[No rebound psychosis in a case of switching from clozapine to quetiapine]

OBJECTIVE: After rapid discontinuation of clozapine treatment rebound psychosis have been reported. Preexposure of D (2) receptors to clozapine may alter their affinity to endogenous dopamine. Clozapine withdrawal may also lead dysfunctional NMDA-receptors to cause dopamine release in the striatum. METHOD: We report a case of a schizophrenic patient treated with clozapine 200 mg and aripiprazole 15 mg per day. After rapid clozapine discontinuation we added quetiapine up to 700 mg daily. RESULTS: No rebound psychosis occurred. Even ten weeks after switching to quetiapine the patient's condition remained stable in the Brief Psychiatric Rating Scale. CONCLUSIONS: The combination of aripiprazole and quetiapine seemed to control supersensitivity effects at the D (2) receptor after clozapin withdrawal in this case.

Study design, baseline patient characteristics and intervention in a cross-cultural framework: results from the ADORE study

OBJECTIVE : To describe the methodology and to present the baseline findings of the Attention-deficit/hyperactivity Disorder Observational Research in Europe (ADORE) study, the primary objective of which is to describe the relationship between treatment regimen prescribed and quality of life of children with ADHD in actual practice. METHODS : In this 2-year prospective observational study, data on diagnosis, prescribed treatment and outcomes of ADHD were collected at seven time points by paediatricians and child psychiatrists on 1,573 children recruited in 10 European countries. The data presented here from the 1,478 patients included in the analyses describe the baseline condition, initial treatment regimen prescribed and quality of life of families with children with ADHD. RESULTS : Patients had a mean age of 9.0 years (SD 2.5) and 84% were male. Physicians diagnoses were made using DSM-IV (43 %), ICD-10 (32%) and both DSM-IV and ICD-10 (12 %). Mean age of awareness of a problem was 5.1 years, suggesting an average delay of approximately 4 years between awareness and diagnosis of ADHD. Baseline ADHD rating scale scores (physicianrated) indicated moderate to severe ADHD. Parent-rated SDQ scores were in agreement and suggested significant levels of co-existing problems. CGI-S, CGAS and CHIPCE scores also indicated significant impairment. Patients were offered the following treatments after the initial assessment: pharmacotherapy (25 %), psychotherapy (19 %), combination of pharmacotherapy and psychotherapy (25 %), other therapy (10 %) and no treatment (21 %). CONCLUSION : The ADORE study shows that ADHD is similarly recognised across 10 European countries and that the children are significantly impaired across a wide range of domains. In this respect, they resemble children described in previous ADHD samples.

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

OBJECTIVE: To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. STUDY DESIGN: Blind, randomized clinical study. ANIMALS: Dogs with femoral (n=18) or pelvic (27) fractures. METHODS: Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. RESULTS: Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. CONCLUSIONS: Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. CLINICAL RELEVANCE: Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Prospective navigator-echo-based real-time triggering of fetal head movement for the reduction of artifacts

The purpose of this study was to evaluate the neuroimaging quality and accuracy of prospective real-time navigator-echo acquisition correction versus untriggered intrauterine magnetic resonance imaging (MRI) techniques. Twenty women in whom fetal motion artifacts compromised the neuroimaging quality of fetal MRI taken during the 28.7 +/- 4 week of pregnancy below diagnostic levels were additionally investigated using a navigator-triggered half-Fourier acquired single-shot turbo-spin echo (HASTE) sequence. Imaging quality was evaluated by two blinded readers applying a rating scale from 1 (not diagnostic) to 5 (excellent). Diagnostic criteria included depiction of the germinal matrix, grey and white matter, CSF, brain stem and cerebellum. Signal-difference-to-noise ratios (SDNRs) in the white matter and germinal zone were quantitatively evaluated. Imaging quality improved in 18/20 patients using the navigator echo technique (2.4 +/- 0.58 vs. 3.65 +/- 0.73 SD, p < 0.01 for all evaluation criteria). In 2/20 patients fetal movement severely impaired image quality in conventional and navigated HASTE. Navigator-echo imaging revealed additional structural brain abnormalities and confirmed diagnosis in 8/20 patients. The accuracy improved from 50% to 90%. Average SDNR increased from 0.7 +/- 7.27 to 19.83 +/- 15.71 (p < 0.01). Navigator-echo-based real-time triggering of fetal head movement is a reliable technique that can deliver diagnostic fetal MR image quality despite vigorous fetal movement.

