Generalized method for adaptive randomization in clinical trials.

A flexible, generalized method of treatment allocation is proposed. The method uses a set of controlling parameters that enables the generic algorithm to produce a family of possible outcomes ranging from simple randomization to deterministic allocation. The method controls balance at stratum level, stratification level and overall without detriment to the predictability of the method. The paper lists the desirable characteristics of allocation methods and shows that the proposed method fulfils the majority and is easy to use in the clinical context, once the coding has been established. An explanation of the method for 2, 3 and 4 treatment group allocations is given. Simulations demonstrate the flexibility of the method.

Treatment fidelity as a predictor of behaviour change in parents attending group-based parent training.

BACKGROUND: Change in parenting skills, particularly increased positive parenting, has been identified as the key component of successful evidence-based parent training (PT), playing a causal role in subsequent child behaviour change for both prevention and treatment of Conduct Disorder. The amount of change in parenting skills observed after PT varies and may be accounted for by both the content of the programme and by the level of PT implementer process skills. Such variation in implementer skills is an important component in the assessment of treatment fidelity, itself an essential factor in successful intervention outcome. AIMS: To establish whether the Leader Observation Tool, a reliable and valid process skills fidelity measure, can predict change in parenting skills after attendance on the Incredible Years PT programme. RESULTS: Positive leader skills categories of the Leader Observation Tool significantly predicted change in both parent-reported and independently observed parenting skills behaviour, which in turn, predicted change in child behaviour outcome. CONCLUSIONS: Delivering an intervention with a high level of treatment fidelity not only preserves the behaviour change mechanisms of the intervention, but can also predict parental behaviour change, which itself predicts child behaviour change as a result of treatment.

Evaluation of the population dose to the UK population from the National Health Service Breast Screening Programme.

In the United Kingdom National Health Service Breast Screening Programme (NHSBSP), women aged between 50 and 70 y are invited for mammography every 3 y. Screening histories for each woman, over four screening rounds, were analysed. Data from five screening programmes were used to select 57,425 women into the study. Cases were selected on the basis of being between the ages of 50 and 53 at the start of the NHSBSP (i.e. between 1989 and 1992). Assessment of the outcome for each screening round for each woman involved assigning a simple outcome code. Each of the possible pathways through the four screening rounds was analysed. This comprises of 500 possible pathways. This data enabled the following information to be determined: (i) The number of times a woman attended the screening programme. (ii) The number of women referred for assessment at each screening round. This information may be used to deduce the population dose to this group of women averaged over four screening rounds. Patient doses have been monitored since the programme's inception and are typically 4.5 mGy for two-view screening. It is possible to determine the mean glandular dose received by this cohort of women over four screening rounds by multiplying the number of examinations by the mean glandular dose for a typical woman. Allowance has to be made for the number of projections taken at each screening round. Once a woman has been screened, she may be invited back for further assessment if an abnormality is found on her mammogram. A stereotactic attachment is used to determine where to place the biopsy device. Although the dose received during a normal screening mammogram is well known, the dose for a stereotactic procedure and other assessment procedures is less well known, partly because only a small part of the breast is directly irradiated during stereotaxis. However, the woman may have multiple exposures during this stage. A prospective survey of doses was completed to deduce the mean glandular dose at the first assessment stage and during stereotaxis. Numbers of films, including magnification films taken at first-stage assessment were established in the North East of England and Scotland by means of a postal survey. Average total mean glandular dose was deduced using previous survey data for the screening programme and a multiplying factor to allow for magnification film dose. On average 1.6 full field and 0.15 collimated contact films are taken for each woman (with 2.25 and 0.75 mGy film(-1)), 1.0 full field and 0.9 collimated magnification views. The mean magnification film dose to the assessed breast was 5.0 and 1.7 mGy for a collimated magnification film. A survey of 134 women at screening centres in the North East of England was performed to deduce the mean glandular dose from digital stereotaxis which is almost universally used in breast screening. A typical woman received a dose to the assessed breast of 4.5 mGy with a range of 1.3-17 mGy. This data may be used to deduce the total mean glandular dose over four screening rounds including the assessment stages. The estimated mean glandular dose to a typical woman invited to the screening programme is approximately 16 mGy, when allowance for attendance rate and assessment rate over each screening round is made. The mean glandular dose to the population is approximately 4700 Sv y(-1).

