific psychophysiological marker of executive control function. Here, we propose an alternative hypothesis - that CVA is associated with early stage attention orientation, promoting the flexible uptake of new information, on which the later operation of such executive control functions depends. We therefore predicted that CVA would predict the interaction between orienting and executive control. This was tested using the revised version of the Attention Network Test (ANT-R) that was developed to distinguish between orienting and executive attention during a stimulus conflict task. METHODS: Healthy adults (N = 48) performed the ANT-R and their resting CVA was measured over a 5 min period using ECG recordings. RESULTS: Multiple regression analyses indicated that, when other factors were controlled for, CVA was more strongly associated with the interaction between the orienting and executive control terms than with either factor individually. CONCLUSION: Higher levels of CVA are specifically implicated in the modulation of executive control by intrinsic orientation operating at early stages of conflict detection. These initial findings of higher CVA on orienting attention in conflict detection need to be replicated in larger samples.

Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs.

Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder in children and adults. Recent meta-analyses have indicated an association between genes involved in dopaminergic signaling and childhood ADHD, but little is known about their possible role in adult ADHD. In this study of adults with ADHD, we evaluated the three most commonly studied ADHD candidate genetic polymorphisms; the dopamine receptor D4 (DRD4) exon 3 VNTR repeat, a microsatellite repeat 18.5 kb upstream of the DRD5 locus and the 3'UTR dopamine transporter SLC6A3 (DAT 1) VNTR. We examined 358 clinically diagnosed adult Norwegian ADHD patients (51% males) and 340 ethnically matched controls. We found a nominally significant overall association with adult ADHD for the DRD5 microsatellite marker (P = 0.04), and a trend toward increased risk associated with the 148-bp allele consistent with recent meta-analyses. The strongest overall association (P = 0.02) and increased risk for the 148-bp allele [odds ratio (OR) = 1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined inattentive/hyperactive group as previously reported for childhood ADHD. No association was found for the DRD4 or SLC6A3 polymorphisms in this patient sample. In conclusion, our results among adults with a clinical diagnosis of ADHD support an association between ADHD and the DRD5 locus, but not the DRD4 or SLC6A3 loci. It is possible that the latter polymorphisms are associated with a transient form of ADHD with better long-term clinical outcome.

Behavioural responses induced by intrathecal injection of 5-hydroxytryptamine in mice are inhibited by a substance P antagonist, D-Pro2, D-Trp7,9-substance P.

Intrathecal injection of 5-hydroxytryptamine (5-HT) in mice produced a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking of the hindquarters. Pretreatment with either metergoline or morphine given intrathecally inhibited the 5-HT-induced behaviour. The response to 5-HT was similar to the effect of substance P (SP), and it was found that the blocker of the substance P receptor, D-Pro2, D-Trp7,9-SP, not only reduced the effect of substance P, but also that of 5-HT. The behaviour induced by substance P was also significantly reduced by intrathecal injection of either morphine or metergoline. These findings indicate a functional interaction between substance P and 5-HT in the modulation of sensory input at the spinal level.

Antinociceptive effects of serotonergic reuptake inhibitors in mice.

The antinociceptive effects of three predominantly serotonergic reuptake inhibitors, alaproclate, citalopram and clomipramine, were examined in mice using the hot-plate, formalin and substance P tests. The effects were compared with those of the noradrenergic reuptake inhibitor, desipramine. Different profiles in the three nociceptive tests were found for all four drugs, using doses of 10 and 40 mg/kg. The selective serotonergic reuptake inhibitor, alaproclate, seemed to have the least antinociceptive effects, and was the only drug that was ineffective in the hot-plate test. The other selective drug, citalopram, had a stronger effect than alaproclate in the substance P test, but in the formalin test, both drugs were approximately equally effective. Clomipramine differed from citalopram by being more effective in the formalin test. These findings thus indicate that selective inhibitors of the uptake of 5-HT have weaker antinociceptive effects than less selective drugs. Desipramine seemed to be no less effective than the serotonergic drugs and was the most potent drug in the hot-plate test.

Changes in nociception after lesions of descending serotonergic pathways induced with 5,6-dihydroxytryptamine. Different effects in the formalin and tail-flick tests.

Intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) in mice selectively lesioned descending serotonergic pathways. Nociception was evaluated 3 days after injection of 5,6-DHT using the tail-flick and formalin tests. In the tail-flick test shortened latencies were found in the lesioned animals. In contrast, the initial behavioural response (0-15 min) to formalin was reduced, while the late response (15-40 min) was not altered. Fourteen days after intrathecal administration of 5,6-DHT the changes in nociception, both in the tail-flick and in the formalin test, had returned to the control level. These findings support the contention that the raphe-spinal serotonergic system participates in the tonic regulation of nociception in the spinal cord. Apparently this system tonically inhibits spinal nociceptive reflexes, but tonically enhances the initial behavioural responses to noxious chemical stimulation, as measured with the formalin test.

