Impact of simulation on multidisciplinary NICU teamwork during delivery and transport of extremely preterm infants.

BACKGROUND AND OBJECTIVES: Multidisciplinary teamwork during delivery room (DR) resuscitation and timely transport to the neonatal intensive care unit (NICU) can reduce morbidity and mortality for infants born Extremely Preterm (EP). We aimed to assess the impact of a multidisciplinary high-fidelity simulation curriculum on teamwork during resuscitation and transport of EP infants. METHODS: In a prospective study conducted at a Level III academic center, seven teams (each consisting of one NICU fellow, two NICU nurses, and one respiratory therapist) performed three high-fidelity simulation scenarios. Videotaped scenarios were graded by three independent raters using the Clinical Teamwork Scale (CTS). Times of completion of key resuscitation and transport tasks were recorded. Pre- and post- intervention surveys were obtained. RESULTS: Overall, time of completion of key resuscitation and transport tasks decreased, with significant decreases in the time to attach the pulse oximeter, transfer of the infant to the transport isolette, and exit the DR. There was no significant difference in CTS scores from Scenario 1 to 3. Scenarios led by first-year fellows showed a trend towards improvement in all CTS categories. A comparison of teamwork scores pre- and post-simulation curriculum during direct observation of high-risk deliveries in real time revealed a significant increase in each CTS category. CONCLUSION: A high-fidelity teamwork-based simulation curriculum decreased time to complete key clinical tasks in the resuscitation and transport of EP infants, with a trend towards increased teamwork in scenarios led by junior fellows. There was improvement of teamwork scores during high-risk deliveries on pre-post curriculum assessment.

Developing clinical decision support within a commercial electronic health record system to improve antimicrobial prescribing in the neonatal ICU.

OBJECTIVE: To develop and implement a clinical decision support (CDS) tool to improve antibiotic prescribing in neonatal intensive care units (NICUs) and to evaluate user acceptance of the CDS tool. METHODS: Following sociotechnical analysis of NICU prescribing processes, a CDS tool for empiric and targeted antimicrobial therapy for healthcare-associated infections (HAIs) was developed and incorporated into a commercial electronic health record (EHR) in two NICUs. User logs were reviewed and NICU prescribers were surveyed for their perceptions of the CDS tool. RESULTS: The CDS tool aggregated selected laboratory results, including culture results, to make treatment recommendations for common clinical scenarios. From July 2010 to May 2012, 1,303 CDS activations for 452 patients occurred representing 22% of patients prescribed antibiotics during this period. While NICU clinicians viewed two culture results per tool activation, prescribing recommendations were viewed during only 15% of activations. Most (63%) survey respondents were aware of the CDS tool, but fewer (37%) used it during their most recent NICU rotation. Respondents considered the most useful features to be summarized culture results (43%) and antibiotic recommendations (48%). DISCUSSION: During the study period, the CDS tool functionality was hindered by EHR upgrades, implementation of a new laboratory information system, and changes to antimicrobial testing methodologies. Loss of functionality may have reduced viewing antibiotic recommendations. In contrast, viewing culture results was frequently performed, likely because this feature was perceived as useful and functionality was preserved. CONCLUSION: To improve CDS tool visibility and usefulness, we recommend early user and information technology team involvement which would facilitate use and mitigate implementation challenges.

The epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit, 2000-2007.

OBJECTIVE: To assess the epidemiology of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections in a neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective chart review was conducted from 2000-2007; demographic and clinical characteristics of infected infants and crude mortality were assessed. RESULTS: During the study period, there were 123 infections caused by MSSA and 49 infections caused by MRSA. Although the types of infections caused by MSSA and MRSA were similar, infants with MRSA infections were younger at clinical presentation than infants with MSSA infections (P=0.03). The overall rate of S. aureus infections was approximately 15-30 per 1000 patient-admissions. The rate of bacteremia and skin and soft tissue infections remained stable over time. Among extremely low birth weight infants (birth weight <1000 g), 4.8 and 1.8% developed an infection caused by MSSA or MRSA, respectively. Infections occurred in a bimodal distribution of birth weight; 53% of infections occurred in extremely low birth weight infants and 27% occurred among term infants birth weight >or=2500 g, many of whom underwent surgical procedures. CONCLUSIONS: MSSA and MRSA remain significant pathogens in the NICU, particularly for extremely premature infants and term infants undergoing surgery. Further work should investigate infection control strategies that effectively target the highest risk groups and determine if vertical transmission of MRSA is responsible for the younger age at presentation of infection.

