[Staff Satisfaction within Duty Hour Models: Longitudinal Survey on Suitability and Legal Conformity at a Surgical Maximum Care Department]. / Mitarbeiterzufriedenheit im Arbeitszeitmodell: Längsschnittstudie zu Praxistauglichkeit und Gesetzeskonformität in einer chirurgischen Klinik der Maximalversorgung.

Background Between the conflicting requirements of clinic organisation, the European Working Time Directive, patient safety, an increasing lack of junior staff, and competitiveness, the development of ideal duty hour models is vital to ensure maximum quality of care within the legal requirements. To achieve this, it is useful to evaluate the actual effects of duty hour models on staff satisfaction. Materials and Methods After the traditional 24-hour duty shift was given up in a surgical maximum care centre in 2007, an 18-hour duty shift was implemented, followed by a 12-hour shift in 2008, to improve handovers and reduce loss of information. The effects on work organisation, quality of life and salary were analysed in an anonymous survey in 2008. The staff survey was repeated in 2014. Results With a response rate of 95% of questionnaires in 2008 and a 93% response rate in 2014, the 12-hour duty model received negative ratings due to its high duty frequency and subsequent social strain. Also the physical strain and chronic tiredness were rated as most severe in the 12-hour rota. The 18-hour duty shift was the model of choice amongst staff. The 24-hour duty model was rated as the best compromise between the requirements of work organisation and staff satisfaction, and therefore this duty model was adapted accordingly in 2015. Conclusion The essential basis of a surgical department is a duty hour model suited to the requirements of work organisation, the Working Time Directive and the needs of the surgical staff. A 12-hour duty model can be ideal for work organisation, but only if augmented with an adequate number of staff members, the implementation of this model is possible without the frequency of 12-hour shifts being too high associated with strain on surgical staff and a perceived deterioration of quality of life. A staff survey should be performed on a regular basis to assess the actual effects of duty hour models and enable further optimisation. The much criticised 24-hour duty model seems to be much better than its reputation, if augmented by additional staff members in the evening hours.

[Artificial intelligence in orthopedics and trauma surgery]. / Künstliche Intelligenz in der Orthopädie und Unfallchirurgie.

Artificial intelligence (AI) is a very relevant topic for the medicine of the future. This article focuses on the field of AI in the context of orthopedics and trauma surgery. The main focus is on the potentials of AI in the analysis of symptoms, radiological images, clinical data sets, use in hospitals and operating theaters as well as for training and education. For the orthopedics and trauma surgery of the future AI is much more than pure fiction; however, there is still a long way to go before the potential of an optimized and individualized patient care can be utilized. Interdisciplinary and international approaches, including personnel, economic, legal and ethical aspects will play a decisive role in this respect.

[A method for reassessment of cost-intensive cases in visceral surgery. Results of project by the German Society for Visceral Surgery]. / Methode zur Abbildung kostenintensiver Fälle in der Viszeralchirurgie. Ergebnisse des DRG-Projekts der Deutschen Gesellschaft für Viszeralchirurgie.

Since the introduction of diagnosis-related groups (DRGs) many surgical departments report inappropriate reimbursement for complex cases and a shift in costly cases. To evaluate this situation, the German Society for Visceral Surgery inaugurated the present cost calculation project. In three university hospitals for 50 cases each, we depicted possible cost separators and utilized the complete cost calculation data (so-called Paragraph 21 data set) to test these separators. We identified "admission from another hospital", "severe surgically relevant concomitant disease", and "reoperation during the same hospital admission". The last was considered the economically most significant and medically most valid factor and was submitted as a possible modification to the german DRG system. The proposed cost separator "reoperation during the same hospital admission" was introduced into the DRG system after validation and leads to better allocation of reimbursements to complex and costly cases.

The German Acromegaly Registry: description of the database and initial results.

