Microbiological quality of ready-to-eat foods: results from a long-term surveillance program (1995 through 2003).

The coordination of food sampling activities across Wales, a part of the United Kingdom with a population of approximately 3 million, led to the establishment in 1995 of a coordinated food-sampling program designed to monitor on a long-term basis the microbiological quality and safety of specific ready-to-eat products. This surveillance system has been ongoing for 9 years and has generated a database of microbiological and associated demographic results for 15,228 ready-to-eat food samples. The food types that had the poorest overall results were sliced meats, unsliced poultry, sandwiches made without salad, and cakes made without dairy cream. For all food types, the overall unsatisfactory rate was 17% for aerobic colony counts, 1.6% for Escherichia coli, and 0.5% for Listeria spp. Overall unsatisfactory or unacceptable rates for pathogens such as Clostridium perfringens, Listeria monocytogenes, Bacillus cereus, and Staphylococcus aureus were all below 0.5%. No Campylobacter-positive samples and only one Salmonella-positive sample were found. The analysis of the results show that the ready-to-eat food types sampled over the 9 years of the program were generally of good microbiological quality when compared with current United Kingdom guidelines. The information contained in the database provides a baseline measurement of the microbial quality of a variety of ready-to-eat foods and allows environmental health officers and food microbiologists to generate hypotheses for targeted surveys or research work.

Maternal serum screening for trisomy 18: assessing different statistical models to optimize detection rates.

We have evaluated three alternative models for trisomy 18 screening using the maternal serum markers alpha-fetoprotein (AFP) and intact human chorionic gonadotrophin (hCG). Using data from 46 affected pregnancies and 48 150 unaffected pregnancies, we calculated distribution parameters for AFP and hCG multiples of the median (MoMs) and the factor comprising AFP MoMxhCG MoM. The trisomy 18 risk at mid-trimester was then calculated using either bivariate analysis of AFP and hCG MoMs or univariate analysis of AFP MoMxhCG MoM. The observed detection rates and positive rates obtained using either published distribution parameters or those derived from the West Midlands population were compared for each model. Using fixed cut-offs for AFP and hCG of 0.66 and 0.40 MoMs resulted in a detection rate of 28.3% for a 0.5% false positive rate (FPR). Using published parameters, the univariate analysis model had a slightly higher detection rate of 32.6% for a 0.5% FPR (cut-off 1:248) compared to the bivariate model which was 28.3% (cut-off 1:239). Locally derived distribution parameters significantly improved the detection rate for the bivariate model for FPRs between 0.4-1.3% but worsened it below 0.4%. For the univariate model there was little difference in detection whether local or published parameters were used. Thus, we have confirmed that trisomy 18 screening using two markers can be a worthwhile addition to Down screening.

Second trimester levels of pregnancy associated plasma protein-A in cases of trisomy 18.

In a study of 70 cases of trisomy 18 and 450 matched controls in the second trimester we have measured the maternal serum levels of the analytes alpha feto protein (AFP), free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A). We have found the median multiple of the median (MoM) of maternal serum free beta-hCG to be significantly lower (0.327) than normal, as was the level of AFP (0.600). Levels of PAPP-A were reduced even further (0.108). Of the markers associated with trisomy 18 at this time PAPP-A was the most discriminatory, being lower than the 5 per cent centile of normal in 93 per cent of cases, compared with 57 per cent of cases for free beta-hCG and 32 per cent of cases for AFP. Combining free beta-hCG and PAPP-A or all three markers with maternal age would have the ability to detect 74 per cent of cases at a 0.5 per cent false positive rate (or 64 per cent at a 0.1 per cent false positive rate). Unlike in cases of trisomy 21, the low PAPP-A values observed in the first trimester are continued into the second trimester. Whether the good discriminatory power of PAPP-A can be realized in second trimester screening programmes will depend on developing two stage screening algorithms. This approach is unlikely to be better than the excellent detection rates achievable with free beta-hCG, PAPP-A and nuchal translucency in the first trimester.

Evaluation of different weight correction methods for antenatal serum screening using data from two multi-centre programmes.

