Mortality in children admitted to Port Moresby General Hospital: how can we improve our hospital outcomes?

A detailed audit, part retrospective and part prospective, of deaths occurring in children admitted to the children's wards of the Port Moresby General Hospital over a 12-month period was made. 238 children died out of the 4898 admitted, an overall case fatality rate of 4.9%, with a monthly range of 3.7%-9.6%. The proportion of deaths approximated the proportion of admissions in each age group. 92% of the children had a weight of less than 80% of the standard weight for age and 30% weighed less than 60% of the standard weight for age. 24 (11%) of the deaths occurred within the first 6 hours of admission, 39 (17%) within the first 12 hours and 58 (26%) within the first 24 hours. 89 children (40%) died more than one week after admission. Pneumonia, meningitis, measles and septicaemia were the four leading certified causes of death and paediatric AIDS was the fifth. Less than half of the deceased children were appropriately immunized for their age. 27 deaths (12%) were assessed as preventable. 150 (67%) were classified as from treatable causes but unavoidable, 18 (8%) from untreatable causes, 22 (10%) of undetermined cause and 34 (15%) avoidable. The factors associated with avoidable deaths were delayed treatment (20 children), inadequate treatment (8 children), incorrect treatment (1 child) and others (5 children). Infant and child mortality could be reduced by general measures such as improving community nutrition and immunization status and improving care-seeking behaviour. Hospital-related measures to reduce mortality include improving the accuracy and effectiveness of triage and provision of adequate staffing levels and bed space. Periodic in-depth audit is necessary to assess quality of patient care, to identify problems and to point towards their solution. Accurate recordkeeping is essential for appropriate audit and planning.     

Neonatal outcome at Modilon Hospital, Madang: a 5-year review

An audit of neonatal care at Modilon Hospital, Madang was performed using obstetric and neonatal data for the five years 1995-1999. The overall perinatal mortality rate (PNMR) was 51.1 per 1000 total births with an early neonatal mortality rate (ENNMR) of 12.7 and a stillbirth rate (SBR) of 38.5. 839 neonates aged 0-28 days were admitted to the Special Care Nursery. The male to female ratio was 1.3:1. 186 babies (22%) died. The case fatality rate was higher in males than females (p<0.001). Babies born at health centres or born before arrival had a significantly higher fatality rate than hospital-born babies (p<0.001). The case fatality rate was highest in babies born preterm and declined with increasing birthweight from less than 1000 to 3999 g. The major recorded causes of admission were neonatal sepsis, prematurity, neonatal jaundice, birth asphyxia, respiratory distress and meconium aspiration syndrome. 60% of deaths occurred within 48 hours of admission, 32% between 48 hours and 7 days and 8% at 7 days or older. The proportion of deaths occurring during the afternoon and night shifts was significantly higher than that during the morning shift (p<0.001). This was most likely to be related to staffing levels. The major causes of death were prematurity or low birthweight (27%), sepsis (23%) and birth asphyxia (17%). Other causes of death included congenital abnormalities, meconium aspiration and meningitis. Antenatal care is still not universally available for Papua New Guinean women. Home delivery of high-risk mothers is commonplace, and women delivering in hospital often present in established labour. Perinatal and neonatal problems are therefore frequent. Newborn babies have the right to the best available care. This can only be provided if hospitals and health facilities understand the basic requirements of neonatal care and provide designated space, adequate staffing and proper equipment.     

fMRI evidence that the neural basis of response inhibition is task-dependent

Event-related fMRI was used to investigate the hypothesis that neural activity involved in response inhibition depends upon the nature of the response being inhibited. Two different Go/No-go tasks were compared-one with a high working memory load and one with low. The 'simple' Go/No-go task with low working memory load required subjects to push a button in response to green spaceships but not red spaceships. A 'counting' Go/No-go task (high working memory load) required subjects to respond to green spaceships as well as to those red spaceships preceded by an even number of green spaceships. In both tasks, stimuli were presented every 1.5 s with a 5:1 ratio of green-to-red spaceships. fMRI group data for each task were analyzed using random effects models to determine signal change patterns associated with Go events and No-go events (corrected P< or =0.05). For both tasks, Go responses were associated with signal change in the left primary sensorimotor cortex, supplementary motor area (SMA) proper, and anterior cerebellum (right>left). For the simple task, No-go events were associated with activation in the pre-SMA; the working memory-loaded 'counting' task elicited additional No-go activation in the right dorsolateral prefrontal cortex. The findings suggest that neural contributions to response inhibition may be task dependent; the pre-SMA appears necessary for inhibition of unwanted movements, while the dorsolateral prefrontal cortex is recruited for tasks involving increased working memory load.     