Factors influencing the prevalence of trypanosome infection of Glossina pallidipes on the Ruvu flood plain of Eastern Tanzania.

We report the pattern of infection of Glossina pallidipes with Trypanosoma vivax and T. congolense at a site in the Coast region of eastern Tanzania, studied between November 1993 and December 1994. Of the 2315 flies dissected 114 (4.9%) were T. congolense positive, 77 (3.3%) were T. vivax positive and 2 (0.1%) were T. brucei positive. Fly age was determined by the pteridine fluorescence method. Prevalence of infection was most strongly affected by month and the linear effect of age with the interaction of month and age having an effect for T. congolense-type infections. Sex and sex by month also have some predictive capacity when data for T. congolense and T. vivax-type infections are combined. In contrast to other similar studies our results suggest that the infection rate is non-linearly related to age of the tsetse fly, with older flies having progressively more chance of infection. The potential biological factors underpinning these interactions are discussed.

The role of temperature and nutritional status in flight initiation by Triatoma infestans.

Flight initiation in Triatoma infestans is associated with low nutritional status and increases with rising temperature; it appears to be largely independent of bug age and sex. A predictive model for the probability of flight initiation was constructed based on weight:length ratios of the bugs and maximum ambient temperature, both of which can be ascertained in the field. The model accurately predicted the proportion of bugs initiating flight in > 85% of the groups used in our study. The predictive equation was found to give significant fits with two independent data sets. From our results it might be expected that flight would be rare during colder (< 20 degrees C) months but that 5-10% of the normal population of an infested house would fly on any given night during the hotter months when temperatures approach 30 degrees C. If bug nutritional status falls significantly, this proportion could be expected to rise to 30%.

Use of cue configuration geometry for spatial orientation in human infants (Homo sapiens).

Research with both rats and human infants has found that after inertial disorientation, the geometry of an enclosed environment is used in preference over distinctive featural information during goal localization. Infants (Homo sapiens, 18-24 months) were presented with a toy search task involving inertial disorientation in 1 of 2 conditions. In the identical condition, 4 identical hiding boxes in a rectangular formation were set within a circular enclosure. In the distinctive condition, 4 distinctive hiding boxes were used. Infants searched the goal box and its rotational equivalent significantly more than would be expected by chance in the identical condition, showing that they were sensitive to the geometric configuration of the array of boxes. Unlike the results of studies using a rectangular enclosure, however, in the distinctive condition, infants searched at the correct location significantly more than at other locations.

Volume assessment of the bovine hoof.

The size of bovine hooves is one factor that may affect their ability to absorb shock. An increase in size could therefore reduce the risk of lameness associated with excessive digit loading. The hooves of 30 mature cattle were assessed by linear measurements with the objective of predicting digit volume, which was measured separately by water displacement. Claw volume was predicted accurately by regression equations including the top hoof width, toe length and heel angle. Replacing toe length and heel angle with the age and weight of the animal also gave an acceptable prediction and would be more appropriate for on-farm measurement. A reasonable prediction could be obtained from the top hoof width alone. Front hooves were larger and had greater heel depth than hind hooves. In 26 of the cattle either the right fore and left rear hooves, or the left fore and right rear hooves, were larger than the other two hooves, indicating that crossed limb laterality (symmetry in diagonally opposed limbs) may be present to a greater degree than has been previously recognised in quadrupeds.

Early elective cholecystectomy--an alternative to early cholecystectomy in acute cholecystitis?

Currently there are two forms of management for patients with acute cholecystitis. Conservative treatment during the acute episode and readmission after 6-8 weeks for elective surgery and early cholecystectomy during the emergency admission. An alternative treatment would be elective surgery before the acute episode which should reduce morbidity and mortality. This study has identified those patients who are likely to present with acute biliary disease so that they can be selected for elective surgery shortly after their attendance in outpatients.

