Representing multi-database study schemas for reusability.

The need for easy, non-technical interfaces to clinical databases for research preceded translational research activities but is made more important because of them. The utility of such interfaces can be improved by the presence of a persistent, reusable and modifiable structure that holds the decisions made in extraction of data from one or more datasources for a study, including the filtering of records, selection of the fields within those records, renaming of fields, and classification of data. This paper demonstrates use of the Web Ontology Language (OWL) as a data representation of these decisions which define a study schema.

Nature of packs used in propellant modeling.

In recent years we have constructed closely packed spheres using the Lubachevsky-Stillinger algorithm to generate morphological models of heterogeneous solid propellants. Improvements to the algorithm now allow us to create large polydisperse packs on a laptop computer, and to create monodisperse packs with packing fractions greater than 70% which display significant crystal order. The use of these models in the physical context motivates efforts to examine in some detail the nature of the packs, including certain statistical properties. We compare packing fractions for binary packs with long-known experimental data. Also, we discuss the near-neighbor number and the radial distribution function (RDF) for monodisperse packs and make comparisons with experimental data. We also briefly discuss the RDF for bidisperse packs. We also consider bounded monodisperse packs, and pay particular attention to the near-wall structure where we identify significant order.

Continuous hemofiltration for anasarca: recovery of renal function after 71 liters of net ultrafiltration.

We report on a 64-year-old female presenting with anasarca secondary to volume loading in the setting of chronic liver disease, acute on chronic renal failure, circulatory failure and sepsis. Over 37 days, a net negative fluid balance of 71 L was achieved using continuous hemofiltration, with spontaneous recovery of urine output, vasopressor independence and resolution of coagulopathy. This case report underlines the pathophysiological role of tissue edema in the downward spiral of hepato-renal and cardio-renal dysfunction and illustrates that very large volumes of tissue fluid can be safely and effectively removed with continuous renal replacement therapy, thereby permitting recovery of organ function. To our knowledge, there have been no previous reports of such large volume net fluid removal by progressive ultrafiltration in the intensive care unit.

Effect of an education programme on the utilization of a medical emergency team in a teaching hospital.

BACKGROUND: Medical Emergency Teams (MET) have been developed to identify, review and manage acutely unwell ward patients. Previous studies have suggested that there may be obstacles to the utilization and activation of the MET. AIMS: To determine the effect of a detailed education programme on the rate of utilization of the MET system 3.5 years after its introduction in a University teaching hospital. METHODS: Prospective interventional study involving a detailed programme of education, feedback and decision support for nursing and medical staff given before, during and after implementation of a MET system. We measured the number of MET calls per month for both medical and surgical patients for 109 250 consecutive admissions to the acute care campus of Austin Health from August 2000 to June 2004. RESULTS: Overall activation of the MET increased from 25 calls per month to a peak of 79 calls per month over the study period (average increase of one MET call/month). After standardization for monthly admissions, the increase in MET utilization for surgical patients (increase by 1.13 MET/1000 admissions/month) was 4.9-fold greater than for medical patients (increase by 0.23 MET/1000 admissions/month; P < 0.0001). At the peak level of activity (April 2004), the MET was called to review 8.4% of surgical and 2.7% of medical admissions (P < 0.0001). CONCLUSIONS: There was a progressive increase in the utilization of the MET service in the 3.5 years after implementation, with the rate of uptake 4.9 times greater for surgical than for medical patients. Sustained uptake of the MET system is possible, but increased utilization may take several years to develop. Short-term studies testing the efficacy of the MET system are likely to significantly underestimate its effect on reducing adverse events. Intensive care unit resource adjustments will become necessary to meet increased demand.

A before and after trial of the effect of a high-dependency unit on post-operative morbidity and mortality.

OBJECTIVE: It has been suggested that the availability of a high-dependency unit (HDU), to facilitate graded admission to, and discharge from, an intensive care unit (ICU), might decrease post-operative morbidity. We wished to determine whether the addition of a 4-bed HDU to a tertiary 17-bed ICU facility at a University-affiliated hospital would decrease post-operative morbidity and mortality. PATIENTS AND METHODS: A prospective controlled before-and-after trial was performed with the opening of a 4-bed HDU. Consecutive patients admitted to hospital for major surgery during a 4-month control (pre-HDU) phase and during a 4-month intervention (HDU) phase were studied for the incidence of serious adverse events (SAEs), mortality after major surgery and mean duration of hospital stay. RESULTS: There were 1319 operations performed in 1125 patients during the pre-HDU period and 1369 operations performed in 1127 patients during the HDU period. During the HDU period there was an excess in unscheduled surgery cases (674 during HDU vs. 531 during the pre-HDU period; p < 0.0001). In the pre-HDU period, there were 414 SAEs in 190 patients compared with 456 SAEs in 209 patients during the HDU period (NS). There were no significant changes in any of the individual SAEs measured except for the incidence of post-operative acute pulmonary edema, which increased from 19 cases to 46 during the HDU period (p = 0.028). This increase was associated with a greater number of patients requiring re-intubation (52 vs. 75 cases; p = 0.044). The introduction of an HDU had no effect on mortality (80 deaths vs. 76; NS) and failed to reduce mean hospital length of stay (21.8 vs. 24 days; NS). CONCLUSIONS: The introduction of a 4-bed HDU in a teaching hospital was associated with a marked increase in unscheduled surgery and failed to reduce the incidence of post-operative SAEs, post-operative mortality, and mean duration of hospital stay.