Whole-body computed tomography for multiple traumas using a triphasic injection protocol

To evaluate a triphasic injection protocol for whole-body multidetector computed tomography (MDCT) in patients with multiple trauma. Fifty consecutive patients (41 men) were examined. Contrast medium (300 mg/mL iodine) was injected starting with 70 mL at 3 mL/s, followed by 0.1 mL/s for 8 s, and by another bolus of 75 mL at 4 mL/s. CT data acquisition started 50 s after the beginning of the first injection. Two experienced, blinded readers independently measured the density in all major arteries, veins, and parenchymatous organs. Image quality was assessed using a five-point ordinal rating scale and compared to standard injection protocols [n = 25 each for late arterial chest, portovenous abdomen, and MDCT angiography (CTA)]. With the exception of the infrarenal inferior caval vein, all blood vessels were depicted with diagnostic image quality using the multiple-trauma protocol. Arterial luminal density was slightly but significantly smaller compared to CTA (P < 0.01). Veins and parenchymatous organs were opacified significantly better compared to all other protocols (P < 0.01). Arm artifacts reduced the density of spleen and liver parenchyma significantly (P < 0.01). Similarly high image quality is achieved for arteries using the multiple-trauma protocol compared to CTA, and parenchymatous organs are depicted with better image quality compared to specialized protocols. Arm artifacts should be avoided.

[Parent satisfaction with a child and family-centered treatment program for primary headache in childhood and adolescence]

Patient satisfaction represents a significant outcome criterion in the context of systemic psychotherapeutic therapy research. This study investigated parent satisfaction with a psychosocial treatment program (comprising three components: child group therapy, parents' evenings, systemic family sessions) for pediatric primary headache (diagnosed according to IHS criteria). 10 weeks after the end of the treatment program, the parents were sent a questionnaire containing open questions and ten-point numerical rating scales. The sample comprised n=48 families. The return rate was 89%. The qualitative content analysis showed a hierarchical category system consisting of 3 major categories, 7 main groups and 69 sub-categories. The parents stated that they were satisfied with (1.) the effects of the treatment program, (2.) the specific treatment techniques and the medical and psychosocial headache-related information provided, and (3.) the therapeutic relationship. The mean satisfaction for all three therapy components on the ten-point numerical rating scale was 8.1 with a standard deviation of 2.0 (child headache group: 8.5; parents' evenings: 8.2; family sessions: 7.5). The results are discussed with reference to methodological aspects: avoidance of ceiling effects and social desirability in measuring customer satisfaction, order effects of items, weighting of the significance of satisfaction levels as an outcome criterion.

Patient satisfaction with primary care: an observational study comparing anthroposophic and conventional care

BACKGROUND: This study is part of a cross-sectional evaluation of complementary medicine providers in primary care in Switzerland. It compares patient satisfaction with anthroposophic medicine (AM) and conventional medicine (CON). METHODS: We collected baseline data on structural characteristics of the physicians and their practices and health status and demographics of the patients. Four weeks later patients assessed their satisfaction with the received treatment (five items, four point rating scale) and evaluated the praxis care (validated 23-item questionnaire, five point rating scale). 1946 adult patients of 71 CON and 32 AM primary care physicians participated. RESULTS: 1. Baseline characteristics: AM patients were more likely female (75.6% vs. 59.0%, p < 0.001) and had higher education (38.6% vs. 24.7%, p < 0.001). They suffered more often from chronic illnesses (52.8% vs. 46.2%, p = 0.015) and cancer (7.4% vs. 1.1%). AM consultations lasted on average 23,3 minutes (CON: 16,8 minutes, p < 0.001). 2. Satisfaction: More AM patients expressed a general treatment satisfaction (56.1% vs. 43.4%, p < 0.001) and saw their expectations completely fulfilled at follow-up (38.7% vs. 32.6%, p < 0.001). AM patients reported significantly fewer adverse side effects (9.3% vs. 15.4%, p = 0.003), and more other positive effects from treatment (31.7% vs. 17.1%, p < 0.001). Europep: AM patients appreciated that their physicians listened to them (80.0% vs. 67.1%, p < 0.001), spent more time (76.5% vs. 61.7%, p < 0.001), had more interest in their personal situation (74.6% vs. 60.3%, p < 0.001), involved them more in decisions about their medical care (67.8% vs. 58.4%, p = 0.022), and made it easy to tell the physician about their problems (71.6% vs. 62.9%, p = 0.023). AM patients gave significantly better rating as to information and support (in 3 of 4 items p [less than or equal to] 0.044) and for thoroughness (70.4% vs. 56.5%, p < 0.001). CONCLUSION: AM patients were significantly more satisfied and rated their physicians as valuable partners in the treatment. This suggests that subject to certain limitations, AM therapy may be beneficial in primary care. To confirm this, more detailed qualitative studies would be necessary.