UNLABELLED: Patient registries are valuable tools to study long-term morbidity and mortality of rare diseases. Acromegaly is rare (incidence 3-4/mill/year, prevalence 40-70/mill; approx. 300 new patients/yr and up to 5700 patients in Germany). Diagnostic and therapeutic possibilities have considerably improved, but treatment results remain often unsatisfactory. The main cause is residual disease activity after surgery, most importantly due to invasive macroadenomas. The German Acromegaly Registry is an initiative of the Pituitary Study Group of the German Endocrine Society (DGE). Formally established in January 2003 by the Board of the DGE, long-term financial support is guaranteed by an unrestricted grant from Novartis Pharma GmbH to the DGE. The registry cooperates closely with the United Kingdom and the Austrian registries. The aim of the German Acromegaly Registry is to establish a database of sufficient epidemiological strength in order to (1) document co-morbidity and mortality, (2) provide data on diagnostic and therapeutic procedures/effectiveness, (3) enable comparison of procedures in different national centres, (4) provide information for patient support groups/interaction with health care providers, (5) enable comparison with other national registries within Europe. The registry has at present 82 participating centres, and 42 have included patients (20 university clinics, 8 non-university hospitals, 14 centres in private practice). The database aims to include all acromegalic patients in Germany who are cared for and treated at present. Up to December 2005 1543 patients have been entered in a retrospective manner. Data collection is by external monitoring by highly trained study nurses who visit the individual centres. Inclusion is planned to continue at a rate of 500 per year. Starting in 2005 centres are revisited every 3 years at a rate of 500 per year (prospective phase of the registry). Quality of the data has been validated by an independent monitoring team which demonstrated high data concordance. CONCLUSIONS: Initial results of the German Acromegaly Registry show that it was possible to include a large number of patients within 3 years into the registry. Data quality has been validated and shown to be satisfactory. Therefore, the registry will be a useful tool to study long-term morbidity and mortality in a large series of patients.

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

A neural network model for the prediction of membrane-spanning amino acid sequences.

The architecture and weights of an artificial neural network model that predicts putative transmembrane sequences have been developed and optimized by the algorithm of structure evolution. The resulting filter is able to classify membrane/nonmembrane transition regions in sequences of integral human membrane proteins with high accuracy. Similar results have been obtained for both training and test set data, indicating that the network has focused on general features of transmembrane sequences rather than specializing on the training data. Seven physicochemical amino acid properties have been used for sequence encoding. The predictions are compared to hydrophobicity plots.

Comparison of quadruple immunosuppression after liver transplantation with ATG or IL-2 receptor antibody.

Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past. The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL-2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation. In two groups of 33 patients each, postoperative survival, graft biopsies, liver function enzymes, and the clinical courses after OLT were evaluated. Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT. Furthermore, our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody. This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation.

Comparison of polymerase chain reaction from plasma and buffy coat with antigen detection and occurrence of immunoglobulin M for the demonstration of cytomegalovirus infection after liver transplantation.

We compared the value of PCR on plasma with PCR on buffy coat leukocytes, Ag assay, and the determination of IgM antibodies by ELISA for the diagnosis and follow-up of cytomegalovirus infection. Thirty patients were followed after liver transplantation (LTX). We compared the tests to assess their clinical usefulness. Fourteen of 30 (46%) patients were both positive in plasma and buffy coat PCR and Ag test. Sixteen patients were negative in both procedures. There was a 97.2% concordance between PCRs done from plasma or buffy coat. The concordance of results of PCR and Ag test in single samples was 94.3%. Discordant results were found in 5.6% of samples. Discordance was observed in the early and the late phase of CMV infection and was due to positive PCRs preceding positive Ag tests for 1-3 weeks in one-half of the patients. IgM antibodies were first observed after a median period of 8 weeks (range, 6-11 weeks) after LTX. Positive PCRs and Ag tests preceded clinical manifestation of CMV disease by a 1 week median (range, 0-3 weeks), whereas positive IgM ELISAs occurred after a median period of 2.5 weeks (range, 0-4 weeks) after the onset of CMV disease. The sensitivity and specificity of both PCR and Ag test were identical, 100% and 76%, respectively. However, for the IgM ELISA, the sensitivity was only 66%, and the specificity was 84%. In conclusion, plasma or buffy coat PCR and Ag test are equally reliable procedures for early detection and monitoring of CMV infection. PCR can become positive earlier than the Ag test, but it is technically more demanding to perform. The demonstration of IgM antibodies is of little practical help because an antibody response occurs too late in relation to infection.

