Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients - A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial.

BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) data on perioperative antibiotic prophylaxis or antibiotic therapy are rare in patients suffering from morbid obesity. Furthermore, dosing regimens should be based on PK/PD models that ensure effective antibiotic exposure not in plasma, but primarily at the site of infection, mostly in the interstitial fluid (ISF). The aim of this trial is to investigate whether current dosing regimens of various antibiotics lead to effective concentrations in the ISF of morbidly obese patients. METHODS: We designed a prospective, parallel group, open-labeled, controlled single center trial to investigate the plasma and tissue pharmacokinetics of the antibiotics linezolid, meropenem, tigecycline, piperacillin/tazobactam, fosfomcyine, cefazolin, metronidazole and as secondary aim the analgesics metamizole and acetaminophen. Inclusion criteria comprise body mass index ≥35 kg/m2 for obese or between 18.5 and 30 kg/m2 for non-obese patients scheduled for elective abdominal surgery. For PK analysis, blood and microdialysate samples of subcutaneous tissue were collected 0-8 h after study drug administration. The primary endpoint is to investigate a possible dependency of the area-under-the-curve (AUC0-8) in the interstitial fluid on body weight and obesity with population based pharmacokinetic analysis. DISCUSSION: Inadequate dosing regimes of antibiotics may be a relevant factor for morbidity and mortality of patients, as well as for the development of bacterial antibiotic resistance. The measurement of plasma and tissue concentrations will provide information necessary for PK/PD-modelling. These data about antibiotic PK/PDcharacteristics in soft tissue and their dependence on weight should help to develop weight-dependent models for calculation of patient's individual doses of different antibiotics. TRIAL REGISTRATION: EU clinical trials register (EudraCT-No. 2012-004383-22) and German Clinical trials Register (DRKS00004776).

Reverse epidemiology in different stages of heart failure.

BACKGROUND: In heart failure (HF), traditional cardiovascular risk factors (RF) as body mass index (BMI), total cholesterol (TC) and systolic blood pressure (SBP) are associated with better survival. It is unknown at which time point along the disease continuum the adverse impact of these RF ceases and may 'start to reverse'. We analyzed the distribution of RF and their association with survival across HF stages. METHODS: We pooled data from four cohort studies from the German Competence Network HF. Employing ACC/AHA-criteria, patients were allocated to stage A (n=218), B (n=1324), C1 (i.e., New York Heart Association [NYHA] classes I & II; n=1134), and C2+D (NYHA III & IV; n=639). RESULTS: With increasing HF severity median age increased (63/67/67/70 years), whereas the proportion of females (56/52/37/35%), median BMI (26.1/28.8/27.7/26.6 kg/m(2)), TC (212/204/191/172 mg/dl), and SBP (140/148/130/120 mmHg) decreased (P<0.001 for trend for all). In the total cohort, higher levels of all RF were associated with better survival, even after extensive adjustment for multiple confounders. If analyses were stratified, however, a higher RF burden predicted better survival only in clinically symptomatic patients: hazard ratio (HR) per +2 kg/m(2) BMI 0.91 (95% confidence interval 0.88; 0.95); per +10 mg/dl TC 0.93 (0.92; 0.95); per +5 mmHg SBP 0.94 (0.92; 0.95). CONCLUSION: In this well-characterized sample of patients representing the entire HF continuum, reverse associations were only consistently observed in symptomatic HF stages. Our data indicate that the phenomenon of a "reverse epidemiology" in HF is subject to significant selection bias in less advanced disease.

[Gelatin-thrombin matrix-mediated hemostasis: application in tonsillectomy]. / Gelatine-Thrombin-Matrix zur Blutstillung: Einsatz bei der Tonsillektomie.

BACKGROUND: To assess the feasibility of omitting thermal coagulation following cold knife tonsillectomy, we compared the use of a local thrombin hemostat (FloSeal®, FS) to bipolar electrocautery (EK). PATIENTS AND METHODS: A total of 181 patients with chronic tonsillitis or tonsillar hypertrophy were stratified in terms of patient characteristics and randomized before undergoing tonsillectomy. The follow-up period continued until postoperative day 20. RESULTS: FS-treated patients reported lower postoperative pain intensity scores (p = 0.011) and significantly reduced pain duration (p < 0.001). Whilst wound healing appeared to be improved in FS patients, the rates of postoperative hemorrhage remained unchanged. Use of an FS enabled inexperienced surgeons (< 100 procedures) to reduce their operating time by 8 min (p = 0.05), although no effect was observed for experienced surgeons. CONCLUSION: Hemostasis is effectively mediated by an FS and its application reduces postoperative pain intensity and duration. Although we observed accelerated wound healing and reduced operating times owing to a more calculable rate of hemostasis, this did not influence the rates of postoperative hemorrhage.

Coronary-like revascularization for atherosclerotic renal artery stenosis--results in 181 consecutive patients.

AIMS: The aim of this study was to document the early outcome of coronary-like revascularization for atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS: A total of 181 consecutive patient, 102 men, mean age 66.1 (+/- 9.2) years and 79 females, mean age 68.4 (+/- 9.2) years and 198 lesions were treated between February 1999 and May 2004 for ARAS and retrospectively analyzed. At least one major cardiovascular risk factor was present in 179 (98.9%) patients. Pre-dilatation ARAS was 81.3+/-9.6%, 27 ARAS were 50-70% and no ARAS was <50%. 135 (68.2%) of the ARAS lesions were ostial and 63 (31.8%) were non-ostial. In 17 (9.4%) patients bilateral ARAS were present. Technical success defined as residual stenosis < or =30% was achieved in 178 (98.3%) of patients and 195 (98.5%) of lesions. In one patient (0.5%) the target ARAS could not be crossed, in two (1.1%) patients residual stenosis was >30%. No major adverse cardiac or cerebral effects were observed. In 3.9% of patients minor local complications of the access site occurred; 4 (2.2%) inguinal hematoma, 3 (1.7%) pseudoaneurysm were documented. Serum creatinine concentrations and systolic and diastolic blood pressure before and after the intervention were not statistically different. CONCLUSIONS: Coronary-like approach to ARAS revascularization is technically feasible and associated with a very low complication rate.