Evaluation of anesthesia recovery quality after low-dose racemic or S-ketamine infusions during anesthesia with isoflurane in horses

OBJECTIVE: To compare anesthesia recovery quality after racemic (R-/S-) or S-ketamine infusions during isoflurane anesthesia in horses. ANIMALS: 10 horses undergoing arthroscopy. PROCEDURES: After administration of xylazine for sedation, horses (n = 5/group) received R-/S-ketamine (2.2 mg/kg) or S-ketamine (1.1 mg/kg), IV, for anesthesia induction. Anesthesia was maintained with isoflurane in oxygen and R-/S-ketamine (1 mg/kg/h) or S-ketamine (0.5 mg/kg/h). Heart rate, invasive mean arterial pressure, and end-tidal isoflurane concentration were recorded before and during surgical stimulation. Arterial blood gases were evaluated every 30 minutes. Arterial ketamine and norketamine enantiomer plasma concentrations were quantified at 60 and 120 minutes. After surgery, horses were kept in a padded recovery box, sedated with xylazine, and video-recorded for evaluation of recovery quality by use of a visual analogue scale (VAS) and a numeric rating scale. RESULTS: Horses in the S-ketamine group had better numeric rating scale and VAS values than those in the R-/S-ketamine group. In the R-/S-ketamine group, duration of infusion was positively correlated with VAS value. Both groups had significant increases in heart rate and mean arterial pressure during surgical stimulation; values in the R-/S-ketamine group were significantly higher than those of the S-ketamine group. Horses in the R-/S-ketamine group required slightly higher end-tidal isoflurane concentration to maintain a surgical plane of anesthesia. Moderate respiratory acidosis and reduced oxygenation were evident. The R-norketamine concentrations were significantly lower than S-norketamine concentrations in the R-/S-ketamine group. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with R-/S-ketamine, anesthesia recovery was better with S-ketamine infusions in horses.

Tunnelled versus straight intravitreal injection: intraocular pressure changes, vitreous reflux, and patient discomfort

PURPOSE: To compare tunnelled scleral intravitreal injection with straight scleral intravitreal injection concerning short-term intraocular pressure (IOP) changes, occurrence and amount of vitreous reflux, and patient discomfort. METHODS: Sixty patients were randomly allocated to two groups (tunnelled intravitreal injection and straight intravitreal injection). IOP was measured before and directly (<1 minute) after the injection of 0.05 mL of an antivascular endothelial growth factor agent and then every 5 minutes until IOP was <30 mmHg. Occurrence and amount of vitreous reflux were recorded. Patient discomfort during injection was assessed with a Wong-Baker faces pain rating scale. RESULTS: IOP (mmHg +/- SD) increased significantly directly after injection to 35.97 +/- 8.13 (tunnelled intravitreal injection) and 30.19 +/- 12.14 (straight intravitreal injection). These pressure spikes differed significantly between both groups (P = 0.01, mean difference: -7.11). Five minutes after injection, there was no significant difference in IOP increase between the groups. All IOP measurements were <30 mmHg after 15 minutes. Occurrence and amount of vitreous reflux were significantly higher with straight intravitreal injection. There was no significant difference in Wong-Baker faces pain rating scale score between both groups. CONCLUSION: Tunnelled intravitreal injection seems to be the technique of choice for low-volume intravitreal injection (0.05 mL). There is neither a difference in patient discomfort nor a difference in IOP increase 5 minutes after injection between both groups. Significantly less vitreous reflux with tunnelled intravitreal injection should lead to less postinjectional drug loss.

Diminished prefrontal brain function in adults with psychopathology in childhood related to attention deficit hyperactivity disorder

The aim of the present study was to investigate prefrontal brain function and cognitive response control in patients with personality disorders who either suffered or did not suffer from psychopathology related to attention deficit hyperactivity disorder (ADHD) during childhood. For this purpose, 36 psychiatric out-patients with personality disorders--24 of whom showed ADHD-related psychopathology during childhood assessed by the German short form of the Wender Utah Rating Scale--and 24 healthy controls were investigated electrophysiologically by means of a cued Go-NoGo task (Continuous Performance Test). Topographical analyses were conducted to individually quantify the NoGo anteriorisation (NGA), a neurophysiological correlate of prefrontal response control that has been suggested to reflect activation of the anterior cingulate cortex. ADHD patients exhibited a significantly reduced mean NGA and diminished amplitudes of the Global Field Power, as well as a reduced increase of fronto-central P300 amplitudes, in NoGo-trials compared with the healthy controls, whereas patients with personality disorders alone did not differ from the control group in any of the electrophysiological parameters. The results indicate that ADHD-related psychopathology is associated with prefrontal brain dysfunction, probably related to processes of response inhibition and/or cognitive response control.

