Genomic epidemiology of the emerging pathogen Batrachochytrium dendrobatidis from native and invasive amphibian species in Chile.

Emerging fungal diseases represent a threat to food security, animal and human health worldwide. Amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and well-documented amphibian population declines and extinctions. For the first time, Bd was cultured from native and non-native wild amphibians in Chile. Phylogenomic analyses revealed that Chilean isolates AVS2, AVS4 and AVS7 group within the global panzootic lineage of Bd (BdGPL) in a single highly supported clade that includes a genotype previously isolated from the United Kingdom. Our results extend the known distribution of BdGPL in South America and suggest a single and relatively recent introduction of BdGPL into the country, providing additional support to the role of anthropogenic activity in the global spread of this panzootic lineage.

Weight bias among UK trainee dietitians, doctors, nurses and nutritionists.

BACKGROUND: Trainee dietitians, nutritionists, nurses and doctors will direct the future of obesity treatment and prevention. To do so effectively, they must be willing and able to engage empathically with overweight and obese people. The present study aimed to assess weight bias among UK trainee healthcare professionals and to investigate the factors predicting weight bias, both static and potentially modifiable. METHODS: A self-completed questionnaire collected data on demographics, weight and height, the Fat Phobia Scale (F-scale), and the Beliefs about Obese People (BOAP) scale from 1130 students. RESULTS: Overall, participants demonstrated significant levels of fat phobia [F-scale score mean (SD) = 3.8 (0.5)]. Only 1.4% of participants could be said to have expressed 'positive or neutral attitudes' (i.e. achieved a F-scale score ≤ 2.5). Hierarchical multiple regression revealed that lower fat phobia (as measured by the F-scale) was uniquely predicted by a higher self-reported body mass index, being on the Nursing BSc course and a stronger perception that obesity is not under a person's control (as measured by the BOAP scale). CONCLUSIONS: There are unacceptable levels of weight bias among UK students training to become nurses, doctors, nutritionists and dietitians. The results of the present study suggest that a promising approach for future interventions would be the provision of balanced education about the controllability of obesity, focusing upon genetic and environmental factors, as well as diet and exercise.

The influence of objective prognostic information on the likelihood of informed consent for decompressive craniectomy: a study of Australian anaesthetists.

The aim of this study was to assess the influence of detailed prognostic information on the likelihood of informed consent for decompressive craniectomy for severe traumatic brain injury. The study was a simulation exercise, asking anaesthetists to give opinions as if they themselves were the injured party. Anaesthetists were chosen as they represent a distinct group likely to be familiar with the procedure and the decision-making process, but not necessarily aware of the longer-term outcomes. A two-part structured interview was used. Seventy-five anaesthetists were shown three cases of differing severity of traumatic brain injury. A visual analogue scale (1 to 10) was used to assess the strengths of their opinion. Initially they were asked their opinion with no predictive outcome data. They were then shown the prediction of an unfavourable outcome (Glasgow Outcome Scale severely disabled, vegetative state or dead) and the observed outcome at 18-month follow-up from a cohort of 147 patients (who had had a decompressive craniectomy for severe traumatic brain injury in Perth, Western Australia between the years 2004 and 2008). The opinions of the participants before and after seeing the prediction outcome data were compared. The participants' preferences to consent to the procedure changed after being informed of the predicted risks of unfavourable outcomes (P values < 0.01). The changes in attitude appeared to be independent of age group, amount of experience in caring for similar patients and religious background. These findings suggest that access to objective information on risks of unfavourable outcomes may influence opinions in relation to consent for decompressive craniectomy for traumatic brain injury.

Readability level of patient information leaflets for older people.

