Off-label use in Germany - a current appraisal of gynaecologic university departments.

OBJECTIVE: The off-label use, referring to the applicability of pharmaceutical drugs beyond the submitted and from the Federal Institute for Drugs and Medical Devices (BfArM, Bundesamt für Arzneimittel und Medizinprodukte) certified and approved administration, is the subject of controversial discussions. The application can be considered in case of severe illness - if no therapeutic alternatives are available - or it exists as a founded perspective for achieving therapeutic success. METHODS: A latitudinal study for evaluating the application of off-label use supplements was performed at 43 German university and academic teaching hospitals. Five doctors at each hospital applied off-label pharmaceutical drugs and were called upon to share their personal experience to the application of those medications. RESULTS: 75 (35%) questionnaires were returned out of 22 (51%) medical centres with 215 contacted physicians. Off-label use was common for 65 (91%) of the physicians. Only 9% of them obviate the application of off-label drugs. About a half of the medication is related to application in obstetrics (54%) and in most cases on an every day basis. Uterotonics were the most commonly used off-label medications (34%). The main part of information about off-label use is obtained from personal information of colleagues (66%) and personal experience (58%). 34% of physicians think that off label use is risky. Interestingly, the view about off label use of medication varies considerably among physicians from various hospitals. CONCLUSIONS: The application of off-label pharmaceutical drugs in Germany seems to be a well established practice. More than 90% of participators of our trial use at least one medication outside the administration. This includes particularly prostaglandins, anti-hypertonic therapeutics and chemotherapeutics.

Hospital treatment - Is it affordable? A structured cost analysis of vaginal deliveries and planned caesarean sections.

INTRODUCTION: The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay. METHODS: To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital's computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services. RESULTS: For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83Euro/1432Euro. About 45% of the summarized costs are calculated on a reliable database. DISCUSSION: The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.

Relapse and survival in early-stage ovarian cancer.

OBJECTIVE: To analyze the prognostic influence of patient characteristics, diagnostic markers or therapeutic procedures in women diagnosed with early ovarian cancer based on relapse and survival in long term follow-up. MATERIALS AND METHODS: All women diagnosed and treated for early ovarian cancer at our institution between 1992 and 2006 were included in this retrospective study. Patient characteristics, clinical data including operative procedure, serum markers, stage and histology at first diagnosis as well as follow-up data were analyzed with regard to survival times and relapse rates. RESULTS: Altogether, 116 patients were included. Mean follow-up time was 7.0 +/- 3.3 years (range 2-14 years). Histology revealed a serous tumor in 64.7% (75/116), mucinous in 19.0% (22/116) and endometiroid tumors in 7.8% (9/116) of all cases. TNM classification was pT1a in 49.1% (57/116), pT1b in 6% (7/116), pT1c in 32.8% (38/116) and pT2a in 12.1% (14/116). Lymph node involvement (N1) was found in 3.4% of all patients. 17 deaths and 17 relapses (each 14.7%) were documented during follow-up time with a mean time to recurrence of 3.3 +/- 2.1 years (range 1-7 years). The general 1-, 2-, 5- and 10-year survival rates were 99, 95.7 and 88.9 and 81.0%, respectively. Patients with tumor stage pT1a and pT1b had a significantly better survival (P = 0.0003) and significantly lower risk of recurrence (P = 0.0138) compared to higher tumor stages. Moreover, patients who experienced recurrent disease or presented with ascites at primary diagnosis had a significantly worse overall survival (recurrence: hazard ratio 0.17, 95% confidence interval 0.0155-0.2182, P = 0.0001; ascites: HR 2.84, CI 1.1919-10.1131, P = 0.0225). The risk for recurrent disease was significantly elevated for patients with low grade (G3) tumors (P = 0.0330). Interestingly, there was neither a worse survival rate nor a higher relapse rate for patients with primary laparoscopic surgical access. CONCLUSION: Patients with early ovarian cancer stage pT1c and pT2a or low grade tumor have to be monitored closely in oncologic follow-up as they bare a significant risk for disease recurrence. Ascites at primary diagnosis, pT1c or pT2a tumor stage or recurrent disease are associated with a poor survival even in early ovarian cancer.

Higher order multiples--socioeconomic impact on family life.

AIMS: Assisted reproduction led to an enormous increase of multifetal gestation. Apart from the obstetrical risks the physical, psychological and socioeconomic problems in families after the birth of higher order multiples often lack attention. STUDY DESIGN: Anonymous questionnaires were sent to 92 families who had delivered higher order multiples at our hospital (1983--1998). In a retrospective analysis (rate of return: 70%) the study group included 54 families with triplets, nine families with quadruplets and one family with quintuplets. The questionnaire was divided into three sections: a joint section to be answered by both parents together, and two identical sections for each separately. RESULTS: Most parents suffered from severe physical and psychological exhaustion mainly caused by worries about the multiples' development, handicaps and acute and chronic diseases as well as by personal and by financial problems. Nearly all of the families had to rely on additional manpower and on financial support. The inability to cope with the "self-inflicted" family-situation as a consequence of "optional" infertility treatment led to feelings of guilt. CONCLUSIONS: Aside from psychological guidance, the need for personnel aid as well as financial and material support in families after the delivery of higher order multiples is striking.

Assessment of different preservation and storage conditions on aortic valves: introduction of a quantitative measuring method of the integrity of endothelial cells.

The fate of human allogeneic aortic valves depends mainly on their histological and immunological condition at the time of transplantation. A screening test making novel use of Alcian Blue was used to determine the integrity of endothelial cells as a prerequisite to their function. The dye uptake into the nucleus was measured quantitatively. The test was used to compare the effect of different storage mediums and temperatures (+4 degrees C, -30 degrees C, -80 degrees C, DMSO, FCS, RPMI, antibiotic solution) on aortic valves of rats. The cell integrity decreased with increasing storage time and higher storage temperature. The cryoprotective agent DMSO had no essential effect on the maintenance of cell integrity.