Patient-reported outcomes in meta-analyses - part 2: methods for improving interpretability for decision-makers

Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients, clinicians and policy-makers facing challenging health care decisions. Based on emerging methods, guidance on improving the interpretability of meta-analysis of patient-reported outcomes, typically continuous in nature, is likely to enhance decision-making. The objective of this paper is to summarize approaches to enhancing the interpretability of pooled estimates of PROs in meta-analyses. When differences in PROs between groups are statistically significant, decision-makers must be able to interpret the magnitude of effect. This is challenging when, as is often the case, clinical trial investigators use different measurement instruments for the same construct within and between individual randomized trials. For such cases, in addition to pooling results as a standardized mean difference, we recommend that systematic review authors use other methods to present results such as relative (relative risk, odds ratio) or absolute (risk difference) dichotomized treatment effects, complimented by presentation in either: natural units (e.g. overall depression reduced by 2.4 points when measured on a 50-point Hamilton Rating Scale for Depression); minimal important difference units (e.g. where 1.0 unit represents the smallest difference in depression that patients, on average, perceive as important the depression score was 0.38 (95%CI 0.30 to 0.47) units less than the control group); or a ratio of means (e.g. where the mean in the treatment group is divided by the mean in the control group, the ratio of means is 1.27, representing a 27%relative reduction in the mean depression score).

Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients.

Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.

Assessment of the wind-up phenomenon in the equine nociceptive trigeminal system.

Repeated sub-threshold nociceptive electrical stimulation resulting in temporal summation of the limb nociceptive withdrawal reflex is a well-established non-invasive model to investigate the wind-up phenomenon in horses. Due to structural similarities of the trigeminal sensory nucleus to the dorsal horn of the spinal cord, temporal summation should be evoked by repeated transcutaneous electrical stimulation of trigeminal afferents. To evaluate this hypothesis repeated transcutaneous electrical stimulation was applied to the supraorbital and infraorbital nerves of 10 horses. Stimulation intensities varied between 0.5 and 1.3 times the trigemino-cervical reflex threshold defined for single stimulation. Evoked electromyographic activity of the orbicularis oculi, splenius and cleidomastoideus muscles was recorded and the signals analysed in the previously established epochs typical to the early and late component of the blink reflex and to the trigemino-cervical reflex. Behavioural reactions were evaluated with the aid of numerical rating scale. The nociceptive late component and the trigemino-cervical reflex were not elicited by sub-threshold intensity repeated transcutaneous electrical stimulation. Furthermore, the median reflex amplitude for the 10 horses showed a tendency to decline over the stimulation train so temporal summation of afferent trigeminal inputs could not be observed. Therefore, the modulation of trigeminal nociceptive processing attributable to repeated Aδ fibre stimulations seems to differ from spinal processing of similar inputs as it seems to have an inhibitory rather than facilitatory effect. Further evaluation is necessary to highlight the underlying mechanism.

Bullous pemphigoid: therapeutic algrorithm and practical management

Introduction: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucosae. BP typically affects the elderly and manifests with severe itch, localised or generalised eczematous, urticated and/or bullous lesions. Its morbidity and impact on the quality of life are important. The disease is significantly associated with neurological disorders, such as stroke, Parkinson disease, major cognitive impairment and multiple sclerosis. Diagnosis of BP critically relies on immunopathologic examinations, particularly direct immunofluorescence microscopy studies. Areas covered: This paper looks at the evidence of therapies commonly used in bullous pemphigoid. Expert opinion: Treatment of BP has been a challenge, given the relative rarity of the disease, lack of good quality randomised controlled trials, the presence of co-morbidities in the affected elderly population and the high mortality rate. Recent controlled studies have indicated that potent topical corticosteroids constitute a more effective therapy for BP when compared to oral corticosteroids in terms of control of the disease, side effect profile and overall survival. Other therapies have been employed with varying success, but are not validated yet. Improved knowledge of the pathophysiology of BP will hopefully allow the development of new immunomodulatory treatments for this debilitating disease.

Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.

RATIONALE: Thyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. OBJECTIVES: This study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. METHODS: This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.