Implementing a guideline for acute tonsillitis using an ambulatory medical unit.

OBJECTIVE: Acute tonsillitis represents a significant proportion of admissions to ENT departments nationally. Given current hospital pressures, it is vital to look for safe alternatives to admission. This study explores the safe management of patients in an ambulatory medical unit, without the need for admission. METHODS: A retrospective review of 48 patients' notes was carried out. Following the development and implementation of a guideline for acute tonsillitis, a prospective re-audit of 41 patients was carried out, measuring length of stay, overnight admissions and re-admissions. RESULTS: The rate of overnight admission following implementation of the guideline fell from 0.75 to 0.29, and average length of stay dropped from 19.2 to 9.5 hours. There were two re-admissions in each cycle of the audit, which represents a non-significant increase. CONCLUSION: The tonsillitis guideline has significantly reduced admissions and length of stay. Re-admissions remain low, demonstrating that this is a safe and cost-effective intervention.

Meat intake in Britain in relation to other dietary components and to demographic and risk factor variables: analyses based on the National Diet and Nutrition Survey of 2000/2001.

BACKGROUND: Red and processed meat intakes have been positively associated with the risk of several major chronic diseases. Understanding population intakes is important when formulating dietary recommendations. The present study investigated the dispersion of intakes of red and processed meat and associations with dietary, socio-demographic and risk factors. METHODS: The present study comprised a secondary analysis of the British National Diet and Nutrition Survey 2000/1, including 7-day dietary records, from 766 male and 958 female respondents aged 19-64 years. Composite dishes were disaggregated into primary ingredients. Self-reported vegetarians (V) were grouped into one stratum and other respondents were stratified into five groups (F1-F5) according to energy-adjusted red plus processed meat (RPM) intake, to give six strata. 7-day RPM intakes were adjusted to estimate 'usual' habitual intakes, using ratios of between-person to total variance in daily intakes. RESULTS: Mean recorded intakes of red, processed, white and total meat were 48, 41, 40 and 129 g day(-1) , respectively, in males and 30, 22, 30 and 82 g day(-1) in females. Estimated habitual intakes of RPM standardised to sex-specific energy intakes across the six strata were: 12 (V), 56, 76, 90, 105 and 137 g day(-1) in males and 5 (V), 34, 46, 55, 65 and 88 g day(-1) in females. Lower RPM consumers tended to be of higher social class and educational level and to have more favourable levels of some risk factors. CONCLUSIONS: Mean intakes of red, processed and white meat were of similar magnitude. Habitual intakes of RPM showed wide dispersion with one-quarter of males < 55 g day(-1) and one-quarter of females < 27 g day(-1) . Lowering overall RPM consumption could be achieved by seeking greater reductions among current high consumers.

Estimating the global and regional burden of suboptimal nutrition on chronic disease: methods and inputs to the analysis.

BACKGROUND/OBJECTIVES: Global burdens of cardiovascular disease (CVD), diabetes and cancer are on the rise. Little quantitative data are available on the global impact of diet on these conditions. The objective of this study was to develop systematic and comparable methods to quantitatively assess the impact of suboptimal dietary habits on CVD, diabetes and cancer burdens globally and in 21 world regions. SUBJECTS/METHODS: Using a comparative risk assessment framework, we developed methods to establish for selected dietary risk factors the effect sizes of probable or convincing causal diet-disease relationships, the alternative minimum-risk exposure distributions and the exposure distributions. These inputs, together with disease-specific mortality rates, allow computation of the numbers of events attributable to each dietary factor. RESULTS: Using World Health Organization and similar evidence criteria for convincing/probable causal effects, we identified 14 potential diet-disease relationships. Effect sizes and ranges of uncertainty will be derived from systematic reviews and meta-analyses of trials or high-quality observational studies. Alternative minimum-risk distributions were identified based on amounts corresponding to the lowest disease rates in populations. Optimal and alternative definitions for each exposure were established based on the data used to quantify harmful or protective effects. We developed methods for identifying and obtaining data from nationally representative surveys. A ranking scale was developed to assess survey quality and validity of dietary assessment methods. Multi-level hierarchical models will be developed to impute missing data. CONCLUSIONS: These new methods will allow, for the first time, assessment of the global impact of specific dietary factors on chronic disease mortality. Such global assessment is not only possible but is also imperative for priority setting and policy making.

Burden of disease due to cancer in England and Wales.