Similar behavioural effects of 5-hydroxytryptamine and substance P injected intrathecally in mice.

Intrathecal injection of 5-hydroxytryptamine (5-HT) or of substance P in mice elicited a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking, directed towards the caudal parts of the body. 5-Hydroxtryptamine elicited more scratching than did substance P, which in turn caused a greater number of biting or licking responses. The 5-HT-induced responses were mimicked by 5,6-dihydroxytryptamine and inhibited by the 5-HT receptor blocker metergoline. The present findings indicate that 5-HT, injected intrathecally, may have similar effects as substance P in stimulating sensory pathways in the spinal cord.

Changes in nociception after acute and chronic administration of zimelidine: different effects in the formalin test and the substance P behavioural assay.

The selective inhibitor of the reuptake of 5-hydroxytryptamine (5-HT), zimelidine, was administered intraperitoneally to mice (10 mg/kg) and nociceptive sensitivity was evaluated using the formalin test (20 microliters of 1% formalin, injected subcutaneously) and the assay for substance P (5 ng administered intrathecally). Zimelidine increased the behavioural response to formalin, but reduced the response to substance P. These effects of zimelidine seemed to be unchanged after chronic treatment (2 X 10 mg/kg for 14 days). It is suggested that zimelidine produces a central antinociceptive effect, but elicits a peripheral hyperalgesia, which predominates in the formalin test.

Intrathecal injection of capsaicin can be used as a behavioural nociceptive test in mice.

Intrathecal injections in mice of substance P (SP), capsaicin and kainic acid elicited a behavioural response similar to that caused by noxious stimulation. Although the agents have different mechanisms of action, they showed a similar response, consisting of biting, scratching and licking the caudal parts of the body. Activation of adenosine receptors in the spinal cord with 5-N-ethylcarboxamide adenosine (NECA) had no effect on the response to substance P or to kainic acid, but reduced the response to capsaicin. It is concluded that different substances, injected intrathecally, can be used to differentiate between pre- and postsynaptic induced nociceptive behaviour, and that this assay may be valuable in assessing central antinociceptive effects of various drugs, especially those affecting systems modulated by substance P.

Changes in nociception after intrathecal administration of 5,6-dihydroxytryptamine in mice.

Intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) (5 micrograms) to mice selectively lesioned descending serotonergic pathways, reducing spinal levels of 5-hydroxytryptamine (5-HT) by 80%, without significantly changing the levels of noradrenaline. Increased sensitivity to noxious stimulation, as measured by the tail-flick and hot-plate tests, was observed 2 days after injection of 5,6-DHT. The tail-flick latencies returned to normal on day 6, but were again reduced by administration of the 5-HT receptor blocker metergoline, suggesting that the normalization process involved compensatory mechanisms in the remaining 5-HT system. In the hot-plate test, the latencies both to shaking or kicking of a hindpaw (kick) and to hindpaw lick were recorded, but the time course for the changes of these two responses was found to be different. The latencies to hindpaw lick were normalized within 2 weeks, whereas the hindpaw kick latencies remained reduced throughout the 21 day observation period.

Development of tolerance to the antinociceptive effect of metergoline.

Metergoline given IP reduced the response to noxious stimulation in the mouse formalin test. Tolerance to this effect developed after a chronic treatment schedule consisting of ten daily injections of 5 mg/kg. Twenty four hours after the last injection a test dose of metergoline (2.5 mg/kg) reduced the licking time in the formalin test by 28% in the chronic metergoline group, compared to 68% reduction in the vehicle-treated animals. In addition, the antinociceptive effect of the 5-hydroxytryptamine releasing compound p-chloramphetamine (PCA) was reduced following chronic treatment with metergoline. The reduced effect of PCA may have been caused by down-regulation of 5-HT2 receptors. However, this finding is also compatible with the contention that metergoline may act as an agonist at postsynaptic serotonergic receptors.

Metergoline elevates or reduces nociceptive thresholds in mice depending on test method and route of administration.

Intrathecal injection of metergoline reduced the response latencies in the tail-flick and hot-plate tests, supporting the contention that descending 5-hydroxytryptamine (5-HT) pathways tonically inhibit pain sensitivity. Elevated latencies were, however, observed after both intraperitoneal (IP) and intracerebroventricular (ICV) injections in the hot-plate test, when hindpaw lick was used as the response criterion. These findings may indicate that supraspinal 5-HT pathways tonically increase pain responsiveness in certain test situations . Alternative hypotheses are that metergoline in supraspinal structures acts as an agonist at post-synaptic 5-HT receptors mediating antinociception, or as an antagonist at pre-synaptic 5-HT receptors. Recording of first reaction latencies on the hot-plate showed increased thresholds after IP, but not after ICV injections. This may indicate an action on 5-HT receptors in the brain not accessible after ICV injections, or that the effect is mediated by blockade of peripheral 5-HT receptors.