Carotid-artery stenting in a high-risk patient population--single centre, single operator results.

AIMS: The aim of this study was to assess the outcome of carotid-artery stenting (CAS) in high-risk patients in routine clinical settings while excluding the impact of multiple operators and the learning curve of individual operators on the outcome, and to determine the impact of individual risk factors, including vascular multimorbidity, on the outcome. METHODS AND RESULTS: A total of 143 consecutive patients, 100 (69.9%) males and 43 (30.1%) females, mean age 68.7+/-8 years treated between February 1999 and May 2004 in the Heart Centre Coswig by a single operator for a symptomatic (n=37) and asymptomatic (n=106) on average greater than 70% (82.3+/-10.7%) or 80% (85.0+/-9.1%) NASCET carotid-artery stenosis, respectively, were studied. At least one NASCET exclusion criteria was present in 140 patients (97.9%), and vascular multimorbidity was present in 94 (65.7%) patients. In 28 (19.6%) patients there was a complete occlusion of the contralateral internal carotid artery and in 12 (8.4%) patients the procedure was performed prior to emergency coronary bypass surgery. In all, 47 (32.9%) procedures were performed without and 96 (67.1%) were performed with thromboembolic protection. Technical success was achieved in all patients. Combined neurological complications, TIA, PRIND and stroke, occurred in 5 (3.5%) patients, of which 3 (2.1%) were PRIND and 2 (1.4%) were strokes. The neurological complications were more frequent and more severe in symptomatic patients compared to asymptomatic patients (PRIND 2.7% vs 1.9%; stroke 0% vs 5.4%). In patients in whom thromboembolic protection was used, the rate of neurological complications was lower compared to those without protection (PRIND 1.0% vs 4.3%; stroke 1.0% vs. 2.1%). There was no death related to the procedure. Neurological complications were more frequent and more severe in patients with vascular multimorbidity compared to those with an isolated carotid-artery stenosis (4.2% vs 2.0%). The rate of neurological complications was similar in type II diabetics and nondiabetics (2.9% vs 4.1%). In 4.2%, minor complications related to the arterial puncture site were observed (3.5% hematoma not requiring blood transfusion, 0.7% pseudoaneurysm). At follow-up after a minimum of 6 months, 9 (6.3%) patients had died, the majority of whom had died of cardiovascular disease (3.5%). CONCLUSIONS: CAS can be performed with an acceptable risk in high-risk patients in routine clinical settings when it is performed by an experienced operator. The use of thromboembolic protection devices reduces the risk of neurological complications. Presence of vascular multimorbidity, but not diabetes, appears to increase the risk of all causes and of neurological complications.

[Quality of diabetes management in the free Saxony state--scientific evaluation of the Saxony model for managing diabetes. EVA group]. / Untersuchungen zur Qualität der Diabetikerbetreuung im Freistaat Sachsen--die wissenschaftliche Begleitung des Sächsischen Modells zur Diabetikerversorgung. EVA-Gruppe.

After the societal change in the "New Federal States" of Germany Saxon diabetologists developed an integrated concept for care of diabetic patients: the Saxon Care Model (SCM). It aims at quality assurance in diabetes care and is based on services by cooperating general practitioners and specialists. This model was evaluated. First results were obtained describing the quality of care for 510 patients at baseline. This sample was collected at two specialized diabetologists (level 2), two specialized out-patient units at universities (level 2) and two general practitioners (level 1). The design of the study is a descriptive evaluation. Process and outcome quality at specialized and primary care units working according to the SCM is relatively high. HbA1c measurements were taken in order to quantify outcome quality. The results for primary as well as specialized care units ranged from acceptable to very good. They unfortunately cannot be generalized. The patients expressed that their quality of life was limited only scarcely. The presented preliminary results indicate a high effectiveness of the SCM with regard to relevant process-related outcome-variables. The large variance between single practices of both levels demonstrates that deficits in early diagnosis of diabetes-related complications still exist. On the other hand this points towards resources of quality improvement. The influence of quality assuring measures, e.g. quality circles, will be assessed in a three-year follow up.

[Concept and outcome of general practice quality circles on the topic of diabetes mellitus]. / Konzept und Ergebnisse hausärztlicher Qualitätszirkel zum Thema Diabetes mellitus.

In Saxonia, an agreement of shared care was reached between health insurances and the society of general practitioners with the objective to have a better medical care for patients with diabetes mellitus. This model of shared care means integrated medical care for out-patient diabetics between general practitioner and specialists. It must be accompanied by quality assurance measures. After a training of moderators according to a structured programme of the Central Research Institute for Outpatient Health Care, quality circles started with seven to ten members and two moderators in five Saxonian cities in May 1994. General practitioners interactively improved their medical knowledge about diabetes mellitus during five sessions with two hours each. The regional specialist participated in the first and the last session. He also answered open questions left in a mail box. Based on patient data the following results were achieved: 553 documentations.