Comorbidities Associated with Worse Outcomes Among Inpatients Admitted for Acute Gastrointestinal Bleeding.

BACKGROUND: Multimorbidity increases healthcare resource utilization. Little is known on specific comorbidity combinations. AIMS: To identify comorbidities associated with increased resource utilization among inpatients admitted for gastrointestinal bleeding (GIB). METHODS: This retrospective cross-sectional study, 1/2010-5/2018 at the University Hospital Zurich, Switzerland, analyzed electronic health records of patients with upper (UGIB) and lower (LGIB) GIB, focusing on length of stay (LOS) and 30-day readmissions for resource use and clinical outcomes, investigated by multivariable regression adjusted for antithrombotics. RESULTS: Of 1101 patients, 791 had UGIB and 310 LGIB, most often melena and bleeding diverticula, respectively. In UGIB, thromboembolic events showed a trend toward 27% increased LOS (1.27; 95% confidence interval [CI] 1.00-1.61), antithrombotics independently associated with 46% increased LOS (1.46; 95% CI 1.32-1.62). Cancer (odds ratio [OR] 2.86; 95% CI 1.68-4.88) independently associated with 30-day readmissions, anemia showed a trend (OR 1.68; 95% CI 1.00-2.84). In LGIB, none of the investigated comorbidities associated with increased LOS, but antithrombotics independently associated with 25% increased LOS (1.25; 95% CI 1.07-1.46). Atrial fibrillation/flutter (OR 2.69; 95% CI 1.06-6.82) and cancer (OR 4.76; 95% CI 1.40-16.20) associated strongly with 30-day readmissions. CONCLUSIONS: In both groups, cancer associated with 30-day readmissions, antithrombotics with increased LOS. Thromboembolic events and anemia showed clinically important trends in UGIB. Atrial fibrillation/flutter associated with 30-day readmissions in LGIB. Prospective studies are needed to investigate these complex multimorbid populations and establish appropriate guidelines.

Home-based color card screening for biliary atresia: the first steps for implementation of a nationwide newborn screening in Germany.

INTRODUCTION: Biliary atresia is a rare neonatal disease and the most common indication for pediatric liver transplantation. Kasai portoenterostomy is the initial treatment, aiming to prevent liver transplantation. Beyond age at Kasai, few prognostic factors are known. Multiple countries have established screening methods to reduce the age at Kasai and recent analysis shows significant better outcomes for screening cohorts. In 2016, we established a decentralized stool color card screening in Lower Saxony and we present our first 2 years of experiences. METHODS: In cooperation with a major German health insurance company and the Medical Association of Lower Saxony, we established the screening project, printed 120,000 color cards, and distributed them to all maternity hospitals. Program advertises were printed in newspapers and medical journals. After the first year, the project was evaluated. Thirty maternity hospitals and local practitioners were contacted via telephone, Internet, intranet, and pediatric journals. RESULTS: One out of seventy-six maternity hospitals (1.3%) refused to participate in the screening. 30 hospitals (40%) were contacted and 93.5% of the interviewed staff reported that stool color cards were handed out regularly and discussed with the parents. Only 20% of local practitioners assessed neonatal cholestasis to be a relevant problem during daily practice, and 55% regarded a stool color card screening to be useful. CONCLUSIONS: In the second year, we extended the screening project to outpatient maternity clinics. Based on the responses of local practitioners, we regard the voluntary screening as insufficient and we have contacted the Federal Joint Committee for the initiation of a nationwide obligatory stool color card screening.

Appendectomy in the pediatric population-a German nationwide cohort analysis.