Charles University and pigment cell research.

A short review on the pigment cell research at Charles University in Prague is presented.

Tradition of pigment cell research at Charles University in Prague.

A short review on the history of pigment cell research at Charles University (Ch.U.) in Prague is presented. The famous Czech physiologist and professor J.E. Purkyne started the pigment cell research at Ch.U. already in 1837. He discovered melanin granules in the cells of substantia nigra of the brain. Later, in 1858, a Czech professor of medicine at Ch.U., B. Eiselt, as the first, described melanogenuria in 3 patients with generalized melanoma. Also some German professors at Ch.U. contributed to the research of melanins and melanogenuria in the past, especially H. Waelsch (1932). After the World War II, a Czech professor of medical chemistry at Ch.U., A.F. Richter with his young assistant J. Duchon continued in the chemical exploration of melanins (1954) and J.D. with Z. Pechan, B. Matous and S. Pavel devoted their attention to melanogenuria in melanoma patients (1962-1980). In 1967 they identified 2 new metabolites in melanoma urine: 5-hydroxy-6-methoxy and 6-hydroxy-5-methoxy-indole-2-carboxylic acids. J. Duchon with J. Borovanský and P. Hach also studied morphology and chemical composition of different melanosomes (1972-1979) and brought the first evidence that melanosomes consist of several proteins (1972). In 1980's 4 groups devoted to the pigment cell research and originated from Ch.U. were formed. The groups of J.B., of B.M. and of J. Vachtenheim in Prague and the group of S.P. who moved to the Netherlands (Leiden). As for the clinical aspects of the pigment cell research, the s.c. Hermanský-Pudlák syndrome published in 1959 and the histopathological classification of malignant melanomas estimated by J. Trapl (1957), should be mentioned. Therefore it is not surprising that, as a result of the tradition of pigment cell research at Ch.U., the 3rd European Workshop on Melanin Pigmentation was held in Prague already in 1981 and that, in 1998 again, Ch.U. was entrusted with the arrangement of the 8th Meeting of the European Society for Pigment Cell Research at the occasion of the Ch.U. 650th anniversary.

Ofloxacin once daily versus twice daily in community-acquired pneumonia and acute exacerbation of chronic bronchitis. A randomized multicenter study.

Eighty-two patients with community-acquired pneumonia (CAP) or acute exacerbation (AE) of chronic bronchitis were randomized to receive ofloxacin (OFL) 400 mg twice daily (39 patients) versus 400 mg once daily (43 patients) orally. Cure rates showed no statistically significant difference (90.1 vs. 94.6%), but more patients receiving 800 mg/day had side effects. Thus, the once daily administration of OFL is equally effective and safer than 400 mg twice daily to treat CAP or AE chronic obstructive pulmonary disease, especially in countries with higher pneumococcal and Haemophilus influenzae resistance in community practice.

Melanogenic factors: regulation of gene expression.

Melanogenesis is a multistep biochemical process resulting in the formation of melanin in pigment cells in the skin and the eye. Three melanogenic factors, tyrosinase, TRP1, and TRP2 participate in the pathway. Here, the regulation of gene expression of these melanocyte-specific markers is shortly reviewed.

Extended workdays in an underground mine: a work performance analysis.