A pragmatic triage system to reduce length of stay in medical emergency admission: feasibility study and health economic analysis.

BACKGROUND: Departments of Internal Medicine tend to treat patients on a first come first served basis. The effects of using triage systems are not known. METHODS: We studied a cohort in an Acute Medical Unit (AMU). A computer-assisted triage system using acute physiology, pre-existing illness and mobility identified five distinct risk categories. Management of the category of very low risk patients was streamlined by a dedicated Navigator. Main outcome parameters were length of hospital stay (LOS) and overall costs. Results were adjusted for the degree of frailty as measured by the Clinical Frailty Scale (CFS). A six month baseline phase and intervention phase were compared. RESULTS: 6764 patients were included: 3084 in the baseline and 3680 in the intervention phase. Patients with very low risk of death accounted for 40% of the cohort. The LOS of the 1489 patients with very low risk of death in the intervention group was reduced by a mean of 1.85days if compared with the 1276 patients with very low risk in the baseline cohort. This was true even after adjustment for frailty. Over the six month period the cost of care was reduced by £250,158 in very low patients with no increase in readmissions or 30day mortality. CONCLUSIONS: Implementation of an advanced triage system had a measurable impact on cost of care for patients with very low risk of death. Patients were safely discharged earlier to their own home and the intervention was cost-effective.

Glandular neoplasia and borderline endocervical reporting rates before and after conversion to the SurePath(TM) liquid-based cytology (LBC) system.

Reporting rates for glandular neoplasia in 464,754 cervical samples reported at six laboratories in 12-month periods before and after the implementation of Surepath™ LBC processing are compared. The introduction of LBC processing is seen to have resulted in a significant (P = 0.001) increase in the detection rate for endocervical glandular neoplasia (from 2.2 per 10,000 tests to 3.9 per 10,000) while maintaining high levels of reporting specificity. An observed fall in the number of samples reported as showing borderline glandular neoplasia falls short of statistical significance, and the reporting of possible endometrial and 'other' glandular abnormalities appears to be unaffected. The underlying reasons for the observed improvement in detection of endocervical glandular neoplasia are discussed.

The impact of group leaders' behaviour on parents acquisition of key parenting skills during parent training.

BACKGROUND: Parent training (PT) is identified as the most effective intervention for the treatment of conduct disorder (CD). Intervention observational outcomes are often reported as summarised composite scores, providing an overview of overall construct change. METHODS AND AIMS: Parents of children aged 3-5 years identified 'at risk' of developing CD were randomly allocated to either PT intervention or waiting list control group. Parent and child behaviours were assessed before and after the intervention period. The current paper aims to establish which individual observed parenting categories change as a result of PT, and which specific observed leader categories predict these changes. RESULTS: Controlling for baseline scores, ANCOVA demonstrated changes in parent praise and reflective behaviours as significant post-intervention. One-way ANOVAs demonstrated higher levels of leader praise and reflective behaviours resulted in greater change in parental praise and reflective behaviours respectively. Regression analyses indicated these leader behaviours predict positive change in parental praise and reflective behaviours for intervention families. CONCLUSIONS: Composite observational scores provide an account of behaviour constructs, whereas individual behaviour categories provide an insight into the core components of these constructs. The results suggest praise and reflection as key leader behaviours that influence the mechanisms of change in parenting behaviours as a result of PT.

Influence of menopausal status and use of hormone replacement therapy on radiation dose from mammography in routine breast screening.