Formalin test in mice, a useful technique for evaluating mild analgesics.

A modification of the formalin test appropriate for testing of mice is described. Formalin 1 or 5% was injected into the dorsal surface of a hindpaw, and the time the animal spent licking the paw was recorded. On the basis of the response pattern, two distinct periods of intensive licking activity were identified; an early (0-5 min after injection) and a late response (20-30 min after injection). The following analgesics were investigated (dose range): acetylsalicylic acid (100-400 mg/kg), paracetamol (100-400 mg/kg) and morphine (0.6-10 mg/kg). Acetylsalicylic acid (200-400 mg/kg early response, 300-400 mg/kg late response), paracetamol (200-400 mg/kg early response, 300-400 mg/kg late response) and morphine (2.5-10 mg/kg) inhibited the responses in a dose-dependent manner. The results indicate that the test is useful for evaluating mild analgesics. It may have advantages over some of the tests that are commonly used for testing analgesics.

Involvement of central serotonergic pathways in nefopam-induced antinociception.

The possible involvement of central serotonergic pathways in the mechanism of action of nefopam was investigated in male albino mice. Nefopam (15 mg/kg i.p.) did not alter the concentration of serotonin or its metabolite 5-hydroxyindole acetic acid in frontal cortex or spinal cord. Lesions of the ascending serotonergic pathways were made by systemic administration of p-chloroamphetamine (PCA). Serotonin depletion in all serotonergic systems was obtained by means of p-chlorophenylalanine (PCPA). Two different nociceptive assays were used, the formalin test and the increasing temperature hot plate test. PCPA pretreatment significantly reduced the effect of nefopam (15 mg/kg) in the formalin test. In contrast, nefopam-induced analgesia was not affected by PCA pretreatment, either in the formalin test or in the increasing temperature hot plate test. In conclusion, the data suggest that descending serotonergic pathways are involved in nefopam-induced antinociception.

Increased sensitivity to intrathecal substance P following chronic administration of zimelidine.

The behavioural response to intrathecal substance P (SP) was evaluated following acute and chronic administration of the selective serotonin reuptake inhibitor zimelidine. A single dose of zimelidine (10 mg/kg) attenuated the response to SP by approximately 40%, in agreement with previous findings that acute administration of zimelidine reduces nociceptive behaviour. Twenty-four hours following the withdrawal of long-term treatment with zimelidine (10 mg/kg X 2 daily for 14 days) the behavioural response to SP was increased by 116%. This may indicate the development of supersensitivity to SP, or may reflect an increased responsiveness to noxious stimuli due to reduced serotonergic inhibition.

The putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin antagonizes the antinociceptive effect of morphine.

The effect of the selective 5-hydroxytryptamine (5-HT-1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on nociception and morphine analgesia was tested with the tail-flick method in mice. 8-OH-DPAT (0.06-1.0 mg/kg) had no apparent effect on the general behavior of the animals and did not change their reactivity to stimulation with noxious radiant heat. The compound did, however, dose-dependently attenuate the antinociception induced by administration of morphine hydrochloride (5.0 and 10.0 mg/kg). Thus, stimulation of a subpopulation of serotonin receptors may counteract the antinociceptive effect of morphine in the tail-flick test.

Acetylsalicylic acid, paracetamol and morphine inhibit behavioral responses to intrathecally administered substance P or capsaicin.

Intrathecally administered substance P (SP) or capsaicin in mice elicited a pain-related behavioral response consisting of vigorous biting, licking and scratching of the caudal part of the body. Pretreatment of the animals with intraperitoneally injected acetylsalicylic acid (300 and 400 mg/kg), paracetamol (300 and 400 mg/kg) and morphine (2.5 and 5 mg/kg) reduced the responses in a dose-dependent manner. The analgesia is probably mediated by inhibition of a postsynaptic SP sensitive mechanism. Thus these results demonstrate central antinociceptive effects of acetylsalicylic acid and paracetamol.

Learned and pharmacologically-induced tolerance to ethanol and cross-tolerance to morphine and clonidine.

The development of tolerance to the inhibitory effect of ethanol on the tail-flick reflex was studied in the spinal rat. This preparation was used in order to avoid uncontrolled learning effects. Tolerance due to intoxicated practice (learned tolerance) and tolerance due to mere ethanol exposure (pharmacologically-induced tolerance) were studied in separate experiments. It was found that that learned tolerance to ethanol also caused tolerance to morphine and clonidine, whereas pharmacologically-induced tolerance did not have the same effect. The results challenge the concept of "behaviorally augmented tolerance" and suggest that learned and pharmacologically-induced tolerance involve different basal mechanisms in the CNS.