BACKGROUND: This study aims to estimate the burden of cancer in England and Wales using disability-adjusted life years (DALYs) and to determine if the ranking of relative importance changes with metric used. METHODS: DALYs are the sum of years of life lost due to mortality and years lost due to disability. Annual DALYs due to cancer were calculated using cancer registration, mortality, disability weights and World Health Organization methodology. RESULTS: There were 8 605 362 DALYs due to cancer (3242 DALYs/100 000 population/year). Of the total, 47% corresponded to lung, prostate and colorectal cancers in males and 56% to breast, lung, colorectal and ovarian cancers in females. Mortality (86% of DALYs) contributed predominantly to DALYs. Individuals of 65-75 years contributed to 28% of DALYs. Among females, lung cancer ranked highest by death rates, whereas the highest DALYs were from breast cancer. CONCLUSIONS: Highest DALYs were due to lung, breast, prostate and colorectal cancers in England and Wales. The addition of the disability component changes the relative position of some of the top cancers. Although metrics based on deaths alone capture most effects of cancer on population health levels, important additional perspectives, relevant to the planning of services, can be gained from burden of disease analyses.

Parametrization of linear dielectric response.

The quantum linear response of a dielectric to an external electric field yields expressions for the dielectric susceptibility and the associated impulse response function. These are measured properties that, during analysis, are often "curve-fitted" to diverse forms of parametric functional forms that shall herein be referred to as fit-functions. The main purpose of this paper is to show, from a very general linear response formalism that encompasses virtually all microscopic models of dielectric response, that there are constraints on the forms that the susceptibilities must obey and to examine common parametrizations of the dielectric function in light of these constraints. Naturally these constraints should, whenever possible, be in-built into the fit-functions employed. The linear response approach due to Madden and Kivelson [Adv. Chem. Phys. 56, 467 (1984)], where the cause is considered to be a uniform external field, E(ext)(t), is utilized as it affords a much more straightforward interaction term, viz., -M·E(ext)(t), (M being the system's total electric dipole moment operator) than would be the case if the mean internal field (or "Maxwell field") were taken as the cause. It is shown that this implies definite relations between the quasipermittivity, ζ(ω), of the Madden-Kivelson approach and the normal permittivity, χ(ω)≡ε(ω)-ε(0). These relations indicate a condition for the divergence of the normal susceptibility, which, arguably, marks the onset of a ferroelectric transition in "sufficiently polar" dielectrics. Finally, some common parametric "fit-function" forms are investigated as to whether they comply with the constraints that the formalism imposes, and examples are given of their associated Cole-Cole plots in typical cases involving one or more relaxation times.

Adherence and chemoprevention in major cardiovascular disease: a simulation study of the benefits of additional use of statins.

BACKGROUND: In everyday practice, adherence to preventive medication for cardiovascular disease (CVD) is lower than in clinical trials and appears to decline to approximately 50% by about 5 years. The UK body for the evaluation of health technologies, NICE, currently recommends that persons with a >20% 10-year risk of incident cardiovascular disease receive statins. METHODS: Publications on adherence to statin medication in clinical trials and in normal practice were systematically reviewed. Data on CVD-free members of a large southern hemisphere cohort study were used to simulate the expected benefits of contrasting strategies to increase the use of statins. Risks of incident CVD and death from CVD were estimated. RESULTS: A strategy to enhance statin adherence among cohort members meeting NICE statin-prescribing guidelines resulted in about twice as large a reduction in the aggregate risk of CVD death as did a strategy to lower treatment thresholds. CONCLUSIONS: The benefits from increased spending on statin medication will be much greater if they result from enhanced adherence rather than from lowering the medication threshold.

Rounded stretched exponential for time relaxation functions.

A rounded stretched exponential function is introduced, C(t)=exp{(tau(0)/tau(E))(beta)[1-(1+(t/tau(0))(2))(beta/2)]}, where t is time, and tau(0) and tau(E) are two relaxation times. This expression can be used to represent the relaxation function of many real dynamical processes, as at long times, t>>tau(0), the function converges to a stretched exponential with normalizing relaxation time, tau(E), yet its expansion is even or symmetric in time, which is a statistical mechanical requirement. This expression fits well the shear stress relaxation function for model soft soft-sphere fluids near coexistence, with tau(E)<

Descriptive epidemiology of blood pressure in a rural adult population in Northern Ghana.