Weight correction of serum markers is widely used when screening for Down's syndrome and open neural tube defects (NTD) because marker concentrations decrease with increasing maternal weight. Log-linear regression is frequently used for determining weight correction factors, but recently reciprocal-linear regression has been suggested to have advantages. We compared both methods of weight correction using data from two screening programmes carried out by this laboratory, one using alpha-fetoprotein (AFP) and total human chorionic gonadotrophin (HCG) (n = 129,143) and the other, AFP and free beta-HCG (n = 39,982). The reciprocal-linear method fitted the data more closely but did not significantly alter the detection rate or screen positive rate (SPR) for Down's syndrome or NTD with either dataset. Without correction, women heavier or lighter than average weight had significantly different SPRs for Down's syndrome and NTD compared with those weighing close to the median weight. Both correction methods smoothed out the variability in the SPR for Down's syndrome to a similar degree, but reciprocal-linear regression was much better at reducing the variability in SPR for NTD and its use is therefore worthwhile.

Spontaneous resolution of an in utero perirenal urinoma associated with posterior urethral valves.

Ultrasound imaging of a 26-week-gestation fetus demonstrated a large, nonemptying bladder. At 27 weeks, a distended, thick-walled bladder, left hydronephrosis, and a perirenal urinoma were present, without ascites. Observation was undertaken, as the amniotic fluid volume was normal. At 29 weeks, the left perirenal fluid collection persisted but, at 30 weeks, was absent. After delivery at 36 weeks, no ultrasound evidence for perirenal urinoma or ascites was present. Isotope renal scan showed preserved renal function bilaterally. This case illustrates that in utero urinomas associated with posterior urethral valves can resolve spontaneously, with preservation of renal function.

Specialty location decisions in the reformed NHS: a case study.

A soft systems approach, largely based on soft systems methodology, was used to steer a study (completed in 1996) of the National Health Service contracting process. It led to action research projects on a number of related issues. One such area that emerged very strongly concerns service rationalization and service planning, and in particular the location of 'small' specialties. A Trust-based study involving patient flow modelling demonstrates the form these problems can take within the internal market and highlights the challenge they make to the contracting process or the new primary care group based commissioning process if they are to be resolved in a rational manner.

Reducing the hindsight bias utilizing attorney closing arguments.

In the legal system, jurors are asked to render a decision after the event in question has already occurred and the final outcome, typically negative, is known. This "after-the-fact" structure of the legal system makes jurors susceptible to a human judgment phenomenon known as hindsight bias. This study focused on reducing hindsight bias in a courtroom context by incorporating a debiasing strategy within the defense's closing argument. Subjects viewed one of three videotaped versions of plaintiff and defense closing arguments in a commercial litigation case (i.e., foresight condition, hindsight condition, and hindsight debiasing condition). Results indicate that the hindsight debiasing strategy was effective in reducing subject-juror hindsight bias.

Making attributions to the physician following closing arguments of a simulated medical malpractice suit: jurors' sex, health locus of control, and locus of authority.

This study examined jurors' health locus of control, locus of authority, sex, and attribution assigned to the physician in a simulated trial by subject-jurors. Subjects viewed videotaped closing arguments of a fictionalized medical malpractice case and assigned fault to each party in the case. The primary finding was that women tended to assign greater responsibility (57.00%) to the physician than did men (37.92%).

Controlling blood glucose: insights from an engineering control systems perspective.

In order to discern areas of potential improvement in various aspects of glycaemic control for patients with insulin dependent (type 1) diabetes mellitus, blood glucose control is analysed in the light of general engineering feedback control systems theory. This approach is based on models of the system being controlled, using appropriate control strategies. The models presently used for glycaemic control are analysed from this perspective, revealing certain limitations that they impose on the control strategies that use them. Current type 1 diabetes regimens are evaluated for the ease with which they may be analysed mathematically, suggesting areas where improvements in control may be effected by simplifying calculation of appropriate insulin quantities. A new model of undergraded insulin action, derived from established insulin action profiles, along with a control strategy which flexibly extends the basal/bolus regimen using patient-specific parameters, is proposed. This may provide the information needed to enable prediction of expected glycaemia several hours into the future, thereby enabling earlier corrective action to be taken should it fail outside the target range, and in turn potentially reduce the degree and frequency of both hyperglycaemia and hypoglycaemia.