Menopausal status and hormone replacement therapy (HRT) cause alterations in breast structure which can affect mammographic image quality. Here we present the results of a study to discover the effect of menopausal status and HRT use on breast dose. Women attending routine screening completed questionnaires which included questions regarding menopausal status and HRT use. Details of the radiographic technique factors were recorded, from which the mean glandular dose (MGD) per film for each woman was calculated. MGD values were analysed with regard to the woman's menopausal status and HRT use. The data from 516 women were analysed. Among the women who had never used HRT, women who had not undergone the menopause had a mean MGD of 2.94 mGy per film, whereas post-menopausal women had a lower mean MGD of 2.52 mGy per film: a difference which was found to be highly significant (p = 0.0045). Post-menopausal women who had never used HRT and those who had previously used HRT, but had ceased using it, had identical mean MGDs (2.54 mGy per film), whereas current HRT users had a significantly greater mean MGD (2.89 mGy per film, p = 0.003). Women currently using HRT receive a statistically significantly larger radiation dose from routine breast screening than other women. However, this effect is small and only occurs during the period of HRT use. Women who have ceased using HRT show no difference in MGD compared with women who have never taken HRT.

A descriptive study of the decline in cervical screening coverage rates in the North East and Yorkshire and the Humber regions of the UK from 1995 to 2005.

Since the mid-1990s, there has been a steady decline in coverage rates for cervical screening in the target age group (25-64 years) across England. This article describes the rate of decline from 1995 to 2005 in the old health authority areas of the North East and the Yorkshire and the Humber (NEYH) regions in relation to age group, deprivation, ethnicity and religion. The results show that the rate of decline is faster in these northern regions than that in England as a whole, with a very strong correlation between age and rate of change of coverage rates. Younger age groups experience the fastest rate of decline, and those over 55 years show an increase in coverage rates. There is an association between the deprivation of the old health authority areas and the rate of change of coverage rates, with weaker evidence that areas with high proportions of Black or Mixed ethnicity may have a faster decline. However, the rate of decline is not associated with other ethnic groups or religions. Therefore, interventions could be targeted at younger women and those who live in deprived areas to prevent the widening of inequalities.

Social and geographical risk factors in Helicobacter pylori infection.

A correlation between childhood crowding and the later development of gastric cancer has been demonstrated by Barker and colleagues, who proposed that the relationship was the consequence of infection by an organism such as Helicobacter pylori. In order to test this hypothesis the presence of IgG antibodies to H. pylori in sera from blood donors in North Wales has been investigated. During donation sessions, donors answered questions relating to social conditions and domicile in childhood (at age 10 years) and adult life (the preceding 2 years). A stepwise logistic regression analysis of the data demonstrated significant independent relationships between seropositivity and the following factors: sharing a bed in childhood, housing density, locality of birth, adult social class and age.

Comparison of a new inorganic membrane filter (Anopore) with a track-etched polycarbonate membrane filter (Nuclepore) for direct counting of bacteria.

Bacterial counts obtained by using a new Anopore inorganic membrane filter were 21 to 33% higher than those obtained by using a Nuclepore polycarbonate membrane filter. In addition, the inorganic filter had higher flow rates, permitting lower vacuum pressures to be used, while the intrinsically flat, rigid surface resulted in easier focusing and sharp definition of bacteria across the whole field of view.

Grouping of trypanosome species in mixed infections in Glossina pallidipes.

Trypanosomes in the dissection-positive proboscis of Glossina pallidipes were identified by PCR using species-specific primers. Of the 3741 flies dissected 643 were proboscis positive. PCR was performed on 406 dissection-positive probosces giving positive identifications in 352 (86.7%) and infection rates of 14.8% for congolense-type infections, 2.8% for vivax-type infections and 1.4% for the unidentified group. Of the 352 PCR identified infections 225 were single, 111 were double, 13 were triple infections and there were 3 quadruple infections. Statistical analysis suggests that mixed infections group into 3 largely separate divisions among the tsetse population (i) Trypanosoma congolense savannah and T. congolense Kenya coast, (ii) T. simiae, T. congolense Tsavo and T. godfreyi and (iii) T. vivax. We conclude that either differing feeding patterns among members of the fly population or the ability of the trypanosomes in each of the infection categories to significantly influence the maturation of trypanosomes in the other categories are the most likely causes of the groupings noted. Chi-squared analysis of dissection and PCR methods of trypanosome identification revealed profound differences (chi 2 = 19.1; D.F. = 1; P > 0.05). If confirmed in other studies these findings have serious implications for our understanding of trypanosome epidemiology in tsetse flies, much of which is founded on data from dissection-based trypanosome identifications.