INTRODUCTION: There are limited data on blood pressure (BP) levels in rural populations in sub-Saharan Africa. This is a cause for concern considering high BP contributes to a substantial public health burden in this population. METHODS: Blood pressure levels were measured in a representative rural sample from Kassena-Nankana District of Northern Ghana, West Africa, and associations with anthropometric indices, age, sex, and time of BP measurement were assessed. This cross-sectional survey was made on a random sample drawn from a population register and included 207 males and 367 females aged between 18 and 65 years. Data collection consisted of anthropometric and blood pressure measurements after questionnaire interviews. Household salt consumption was also measured in 20 randomly selected households. RESULTS: Overall prevalence of casual high BP was 19.3% (111/574). Age-adjusted mean (standard deviation) systolic BPs (SBPs) and diastolic BPs (DBPs) were 124.25 (18.67) and 69.92 (12.09) mmHg in males and 122.07 (22.01) and 72.11 (12.35) mmHg in females. Mean body mass index (BMI) was 21.78 (3.09) kg/m2; 21.13 (2.27) for males and 22.15 (3.41) kg/m2 for females (p > 0.05). Blood pressures increased with age, 4 and 3 mmHg per decade for SBP and DBP, respectively (p < 0.000). Regression analyses showed that SBP was significantly associated with age, BMI, waist circumference and time of BP measurement (p < 0.000). In multiple regression analyses, age and BMI were independently associated with SBP and DBP in women (p < 0.001). Time of BP measurement was independently associated with SBP but only in men (p < 0.001). There was no increase in BMI with age. Repeat measurements in 89 subjects yielded a regression dilution factor of 0.57 for SBP. Salt consumption per individual was estimated as equivalent to 12.5 g of pure salt/day. CONCLUSION: Average BPs are not notably high in this predominantly lean rural West African population. Blood pressures do, however, increase as expected with age and BMI. Population-wide approaches need to be developed, appropriate to the level of medical provision, in order to address vascular disease risks resulting from higher than optimal BPs. These should include programs to reduce salt consumption.

Monte Carlo simulations of fluids whose particles interact with a logarithmic potential.

Monte Carlo simulations of a model fluid in which the particles interact via a continuous potential that has a logarithmic divergence at a pair separation of sigma, which we introduced in J. G. Powles et al., Proc. R. Soc. London, Ser. A 455, 3725 (1999), have been carried out. The potential has the form, phi(r)= -epsilon ln(fr), where epsilon sets the energy scale and fr=1-(sigma/r)m. The value of m chosen was 12 but the qualitative trends depend only weakly on the value of m, providing it is greater than 3. The potential is entirely repulsive and has a logarithmic divergence as approximately -ln(r/sigma-1) in the r-->sigma limit. Predictions of the previous paper that the internal energy can be computed at all temperatures using the standard statistical mechanics formula for continuous potentials are verified here. The pressure can be calculated using the usual virial expression for continuous potentials, although there are practical limitations in resolving the increasingly important contribution from the r-->sigma limit at reduced temperatures greater than approximately 5. The mean square force F2 and infinite frequency shear Ginfinity and bulk Kinfinity moduli are only finite for T*=kBT/epsilon<1. The logarithmic fluid's physical properties become increasingly more like that of the hard sphere fluid with increasing temperature, showing a sharp transition in the behavior of the mean square force and infinite frequency elastic constants at T*=1. The logarithmic fluid is shown to exhibit a solid-fluid phase transition.

Screening patients with sensorineural hearing loss for vestibular schwannoma using a Bayesian classifier.

OBJECTIVES: Selecting patients with asymmetrical sensorineural hearing loss for further investigation continues to pose clinical and medicolegal challenges, given the disparity between the number of symptomatic patients, and the low incidence of vestibular schwannoma as the underlying cause. We developed and validated a diagnostic model using a generalisation of neural networks, for detecting vestibular schwannomas from clinical and audiological data, and compared its performance with six previously published clinical and audiological decision-support screening protocols. DESIGN: Probabilistic complex data classification using a neural network generalization. SETTINGS: Tertiary referral lateral skull base and a computational neuroscience unit. PARTICIPANTS: Clinical and audiometric details of 129 patients with, and as many age and sex-matched patients without vestibular schwannomas, as determined with magnetic resonance imaging. MAIN OUTCOME MEASURES: The ability to diagnose a patient as having or not having vestibular schwannoma. RESULTS: A Gaussian Process Ordinal Regression Classifier was trained and cross-validated to classify cases as 'with' or 'without' vestibular schwannoma, and its diagnostic performance was assessed using receiver operator characteristic plots. It proved possible to pre-select sensitivity and specificity, with an area under the curve of 0.8025. At 95% sensitivity, the trained system had a specificity of 56%, 30% better than audiological protocols with closest sensitivities. The sensitivities of previously-published audiological protocols ranged between 82-97%, and their specificities ranged between 15-61%. DISCUSSION: The Gaussian Process ORdinal Regression Classifier increased the flexibility and specificity of the screening process for vestibular schwannoma when applied to a sample of matched patients with and without this condition. If applied prospectively, it could reduce the number of 'normal' magnetic resonance (MR) scans by as much as 30% without reducing detection sensitivity. Performance can be further improed through incorporating additional data domains. Current findings need to be reproduced using a larger dataset.

