Subject-specific cardiovascular system model-based identification and diagnosis of septic shock with a minimally invasive data set: animal experiments and proof of concept

A cardiovascular system (CVS) model and parameter identification method have previously been validated for identifying different cardiac and circulatory dysfunctions in simulation and using porcine models of pulmonary embolism, hypovolemia with PEEP titrations and induced endotoxic shock. However, these studies required both left and right heart catheters to collect the data required for subject-specific monitoring and diagnosis-a maximally invasive data set in a critical care setting although it does occur in practice. Hence, use of this model-based diagnostic would require significant additional invasive sensors for some subjects, which is unacceptable in some, if not all, cases. The main goal of this study is to prove the concept of using only measurements from one side of the heart (right) in a 'minimal' data set to identify an effective patient-specific model that can capture key clinical trends in endotoxic shock. This research extends existing methods to a reduced and minimal data set requiring only a single catheter and reducing the risk of infection and other complications-a very common, typical situation in critical care patients, particularly after cardiac surgery. The extended methods and assumptions that found it are developed and presented in a case study for the patient-specific parameter identification of pig-specific parameters in an animal model of induced endotoxic shock. This case study is used to define the impact of this minimal data set on the quality and accuracy of the model application for monitoring, detecting and diagnosing septic shock. Six anesthetized healthy pigs weighing 20-30 kg received a 0.5 mg kg(-1) endotoxin infusion over a period of 30 min from T0 to T30. For this research, only right heart measurements were obtained. Errors for the identified model are within 8% when the model is identified from data, re-simulated and then compared to the experimentally measured data, including measurements not used in the identification process for validation. Importantly, all identified parameter trends match physiologically and clinically and experimentally expected changes, indicating that no diagnostic power is lost. This work represents a further with human subjects validation for this model-based approach to cardiovascular diagnosis and therapy guidance in monitoring endotoxic disease states. The results and methods obtained can be readily extended from this case study to the other animal model results presented previously. Overall, these results provide further support for prospective, proof of concept clinical testing with humans.     

Improved outcomes of children with malignancy admitted to a pediatric intensive care unit

OBJECTIVE: To assess the acute and long-term outcomes of children admitted to the intensive care unit with cancer or complications after bone marrow transplantation. DESIGN: Retrospective analysis of databases from a prospective pediatric intensive care unit (PICU) database supplemented by case notes review. SETTING: A PICU in a tertiary pediatric hospital. PATIENTS: All children with malignancy admitted to the PICU between May 1, 1987, and April 30, 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 206 admissions to the PICU during a 9-yr study period of 150 children with malignancies or complications after bone marrow transplantation. Forty patents died in the PICU (27% mortality rate). The most frequent indications for PICU admission were shock and respiratory disease. Of 56 children admitted with shock, there were 16 deaths (29% mortality rate). In 24 episodes of sepsis, inotropic and ventilatory support were required and 13 patients (54%) survived. Analysis of long-term survival gave estimates of 50% survival for all oncology patients admitted to the PICU and 42% for those admitted for shock. CONCLUSIONS: A high proportion of oncology patients admitted to the PICU requiring intensive intervention survive and go on to be cured of their malignancy. Our study suggests the PICU outcome for these patients has improved.     

Measuring against clinical standards

Systematic improvement of health services requires the objective measurement of people, practices and organisations against valid and explicit standards in order to identify and implement appropriate change. Effective quality systems must embrace a wide range of definitions of quality, and a similar variety of approaches to defining, measuring and improving. Clinical performance may be examined from three professional viewpoints--clinical competence: assessment of individual practitioners against explicit criteria to recognise achievement and to promote continuing development. Traditional mechanisms of training, registration and accreditation enable clinicians to reach career grades but responsibility for subsequent support is often unclear between employers, professions and registering bodies. Clinical practice: assessment of actual clinical process and outcomes against research-based "best practice" to identify and reduce variation. Peer review, clinical audit and confidential enquiries are examples of this approach, which may involve single or multiple professional groups and their interface with management. Service accreditation: systems to assess health care organisations against published standards in order to encourage best management practice. These are usually run on a regional or national basis and, though sensitive to expectations of patients, managers, clinicians, paying agencies and government, they are usually managed by an impartial but authoritative organisation.     