BACKGROUND: Meta-analyses indicate advantages of laparoscopic compared to open appendectomy. Nationwide analyses on results of laparoscopic appendectomy are scarce and studies from Germany are not available. This observational cohort study based on a nationwide insurance database was performed to analyze results of pediatric laparoscopic versus open appendectomy in general use. METHODS: Data were extracted from the largest German statutory health insurance TK (∼9 million clients) in a 3-year period (2010-2012). All patients aged 4-17 years with International Classification of Procedures in Medicine (ICPM) code "appendectomy" were included. Logistic regression analysis for the risk of a surgical complication within 180 postoperative days was performed. RESULTS: Appendectomy was performed in 8110 patients (52.6 % male; 47.4 % female) and conducted laparoscopically in 75.0 % of the patients (conversion rate = 1.2 %). Laparoscopic compared to open surgery was associated with a shorter length of hospital stay in both uncomplicated and complicated appendicitis. Patients with complicated appendicitis had lower readmission rates for surgical complications after laparoscopic appendectomy and logistic regression analysis confirmed a significantly lower risk of readmission for surgical complications after laparoscopic compared to open operation in adolescents. Pediatric surgeons operated 23.9 % and general surgeons 76.1 % of patients. Laparoscopy was less frequently used and the conversion rate was significantly higher in pediatric surgical departments. CONCLUSION: This first nationwide German cohort study confirms that laparoscopic appendectomy is associated with a less complicated postoperative course compared to open appendectomy, particularly in patients with complicated appendicitis. Pediatric surgeons used laparoscopy less frequently compared to general surgeons. Laparoscopic appendectomy should therefore be further promoted in pediatric surgical centers in Germany.

Early complications after esophageal atresia repair: analysis of a German health insurance database covering a population of 8 million.

The treatment of esophageal atresia is not centralized in Germany. Therefore, high numbers of departments are involved. Data on the results of esophageal atresia repair from Germany are lacking. The aim of this study was to evaluate the early postoperative results after repair of esophageal atresia based on unbiased data of a German health insurance. We aimed to determine whether characteristics of the departments had an impact on outcome and compared the results from this study with the literature data from centers with a high caseload. Data of a German health insurance covering ∼10% of the population were analyzed. All patients who had undergone esophageal atresia repair from January 2007 to August 2012 were included. Follow-up data of 1 year postoperatively were analyzed. The potential impact of various characteristics of the treating surgical institutions was assessed. Results were compared with the latest international literature. Seventy-five patients with esophageal atresia underwent reconstructive surgery in 37 departments. The incidences of anastomotic leak (3%) and recurrent tracheoesophageal fistula (7%) were comparable with the literature (both 2-8%). Anastomotic stricture required dilatation in 57% of patients (mean 5.1 ± 5.6 dilatations) comparing unfavorably to most, but not all international reports. During 1-year follow-up, 93% of the patients were readmitted at least once (mean 3.9 ± 3.1 admissions). The incidence of complications did not correlate with any of the characteristics of the treating institutions such as academic affiliation, the number of consultants, beds, and preterm infants treated per year (all P > 0.05). Based on unbiased data, postoperative results after repair of esophageal atresia in Germany are comparable with recently published reports from international single centers. A correlation between the complication rate and characteristics of the treating institutions was not identified.

Impact of electronic reminders on venous thromboprophylaxis after admissions and transfers.

OBJECTIVE: Clinical decision support has the potential to improve prevention of venous thromboembolism (VTE). The purpose of this prospective study was to analyze the effect of electronic reminders on thromboprophylaxis rates in wards to which patients were admitted and transferred. The latter was of particular interest since patient handoffs are considered to be critical safety issues. METHODS: The trial involved two study periods in the six departments of a university hospital, three of which were randomly assigned to the intervention group displaying reminders during the second period. At 6 h after admission or transfer, the algorithm checked for prophylaxis orders within 0-30 h of the patient's arrival, increasing the specificity of the displayed reminders. RESULTS: The significant impact of the reminders could be seen by prophylaxis orders placed 6-24 h after admission (increasing from 8.6% (223/2579) to 12% (307/2555); p<0.0001) and transfer (increasing from 2.4% (39/1616) to 3.7% (63/1682); p=0.034). In admission wards, the rate of thromboprophylaxis increased from 62.4% to 67.7% (p<0.0001), and in transfer wards it increased from 80.2% to 84.3% (p=0.0022). Overall, the rate of prophylaxis significantly increased in the intervention group from 69.2% to 74.3% (p<0.0001). No significant changes were observed in the control group. Postponing prophylaxis checks to 6 h after admissions and transfers reduced the number of reminders by 62% and thereby minimized the risk of alert fatigue. CONCLUSIONS: The reminders improved awareness of VTE prevention in both admission and transfer wards. This approach may contribute to better quality of care and safer patient handoffs.