BACKGROUND: Limited literacy is associated with a nearly twofold increase in mortality in older patients. AIMS: The aim was to assess the readability level of patient information leaflets in Ireland. METHODS: The SMOG formula is a validated tool to assess readability of text, providing an estimate of the years of education needed to understand a piece of writing. We evaluated 45 common patient information leaflets for older people, and compared them to newspapers. RESULTS: The mean readability level of the patient education leaflets was 12.57 (range 9.4-16.33). The mean readability level of broadsheet newspapers was 12. A majority of patient education materials are written at an excessively high readability level. CONCLUSION: Patient education information should be aimed at an appropriate level for the target audience. This is of particular relevance in the older population, who are at a higher risk of inadequate or marginal health literacy.

A multidisciplinary audit of clinical coding accuracy in otolaryngology: financial, managerial and clinical governance considerations under payment-by-results.

OBJECTIVES: To audit the accuracy of otolaryngology clinical coding and identify ways of improving it. DESIGN: Prospective multidisciplinary audit, using the 'national standard clinical coding audit' methodology supplemented by 'double-reading and arbitration'. SETTINGS: Teaching-hospital otolaryngology and clinical coding departments. PARTICIPANTS: Otolaryngology inpatient and day-surgery cases. MAIN OUTCOME MEASURES: Concordance between initial coding performed by a coder (first cycle) and final coding by a clinician-coder multidisciplinary team (MDT; second cycle) for primary and secondary diagnoses and procedures, and Health Resource Groupings (HRG) assignment. RESULTS: 1250 randomly-selected cases were studied. Coding errors occurred in 24.1% of cases (301/1250). The clinician-coder MDT reassigned 48 primary diagnoses and 186 primary procedures and identified a further 209 initially-missed secondary diagnoses and procedures. In 203 cases, patient's initial HRG changed. Incorrect coding caused an average revenue loss of 174.90 pounds per patient (14.7%) of which 60% of the total income variance was due to miscoding of a eight highly-complex head and neck cancer cases. The 'HRG drift' created the appearance of disproportionate resource utilisation when treating 'simple' cases. At our institution the total cost of maintaining a clinician-coder MDT was 4.8 times lower than the income regained through the double-reading process. CONCLUSIONS: This large audit of otolaryngology practice identifies a large degree of error in coding on discharge. This leads to significant loss of departmental revenue, and given that the same data is used for benchmarking and for making decisions about resource allocation, it distorts the picture of clinical practice. These can be rectified through implementing a cost-effective clinician-coder double-reading multidisciplinary team as part of a data-assurance clinical governance framework which we recommend should be established in hospitals.

Do we need community geriatrics?

Community geriatrics has evolved as a specific aspect of geriatric medicine in the UK. In Ireland there is uncertainty as to how it should be planned. This is the first national survey of consultants, specialist registrars and general practitioners to seek their opinions. Most consultants and GPs reported already having a community aspect to their current practice, e.g. nursing home visits or community hospital visits, whereas most SpRs did not. Forty three of 62 respondents (69%) agreed that there is a need for community geriatricians and that there should be integration with hospital medicine. Fifty seven of 62 respondents (92%) felt that there would be a beneficial effect on GP services, though some expressed concern about work overlap. Thirteen of the 25 SpRs (52%) in training hoped to begin practice in community geriatrics in the future.

Delivering intravenous therapy in the community setting.

This article provides an overview of how an intravenous (IV) therapy service was developed in one primary care trust in England, the challenges that were faced and how they were overcome. The article includes some recommendations for others considering setting up a community IV therapy team.

Thromboprophylaxis in ENT patients: A national survey.

The aim of this survey was to establish whether ENT departments in England follow British Medical Journal guidelines on thromboprophylaxis. A telephone survey of doctors in 80 ENT departments was used to present six clinical scenarios. The participants were asked what their local department routinely did. They were also asked whether they were aware of a local or national thromboprophylaxis policy. For patients undergoing procedures other than major head and neck procedures, compliance was poor and ranged between 7.5% and 37.5%. For laryngectomy, the rate was 82.6%. There was no statistical difference in answers given by doctors of different levels of seniority. Where local thromboprophylaxis guidelines exist, compliance is found to be statistically better. These results suggest that most ENT departments do not follow national or local guidelines on thromboprophylaxis. Greater awareness of existing guidelines is required.

