[Mentoring and workplace-based assessments for final year medical students : An effective way to increase satisfaction and competence?] / Mentoring und arbeitsplatzbasierte Prüfungen im Praktischen Jahr : Ein effektiver Weg zur Steigerung von Zufriedenheit und Kompetenz?

BACKGROUND: The final year of medical training in Germany is one of the least structured and standardized years of medical school. Medical students often complain about a lack of guidance, supervision and feedback. They are mostly asked to perform delegable nonmedical tasks even though student experiences in this period critically determine future decisions for certain medical specialties. Consequently, right from the beginning many young professionals feel overburdened especially by the time pressure of everyday clinical practice. The planned amendment of the medical licensing regulations will make competence-based training even more important. This article therefore aims to examine the extent to which a mentoring-based curriculum with workplace-based examinations during the final year of medical studies can make a valuable contribution to this. METHODS: After a needs assessment (structured literature search, results evaluation and focus groups with both students and medical specialists), a mentoring-based curriculum for final year medical students was developed following the Kern cycle. In 2 work sessions 10 discipline-specific competencies for the fields of anesthesiology, critical care, emergency and pain medicine were established and prioritized, which had to be mastered by every student independently at the end of the training period. Assessment of these competencies was performed on a regular basis by trained mentors in the form of workplace-based assessments (mini-clinical evaluation exercise, mini-CEX, direct observation of procedural skills, DOPS). Multiperspective evaluation was and is the foundation of continuous program development. By September 2019 a total of 40 students had completed the modified curriculum and were subsequently interviewed online about various aspects of the tertial. RESULTS: The response rate to the survey was 80% (n = 32). The gender ratio was balanced (male = 50%, female = 50%). Prioritization and assessment of 10 competencies by trained mentors enabled a focused, demand-driven and high-quality training of final year medical students. Surveyed students found the section mentoring and feedback to be very positive and it supported their learning success (grade 1.5). Despite firmly established feedback structures, in retrospect almost half (51.6%) wanted more structured feedback. Workplace-based assessments were mostly previously unknown (64.6%) but were experienced as helpful and meaningful (76.7%). Students felt confident and prepared for the final state examination (81.3%) and their career start (71.0%) after being part of the program. These findings were accompanied by a high level of satisfaction (grade 1.7) as well as a high recommendation rate for this institution (as a training program for final year medical students and as a career start for residents, both with 93.7%). Thus, the good evaluation results of the department before the start of the project could again be slightly improved. CONCLUSION: A demand-driven, mentoring-based curriculum with integrated workplace-based assessments not only led to high overall student satisfaction but also promoted the quality of teaching in an effective and resource-saving way. Mentoring promotes learning success mainly through feedback and individual learning support and also supports the communicative and social skills of students and mentors alike.

[Perioperative adverse respiratory events in overweight and obese children]. / Atemwegskomplikationen bei übergewichtigen und adipösen Kindern.

BACKGROUND: Overweight and obesity are increasing problems in pediatric anesthesia. This observational study was designed to examine how airway-related complications occur in overweight children and adolescents during general anesthesia and if this is a relevant problem in Germany. METHODS: From October 2008 until August 2009, at the university clinic in Leipzig, 504 in- and outpatients, aged 2-18 years, ASA I-III, undergoing elective procedures (ENT and pediatric surgery), were observed. With the aid of special data sheets, the following parameters were determined: Mallampati Score, difficult mask ventilation and intubation, use of a Guedel/Wendl tube, Cormack-Lehane Score, number of intubation attempts, airway obstructions (broncho- and laryngospasms), coughing as a sign of airway irritation, and decreases in oxygen saturation >10 %. RESULTS: Overweight and obese children had a significantly higher Mallampati Score and a significantly higher prevalence of coughing (p < 0.05). None of the other parameters showed any significant differences between the groups. However, the incidence of desaturation was 9.5 % in overweight children and 6.3 % in children of normal weight, and that of airway obstructions was 4.1 vs 2.7 %. CONCLUSION: This study demonstrated a very low incidence of respiratory problems, which may be caused by the low proportion of morbidly obese children and the older age of overweight children in comparison with other studies.