Physician compliance with advanced electronic alerts for preventing venous thromboembolism among hospitalized medical patients.

BACKGROUND: Worldwide, more than half of the hospitalized medical patients at high risk do not receive venous thromboembolism (VTE) prophylaxis. Although VTE among hospitalized patients at risk is reduced with electronic alerts (eAlerts), the majority of eAlerts are being ignored by the responsible physician. METHODS: We investigated physician compliance with an advanced eAlert system in 1027 (age 59 +/- 17 years) hospitalized medical patients. A continuously flashing non-interruptive eAlert, visible to all healthcare professionals, was issued in the electronic patient chart 6 h after admission if the physician did not order prophylaxis. RESULTS: The rate of appropriate prophylaxis increased from 44% before to 76% after the implementation of the eAlert system. Although the patients whose physicians cared for > or = 20 patients during the study period had a more frequent physician response to the eAlert than patients whose physicians cared for fewer patients (69% vs. 40%, P < 0.001), they received appropriate prophylaxis less often (72% vs. 81%, P = 0.016). After adjustment for significant patient predictors of appropriate prophylaxis, including cancer, age, duration of hospital stay, and thrombocytopenia, patients whose physicians cared for > or = 20 patients during the study period were less likely to receive appropriate prophylaxis (odds ratio 0.65, 95% confidence interval 0.44-0.96; P = 0.032) than patients whose physicians cared for fewer patients. CONCLUSIONS: The introduction of an advanced eAlert system accompanied by continuing medical education for the prevention of VTE resulted in a substantial increase in the rate of appropriate prophylaxis among hospitalized medical patients. However, many eAlerts may cause decreased physician compliance owing to 'alert fatigue'.

[Speech recognition in clinical routine, a pilot trial at the Zurich University Hospital]. / Spracherkennung im klinischen Alltag, ein Pilotversuch am Universitätsspital Zürich.

Two systems for continuous German speech recognition were evaluated in pilot installations in a Department of Medicine. Word recognition accuracies of 92-94% were achieved one month after implementation. For standardized text the performance increased to 97%. Speech recognition proved to be economical for physicians when producing short reports, whereas for comprehensive discharge summaries no significant time savings were observed. All reports could be made available much faster by using speech recognition. However, some particle difficulties may still limit the success of comprehensive installations in clinical settings. Adequate hardware, appropriate choice of areas of application, reasonably quiet working conditions and well motivated users are essential for successful implementations.

Factors compromising antibiotic activity against biofilms of Staphylococcus epidermidis.

Several factors associated with bacterial biofilms were studied for their role in phenotypic resistance to antibiotics. These factors included bacterial slime extracted from biofilms, reduced growth rates of biofilm-embedded bacteria and high bacterial inocula. Antibiotic activity against suspended bacteria in the presence of these factors, either alone or combined, was compared with activity against adherent biofilms. All MICs, determined by standard susceptibility tests, were below the sensitivity breakpoints for Staphylococcus epidermidis strain V2. The addition of bacterial slime to suspended bacteria reduced the bactericidal activity of glycopeptides but had less or no effect on the activity of the other antibiotics tested. High bacterial inocula affected the activity of flucloxacillin and quinolones only moderately or not at all, though a more pronounced effect on glycopeptides was observed. In contrast, the bactericidal activity of most antibiotics was severely compromised when adherent bacterial biofilms were used as inocula. In conclusion, the presence of slime, slow growth rates and high bacterial counts may explain the poor activity of glycopeptides against biofilm-embedded organisms, but these factors, either alone or in combination, do not explain the lack of bactericidal activity of other drugs against biofilms. Thus, additional factors need to be identified.

Multiple myeloma involving the myocardium and coronary vessels.