Calciphylaxis in moderate renal insufficiency: changing disease concepts.

Calciphylaxis is a rare but frequently fatal complication in patients with end-stage renal disease. Original concepts regarding groups at risk for the disease, predisposing factors, and associated morbidity have changed significantly in the past few years as more cases are reported. We present a patient who developed fatal calciphylaxis in the setting of moderate renal insufficiency to illustrate some of the evolving concepts in this disease process.

Beyond aspirin: how glycoprotein inhibitors ease acute coronary syndromes.

Glycoprotein IIb/IIIa receptor inhibitors can improve vessel patency for patients with myocardial infarction and angina. Patients who receive these drugs can be managed more conservatively, without invasive procedures, and may have less risk of recurrent infarction and death.

Rapid characterization of the major drug-metabolizing human hepatic cytochrome P-450 enzymes expressed in Escherichia coli.

The major drug-metabolizing human hepatic cytochrome P-450s (CYPs; CYP1A2, 2C9, 2C19, 2D6, and 3A4) coexpressed functionally in Escherichia coli with human NADPH-P-450 reductase have been validated as surrogates to their counterparts in human liver microsomes (HLM) using automated technology. The dealkylation of ethoxyresorufin, dextromethorphan, and erythromycin were all shown to be specific reactions for CYP1A2, CYP2D6, and CYP3A4 that allowed direct comparison with kinetic data for HLM. For CYP2C9 and CYP2C19, the kinetics for the discrete oxidations of naproxen and diazepam were compared to data obtained using established, commercial CYP preparations. Turnover numbers of CYPs expressed in E. coli toward these substrates were generally equal to or even greater than those of the major commercial suppliers [CYP1A2 (ethoxyresorufin), E. coli 0.6 +/- 0.2 min(-1) versus B lymphoblasts 0.4 +/- 0.1 min(-1); CYP2C9 (naproxen), 6.7 +/- 0.9 versus 4.9 min(-1); CYP2C19 (diazepam), 3.7 +/- 0.3 versus 0.2 +/- 0.1 min(-1); CYP2D6 (dextromethorphan), 4.7 +/- 0.1 versus 4.4 +/- 0.1 min(-1); CYP3A4 (erythromycin), 3 +/- 1.2 versus 1.6 min(-1)]. The apparent K(m) values for the specific reactions were also similar (K(m) ranges for expressed CYPs and HLM were: ethoxyresorufin 0.5-1.0 microM, dextromethorphan 1.3-5.9 microM, and erythromycin 18-57 microM), indicating little if any effect of N-terminal modification on the E. coli-expressed CYPs. The data generated for all the probe substrates by HLM and recombinant CYPs also agreed well with literature values. In summary, E. coli-expressed CYPs appear faithful surrogates for the native (HLM) enzyme, and these data suggest that such recombinant enzymes may be suitable for predictive human metabolism studies.

Merits and limitations of recombinant models for the study of human P450-mediated drug metabolism and toxicity: an intralaboratory comparison.

A wide variety of pharmacological and toxicological properties of drugs are determined by cytochrome P450-mediated metabolism. Characterization of these pathways and of the P450 isoenzymes involved constitutes an essential part of drug development. Similarly, because P450s are catalyzing the toxication and detoxication of environmental pollutants, an understanding of these reactions facilitates risk assessment in environmental toxicology. Recently, a variety of recombinant expression systems has been employed to study the role of human P450s in these reactions. These include insect, bacterial, yeast, and mammalian models. As these were developed and characterized by different laboratories, evaluation of their merits and limitations is inherently difficult. To resolve this problem, we have established and characterized the latter three systems and present the key results here. In general, the catalytic properties of P450 isozymes in the various models were rather similar. However, taking technical considerations into account as well as the high level of functional expression of P450s achieved in bacteria make this system ideally suited for drug metabolism research, including the generation of milligram quantities of metabolites for structural determinations. For toxicological studies, however, expression of P450s in mammalian cells was most appropriate. This is exemplified here by studies into the role of human P450s in the activation and inactivation of chemotherapeutic drugs.