Cancer detection rates following enrolment in a disease management programme for type 2 diabetes.

AIMS/HYPOTHESIS: Recent prospective studies found an elevated cancer risk shortly after diabetes diagnosis, and this was probably due to increased ascertainment. This study investigated whether site-specific cancer risks are also raised following enrolment in a disease management programme for type 2 diabetes mellitus (DMP-DM2). METHODS: We linked records from a DMP-DM2 to population cancer registry data. The study period was from June 2003 to December 2009. Standardised incidence ratios (SIRs) were calculated for time intervals following DMP enrolment using the cancer incidence rates of the general source population. Additionally, Poisson regression with natural splines was used to assess time-dependent cancer incidence by diabetes duration. RESULTS: There were 2,034 first invasive cancer cases identified over 163,738 person-years of follow-up. Pancreatic cancer risk was significantly increased mainly in the first year after enrolment (SIR 1.62); the increment was only seen for patients in whom diabetes had been diagnosed less than 1 year before DMP-DM2 enrolment. Risk of endometrial cancer was similarly raised in the first year after DMP-DM2 enrolment among individuals newly diagnosed with diabetes but decreased rapidly thereafter. There was no time dependence in the incidence of cancers of the liver, lung, colon, breast and prostate. CONCLUSIONS/INTERPRETATION: Enrolment in a DMP-DM2 did not appear to induce ascertainment bias for most cancers. Cancer risks were initially increased, especially for pancreatic cancer, potentially as a result of reverse causality. Ascertainment bias and time-dependent incidence of cancer appear to be less of a problem in settings using DMP-like structures for the study of the association between diabetes duration, glucose-lowering medication and cancer incidence.

[The PRISCUS list in clinical routine. Practicability and comparison to international PIM lists]. / Die PRISCUS-Liste im klinischen Test. Praktikabilität und Vergleich mit internationalen PIM-Listen.

BACKGROUND: Certain drugs are classified as potentially inappropriate medications (PIM) for the elderly. In 2010, the PRISCUS list was published, specifically designed for its applicability in the German pharmaceutical market. The aim of this study was to evaluate the PRISCUS list compared to international PIM lists. METHODS: Based on selected PIM lists (PRISCUS, STOPP/START, Beers), the medications of 308 patients at a clinic of geriatric rehabilitation were screened for PIMs. Applying START criteria, omission of indicated drug therapies was detected. RESULTS: Regarding the rate of PIM detection, the PRISCUS list was less sensitive than the application of STOPP criteria. While hospitalized, the mean number of administered PIMs per patient was 1.2 based on STOPP criteria and 0.5 based on the PRISCUS list. The lowest number of PIMs per patient was detected by applying the Beers list (0.4 PIMs). CONCLUSION: The Beers list should not be used in the German pharmaceutical market. The amendment of diagnosis-related STOPP criteria to the PRISCUS list would be useful to significantly advance therapeutic success and drug safety in the elderly.

[Deep sedation in neonates and infants for diagnostic procedures]. / Analgosedierung von Neugeborenen und Säuglingen für diagnostische Prozeduren.

Many diagnostic and interventional procedures in neonates and infants need to be performed under sedation. Depending on the level of sedation this can lead to a total immobilisation of the children combined with a reduction of stress and pain and good diagnostic conditions. Therefore a deep sedation often is comparable with general anaesthesia. When performing sedations, established safety standards need to be observed. Apart from a skilled physician, well defined structures and procedures for pre- and postprocedural care are necessary. This includes standardised monitoring, medications and adapted medical engineering. The article gives an overview of the principle requirements for the working area, the monitoring and the physician him/herself. Furthermore after an illustration of the widely used medications, guidance for the practical proceeding in common procedures is given. With such a professional management. it is possible to increase the quality and safety of care for the children and not least the satisfaction of the parents even more.

Pharmacokinetic monitoring of intravenous cyclosporine A in pediatric stem-cell transplant recipients. The trough level is not enough.