We report a case of metastatic plasmacytoma to the myocardium and coronary vessels in a 57-year-old man with multiple myeloma. Originally, the patient had a large plasmacytoma in his left chest wall and lung. He received local radiation and chemotherapy. Subsequently, the patient presented with symptoms of congestive heart failure. He had no prior history of cardiac disease. The patient was treated medically and later died from respiratory failure. At autopsy, a metastatic plasmacytoma was identified within the myocardium and externally compressing the coronary arteries. The tumor infiltrated into the coronary sinus. It is difficult to speculate whether the patient's symptoms were due to cardiac involvement since the tumor burden in his chest was also considerable. To our knowledge, coronary vessel involvement with plasmacytoma has not been previously described.

Peripheral database module for clinical management and research in sleep medicine.

Hospital-wide information systems may provide economical solutions for communication processes or for documentation by means of centralized digital medical records. Within a large university hospital, however, there may be too many diverse subspecialties and too many special medical procedures to be supported comprehensively by a single database information system. A peripheral modular system has been tailored to the specific needs of a sleep disorder clinic as an adjunct to the main clinical information system. The client server application allows for automatic data acquisition by on-line devices and by a graphical user interface. It supports administrative tasks for patient management, specific encounter interactions and data retrieval for research. Performance and acceptance of the system was assessed during clinical use, revealing positive response by the users, also with respect to significant time savings. Our experience suggests that the concept of peripheral database modules as "satellites" to a main clinical system provides flexibility in design and implementation of the specialized databases while providing access to data of more general relevance via the main database.

Bacterial concentrations in pus and infected peritoneal fluid--implications for bactericidal activity of antibiotics.

Little is known about how many bacteria are present at an infectious focus at the onset of antibiotic therapy. The number of cfu was determined in pus and infected peritoneal fluids obtained from 41 patients. Pathogens were detected in 71% of specimens. There were high concentrations of bacteria in culture-positive samples, in both soft-tissue and peritoneal infections, averaging 2 x 10(8) cfu/mL. These concentrations were much higher than the standard inoculum size used in in-vitro susceptibility tests, 5 x 10(5) cfu/mL. The impact of this discrepancy on antibacterial efficacy was studied with amikacin, ciprofloxacin, imipenem and piperacillin against Escherichia coli and Staphylococcus aureus. The inhibitory and bactericidal activities of amikacin and ciprofloxacin determined with high inocula were two to four times lower than with standard inocula, whereas the activity of piperacillin was diminished at least 128-fold. Similar activity was observed with these drugs in Mueller-Hinton broth and peritoneal fluid. The bactericidal activity of imipenem was reduced in peritoneal fluid. Thus, conditions prevailing at the infection site may compromise antibiotic activity determined in vitro.

The association between telomerase, p53, and clinical staging in colorectal cancer.

BACKGROUND: A proposed etiology of tumor activation involves p53 mutations while telomerase may serve as a key enzyme for maintenance of tumor cell proliferation. METHODS: Telomerase activity levels were measured in colorectal adenocarcinomas and corresponding normal tissue using a modified telomeric repeat amplification protocol, and p53 mutations were identified using immunohistochemical staining. Results were compared with staging data using regression analysis. RESULTS: Telomerase activity was present in 23 of 23 (100%) of the tumors and only 2 (9%) of normal specimens (P <0.0001). The p53 mutations were present in 18 of 23 (78%) of the tumors. No significant correlation between p53 mutations, telomerase activity levels, and staging was found. CONCLUSIONS: Telomerase activity in 100% of the tumors suggests telomerase activation is a universal event in colorectal tumor progression; however, telomerase activity appears to be independent of p53 mutations and clinical staging.

Molecular characterization of the Helicobacter pylori uvr B gene.