Minimal model of food absorption in the gut.

Of the physiological subsystems involved in glucose metabolism, all have now been modelled with continuous-time compartmental models except the gut. To address this omission, three progressively more complex models of the conversion of food by the gut into the rate of appearance of glucose in plasma were identified, using two different sample input foods which were tested on a type 1 diabetic patient. The minimal model that achieved a reasonable match with measured values had one compartment. Two model parameters specific to the food modelled were glycaemic value (grams of glucose per gram of food), and the fractional turnover rate, corresponding to a combination of the gastric emptying time constant and other rate limiting metabolic processes. Parameters specific to the individual were compartmental volumes, specifically for the glucose distribution space. It was only possible to achieve an adequate model prediction with a one compartmental model by explicitly incorporating transport delay into the model. By combining this model with models of insulin production and glucose disposal, the glycaemic response of an identified food may also be predicted for patients with type 2 diabetes mellitus. This predicted responses, along with the predicted response for bread or glucose, enables calculation of the Glycaemic Index for the food from its glycaemic value, time constant, and transport delay, along with the insulin production and glucose disposal model parameters for the individual patient. These three minimal model parameters therefore embody all the information of the Glycaemic Index, and more, allowing a continuous prediction of the effect of eating a given food over time. Together with a means of combining the parameters of individual foods into a combination set for a composite meal, this minimal model could enable diabetic patients to predict the time course of glycaemic action for a meal and to adjust treatment accordingly.

Nebulised amiloride in respiratory exacerbations of cystic fibrosis: a randomised controlled trial.

OBJECTIVE: To assess the benefit of nebulised amiloride added to the standard inpatient treatment of a respiratory exacerbation in cystic fibrosis. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SUBJECTS: 27 cystic fibrosis patients (mean age 12.8 years). SETTING: Two hospitals in Leeds, UK. RESULTS: Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) showed improvements over the course of treatment, although there was no difference in respiratory function between the two groups at any of three time periods during the study. The time to reach peak FVC was significantly reduced in the amiloride group (4.2 v 7.6 days; 95% CI 0.4 to 6.4 days), but not in the time to reach peak FEV1 (5.7 v 7.9 days; 95% CI -1.2 to 5.6 days). CONCLUSIONS: Amiloride did not result in a greater overall improvement in respiratory function. There was a suggestion that it may have an effect on the rate of improvement, and thus may possibly influence the duration of treatment. This hypothesis deserves further evaluation.

The prognostic significance of caffeine half-life in saliva in children with chronic liver disease.

To evaluate its clinical value, the half-life of caffeine (1,3,7-trimethylxanthine) in saliva (SCT) after 3 mg/kg-1 oral caffeine was measured in 53 children with chronic liver disease (mean age, 4.41 years) and 48 control children (mean age, 6.26 years) in five samples over 24 h and compared with parameters of liver function and outcome. Sensitivity was 60.3% and specificity 97% of SCT for diagnosis of chronic liver disease. The correlation of SCT with serum albumin (ALB) was -0.52 (p < 0.001), total bilirubin (SBR) was 0.585 (p < 0.001), prolonged prothrombin time (PT) was 0.387 (p = 0.004), and aspartate aminotransferase (AST) was 0.538 (p = 0.001). The correlation of SCT with a clinical score of liver dysfunction calculated from the presence of features of hepatic decompensation was 0.627 (p < 0.001) and with Malatack's paediatric prognostic score was 0.505 (p < 0.001). Serial SCT and liver function tests were performed on 53 patients on 127 occasions during a mean follow-up of 361 days (range, 4-709). Of this group, 18 were listed for liver transplantation. Predictive values of outcome by analysis of variance expressed as ratio of mean squares were SBR, 34.1 (p < 0.001); log10 SCT, 20.6 (p < 0.001); ALB, 5.2 (p < 0.05); PT, 1.2 (NS). SCT correlated with clinical and biochemical parameters of severity of liver disease, but SBR was a better predictor of listing for liver transplantation in this group of paediatric patients.