Many companies in different industrial sectors are exploring alternative work schedules to deal with diverse problems associated with shiftwork. The use of extended workday schedules (regular shift lengths exceeding 8 h with compressed workweeks) is attracting growing interest in many industries that use continuous operations. To address concerns regarding possible fatigue effects on safety and work performance associated with such schedules, the U.S. Bureau of Mines conducted a two-phase study at an underground metal mine in western Canada. Data were collected before and after a group of workers employed at the mine changed from an 8- to a 12-h schedule. Results indicate nearly unanimous acceptance and improved sleep quality associated with the new schedule. In general, fatigue-sensitive behavioral and physiological performance measures show either no change or improvement with 12-h shifts. We conclude that the extended workday schedule should be retained but periodically reevaluated.

Melanogenuria: the past--the present--the future.

A short review on the development of the study of melanogenuria in malignant melanoma is presented.

Shiftwork and the older worker.

The number of workers employed on shiftwork is large, and it appears to be increasing. The impact of shiftwork on the occupational safety and health of workers is complex and involves both biological and behavioral variables. Current conceptual models propose that the impact of shiftwork, where night work is involved, increases with exposure. At some point the worker is said to reach a tolerance limit beyond which shiftwork is no longer safe. Sleep variables have proven to be sensitive markers for the effects of night shiftwork. Data from U.S. workers show a statistically significant interaction among age, gender, and shift for the workday sleep length of workers on permanent day, afternoon/evening, and night shifts. Sleep length declines with age for both male and female night workers, as well as for male workers on afternoon/evening shifts. In addition, female night workers in the 18-49 age range sleep significantly less than same-age male night workers. Nap behavior also varies with shift, but age and gender effects do not appear to account for the variance. The results support the assumption that most night shiftworkers are at risk even though they often give the appearance of being able to tolerate nocturnal work hours. However, it is not yet clear how age and gender are related to the social, circadian, and environmental factors that influence the sleep length of shiftworkers.

Protein determination in materials containing melanin.

Strategy of protein determination in melanin containing samples was analyzed, and the prerequisites under which the Lowry procedure could be used were established. (a) Complete solubilization of proteins from melanosomes was not reached until the treatment with 3% sodium dodecylsulfate at 100 degrees C was prolonged to 5 h. (b) It is necessary to correct the data obtained with Folin reaction to eliminate melanin interference. (c) The correction is based upon the determination of the extent of solubilized melanin and subtraction of the corresponding Folin-Ciocalteu reaction values. (d) The extent of correction due to the melanin interference was found to be about 40% of the absorbance value. It was concluded that correction of the data obtained with Lowry assay is possible, but the procedure is complicated and time-consuming. However, a more simple modification has not been developed.

Tyrosinase of hamster melanoma: its purification and estimation by radioimmunoassay.

1. Tyrosinase was purified from melanosomal fraction of hamster melanoma. 2. A radioimmunoassay was developed to quantitate the tyrosinase protein in hamster serum and hamster melanoma tissue using polyclonal anti-tyrosinase antibodies and 125I-labeled enzyme. 3. The serum tyrosinase levels were found to be about 0.24 micrograms and 1.14-4.48 micrograms/ml in normal hamsters and melanoma-bearing hamsters, respectively. 4. Tyrosinase protein in serum correlated significantly with the enzyme activity in hamsters with melanoma (r = 0.733). 5. In the cytosol fraction of hamster melanoma, a level of 2.2 micrograms of tyrosinase/mg protein was determined. 6. The usefulness and possible applications of the tyrosinase radioimmunoassay are discussed.

RNA and DNA in melanosomes of hamster melanoma.

The melanosomes were isolated from Syrian hamster melanoma Ma by three different methods. Levels of about 0.2% RNA and less than 0.05% of DNA were detected in the melanosome preparations. The higher the purification of the melanosome samples, the lower the DNA content observed. Consequently, traces of DNA in melanosomes could originate from contamination. The irreversible interaction of DNA with melanosomes in vitro was not demonstrated.

Biochemical markers of malignant melanoma.