In order to monitor CsA serum levels after SCT, trough levels (C0) are widely used. The aim of this study was to estimate the population and individual PK parameters for patients receiving intravenous CsA after SCT. In 27 pediatric patients after SCT receiving CsA (3 mg/kg/day) every 12 h, a total of 289 CsA concentrations was obtained. To describe the PK parameters of CsA, a two-compartment model with first order elimination was used. Covariate analysis identified body weight, age, and the co-administration with itraconazole and tobramycine as factors influencing the Cl. The statistical comparison of AUC, trough level, and C2 indicates a correlation between AUC and C2, but no correlation between the AUC and C0, r = 0.24 (p = 0.146) vs. r = 0.526 (p = 0.000692), respectively. Our results underscore the fact that CsA trough levels do not reflect the drug exposure in patients receiving intravenous CsA after SCT. By contrast, CsA blood levels measured 2-6 h after CsA infusion showed a better correlation with the AUC. Our data provide new information to optimize the balancing act between GvHD-prophylaxis, graft vs. leukemia effect, and CsA side-effects after SCT.

Plasma and tissue pharmacokinetics of epirubicin and Paclitaxel in patients receiving neoadjuvant chemotherapy for locally advanced primary breast cancer.

The objective of the study was to assess individual distribution of antineoplastic drugs into the tumor. Twelve advanced-stage primary breast cancer patients with neoadjuvant epirubicin+paclitaxel chemotherapy were studied. Plasma concentrations of epirubicin and paclitaxel were monitored for 24 h. Epirubicin concentrations in subcutaneous and tumor tissues were measured using microdialysis up to 12 h postdose. Epirubicin concentrations were described by a compartmental population pharmacokinetic model (NONMEM). Noncompartmental analysis was used for paclitaxel. Plasma pharmacokinetics corresponded to published data. Mean epirubicin exposure in the tumor and in subcutaneous tissue was very similar, but tissue Cmax and area under the curve values reached only (means) 1% and 11%, respectively, of plasma values. Epirubicin doses were significantly correlated to tumor exposure irrespective of body surface area. There is no specific barrier for epirubicin to reach primary breast cancer tumors.

Monitoring paracetamol metabolism after single and repeated administration in pediatric patients with neoplastic diseases.

INTRODUCTION: Paracetamol (PCM) is frequently used in pediatric patients with neoplastic disease. It is metabolized mainly by conjugation, but at therapeutic concentrations, a small fraction of the drug undergoes oxidative metabolism via cytochrome P450 forming the hepatotoxic intermediate N-acetyl-p-benzo-quinone-imine (NAPQI) which is usually conjugated with glutathione and excreted as paracetamol mercapturate and paracetamol cysteine. OBJECTIVE: The aim of this monitoring study was to evaluate PCM metabolism with minimal intervention during routine treatment with single and repeated administration in patients undergoing antineoplastic therapy. METHOD: A total of 107 urine samples collected 4-12 h after PCM administration from 29 children undergoing antineoplastic treatment, and 10 children without antineoplastic treatment were analyzed for PCM, PCM glucuronide (PCM-G), PCM sulfate (PCM-S), PCM mercapturate (PCM-M) and PCM cysteine (PCM-C). RESULTS: The median (range) percentages for metabolites in urine were: a) in children with and without chemotherapy after the first administration: PCM: 0 (0-100) and 4 (0-11)%, PCM-G: 55 (0-88) and 51 (18 - 68)%, PCM-S: 30 (0-73) and 32 (22-57)%, PCM-(M+C): 13 (0-52) and 9 (0-24)%, respectively; b) after repeated administration in children with chemotherapy: PCM: 0 (0-51)%, PCM-G: 42 (7-100)%, PCM-S: 28 (0-70)%, PCM-(M+C): 24 (0-66)%. CONCLUSION: The pattern of PCM excretion in children undergoing antineoplastic treatment regimens is highly variable. Repeated administration is associated with a significant increase in the products of oxidative metabolism. This might indicate an increase in metabolism via the hepatotoxic NAPQI.

[Traumatology in the elderly : Multimodal prevention of delirium and use of augmentation techniques]. / Alterstraumatologie : Multimodale Delirprävention und Verwendung von Augmentationstechniken.