Comparison of FK506- and cyclosporine-based immunosuppression in primary orthotopic liver transplantation. A single center experience.

FK506 has been proven effective for prevention and treatment of liver allograft rejection. Herein, we compare FK506-based immunosuppression with an effective quadruple immunosuppressive regimen, including cyclosporine and antithymocyte globulin. The results of a single center participating in the European multicenter FK506 study are reported, including immunosuppressive efficacy as well as toxicity. One-year patient and graft survival was 96.7% and 90.0% for the CsA group and 90.2% and 88.5% for the FK506 group, which is not statistically different. The incidence and severity of acute rejection episodes during the first postoperative year was similar in both treatment groups with 34.4% and 33.3% for the FK506 and CsA treatment group, respectively. Immunosuppressive potency was better for the FK506 group compared with the CsA group according to the incidence of chronic rejection. Furthermore, 5 patients (8.3%) required conversion to FK506 for immunological reasons, i.e., refractory acute or chronic rejection. The incidence of moderate and severe neurotoxicity during the early postoperative period was higher in the FK506 group (21.3%) compared with the CsA group (11.7%), while the incidence of renal insufficiency and acute renal failure was similar (18.0% and 18.3% for the FK506 and CsA treatment groups, respectively). The incidence of CMV infection was significantly higher under treatment with CsA (25.0%) than with FK506 (6.6%) (P < or = 0.05), while the incidence of pneumonia (13.1% and 13.3%), cholangitis (29.5% and 26.7%), and urinary tract infection (39.3% and 28.3% for the FK506 and CsA treatment groups, respectively) was similar in both treatment groups. However, infection was more serious in some cases treated with FK506, and evolved as the main cause of death in the FK506 treatment group. Therefore, caution should be paid to over immunosuppression and toxicity in FK506-treated patients. Regarding the monitoring of FK506, FK506 plasma level failed to be a reliable indicator, and therefore we recommend measurement of whole blood FK506 levels. Our data indicate that immunosuppressive potency of FK506 is greater than that of CsA, especially concerning the incidence of chronic rejection.

A prospective study of human herpesvirus type 6 detected by polymerase chain reaction after liver transplantation.

Human herpesvirus type 6 (HHV-6) causes roseola infantum (exanthema subitum) upon primary infection in young children. Thereafter it persists lifelong in the organism. Like other herpesviruses, HHV-6 can be reactivated in periods of immunosuppression - e.g., after organ transplantation. In order to study the incidence and the time to reactivation after orthotopic liver transplantation (OLT) we tested buffy coat lysates before and up to 10 weeks after transplantation for the presence of HHV-6 DNA by polymerase chain reaction (PCR). Forty-six patients (male n=27, female n=19) with a median age of 48 years (range 20-66) were studied. Altogether, 30 of 287 (10.5%) buffy coat samples were PCR-positive. Before OLT 2 of 21 (9.5%) patients were positive. This ratio is not different from healthy blood donor controls. After OLT 13 of 46 (23.8%) patients were positive on one or more occasions. However, there was no statistically significant difference before and after OLT. Ten patients were analyzed for HHV-6 variants by restriction enzyme digestion of PCR products. One patient carried variant A and 9 variant B. In conclusion, HHV-6 can be detected in buffy coat cells after OLT. Our observations do not argue in favor of a reactivation.

Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: results of a prospective, randomized trial.

