Non-accidental head injury: a consequence of deprivation?

BACKGROUND: Non-accidental head injury (NAHI) is a significant personal and public health problem, with considerable mortality and morbidity. The evidence base for risk factors specific for NAHI is limited due to difficulties with case definition and study design. The risk factors associated with NAHI in infants was evaluated in this study, and the extent to which indices of deprivation influence this health problem was addressed. METHODS: A 10-year prospective study was conducted in Scotland involving all paediatric hospitals and other general hospital departments admitting children. Subjects were children ≤2 years of age, with a diagnosis of "suspected NAHI". Socioeconomic characteristics of the index cases were compared to the general population, using the Scottish Index of Multiple Deprivation (SIMD) 2006. RESULTS: There were highly significant differences (p<0.001) between the SIMD rank scores of the NAHI cases and scores for the whole Scottish population. For the cohort, SIMD ranks ranged from 34 to 6253 (median 1210; mean 1577) compared to the population range of 1-6505 (median and mean=3253). Similar differences were found for each of the component domains of income, employment, health, education, crime and housing (p<0.001). In contrast, the scores for "geographic access" (to essential service) were higher than for the whole population (p<0.001), indicating that the deprivation was not due to lack of local services. CONCLUSION: In Scotland, children who present with suspected NAHI originate predominantly from the most deprived areas of the community. Public health and intervention strategies should be focused in these areas.

A comparison of diabetes clinics with different emphasis on routine care, complications assessment and shared care.

OBJECTIVE: To compare clinical outcomes of patients attending diabetes clinics with different models of care. METHODS: Diabetes centres which participated in the Australian National Diabetes Information Audit and Benchmarking (ANDIAB) data collection were invited to nominate whether they provided (i) routine diabetes care only (model A), (ii) routine care and structured annual complications screening (model B) or (iii) annual review and complications screening in a system of shared care with general practitioners (model C). De-identified case data were extracted from ANDIAB and outcomes according to the three clinic models were compared. RESULTS: Data on 3052 patients from 18 diabetes centres were analysed. Centres which practised annual complications screening (models B and C) had higher rates of nephropathy and lipid screening and a higher rate of attainment of recommended blood pressure and glycated haemoglobin (HbA(1c)) targets. The implementation of appropriate treatment for patients who had not attained the targets was similar for all three clinic models. CONCLUSIONS: In our study, clinic models which incorporate a system of structured complications screening were more likely to have met screening guidelines. Patients in a shared-care model were at least as likely to have met management targets as those attending diabetes clinics for their routine care. Therefore, a system of shared care by general practitioners supported by annual review at a diabetes clinic may be an acceptable model which improves the capacity to manage large numbers of people with diabetes, without loss of quality of care.

In-house assessment of a modified in vitro cytotoxicity assay for higher throughput estimation of acute toxicity.

The main objective of this study was to assess an in-house 3T3 NRU cytotoxicity assay for compatibility with a prediction model for acute rodent oral toxicity endorsed by an NIEHS-ICCVAM workshop. The aim is to use the NRU assay as one test component of HTS strategies for both acute oral toxicity and acute skin irritation, enabling the rejection of the most toxic materials and prioritisation of other materials for further testing. Groups of model cytotoxins and irritants were tested using the NRU assay and their EC50 values obtained from dose-response curves. These values were compared with those estimated from a limited (three)-dose protocol, deemed more suitable for HTS. A good correlation was observed between the EC50 values from both dose-response curves (R2=0.94). The relationships between EC50 values and acute rodent oral toxicity were compared by application of the prediction model to the model cytotoxins. The results from both full and limited dose-responses fitted within the acceptance limits of the prediction model, with regression lines similar to that of the model. Results indicated that the performance of the currently used 3T3 NRU cytotoxicity assay was similar to that of the assays used to generate the data employed in developing the prediction model. This prediction model can be applied with both the standard and HT assays to estimate acute rodent oral toxicity.

An assessment of the phototoxic hazard of a personal product ingredient using in vitro assays.

Where substances are intended for use in personal products applied to the skin an assessment of potential phototoxic hazard is required. This report describes a tiered testing strategy involving in vitro assays used for the phototoxic hazard assessment of a personal product ingredient (Ingredient X). The initial assay was measurement of a UV/visible absorption spectrum to identify absorption at relevant wavelengths. This was followed by in vitro assays for phototoxicity (3T3 cell neutral red uptake phototoxicity test) and photoallergy (photobinding to human serum albumin). These in vitro screens gave equivocal results for Ingredient X which appeared to suggest a weak phototoxic reaction. To further evaluate the phototoxic hazard of Ingredient X to human skin, a phototoxicity assay using a 3-D human skin model was conducted. Ingredient X did not cause phototoxicity in this assay. Overall conclusions from these studies were that although Ingredient X showed slight intrinsic potential for photoactivation, it was unlikely to present a hazard to human skin. This report illustrates the value in a step-wise strategy of the use of human skin models to help interpret the results of other in vitro phototoxicity assays.

Discussing anomalous situations using decision trees: a head injury case study.

OBJECTIVES: Predicting the outcome of seriously ill patients is a challenging problem for clinicians. METHODS: One alternative to clinical trials is to analyse existing patient data in an attempt to predict the several outcomes, and to suggest therapies. In this paper we use decision tree techniques to predict the outcome of head injury patients. The work is based on patient data from the Edinburgh Royal Infirmary which contains both background (demographic) data and temporal (physiological) data. RESULTS: The focus of this paper is the discussion of the anomalous cases in the decision trees with the domain experts (the clinicians). CONCLUSIONS: These analyses led to the detection of several situations where both the data analysis and patient data collection should be enhanced, which in turn should lead to improved patient care.