The excretion of Thormählen positive melanogens (TPM), zincuria, serum dopaoxidase activity of tyrosinase and serum sialic acid were determined in 60 patients with primary and/or metastatic cutaneous melanoma and in 20 healthy persons. On the basis of our results we can recommend the following of TPM urinary excretion and serum dopaoxidase activity in the course of malignant melanoma as specific markers of the tumor growth. The following of serum sialic acid in the course of malignant melanoma is valuable from the standpoint of prognosis of the disease. The following of zincuria in the course of malignant melanoma is not recommended because of its low value for monitoring melanoma patients.

Specific inhibition by antityrosinase antibodies of tyrosinase-mediated melanogenesis.

Polyclonal antibodies to hamster melanoma tyrosinase were raised in rabbits, and series of immunoinhibition experiments with a purified enzyme and specific immunoglobulins were carried out. Tyrosinase activity was determined by a set of radiochemical and spectrophotometric methods utilizing tyrosine, dopa, dopamine, or dihydroxyindole (DHI) as substrates. The quantitative data obtained indicated that the complexing of tyrosinase with its specific antibody inhibited melanogenesis in a specific manner: dopachrome formation from dopa and dopamine conversion to melanin were not affected and all other enzyme activities comprising the DHI oxidation step were inhibited to various degrees. Additionally, tyrosine hydroxylation was also slightly inhibited. The data obtained implied that melanogenesis was restricted at the point of DHI oxidation. From observations on the immunoinhibition of a DHI oxidation at varying dopa-cofactor concentrations, we propose that dopa-cofactor may be bound at separate site than DHI and thus may act as a positive allosteric effector for DHI oxidation by tyrosinase. Study of tyrosinase immunoinhibition by the antibodies against the enzyme thus seems to provide a valuable system for investigating the tyrosinase-mediated melanogenesis.

Lipid composition in melanosomes of tumor- and chorioidea cells.

The lipid composition of melanosomes from hamster and bovine eye pigmented tissues (chorioidea) and of melanosomes from Harding-Passey mouse melanomas, hamster melanomas Ma and human liver melanoma metastases was investigated. The lipid composition of melanosomes was analogous to that of other subcellular melanocytic fractions as it had been reported in literature. The main difference between tumor and chorioidea melanosomes consisted in the absence of phospholipids in the latter case, other differences were quantitative. The role of melanosomes in melanomas should not be different from that in normal pigmented tissues.

A spectrophotometric assay for mammalian tyrosinase utilizing the formation of melanochrome from L-dopa.

A simple spectrophotometric method for a rapid determination of tyrosinase (EC 1.14.18.1) is described. The basis of the assay is the incubation of the enzyme with L-dopa in the presence of an optimal concentration of Zn2+ ions and the measurement of the formation of melanochrome, as indicated by the rise in absorbance at 540 nm. Final absorbance change reflects probably two activities of tyrosinase: the oxidation of dopa to dopaquinone and the conversion of 5,6-dihydroxyindole to melanochrome. Using a purified preparation from hamster melanoma, the assay was found to be more sensitive than the commonly used dopachrome assay. Comparison with some other currently available methods for assaying tyrosinase is presented and potential applications of the assay are discussed.

An animal model for the survival of tyrosinase isozymes in serum.

Two tyrosinase isozymes were purified from pigmented hamster melanoma and injected i.v. into rats. It was shown that while T1 (sialylated) isozyme survived in the circulation, native asialo (T2) isozyme and neuraminidase-desialylated T1 isozyme disappeared from the circulation in a few minutes. Desialylated fetuin had a marked inhibitory effect on the removal of asialo-T1 tyrosinase. These data indicate that the enzyme tyrosinase shares the common pattern of clearance from circulation known for the majority of serum glycoproteins. The electrophoretic pattern of tyrosinase isozymes partially purified from the sera of melanoma-bearing animals were compared with those from the soluble fraction of the tumors. In hamsters, melanoma tissue revealed both T1 and T2 isozymes while serum exhibited T1 and very weak T2, supporting the mechanism of clearance demonstrated in rats. In mice bearing Cloudman S-91 or B-16 melanomas, only T1 isozyme was seen in sera and in tumors.