BACKGROUND: Tacrolimus in combination with prednisolone has been proven to be a safe and effective immunosuppressive induction therapy in solid organ transplantation. However, it remains unclear whether a tacrolimus-based quadruple induction regimen with azathioprine and an antilymphocytic preparation could further improve the results after orthotopic liver transplantation. Therefore, we designed a prospective, randomized study to compare the immunosuppressive efficacy of dual (tacrolimus and prednisolone) and quadruple (tacrolimus, azathioprine, ALG Merieux and prednisolone) induction after liver transplantation. METHODS: After randomization, 120 consecutive patients of primary liver transplants were divided into the dual group (n=59) and the quadruple group (n=61) and followed for a minimum of 3 years. RESULTS: Patient survival at 3 years was 88.2% in the dual versus 94.9% in the quadruple group. Overall 25 patients in each group (41 and 42%, respectively) developed acute rejection. There was no difference in the number and severity of rejections. In each group only four patients required OKT3-therapy, however, although three of four patients in the quadruple group responded to OKT3 and cleared rejection, none of the four patients in the dual group were treated successfully with OKT3 (P<0.02). Rejection in these patients resolved only after additional treatment with mycophenolate mofetil. Adverse events and infections were equally distributed in both groups. Asymptomatic Cytomegalovirus infections were more common in the quadruple group (P<0.02). As of today, only one patient developed posttransplant lymphoproliferative disease (dual group). CONCLUSIONS: The data from our single-center study indicate that both tacrolimus-based dual and quadruple immunosuppressive induction regimens yield similar safety and effectiveness after liver transplantation.

A prospective randomized trial comparing interleukin-2 receptor antibody versus antithymocyte globulin as part of a quadruple immunosuppressive induction therapy following orthotopic liver transplantation.

BACKGROUND: Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted. METHODS: Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine. RESULTS: Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups. CONCLUSIONS: Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.

Effects of zinc and cadmium on apoptotic DNA fragmentation in isolated bovine liver nuclei.

Isolated nuclei from mammalian cells contain a calcium-dependent endonuclease. The produced DNA fragmentation is a necessary step in the sequence of events resulting in apoptosis (programmed cell death). We report here that zinc and cadmium inhibit the calcium-dependent endonuclease. The essential metal ion zinc may counterbalance the calcium-mediated apoptosis. In contrast to zinc, cadmium alone stimulates the endonuclease by replacing calcium. Thus cadmium exerts a dual effect: micromolar concentrations inhibit the apoptotic endonuclease in the presence but activate the enzyme in the absence of calcium.

Proficiency testing of platelet counting in Ontario.

Proficiency testing results provide data for interlaboratory comparisons. The Laboratory Proficiency Testing Program of Ontario, Canada, has tested platelet counting for a decade and other hematology parameters for 15 years. Despite the fact that all testing programs are compromised by the type of testing material used, for platelet count testing, conclusions are possible. The data indicate that most laboratories in Ontario have greater difficulty performing reproducible platelet counting as compared with other components of hematologic cytometry. A major contributor to this shortfall is the method used by the laboratory. It was not a surprise that manual counting had a high coefficient of variation. Unexpectedly, the semiautomated methods used in the mid-1980s also displayed a high coefficient of variation.

Stimulation of rat hepatic amino acid transport by burn injury.

Burn injury accelerates hepatic amino acid metabolism, but the role of transmembrane substrate delivery in this response has not been investigated. We therefore studied the effects of cutaneous scald injury on the Na+-dependent transport of glutamine and alanine in isolated rat liver plasma membrane vesicles. Scald injury resulted in liver damage and a 1.4- to 2.3-fold and 1.5- to 2.8-fold stimulation of hepatic transport rates for glutamine and alanine, respectively, proportional to the total burned surface area (TBSA) after 24 hours. Enhanced uptake of glutamine and alanine was attributable to increases in the maximum velocity (Vmax) of system N and system A activities, respectively. Hepatic amino acid transport activity remained elevated in vesicles from burned animals after 72 hours, but the degree of stimulation (1.3- to 1.7-fold for glutamine and 1.3- to 1.6-fold for alanine) was less than that observed 24 hours after thermal injury. Liver function tests returned to control values after 72 hours as well, indicating rectification of hepatic damage. In contrast to the induction of hepatic system A and system N activity in catabolic states such as cancer and endotoxemia, further studies showed that tumor necrosis factor (TNF) failed to play a significant role in burn-stimulated amino acid transport rates. When combined with plasma liver enzyme profiles, early transient hepatic amino acid transporter stimulation may support amino acid-dependent pathways involved in the repair of burn-dependent hepatic damage.

Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice.