Fluctuating and/or progressive sensorineural hearing loss in children.

Sensorineural hearing loss (SNHL) which is sudden in onset, fluctuating, and/or progressive complicates medical management, hearing aid selection, and individualized educational planning for a hearing-impaired child. In spite of multidisciplinary evaluation and intervention, a gradual decrease in auditory acuity may continue unabated in a significant number of cases. Intercurrent middle ear disease and inconsistent audiologic technique can account for threshold variation in some cases. The study population consisted of 229 children (132 boys; 97 girls) aged 1 to 19.9 years at first audiogram which revealed at least a mild degree of sensorineural hearing loss in one or both ears (35 unilateral), and who demonstrated threshold variation of 10 dB or more in at least one ear at one or more of the standard audiometric test frequencies (250, 500, 1000, 2000, 4000, and 8000 Hz) and were without concurrent middle ear disease (mean length of follow-up, 4.9 years; mean number of audiograms, 10.3). Of 365 ears demonstrating threshold variation of 10 dB or more, 22 (6%) had purely progressive losses without intercurrent upward fluctuation, 208 (57%) had fluctuating thresholds with gradually progressive losses, and 135 (37%) had intermittent threshold fluctuation without permanent deterioration. The probability of contralateral threshold fluctuation if one ear fluctuated was 0.91, while the probability of contralateral progressive SNHL if one ear progressed was 0.67. Demographic data, presumptive etiology, degree of initial SNHL, audiometric configuration, and symmetry of threshold variation were considered as potential predictors of the likelihood of threshold fluctuation and/or progression.

Physiologic chest sounds and helicopter engine noise.

To develop an amplification system for physiologic chest sounds during air medical transport in jet helicopters, we compared frequency spectra of physiologic chest sounds and Allison C-28 equipped jet helicopter noise. We found that the frequency spectrum of physiologic chest sounds is contained entirely within that of jet rotocraft noise. Attempts to amplify physiologic chest sounds or to filter jet rotorcraft noise will invariably fail to improve perception of chest sounds. Future research must focus on assessment of actual movement of the chest and of each hemithorax, as well as an carbon dioxide production, as indicators of adequate ventilation and proper endotracheal tube position.

Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial.

We report a multicentre clinical field trial of a novel dual analyte enzyme immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and free beta-human choriogonadotropin (hCG) in the same microtitre well. The assay was shown to have good technical performance in the hands of all trial centres, with between assay coefficients of variation better than 10% for both analyte across the whole of the assay ranges. The method compared well with single analyte measuring procedures and produced acceptable performance as judged by external quality assurance criteria. Recovery of added analyte and analyte dilution curves also showed acceptable performance. In clinical evaluation of a large set of neural tube defect cases, good clinical discrimination from unaffected cases was observed using AFP. With over 150 Down's syndrome cases, the combination of AFP and free beta hCG confirmed the high detection rates achievable using this marker combination, with detection rates in excess of 70% in early gestation. We conclude that the combination of clinically superior markers coupled with technologically innovative assay design will lead to more efficient Down's screening programmes.

The assessment of subclinical ifosfamide-induced renal tubular toxicity using urinary excretion of retinol-binding protein.

The excretion of retinol-binding protein in early morning urine samples, expressed as a ratio to urinary creatinine (RBPCR), was used as a measure of proximal renal tubular toxicity in children during or after treatment with ifosfamide-containing chemotherapy. The results showed a progressive increase in renal tubular leak after exposure to ifosfamide that persisted after treatment. The toxic effect appeared to be greatest in younger children and at least partly dose-dependent, although partially reversible after each course of chemotherapy. However, few patients had related symptoms and none experienced major metabolic difficulty. RBPCR appears to offer a sensitive and noninvasive way of monitoring sequential change in renal tubular function after exposure to ifosfamide. Further studies are required to define more clearly the effect of cumulative dose, age, and drug scheduling and to identify whether a level of renal tubular dysfunction, measured by RBPCR or a similar noninvasive technique, can identify a threshold beyond which further exposure to ifosfamide is likely to be significantly and permanently damaging.