Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

Psychosocial functioning in patients with schizophrenia treated with aripiprazole - an office-based real-world setting. Results from the German post-marketing surveillance study.

AIM: Aripiprazole (ABILIFY) is an effective antipsychotic used in a dose range from 10 to 30 mg, administered once daily. Soon after its approval in Germany for treatment of schizophrenia, a 12-month post-marketing surveillance study was initiated that included 1 096 patients cared for by 408 office-based psychiatrists and/or neurologists in private practice. The aim was to gain further insights into safety and efficacy of aripiprazole in an outpatient real-life setting focusing on general health, well-being and psychosocial functioning. PATIENTS AND METHODS: Efficacy was rated by using standard CGI, SF-12 and SIWM-PsySo instruments for severity of disease, physical and mental health outcomes and psychosocial state, respectively. Safety was evaluated according to the reports of adverse events. Mean total daily dose of aripiprazole increased from 15.4 mg at the visit after 1 month to 17.6 mg at the visits after 6 to 12 months, the most frequently administered maintenance dose being 15 mg. RESULTS AND DISCUSSION: Within the observation period significant improvements of CGI, SF-12 and SIWM-PsySo scores over time versus baseline values were observed (p<0.001) when starting with or switching to aripiprazole. Physicians observed improvements in 80.7% of the patients at endpoint; in 62% of the patients the disease state was considered "much" or "very much" improved. Aripiprazole was overall well tolerated; 19.9% of patients discontinued treatment after 12 months. Adverse effects in general were moderate to mild and corresponded to the known tolerability profile of aripiprazole. Psychotic side effects reported were probably due to a recurrence of the underlying schizophrenic disorder. CONCLUSION: The results indicate that aripiprazole may be an efficacious and safe treatment option for pre-treated patients with schizophrenia also in a naturalistic psychiatrist/neurologist practice setting with effects on health and psychosocial functioning and a comparably low dropout rate.

[The psychiatrist and the psychiatric hospital--an analysis of referral and aftercare]. / Der niedergelassene Psychiater und die psychiatrische Klinik.

OBJECTIVE: Against the background of the problematic interface between outpatient and inpatient care in the German psychiatric health care system, the role of psychiatrists in private practice concerning the pathways of psychiatric inpatients before and after their hospital stay should be evaluated. METHODS: Based on data of the psychiatric basic documentation (DGPPN-BADO) of 4905 patients admitted to the psychiatric hospital in 2003, predictors of the type of referral as well as the outpatient aftercare were analysed by means of logistic regression analyses. RESULTS: 9.8 % of patients were referred by psychiatrists in private practice. Patients sent by psychiatrists more seldom had an addiction disorder, more often were residents of sheltered homes, showed a present episode lasting more than three months and had a psychopharmacological pre-treatment with an atypical antipsychotic or SSRI. At discharge, outpatient aftercare by psychiatrists in private practice was recommended to 32.1 % of inpatients. Referral by a psychiatrist in private practice as well as the diagnosis of schizophrenia or affective disorder led more often to an outpatient aftercare by a psychiatrist. CONCLUSIONS: Due to the small number of patients referred by psychiatrists, the cooperation between psychiatric hospital and psychiatrists in private practice has to be focused by the quality management of the hospital.

[Pathological jealousy]. / Zwischen Wahn, Zwang und Alkoholmissbrauch. Wenn aus Liebe Eifersucht wird.

Pathological jealousy can make life unbearable for all concerned. The proximity of this condition to obsessive-compulsive phenomena has given rise to the notion that it might respond to substances of proven value in the treatment of obsessive-compulsive disorders. This case history exemplifies the successful treatment of pathological jealousy with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The substance not only proved to be a successful antidepressant, but also effectively mitigated the anguish of the patient's pathological jealousy. On the basis of these findings, fluoxetine--as also other SSRIs--should always be considered as a possible effective pharmacological strategy for the treatment of pathological jealousy.

Anaemia in schoolchildren in eight countries in Africa and Asia.

OBJECTIVE: To report on the haemoglobin concentrations and prevalence of anaemia in schoolchildren in eight countries in Africa and Asia. DESIGN: Blood samples were collected during surveys of the health of schoolchildren as a part of programmes to develop school-based health services. SETTING: Rural schools in Ghana, Indonesia, Kenya, Malawi, Mali, Mozambique, Tanzania and Vietnam. SUBJECTS: Nearly 14 000 children enrolled in basic education in three age ranges (7-11 years, 12-14 years and > or =15 years) which reflect the new UNICEF/WHO thresholds to define anaemia. RESULTS: Anaemia was found to be a severe public health problem (defined as >40% anaemic) in five African countries for children aged 7-11 years and in four of the same countries for children aged 12-14 years. Anaemia was not a public health problem in the children studied in the two Asian countries. More boys than girls were anaemic, and children who enrolled late in school were more likely to be anaemic than children who enrolled closer to the correct age. The implications of the four new thresholds defining anaemia for school-age children are examined. CONCLUSIONS: Anaemia is a significant problem in schoolchildren in sub-Saharan Africa. School-based health services which provide treatments for simple conditions that cause blood loss, such as worms, followed by multiple micronutrient supplements including iron, have the potential to provide relief from a large burden of anaemia.

Drug contamination from opening glass ampules.

Recently there have been several reports of postoperative sepsis due to the intravenous injection of contaminated solutions of propofol (Diprivan). The mechanism by which this contamination occurred has not been identified. This study sought to determine whether bacterial contamination of the contents of glass ampules can be decreased by swabbing the neck of the vial with alcohol prior to opening. Glass ampules of 1% propofol and 1% lidocaine were swabbed with a solution of Staphylococcus epidermidis. Half of these ampules were subsequently wiped with alcohol pads prior to being opened. An aliquot from each ampule was pipetted into a nutrient broth and allowed to incubate overnight at 37 degrees C. These solutions were plated on agar, incubated for 24 h, and then examined for bacterial growth. Three of the eight lidocaine ampules and six of the eight propofol ampules not cleaned with alcohol demonstrated evidence of bacterial contamination. The contents of all ampules that had been wiped with alcohol prior to being opened remained sterile (P less than 0.001 vs. non-alcohol-treated group for propofol ampules and P = 0.20 vs. non-alcohol-treated group for lidocaine ampules). These data suggest that bacterial contamination of propofol and lidocaine may occur as a result of opening glass ampules. Wiping the outside of the ampule with alcohol immediately prior to opening may decrease this risk.

[Writer's cramp--focal dystonia or psychogenic movement disorder? A critical literature study]. / Der Schreibkrampf--fokale Dystonie oder psychogene Bewegungsstörung? Eine kritische Literaturstudie.

For more than 100 years there has been a discussion as to whether writer's cramp is caused by a disease of the central nervous system, or if it is to be considered as a disturbance of psychogenic origin. Whereas before 1982 there seemed to be a lot of evidence for the psychogenic theory many authors now tend to stress the opinion of Sheehy and Marsden who had explained that "writer's cramp" should be seen as a "focal dystonia". This article discusses the statements of Sheehy and Marsden in comparison with other scientific findings regarding the occupational cramps--above all "writer's cramp". It is concluded that there are different therapeutic approaches derived from the respective theory and which are considered to lessen the movement disorder. Scientific literature suggests that psychotherapy or some therapeutic approaches of behaviour therapy are more effectful in mastering this "mysterious" disorder than any pharmacological substance tested upto now.