Recent data show that 20-80% of surgery patients are affected by delirium during inpatient clinical treatment. The medical consequences are often dramatic and include a 20 times higher mortality and treatment expenses of the medical unit increase considerably. At the University Hospital of Münster a multimodal and interdisciplinary concept for prevention and management of delirium was developed: all patients older than 65 years admitted for surgery are screened by a specialized team for the risk of developing delirium and treated by members of the team if there is a risk of delirium. Studies proved that by this multimodal approach the incidence of delirium was lowered and therefore the quality of medical care improved.When surgical treatment of fractures in the elderly is required, limited bone quality as well as pre-existing implants can complicate the procedure. Secondary loss of reduction after osteosynthesis and avulsion of the implant in particular must be prevented. Augmentation of the osteosynthetic implant with bone cement can increase the bone-implant interface and therefore stability can be improved. Additional intraoperative 3D imaging can be necessary depending on the localization of the fracture. In biomechanical studies we could prove greater stability in the osteosynthesis of osteoporotic fractures of the distal femur when using additional bone cement; therefore, the use of bone cement is an important tool, which helps to prevent complications in the surgical treatment of fractures in the elderly. Nevertheless, special implants and technical skills are required and some safety aspects should be considered.

Asymmetrical flow field-flow fractionation for the analysis of PEG-asparaginase.

Monomethoxypolyethylene glycol L-asparaginase (PEG-ASNASE) is the PEGylated version of the enzyme L-asparaginase (ASNASE). Both are used for remission induction in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The treatment control is generally carried out by performing activity assays, though methods to determine the actual enzyme rather than its activity are rare. Using asymmetrical flow field-flow fractionation (AF4) offered the chance to develop a method capable of simultaneously measuring PEG-ASNASE and PEG. A method validation was performed in accordance with FDA guidelines for PEG-ASNASE from non-biological solutions. The method unfolded a linearity of 15-750 U/mL with coefficients of correlation of r(2)>0.99. The coefficients of variation (CV) for within-run and between-run variability were 1.18-10.15% and 2.43-8.73%, respectively. Furthermore, the method was used to perform stability tests of the product Oncaspar® (PEG-ASNASE) and estimation of the molecular weight by multi-angle light scattering (MALS) of stressed samples to correlate them with the corresponding activity. The findings indicate that Oncaspar® stock solution should not be stored any longer than 24 h at room temperature and cannot be frozen in pure aqueous media. The validated method might be useful for the pharmaceutical industry and its quality control of PEG-ASNASE production.

Effects and interaction of 7-hydroxy methotrexate and methotrexate in leukaemic cells ex vivo measured by the thymidylate synthase inhibition assay.

In high dose therapy with methotrexate (MTX) the main metabolite 7-hydroxy-methotrexate (7-OH MTX) exceeds the plasma concentration of MTX achieving about tenfold higher levels. To investigate the interaction between 7-OH MTX and MTX ex vivo, the thymidylate synthase inhibition assay was used to quantify antifolate effects in patient blast samples, measuring the inhibition of the key enzyme thymidylate synthase (TS). In 18 leukemic samples (7 ALL, 11 AML) no dose-dependent TS inhibition was observed for 7-OH MTX. However, a statistically significant increase of TS inhibition (p<0.05) was observed for a 1:1 mixture of MTX and 7-OH MTX as compared to the effect of MTX alone. The half-maximal inhibitory concentrations in the short-exposure assay were 0.857 microM for MTX alone versus 0.088 microM for the 1:1 mixture with 7-OH MTX, respectively (p< or =0.05). This interaction was not observed with an excess of 7-OH MTX. Similar results were obtained in long exposure experiments. We conclude that there is a dose-dependent interaction between 7-OHMTX and MTX, despite the lack of TS inhibitory effects of the metabolite alone.

Population pharmacokinetic-pharmacodynamic modeling of moxonidine using 24-hour ambulatory blood pressure measurements.

