[Perioperative CRP quantification for appendectomy: Clinically useful or a waste of money?]. / Perioperative CRP-Bestimmung bei der Appendektomie : Klinischer Nutzen oder Geldverschwendung?

BACKGROUND: Appendectomy is the most frequently performed non-elective surgical procedure in general surgery. Despite the questionable benefit, inflammatory markers, such as leukocyte count and C-related protein (CRP) are often determined before and after the surgical procedure. Clinicians are not infrequently confronted with the question whether a patient can be discharged despite an increase in inflammatory laboratory parameters. OBJECTIVES: The aim of the current study was to retrospectively evaluate the clinical course of patients after appendectomy and the correlation with inflammatory laboratory findings. MATERIAL AND METHODS: A total of 969 patients underwent a surgical procedure due to clinically suspected acute appendicitis. All clinical, laboratory and histopathological data were obtained from the patient records and a quality control database. Laboratory results were correlated with clinical and histopathological data (e.g. t-test, χ (2)-test, regression analysis and ROC curves). RESULTS: In patients without acute appendicitis operative trauma caused an increase in CRP up to a median of 31 mg/dl on the first postoperative day and up to 47 mg/dl on postoperative day 2. The overall morbidity was 6.2%. The strongest predictive parameter for complications was a CRP of more than 108 mg/l on the first postoperative day with an odds ratio of 16.6 (96% CI 6.4/42.8, p < 0.001, specificity 88% and sensitivity 69%). Patients with CRP values below the threshold suffered from complications in 1.1 % of cases in contrast to patients above the threshold in 16.8% of cases (p < 0.001). CONCLUSION: A moderate postoperative elevation of CRP values is not a general contraindication for discharge; however, postoperative determination of CRP serum values after appendectomy might be an effective predictor for complications and should therefore be measured in the clinical routine.

Therapeutic drug monitoring of children and adolescents treated with fluoxetine.

INTRODUCTION: Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfluoxetine (NORFLX) in children and adolescents is scarce. METHODS: Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10-60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed. RESULTS: Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL (mean concentration of 213 ± 118 ng/mL, median: 185 ng/mL). High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant eff ect on the serum concentration. DISCUSSION: It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high.

Serum concentrations, therapeutic response and side effects in children and adolescents with impulsive-aggressive symptoms during risperidone therapy.

INTRODUCTION: The aim of this prospective naturalistic study was to examine for the first time the relationship between dosage, serum concentration and clinical outcome in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. METHODS: Steady state trough serum concentrations of risperidone and 9-hydroxyrisperidone (the active moiety) were measured in 103 subjects. The therapeutic effect was assessed by the clinical global impression improvement subscale and side effects by the Udvalg for Kliniske Undersogelser-side effect rating scale. RESULTS: We found a linear relationship between the risperidone dose and the serum concentration of the active moiety (Spearman rho=0.53) and no correlation between the serum concentration and either the therapeutic effect or side effects. There was no effect of gender and co-medication. DISCUSSION: This study has the typical limitations of naturalistic studies, therefore our results should be interpreted with caution. Based on the serum concentrations at the therapeutically effective dose range (0.25-1.5 mg/day) we obtained first information on a possibly appropriate therapeutic serum range for the risperidone treatment of children and adolescents with impulsive-aggressive symptoms. Further studies with greater sample sizes are needed to validate our results and to examine the influence of genetic polymorphisms on the serum concentration of risperidone.

Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders.

INTRODUCTION: There are developmental and age-dependent differences in the pharmacokinetics and the pharmacodynamics of drugs in children and adolescents. Therefore, there is a need to carry out standardised studies to find out therapeutic ranges of plasma/serum concentrations in psychopharmacotherapy of children and adolescents. The aim of this prospective study was to examine the relationship between quetiapine serum concentration, treatment response, and side effects in a clinical setting to elucidate the age-specific therapeutic range of quetiapine in adolescents. METHODS: Over a period of two years, therapeutic drug monitoring (TDM) was routinely performed in 21 adolescents (mean age was 15.9+/-1.5 years, 57% male) with psychotic disorders according to the guidelines of the AGNP TDM expert group. The psychopathology was assessed by using the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS). Side effects were assessed by using the Dose Record and Treatment Emergent Symptom Scale (DOTES). Trough quetiapine concentrations were determined under steady state conditions after multiple-dose regimes (median 600 mg/day; range 100-800 mg/day). RESULTS: There was a marked variability of the serum concentrations, ranging from 19-877 ng/ml. 40.8% of the determined values were below and 24.5% above the therapeutic range (70-170 ng/ml) recommended for adults. None of the patients had severe side effects. We found a weak correlation between dose and serum concentration of quetiapine and no relationship between serum concentration and treatment response. DISCUSSION: There are several limitations of this study, and our results should therefore be interpreted with caution. Notwithstanding, differences in the ontogenesis of pharmacokinetics and pharmacodynamics may be the reason for the difference in the relationship between blood concentrations and therapeutic response to psychopharmaca in children, adolescents and adults. Further studies using larger samples, baseline assessment of psychopathology, definition of the treatment interval and investigation of clinically relevant interactions with various co-medications are warranted to improve the limitations of this pilot study.

Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods.

UNLABELLED: The hippocampus is discussed as one of the key regions in the pathogenesis of Posttraumatic Stress Disorder (PTSD). MRI results concerning the volume of the hippocampus are, however, inconsistent. This may be due to the heterogeneity of patients' traumata or postprocessing of the imaging data. To overcome these problems, the present study investigates volume changes in well-characterized chronic PTSD patients in comparison to controls using two different evaluation methods. MATERIAL AND METHODS: 15 patients with chronic PTSD, traumatized at the same air show plane crash in 1988 (Ramstein, Germany), and 15 matched healthy controls participated in this study. All patients suffered from significant impairment by the PTSD; none had a history of drug or alcohol abuse. Hippocampus volume changes were processed by a semi-automated standard procedure performed with BRAINS2 as well as the voxel based morphometry (VBM) using SPM2. RESULTS: No differences in total brain grey or white matter were detected between patients and controls. No differences in total hippocampal volume or in right and left parts were seen, even when hippocampal volumes were corrected by total brain volume or correlated with clinical data. Finally, no significant differences were detected between patients and controls in hippocampal regions using VBM. DISCUSSION: This is the first study examining long-term changes in hippocampal volumes in chronic PTSD patients compared to matched controls using two different evaluation methods. Neither conventional volumetry nor VBM could detect any differences in the volume and structure. This supports the hypothesis that previously described hippocampal volume reduction is not necessarily due to PTSD or at least that, after 15 years, volume changes have been restored or have not yet developed.