Competition between cytochrome P-450 isozymes for NADPH-cytochrome P-450 oxidoreductase affects drug metabolism.

NADPH-cytochrome P-450 oxidoreductase (CPR) is essential for the catalytic activity of cytochrome P-450 (P-450). On a molar basis, the amount of P-450 exceeds that of CPR in human liver. In this study, we investigated whether drug-drug interactions can occur as a result of competition between P-450 isozymes for this ancillary protein. For this purpose, combinations of P-450 isozymes were coexpressed together with P-450 reductase in Escherichia coli. We show that testosterone inhibited the CYP2D6-mediated bufuralol 1'-hydroxylase activity in bacterial membranes containing both CYP2D6 and CYP3A4 but not in membranes containing CYP2D6 alone. Conversely, bufuralol inhibited the CYP3A4-mediated testosterone 6beta-hydroxylase activity in bacterial membranes containing both CYP3A4 and CYP2D6 but not in membranes containing only CYP3A4. In each case, inhibition was seen even at a P-450 to P-450 reductase ratio of 1.9:1, which is more favorable than the ratio of 4 reported for human liver. The physiological significance of this mechanism was demonstrated by the observation that testosterone inhibited several prototypical P-450 enzyme activities, such as bufuralol 1'-hydroxylase, coumarin 7-hydroxylase, and 7-ethoxyresorufin O-dealkylase, in human liver microsomes, but not if tested against a panel of bacterial membranes containing the human P-450 isozymes that mainly catalyze these reactions.

Oral cancer in the North-East of England: incidence, mortality trends and the link with material deprivation.

This study set out to determine the incidence of, and mortality from, oral cancer in the North-East of England between the mid-1970s and the early 1990s; to investigate its relation to material deprivation; and to test the completeness of cancer registry data. The Northern Region Cancer Registry provided details of registrations, deaths and population estimates. For analyses by deprivation, Small Area Statistics were obtained from the 1981 and 1991 censuses. In a selected sample district, 100% completeness and 89% accuracy of cancer registration of these conditions were found. For both tongue and mouth cancer, age- and sex-specific incidence and mortality rates rose with age and there was little change with time. When age-standardised registration and mortality ratios were compared between the Northern Region and England & Wales, only those for mouth cancer in males were significantly different. Crude survival from cancer of the tongue in males improved in the Northern Region from 1971-74 to 1983-86 but there was no improvement in females nor for cancer of the mouth in both sexes. In males for both tongue and mouth cancer, there was a graded increase in the standardised registration and mortality ratios from the most affluent to the most deprived areas but these differences were less marked in females. These differences in mouth cancer incidence found between England & Wales and the Northern Region probably reflect differences in lifestyles. The North ranks worst among the regions of England & Wales on a number of criteria of material deprivation, and long-term unemployment is one of the highest in the country. The analysis by deprivation has shown a clear relation to material deprivation. Whether socio-economic deprivation per se or a different risk factor behaviour associated with deprivation (smoking, alcohol consumption, poor diet) is the cause of these differences is not known. However, it is very likely that different risk factor behaviour plays a major part.

Expected hemoglobin decrease following percutaneous transluminal coronary angioplasty.

To establish expected changes in hemoglobin during and after percutaneous transluminal coronary angioplasty (PTCA), we measured hemoglobin before, at the end of, and on the 2 mornings after PTCA in 177 consecutive patients without obvious out-of-laboratory blood loss. From these data, we calculated confidence intervals that can be used to compare group data, possibly to identify excessive blood loss with new devices or antithrombotic agents, and prediction intervals to identify unexpected blood loss in an individual patient.