The performance of C57BL/6J (6J), C57BL/6N (6N), DBA/2J (2J) and DBA/2N (2N) mice in context- and tone-dependent fear conditioning was determined 24 h after fear conditioning to evaluate and compare different behavioral measures as indices of emotional learning. Freezing, the change in activity and the size of the explored area were evaluated as behavioral parameters indicating fear. Additionally, the heart rate (HR) increase elicited by tone presentation was evaluated as an autonomic indicator of fear. During the context-dependent memory test, freezing was high only in 6J and 6N mice, whereas a drop of activity and a reduced exploratory area was measured in all strains. During the tone-dependent memory test, high freezing, low activity, reduced exploratory area and a strong HR increase were demonstrated only in 6N and 6J mice, whereas behavioral and HR changes of 2J and 2N mice were always low. In extinction tests, context- and tone-dependent freezing of 6J mice decayed significantly faster than the freezing of 6N mice, whereas in both substrains the conditioned tachycardia to tone extinguished similarly in the home cage. The data demonstrate that monitoring of additional behavioral measures besides freezing and autonomic measures is necessary to interpret differences in associative learning performance of mouse strains that could be related to a differential expression of fear.

P-glycoprotein expression in chronic lymphocytic-leukemia - association with chemotherapy.

P-glycoprotein (PgP), a transmembrane protein, has been associated with multiple drug resistance. We examined 42 patients with chronic lymphocytic leukemia immunohistochemically using the monoclonal antibody JSB-1 to determine the prevalence of PgP expression and its relationship with chemotherapy exposure. Of the 42 patients, 31 (74%) had detectable PgP. No relationship was found between PgP expression, patient age, duration of disease or stage. Moderate and strong intensity staining was found in 22% of untreated patients versus 56% patients treated with chemotherapy (p<0.05). Temporal fluctuations in P-glycoprotein staining intensity was seen in 6 of 7 cases which paralleled the initiation or withdrawal of the therapy.

Oral indomethacin and ranitidine in advanced melanoma: a phase II study.

As a result of preclinical data demonstrating the antitumour and antimetastatic efficiency of indomethacin in murine models, and the clinical observation of occasional tumour regression in patients with advanced melanoma treated with indomethacin together with ranitidine, a Phase II study was performed of prolonged administration of these two oral agents in combination. Seventeen patients were entered into the study and commenced on indomethacin 50 mg three times daily; the dose was escalated to a maximum of 75 mg three times daily in patients who tolerated the starting dose. Ranitidine was administered concurrently at a dose of 150 mg twice daily. One patient with uveal melanoma metastatic to the liver achieved a partial response, with slow shrinkage of a biopsy-proved liver metastasis (objective response rate 6 percent; 95 percent CI0-29). Another patient demonstrated a minor response in pelvic lymph nodes. The combination of indomethacin and ranitidine has negligible activity in advanced malignant melanoma; a response may require months to be achieved.

Acute non-lymphocytic leukaemia and myelofibrosis following sequential hemibody irradiation for prostatic carcinoma.

Sequential hemibody radiotherapy (SHBI) is currently being evaluated in clinical trials as adjuvant treatment in cancer patients who are potential long-term survivors. The potential late adverse effects of this therapeutic modality on the bone marrow may place patients at risk for the complications of aplasia, leukaemia, and myeloproliferative syndromes. We describe a case of acute non-lymphocytic leukaemia and myelofibrosis following SHBI for prostate carcinoma. The possible role of radiation in the induction of these abnormalities is discussed.

A seasonal association between SIDS deaths and kindergarten absences.

Data from linked birth and death certificates from the State of Oregon were used to determine the monthly distribution of deaths from sudden infant death syndrome (SIDS) for the years 1976 through 1984. The monthly number of SIDS deaths increased in winter and decreased in summer, when schools usually are not in session. Absences from kindergarten were determined from school records for the period 1979-84. School absences, previously shown to reflect incidence of predominantly infectious diseases, were found to be positively correlated with occurrences of SIDS. The role of ordinarily nonlethal infections in occurrences of SIDS has been established by history, histology, and viral isolation. The authors concluded that the seasonality of SIDS is related to the seasonality of respiratory infections and that the seasonality is influenced by respiratory infections being spread from school children to infants during periods when schools are in session.