Helicobacter pylori persists in the human stomach where it may encounter a variety of DNA-damaging conditions, including gastric acidity. To determine whether the nucleotide excision repair (NER) pathway contributes to the repair of acid-induced DNA damage, we have cloned the putative H. pylori NER gene, uvrB. Degenerate oligonucleotide primers based on conserved amino acid residues of bacterial UvrB proteins were used in PCR with genomic DNA from H. pylori strain 84-183, and the 1.3-kb PCR product from this reaction was used as a probe to clone uvrB from an H. pylori genomic library. This plasmid clone had a 5.5-kb insert containing a 2.0-kb ORF whose predicted product (658 amino acids; 75.9 kDa) exhibited 69.5% similarity to E. coli UvrB. We constructed an isogenic H. pylori uvrB mutant by inserting a kanamycin-resistance cassette into uvrB and verified its proper placement by Southern hybridization. As with uvrB mutants of other bacteria, the H. pylori uvrB mutant showed a greatly increased sensitivity to the DNA-damaging agents methylmethane sulfonate and ultraviolet radiation. The uvrB mutant also was significantly more sensitive than the wild-type strain to killing by low pH, suggesting that the H. pylori nucleotide excision repair (NER) pathway is involved in the repair of acid-induced DNA damage.

Impact of bacterial biofilm formation on in vitro and in vivo activities of antibiotics.

The impact of bacterial adherence on antibiotic activity was analyzed with two isogenic strains of Staphylococcus epidermidis that differ in the features of their in vitro biofilm formation. The eradication of bacteria adhering to glass beads by amikacin, levofloxacin, rifampin, or teicoplanin was studied in an animal model and in a pharmacokinetically matched in vitro model. The features of S. epidermidis RP62A that allowed it to grow on surfaces in multiple layers promoted phenotypic resistance to antibiotic treatment, whereas strain M7 failed to accumulate, despite initial adherence on surfaces and growth in suspension similar to those for RP62A. Biofilms of S. epidermidis M7 were better eradicated than those of strain RP62A in vitro (46 versus 31%; P < 0.05) as well as in the animal model (39 versus 9%; P < 0.01).

Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine.

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.

Autosterilization of biodegradable implants by injection molding process.

Sterilization of degradable implants by standard procedures may damage the parts due to the labile chemical nature of the polymers. This study examined whether the injection molding process used for the production of polymeric parts may itself sterilize the implant due to high temperature, pressure, and shear forces applied. Poly-D,L-lactic acid (PDLLA) and poly-L-lactic acid (PLLA) granules were contaminated with thermoresistant spores of Bacillus stearothermophilus (>10(5) spores/g). Sterile and contaminated granules of both polymers were injection molded and tested for sterility. All 27 samples produced with sterile PDLLA and processed at 120 degrees C and all 18 samples produced with sterile PLLA at 200 degrees C remained sterile after injection molding and handling. However, in five out of 28 PDLLA samples and in one out of 26 PLLA samples produced with contaminated material, spores had survived the process. In conclusion, the injection molding process could not reliably sterilize parts produced with polylactic acid granules that were heavily contaminated with thermoresistant organisms. However, the number of viable spores was significantly reduced by more than 99.99%. Thus, the injection molding process might allow the autosterilization of parts produced with raw material that is not heavily contaminated.

Angiogenin plasma levels during pregnancy.

OBJECTIVE: Our purpose was to determine the levels in plasma of angiogenin in healthy pregnant women and to examine whether there are differences between uncomplicated pregnancies and patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets, preeclampsia-eclampsia, and highly pathologic Doppler flow findings without additional complications. STUDY DESIGN: Angiogenin was measured with a novel enzyme-linked immunosorbent assay. A case control and observational study was conducted in 68 healthy women from the tenth to fortieth weeks of pregnancy and in 18 patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets, 21 with preeclampsia/eclampsia and 13 with highly pathologic Doppler flow findings at admission for delivery. RESULTS: Between the tenth and fortieth weeks of uncomplicated pregnancy angiogenin plasma levels rose from 150 to 250 ng/ml (significant correlation). In patients with highly pathologic Doppler flow findings angiogenin is significantly reduced compared with healthy pregnant matched pairs (150 vs 219 ng/ml, p < 0.01). CONCLUSION: Rising plasma angiogenin levels in pregnancy may reflect persisting placental transformation and remodeling processes: in patients with highly pathologic Doppler flow findings these processes are disturbed and thus placental function is impaired.

Once-versus thrice-daily netilmicin combined with amoxicillin, penicillin, or vancomycin against Enterococcus faecalis in a pharmacodynamic in vitro model.

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.