Self-diffusion coefficient of the hard-sphere fluid: system size dependence and empirical correlations.

Molecular dynamics simulations have been used to calculate the self-diffusion coefficient, D, of the hard sphere fluid over a wide density range and for different numbers of particles, N, between 32 and 10 976. These data are fitted to the relationship D = D(infinity) - AN(-alpha) where the parameters D(infinity), A, and alpha are all density-dependent (the temperature dependence of D can be trivially scaled out in all cases). The value alpha = 1/3 has been predicted on the basis of hydrodynamic arguments. In the studied system size range, the best value of alpha is approximately 1/3 at intermediate packing fractions of approximately 0.35, but increases in the low- and high-density extremes. At high density, the scaling follows more closely that of the thermodynamic properties, that is, with an exponent of order unity. At low packing fractions (less than approximately 0.1), the exponent increases again, appearing to approach a limiting value of unity in the zero-density limit. The origin of this strong N dependence at low density probably lies in the divergence in the mean path between collisions, as compared with the dimensions of the simulation cell. A new simple analytical fit formula based on fitting to previous simulation data is proposed for the density dependence of the shear viscosity. The Stokes-Einstein relationship and the dependence of D on the excess entropy were also explored. The product Deta(s)p with p = 0.975 was found to be approximately constant, with a value of 0.15 in the packing fraction range between 0.2 and 0.5.

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia.

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5-10 years, 40-98% [corrected] of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals.

Incidence trends of prostate cancer in East Anglia, before and during the era of PSA diagnostic testing.

We investigated prostate cancer incidence in East Anglia from 1971 to 2000. Using age-period-cohort modelling, the number of cases expected in 1991-2000, based on pre-PSA trends, 1971-1990, was compared with that observed. Based on pre-1991 trends, 9203 new cases were expected in 1991-2000, but 9788 cases were observed, an excess of 6%.

Head and neck cancer in patients with human immunodeficiency virus-1 infection: incidence, outcome and association with Epstein-Barr virus.

Head and neck cancers have been described in patients with human immunodeficiency virus-1 (HIV-1) infection. However the incidence, aetiology and clinical features of the disease remain unclear. Patients with head and neck cancer and HIV were identified from a large HIV centre. The incidence and clinical features were recorded, and the tumours were stained for Epstein-Barr virus (EBV). Head and neck cancer occurred more frequently than in an age-matched control group (1.66 vs 0.55/10,000 patient years respectively p < 0.05). Highly active anti-retroviral therapy has not significantly altered the incidence of the disease. All of the tumours tested were positive for EBV. Patients were moderately immunosuppressed at diagnosis and had aggressive tumours. All but one of the patients died of cancer with a median survival of 28 months. Head and neck cancer occurs more frequently in HIV. It is an aggressive disease and EBV may play a role in its pathogenesis.

A comparison of the alcohol-attributable mortality in four European countries.

BACKGROUND: Deaths due to alcohol consumption are an important component of all-cause mortality, particularly premature mortality. However, there are considerable regional variations, the reasons for which are unclear. METHODS: Estimates were made as reliably as possibly using vital statistics and best estimates of risk of the alcohol-attributable mortality, by age, sex and cause for four European countries (England and Wales, Germany, Denmark and Italy). Twenty-seven alcohol-related conditions were considered including the possible cardio-protective effects of alcohol. RESULTS: It was estimated that there are approximately 2% fewer deaths annually in England and Wales than would be expected in a non-drinking population and 0.3% fewer deaths among East German females. In West Germany, Denmark, Italy and among East German males there are more deaths caused by alcohol than are prevented (between 0.7 and 2.6% of all deaths). The highest age-specific proportion of alcohol-attributable deaths is found in East Germany where around 30% of deaths among males aged 25-44 years are due to drinking. Among young men in all four countries the largest contributor to alcohol-related deaths is road traffic accidents involving alcohol. CONCLUSIONS: Possible explanations for the variation in alcohol-attributable deaths between countries include different underlying heart disease rates, different patterns of alcohol consumption and beverage preferences, and different use of mortality classification. Differences in the reported alcohol consumption levels explain little of the variation in alcohol-attributable deaths. Estimating alcohol-attributable mortality by age and sex across countries may be a useful indicator for developing alcohol strategies and exploring ways of preventing premature mortality.

Synthesis and pharmacological activity of metabolites of the 5-HT(4) receptor antagonist SB-207266.

Three metabolites of N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2_a]indole-10-carboxamide (SB-207266) (1) were synthesised and their pharmacological activity determined.