OBJECTIVES: To develop a model for 24-hour ambulatory blood pressure measurements (ABPM) that can be applied in a pharmacokinetic-pharmacodynamic model. METHODS: Four different data sets were prepared from 2 studies to accommodate different modeling strategies. In study A, a double-blind placebo-controlled study in 47 patients, 24-hour ABPM profiles (74 to 99 measurements per profile) were obtained during the placebo run-in phase and after 3, 5, and 11 weeks during the treatment. Three to 5 plasma samples were taken. Cosine and polynomial models were evaluated to describe the circadian rhythm in blood pressure based on 3 data sets (1: only run-in data; 2: only placebo data; 3: all data). In study B, a double-blind placebo-controlled study in 94 patients, two 24-hour ABPM profiles per patient (during placebo run-in and after 8 weeks) were recorded and randomly reduced to 15 measurements per profile to evaluate the robustness of the baseline model. RESULTS: The mean moxonidine clearance was 35 L/h, and the volume of distribution was 132 L. The final baseline model consisted of 2 cosine terms with fixed-effect parameters for rhythm-adjusted 24-hour mean blood pressure, amplitude, phase, and period; random-effect parameters for interindividual variability in rhythm-adjusted 24-hour mean, amplitude, and clock time; and interoccasion variability in rhythm-adjusted 24-hour mean and clock time. The final baseline model was combined with an Emax model for the drug effect. An effect compartment was used (kco = 0.198 h-1). The maximum decrease in diastolic blood pressure (Emax) was 16.7%, and EC50 was 0.945 microgram/L. CONCLUSION: The pharmacokinetic-pharmacodynamic model for 24-hour ABPM can be used to estimate the concentration-effect relationship of antihypertensive drugs.

Enhanced expression of ELAM-1 on endothelium of renal cell carcinoma compared to the corresponding normal renal tissue.

Renal cell carcinoma (RCC) has been shown to respond to an immunological therapy with tumor infiltrating lymphocytes (TIL), which accumulate in RCC at a higher density than in normal renal tissue, suggesting that there is selective tumor invasion. Since invasion of TIL into the malignant tissue is mediated by adhesion molecules, we examined the different expression of the adhesion molecule endothelial-leukocyte-adhesion-molecule-1 (ELAM-1) on endothelial cells of RCC versus normal renal tissue. For a specific quantification, the level of ELAM-1 mRNA was investigated by both semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis and referred to the content of endothelial cells in the tissue, determined by endothelium specific staining. Quantification of mRNA was evaluated by computer-aided integration. We observed a significantly lower amount of endothelial cells in RCC compared to normal renal tissue. The specific transcription rate of ELAM-1 in RCC, determined by RT-PCR was about 5.2 times that of normal tissue, while Northern blot analysis indicated an approximately 11.8 times increase. Our investigations show a significantly increased expression of ELAM-1 in tumor tissue compared to normal renal tissue, presumably caused by a higher amount of cytokines in the tumor tissue. This enhanced expression may be responsible for the high concentration of TIL in renal tumors.

Autologus saphenous vein femoropopliteal bypass: analysis of 298 cases.

A retrospective review of 298 saphenous vein femoropopliteal bypasses performed for femoral artery occlusive disease over a 13 year period was carried out. The purpose of the study was to assess factors which influence long-term graft patency. Follow-up was 95.3 percent complete. Results were analyzed with the aid of IBM data processing equipment and standard statistical methods.

Investigation of the major human hepatic cytochrome P450 involved in 4-hydroxylation and N-dechloroethylation of trofosfamide.