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND: We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS: Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS: Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS: An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery.

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Effect of ventilation equipment on imposed work of breathing.

OBJECTIVE: To determine the imposed work of different ventilation systems at 3 levels of pressure support. DESIGN: Laboratory study. SETTING: Teaching hospital respiratory laboratory. PARTICIPANTS: Healthy, human volunteers. INTERVENTIONS: Measurement of imposed work of breathing (WOB(i)) in six ventilators with alteration of ventilatory settings, humidification device, and triggering mechanisms. RESULTS: At 0 cmH2O CPAP and 0 cmH2O PSV, clinically significant (> 0.1 joules per litre or J/L) WOB(i )occurred in all systems. At 5 cmH2O pressure support ventilation (PSV) median WOB(i) ranged from 0.01 to 0.11 J/L. Removal of the pleated membrane heat and moisture exchanger (HME) significantly reduced WOB(i) (0.38 vs. 0.11 J/L, p < 0. 0001). Drawover humidification marginally increased WOB(i) (0.16 vs. 0.11 J/L, p = 0. 0001). Flow triggering reduced WOB(i) with the Servo (p < 0.0001) and Bennett ventilators (p = 0.001) but not with the Bear 1000 ventilator. CONCLUSIONS: Up to 7 cmH2O of PSV may be required to reduce WOB(i) related to the ventilator, circuit and humdification devices. This pressure support does not address the additional resistive effect of the endotracheal or tracheotomy tube. Higher levels of PSV may therefore be required to offset WOB(i).

Elevated second trimester maternal serum beta-HCG concentrations and subsequent adverse pregnancy outcome.

Previous studies have found an association between elevated second trimester maternal serum alpha-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum beta-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester beta-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum beta-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated mid-trimester maternal serum beta-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.

Steroid production by early pregnancy human placental villi in culture.

Organ cultures prepared from human placentae obtained at 7-12 weeks of gestation were maintained for 3-13 days in Dulbecco's modified Eagle medium (DMEM). The addition of pregnenolone to the medium resulted in a dose-related increase in progesterone production and the addition of androstenedione resulted in a dose related increase in oestrogen production. More oestrone than oestradiol was measured in medium collected at the end of the first day of culture, but, on all subsequent days, oestradiol was the predominant oestrogen produced when androstenedione was added to the culture medium. When villi were incubated with [3H]androstenedione immediately after dissection most of the radiolabelled oestrogen recovered from the tissue and medium was oestrone; however, more [3H]oestradiol was recovered when villi were tested after 3 days of culture in DMEM. The addition of oestrone to the culture medium resulted in a dose related increase in oestradiol production with oestradiol accounting for a larger proportion of the total oestrogen in the day 2 and 3 medium samples than in the day 1 samples. These data demonstrate that the enzymes required for biosynthesis of progesterone and oestrogen from exogenous substrate are maintained for at least 13 days when early pregnancy placental villi are cultured in serum-free DMEM. However, a temporal change in the pattern of oestrogen synthesis does occur in culture, such that oestradiol rather than oestrone becomes the major product of androstenedione metabolism.

Outcome for fetus with ascites and cytomegalovirus infection.

The prenatal and neonatal course of a fetus with cytomegalovirus infection and ascites found on ultrasonographic examination at 27 weeks' gestation is reported. The ascites resolved within 4 weeks and the neonate had evidence only of mild congenital cytomegalovirus infection at birth. The factors predictive of the long-term outcome for an infant with congenital cytomegalovirus infection are reviewed. In this case, the finding that signs of significant disease in the fetus do not necessarily correlate with signs of severe congenital infection in the neonate is reported. It is suggested that prospective data are needed to aid in prediction of the course of fetal cytomegalovirus infection.

Comparison of maternal and fetal chromosome heteromorphisms to monitor maternal cell contamination in chorionic villus samples.

Maternal cell contamination (MCC) presents a potential problem in the analysis of chorionic villus sampling (CVS) preparations for early prenatal diagnosis by chromosomal, biochemical and molecular methods. Through the comparison of fluorescent chromosome variants from CVS and maternal cells, we found three out of 50 samples to have MCC. One of these was observed on a direct preparation. Routine chromosome heteromorphism analysis is suggested as a reliable method for monitoring MCC in CVS specimens.

Prenatal diagnosis of cystinosis utilizing chorionic villus sampling.

The prenatal diagnosis of cystinosis is currently based on the increased amount of free-cystine present in amniotic fluid cells. Amniocyte cultures must be grown for at least 2 weeks to obtain sufficient cells for such measurements. Thus, the diagnosis cannot be made until close to 20 weeks gestational age by this method. We report a case in which chorionic villi were used for direct cystine measurement resulting in the in utero diagnosis of cystinosis at 9 weeks gestational age. The diagnosis was confirmed by the study of cultured chorionic villus cells, and of the 10-week abortus.

Chorionic villus sampling: first-trimester prenatal diagnosis of partial 10q trisomy in a family with a 4/10 translocation.

Direct chromosome preparations of cells obtained through chorionic villus sampling at 8 weeks' gestation in a patient whose spouse is a balanced translocation carrier revealed a fetus with an unbalanced karyotype. Knowledge of the abnormality allowed the family to make a decision in regard to continuation of the pregnancy earlier than would have been possible with the routine procedure of amniocentesis. Although the risks of chorionic villus sampling are currently being investigated, it appears that this technique has great potential for early diagnosis, affording psychological advantages, as well as a safer termination in the event of an abnormal fetus.