Nomograms for estimating coronary artery disease prognosis with gated stress myocardial perfusion SPECT

Background  

Nomograms can be useful tools for estimating coronary artery disease (CAD) risk. We sought to devise risk-based nomograms for stress myocardial perfusion SPECT to include measures of % ischemic myocardium and left ventricular function.     

Role of P glycoprotein in the course and treatment of Encephalitozoon microsporidiosis

Encephalitozoon microsporidia are obligate intracellular protozoan parasites that proliferate and differentiate within a parasitophorous vacuole inside host cells that are usually epithelial in nature. Isolates of the three species of the Encephalitozoon microsporidia, E. cuniculi, E. hellem, and E. intestinalis, were obtained from AIDS patients and cultured in green monkey (E6) kidney cells. Anti-P-glycoprotein (anti-Pgp) and anti-multidrug resistance-associated protein (anti-MRP) monoclonal antibodies were used to probe for multidrug resistance (MDR) pump epitopes and verapamil- or cyclosporin A- and probenecid-modulated intracellular calcein fluorescence were used to assess the expression of Pgp and MRP respectively in uninfected and infected cells. Pgp, but not MRP, was detected immunocytochemically and by verapamil- and cyclosporin A-potentiated intracellular fluorescence in both host cells and parasite developing stages. When an in vitro infection assay was employed, verapamil and cyclosporin A acted as chemosensitizing agents for the antiparasitic drug albendazole. These observations suggest that inhibiting host cell and perhaps parasite MDR pumps may increase the efficacy of antiparasitic agents in these and other microsporidia species.     

Comparison of plain ice and flavoured ice for preventing oral mucositis associated with the use of 5 fluorouracil

Aims and objectives. The study aimed to compare the use of plain ice, flavoured ice and standard care, to evaluate the effect on mucositis and to determine patients’ perceptions of the two forms of oral cryotherapy. Background. Despite evidence that oral cryotherapy is useful in preventing mucositis in patients receiving 5‐fluorouracil, concerns have been expressed about its clinical utility, due to potential side effects and negative perceptions. Design. A randomized, controlled, crossover trial was conducted in the outpatient chemotherapy department of an acute care teaching hospital in Perth, Western Australia. Patients were randomized to receive each of three interventions across three cycles of chemotherapy: standard care alone; standard care plus plain ice; and standard care plus flavoured ice. Methods. Oral mucositis was assessed by nurses prior to each of the three chemotherapy cycles and 15 days after each intervention. Two assessment tools were used, the Oral Assessment Guide, and the Western Consortium Cancer Nursing Research Scale. Participants completed a questionnaire to determine their comfort and satisfaction with oral cryotherapy, as well as factors affecting compliance. Results. Findings from 67 patients revealed that when participants used standard care alone, they were significantly more likely to experience symptoms of mucositis than when they used either plain or flavoured ice. Odds ratios were at least threefold higher for standard care alone, varying according to the instrument used. The two main concerns reported were the taste of flavoured ice and the time required to complete the cryotherapy interventions. Side effects such as nausea, sensitivity and headache were reported more frequently for flavoured ice (n = 11) compared with plain ice (n = 5) and standard care (n = 1). Conclusions. Both forms of oral cryotherapy were effective in reducing the severity of oral mucositis after chemotherapy and were more effective than standard care alone. Flavoured ice was associated with the highest frequency of side effects. Relevance to clinical practice. The benefits of cryotherapy appear to outweigh the problems in this sample of patients. The intervention should be tailored to individual patients, based on preferences for plain versus flavoured ice and small chips vs. larger blocks. Unsweetened frozen fruit juices should be evaluated. Time constraints could be addressed by providing transportable containers of ice.     

Country profile: travelling to Australia

Australia has a well-developed tourism industry and health care system. Despite the precautions recommended in this paper, Australia has been virtually free of local outbreaks of life threatening tropical diseases in recent decades. This paper focuses on health and safety issues for travellers to Australia, especially the special precautions for those travelling to more rural and remote areas in outback Australia. Travellers to Australia should be advised that, in general, Australia is a relatively safe country in which to travel, and it has high standards of health and hygiene.