Glasgow head injury outcome prediction program: an independent assessment.

Using an independent data set, the utility of the Glasgow Head Injury Outcome Prediction Program was investigated in terms of possible frequency of use and reliability of outcome prediction in patients with severe head injury, or haematoma requiring evacuation, or coma lasting 6 hours or more, in whom outcome had been reliably assessed at 6 to 24 months after injury. Predictions were calculated on admission, before evacuation of a haematoma, or 24 hours, 3 days, and 7 days after onset of coma lasting 6 hours or more. Three hundred and twenty four patients provided 426 predictions which were possible in 76%, 97%, 19%, 34%, and 53% of patients on admission, before operation, 24 hours, 3 days, and 7 days respectively. Major reasons for non-feasible predictions were that patients were paralysed/ventilated as part of resuscitation or management. Overall, 75.8% of predictions were correct, 14.6% were pessimistic (outcome better than predicted), and 9.6% optimistic (outcome worse than predicted). Of 197 patients (267 predictions) whose eventual outcome was good or moderate, 84.3% of predictions were correct. For death or vegetative survival (96 patients with 110 predictions), 83.6% of predictions were correct but for severe disability (31 patients with 49 predictions), only 12.2% were correctly predicted. The utility of the Glasgow Head Injury Outcome Prediction Program compares favourably with other outcome prediction algorithms for patients with head injury.

Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays.

Phytosterols are natural constituents of the human diet, and as part of an extensive programme of safety evaluation studies investigating their use as a novel food ingredient, the possible oestrogenic effects of phytosterols have been investigated using a combination of in vitro and in vivo assays. Competitive binding with the immature rat uterine oestrogen receptor (ER) has been used to measure the ability of phytosterols to bind to ERs while the transcriptional activation of oestrogen-responsive genes has been examined in an oestrogen-inducible yeast screen. Phytosterols did not display any activity in these in vitro assays. Uterotrophic assays have been conducted to investigate the potential for phytosterols to elicit an oestrogenic response when administered orally to immature female rats (n = 10) at doses of 0, 5, 50 or 500 mg/kg/day for 3 consecutive days. Phytosterols (a well characterized mixture of beta-sitosterol, campesterol and stigmasterol) and phytosterol esters (the previous phytosterol mixture esterified with fatty acids from sunflower oil) did not exhibit oestrogenic activity in the immature female rat using uterine wet weight as the endpoint. Beta-oestradiol (0.4 mg/kg/day) consistently produced a significant increase in uterus weights. Coumestrol (a known phytoestrogen) was also tested as a weak positive control and produced a dose response at doses of 20, 40 and 80 mg/kg/day in the uterotrophic assay. In conclusion, we have shown that phytosterols do not bind to the ER and do not stimulate transcriptional activity of the human ER in a recombinant yeast strain. In addition, there was no indication of oestrogenicity from the uterotrophic assay when the material was administered by oral gavage to immature female rats.

A comparison of Doppler flowmetry with conventional assessment of acute changes in hepatic blood flow.

The validity and clinical relevance of Doppler flowmetry in measuring changes in regional blood flow are uncertain. In the present study we compared changes induced ketanserin in regional splanchnic blood flow as measured by Doppler flowmetry with changes in conventionally measured systemic and in hepatic haemodynamic indices estimated pharmacokinetically using indocyanine green. Fourteen patients with alcoholic cirrhosis and portal hypertension were evaluated. On multivariate analyses, significant associations were noted for only three indices: changes in estimated hepatic blood flow were predicted jointly by changes in flow in the main and right portal veins and hepatic artery (R2 = 0.80); changes in intrahepatic shunting (indocyanine green extraction) were predicted by changes in flow in the main and right portal veins (R2 = 0.55); and changes in sinusoidal perfusion (indocyanine green clearance) were significantly predicted by changes in main portal vein flow alone (R2 = 0.76). These data support the validity of Doppler flowmetry in quantifying change in regional blood flow, but highlight the limitations in its clinical application and interpretation. The association of changes in main portal vein flow with changes in sinusoidal perfusion has clinical potential but requires confirmation using other modulating drugs.

Tapering or discontinuing cyclosporine for financial reasons--a single-center experience.

In patients with primary cadaveric renal transplants and stable allograft function, we assessed the impact of tapering or discontinuing cyclosporine A (CsA) for financial reasons. Forty-two patients whose CsA was discontinued ("no-dose") and 29 patients whose CsA was tapered to 100 to 150 mg/d ("low-dose"; mean, 1.7 mg/kg/d) were examined. Results were compared with 70 age- and race-matched control patients maintained on at least 200 mg/d of CsA (mean, 3.9 mg/kg/d). Follow-up time for all patients averaged 55 +/- 18 months. Late acute rejection episodes occurred more frequently in no-dose than in low-dose (P = 0.017) or control (P = 0.001) patients. In the no-dose group, blacks experienced a greater number of late acute rejections than whites. These late acute rejections often coincided with the discontinuation of CsA and contributed to an increased rate of allograft loss in blacks in the no-dose group compared with black and white controls (P = 0.011). In contrast, no increase in late acute rejection episodes occurred in blacks tapered to low doses of CsA. Black patients who remained on low doses of CsA also exhibited a trend toward allograft survival that was intermediate between that of control and no-dose patients. In those patients who retained functional allografts, mean serum creatinine concentration did not differ between the study groups at the beginning and end of the follow-up period. These findings support continuance of CsA in black primary cadaveric renal transplant patients, even if dosages must be reduced to 100 to 150 mg/d.(ABSTRACT TRUNCATED AT 250 WORDS)