Gastric cancer in Gwynedd. Possible links with bracken.

One hundred and one histologically confirmed gastric cancer patients in Gwynedd, North Wales, were matched by sex, age and social class to two hospital inpatients without cancer. Seventy-seven of the gastric cancer cases were also matched, using the same criteria, to a patient with a confirmed cancer of a different site (excluding oesophagus). A questionnaire was used to determine bracken exposure and source of water in childhood. Residential and occupational histories were obtained and the consumption of buttermilk, a potential vector of the bracken carcinogens, was quantified. Comparison of the gastric cancer patients with the non-cancer controls indicated that exposure to bracken in childhood had an increased risk (RR = 2.34, P less than 0.001) compared to no exposure and that length of residence in Gwynedd was associated with increased risk (RR = 2.46 for durations of 61 years and over, P less than 0.01). Consumption of buttermilk in childhood and adulthood was attended by increased risk (RR = 1.61 and 1.86 respectively, the latter being statistically significant, P less than 0.05). Neither the residence effect nor consumption of buttermilk in adulthood remained significant when considered in a multivariate analysis with bracken exposure.

Oral and pharyngeal cancer in the North-west and West Yorkshire regions of England, and occupation.

Patients with oral or pharyngeal cancer in the two main textile regions of England were matched for age and sex with patients having cancers not known to be associated with textile work. Data were recorded on age, sex, cancer site, and smoking, chewing and drinking habits together with dental and occupational history. There were 102 and 61 matched pairs of males and 52 and 60 matched pairs of females in the North-west and West Yorkshire regions respectively. There were significantly (P less than 0.05) more textile workers in the cases compared with their matched controls for only the females in the North-west. No particular type of textile work occurred more frequently for the cases than the controls in all four matched comparisons. Only for the males in the North-west were there significant differences (P less than 0.05) in the proportions of textile workers in the three cancer sites of the tongue, mouth and pharynx. These results do not confirm the association between textile work and oral or pharyngeal cancer found by the mortality study of Moss and Lee (1974). The results for the association between oral or pharyngeal cancer and smoking, drinking, chewing and wearing of dentures are discussed.

Ventilatory function in workers exposed to tea and wood dust.

Changes in ventilatory capacity during the work shift were studied in workers exposed to tea dust in tea-packing plants, wood dust in two furniture factories, and virtually no dust in an inoperational power station. The FEV1 and FVC in workers exposed to dust were found to decline during the work shift by a small but significant volume. The MMFR, Vmax 50% and Vmax 75% were to variable to display any trend. No dose-response relationship could be discerned between the fall in workers' ventilatory capacity and the concentrations of airborne dust or microbes to which they were exposed. Bronchodilators could reverse the fall in FEV1.

Photosensitization of pancreatic tumour cells by delta-aminolaevulinic acid esters.

A series of straight chain, branched and cyclo-delta-aminolaevulinic acid (ALA) esters have been synthesized and their photosensitizing properties analysed using an in vitro system of rat pancreatoma cells. Structurally favourable ALA esters not only induced the formation of more of the endogenous photosensitizer, protoporphyrin IX (PpIX), but they did so at a faster rate than ALA itself. This action was reflected in a substantial increase in photocytotoxicity of some 270 times, using the more potent ALA esters. An important structural feature was identified in two of the ALA esters which greatly limited PpIX production, i.e. a branch point located next to the site of ester cleavage. Experiments on the transport of ALA and of ALA esters across the cell membrane showed that ALA, but not ALA esters, gain access to the cell via the di- and tripeptide transporter, PEPTI. Finally, these results show that the esterification of ALA can greatly increase its cellular uptake, so generating more intracellular PpIX, improved tumour cell photosensitization and enhanced photocytotoxicity.