Trofosfamide and its congeners ifosfamide and cyclophosphamide are cell-cycle-nonspecific alkylating agents that undergo bioactivation catalyzed by liver cytochrome P450 (CYP) enzymes. Two NADPH-dependent metabolic routes for the anticancer drug trofosfamide, i.e., 4-hydroxylation and N-dechloroethylation, were studied in human liver microsomes and in seven recombinant human CYP isoforms (i.e., CYP1A1, 1A2, 2A6, 2B6, 2D6, 2E1, and 3A4-OR) to identify the CYP enzymes involved. Recombinant human CYP3A4 and CYP2B6 exhibited catalytic activity with respect to both pathways of trofosfamide. Enzyme kinetic analyses revealed the dominant role of human CYP3A4 in 4-hydroxylation and N-dechloroethylation of trofosfamide. This was confirmed by the observation that only the CYP3A4 contents of five samples of human liver microsomes correlated with both pathways of trofosfamide. Furthermore, ketoconazole, a selective inhibitor of CYP3A4, substantially inhibited microsomal trofosfamide 4-hydroxylation and N-dechloroethylation (50% inhibitory concentration < 1 microM for both reactions). The present study indicates that human liver microsomal CYP3A4 preferentially catalyzes the two NADPH- dependent metabolic routes of trofosfamide, which emphasizes the necessity for awareness of potential interactions with any coadministered drugs that are CYP3A4 substrates.

Pharmacokinetics of trofosfamide and its dechloroethylated metabolites.

To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m2 Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUCTrofo:AUCIfo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUC(Ifo):AUC(Cyclo) 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechlorethylifosfamide in varying quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose. Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting agent for oral chemotherapy.

Superslow backbone protein dynamics as studied by 1D solid-state MAS exchange NMR spectroscopy.

Superslow backbone dynamics of the protein barstar and the polypeptide polyglycine was studied by means of a solid-state MAS 1D exchange NMR method (time-reverse ODESSA) that can detect reorientation of nuclei carrying anisotropic chemical shift tensors. Experiments were performed on carbonyl 13C in polyglycine (natural abundance) and backbone 15N nuclei in uniformly 15N-enriched barstar within a wide range of temperatures in dry and wet powders for both samples. Two exchange processes were observed in the experiments: molecular reorientation and spin diffusion. Experimental conditions that are necessary to separate these two processes are discussed on a quantitative level. It was revealed that the wet protein undergoes molecular motion in the millisecond range of correlation times, whereas in dry protein and polyglycine molecular reorientations could not be detected. The correlation time of the motion in the wet barstar at room temperature is 50-100 ms; the activation energy is about 80 kJ/mol. Previously, protein motions with such a long correlation time could be observed only by methods detecting chemical exchange in solution (e.g., hydrogen exchange). The application of solid-state MAS exchange spectroscopy provides new opportunities in studying slow biomolecular dynamics that is important for the biological function of proteins.

Determination of purines including 2,8-dihydroxyadenine in urine using capillary electrophoresis.

For the purpose of rapid drug monitoring, methods have been developed for the determination of 2,8-dihydroxyadenine, allopurinol, oxypurinol, adenine, hypoxanthine, hippuric acid and xanthine in urine with and without sodium dodecyl sulfate as additive in sodium tetraborate running buffer. No sample preparation is necessary. 6-methylmercaptopurine and etofylline have been used as the internal standards. The limit of detection is 5 microM and the range of quantification stretches from 20 to 2000 microM. The capillary electrophoresis methods are simple, fast and robust.

Determination of paclitaxel in biological fluids by micellar electrokinetic chromatography.

A method has been developed for the determination of paclitaxel (Taxol) in plasma and urine using capillary electrophoresis with sodium dodecyl sulfate as additive in the run buffer. The samples are extracted and preconcentrated with tert.-butyl methyl ether. Taxotere has been used as the internal standard. The limit of detection of paclitaxel is 20 ng/ml. In comparison to high-performance liquid chromatography, the capillary electrophoresis method is simple and needs less organic solvents.

Benzene-lecithin interaction interaction in lecithin-benzene solutions. Part L Magnetic deuterium relaxation studies.

2D relaxation times of deuterobenzene in lecithin-benzene solutions were measured at 4.4 and 11 MHz with respect to concentration and temperature. At the temperature of the transition from the micellar solution to the gel state the relaxation behaviour was drastically changed. Analysis of the experimental results performed on the basis of familiar relaxation theory shows that there are sites at which benzene interacts with lecithin in the micellar solution as well as in the gel state. The interaction enthalpies and entropies determined for the two benzene species existing in the gel state are--1.3 kcal/mol,--20 eu and--3.1 kcal/mol, --24 eu.