Combination HCV core antigen and antibody assay on a fully automated chemiluminescence analyzer

BACKGROUND: HCV exposure among blood donors is serologically determined by detection of antibodies to HCV (anti-HCV); however, the recent development of an assay for the detection of HCV core antigen identifies infection before anti-HCV development. Simultaneous detection of HCV core antigen and anti-HCV would shorten the window period before seroconversion over conventional HCV antibody screening assays. STUDY DESIGN AND METHODS: A prototype chemiluminescent immunoassay was developed for simultaneous detection of HCV core antigen and anti-HCV in human sera and plasma. The assay was performed on a single-channel instrument representing an automated serologic analyzer (PRISM, Abbott Laboratories) system. Sensitivity and specificity were evaluated by testing 23 HCV seroconversion panels and plasma or sera from volunteer blood donors. RESULTS: The prototype HCV core antigen and antibody combination assay detected 80 of 89 (89.9% ) HCV RNA-positive and antibody-negative specimens from 23 panels, thereby reducing the seroconversion window period by an average of 34.3 days compared to PRISM HCV antibody detection. All PRISM HCV antibody-positive specimens were detected by the combination assay for a relative sensitivity of 100 percent. The repeatedly reactive rate was 0.20 percent based on testing of 3017 screened anti-HCV-negative sera and plasma. CONCLUSIONS: The prototype combination assay was shown to detect HCV core antigen and anti-HCV simultaneously and significantly closed the time gap between the initial detection of HCV RNA and the first appearance of detectable antibodies to HCV.     

Low birthweight at a Papua New Guinea highlands hospital

A prospective case-control study involving 75 low birthweight (LBW) babies and 224 controls was carried out at the Mount Hagen General Hospital over a period of 7 months, from June to December 1997. Identified risk factors for LBW in this population included maternal age (age less than 22 years or over 35 years, p = 0.03), a birth interval of less than 2 years (p = 0.006), no antenatal booking (p = <0.005), low attendance at antenatal clinic (p = <0.005), fever during pregnancy (p = <0.005), PET (p = 0.05), APH (p = <0.015), and maternal smoking during pregnancy (p = 0.008). Other well-established risk factors for LBW, i.e. small stature, low body mass index (BMI), haemoglobin less than 8 g/dl, and low educational attainment, appeared to be more frequent in the mothers of the LBW babies than the controls but differences did not reach statistical significance. The results suggest the need for improved provision of, and efforts to increase the use of, antenatal and family planning services. The results also provide clear evidence of the deleterious effects of smoking during pregnancy in a developing country.     

Effect of synthetic matrix-metalloproteinase inhibitors on invasive capacity and proliferation of human malignant gliomas in vitro

Glioma invasion into the surrounding brain tissue is still a major obstacle for any therapeutical approach. As in other solid tumors, matrix-metalloproteases (MMPs) have been suggested as being involved. The aim of this study was to evaluate whether the use of MMP inhibitors to target the protease-mediated invasion process could be a feasible approach. Two human cell lines (U251 and GaMG) and surgical specimens of 6 patients with malignant gliomas were grown as monolayers and spheroid cultures respectively. MMP- and u-PA-mRNA expression was investigated by semi-quantitative RT-PCR. Invasion was studied in Matrigel-coated Boyden chamber transwell assays for monolayers and in confrontation cultures of tumor spheroids with fetal rat brain aggregates in the presence of the synthetic MMP inhibitors batimastat (BB-94) and marimastat (BB-2516). Cytotoxicity/cytostatic effects of high concentrations of both compounds were assessed by growth curves, MTT assays and flow cytometry in human glioma cell lines. Batimastat and marimastat revealed a cytostatic effect at high concentrations (above 1 microM) without cytotoxicity. Both MMP inhibitors effectively reduced glioma invasion in Boyden-chamber assays at low concentrations of 0.3 microM. In confrontation cultures, concentrations of 10 microM and above were necessary to reduce invasion. This effect was observable with inter-individual heterogeneity in the patient's tumor material. MMP inhibitors effectively reduce glioma invasion, although high concentrations were required in 3-dimensional culture systems. At these concentrations, both compounds revealed a cytostatic, but no cytotoxic effect. Thus, high local concentrations of MMP inhibitors could offer a new therapeutic strategy for the treatment of gliomas.     

A Review of Challenges in the Use of fMRI for Disease Classification / Characterization and A Projection Pursuit Application from A Multi-site fMRI Schizophrenia Study

Functional magnetic resonance imaging (fMRI) is a fairly new technique that has the potential to characterize and classify brain disorders such as schizophrenia. It has the possibility of playing a crucial role in designing objective prognostic/diagnostic tools, but also presents numerous challenges to analysis and interpretation. Classification provides results for individual subjects, rather than results related to group differences. This is a more complicated endeavor that must be approached more carefully and efficient methods should be developed to draw generalized and valid conclusions out of high dimensional data with a limited number of subjects, especially for heterogeneous disorders whose pathophysiology is unknown. Numerous research efforts have been reported in the field using fMRI activation of schizophrenia patients and healthy controls. However, the results are usually not generalizable to larger data sets and require careful definition of the techniques used both in designing algorithms and reporting prediction accuracies. In this review paper, we survey a number of previous reports and also identify possible biases (cross-validation, class size, e.g.) in class comparison/prediction problems. Some suggestions to improve the effectiveness of the presentation of the prediction accuracy results are provided. We also present our own results using a projection pursuit algorithm followed by an application of independent component analysis proposed in an earlier study. We classify schizophrenia versus healthy controls using fMRI data of 155 subjects from two sites obtained during three different tasks. The results are compared in order to investigate the effectiveness of each task and differences between patients with schizophrenia and healthy controls are investigated.