Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: Towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies

This paper describes the background and current status of an OMERACT facilitated effort to improve the consistency of adverse event reporting in rheumatology clinical trials, The overall goal is the development of an adverse event assessment tool that would provide a basis for use of common terminology and improve the consistency of reporting severity of side effects within rheumatology clinical trials and during postmarketing surveillance. The resulting Rheumatology Common Toxicity Criteria Index encompassed the following organ systems: allergic/immunologic, cardiac, ENT, gastrointestinal, musculoskeletal, neuropsychiatric, ophthalmologic, pulmonary and skin/integument. Before this tool is widely accepted, its validity, consistency, and feasibility need to be assessed in clinical trials.

A for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study

Purpose: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients and methods: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Results: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P = 0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P = 0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P = 0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P < 0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P < 0.05), except for the mucous membrane where late effects were similar in both arms. Conclusions: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

The walkeriana species-group of Euhesma Michener (Hymenoptera: Colletidae: Euryglossinae)

The walkeriana species-group of iridescent Euhesma bees is described with the following nine species considered new: E. allunga, E. banksia, E. bronzus, E. dongara, E. lobata, E. spinola, E. sybilae, E. viridescens and E. xana. Two new synonymies are proposed: E. mica (Cockerell) with E. neglectula (Cockerell), and E. halictoides (Rayment) with E. latissima (Cockerell). A key enables the separation of species, and distributions are mapped.

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: A phase II trial for the Trans-Tasman Radiation Oncology Group

Purpose: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. Methods and Materials: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. Results: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. Conclusion: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications. (C) 2001 Elsevier Science Inc.

Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Effect of gender on ownership and income in veterinary practice

Objective To estimate the effect of gender on ownership and income in veterinary practice in Australia. Methods Questionnaire completed by private veterinary practitioners, and analysed using the SAS System for Windows 7.0. Results More than three-quarters (78%) of male but 36% of female private practitioners were partial or sole owners of practices. The median annual income for all male practitioners working more than 40 hours/week was $70K, but that for females was $43K. These disparities existed in both city and country practices, and in the case of income it increased with increasing time in the workforce. Male practice owners also reported higher incomes than female owners. Conclusions Female veterinary practitioners are less likely to own practices, and more likely to earn low incomes than males. These differentials do not appear to be due to location, hours worked or years since graduation or, in the case of income, to whether they are owners or employees. The evidence points to a lower interest by women than men in the business aspects of veterinary practice.

Reconciling value estimates from the discounted cash flow model and the residual income model

This paper examines why practitioners and researchers get different estimates of equity value when they use a discounted cash flow (CF) model versus a residual income (RI) model. Both models are derived from the same underlying assumption -- that price is the present value of expected future net dividends discounted at the cost of equity capital -- but in practice and in research they frequently yield different estimates. We argue that the research literature devoted to comparing the accuracy of these two models is misguided; properly implemented, both models yield identical valuations for all firms in all years. We identify how prior research has applied inconsistent assumptions to the two models and show how these seemingly small errors cause surprisingly large differences in the value estimates. [ABSTRACT FROM AUTHOR]

Relationship of high energy expenditure and variation in dietary intake with reporting accuracy on 7 day food records and diet histories in a group of healthy adult volunteers

Objectives: To assess the accuracy of reporting from both a diet history and food record and identify some of the characteristics of more accurate reporters in a group of healthy adult volunteers for an energy balance study. Design: Prospective measurements in free-living people. Setting: Wollongong, Australia. Subjects: Fifteen healthy volunteers (seven male, eight female; aged 22 -59 y; body mass index (BMI) 19 - 33 kg/m(2)) from the local community in the city of Wollongong, Australia. Interventions: Measurement of energy intake via diet history interview and 7 day food records, total energy expenditure by the doubly labelled water technique over 14 days, physical activity by questionnaire, and body fat by dual-energy X-ray absorptiometry. Results: Increased misreporting of energy intake was associated with increased energy expenditure (r = 0.90, P < 0.0001, diet history; r(s)=0.79, P=0.0005, food records) but was not associated with age, sex, BMI or body fat. Range in number of recorded dinner foods correlated positively with energy expenditure (r(s)=0.63, P=0.01) and degree of misreporting (r(s)=0.71, P=0.003, diet history; r(s)=0.63, P=0.01, food records). Variation in energy intake at dinner and over the whole day identified by the food records correlated positively with energy expenditure (r=0.58, P = 0.02) and misreporting on the diet history (r=0.62, P=0.01). Conclusions: Subjects who are highly active or who have variable dietary and exercise behaviour may be less accurate in reporting dietary intake. Our findings indicate that it may be necessary to screen for these characteristics in studies where accuracy of reporting at an individual level is critical. Sponsorship: The study was supported in part by Australian Research Council funds made available through the University of Wollongong.

Reconciling Globalisation and Technological Change: Growing Income Inequalities and Remedial Policies

From the mid-1970s through the 1980s and into the 1990s, wage inequality and skill differentials in earnings and employment increased sharply in OECD countries. After 1973 and especially in the 1980s, the US experienced a dismal real wage performance for the less skilled. Among the factors singled out by economists as possible major contributors to this development are economic globalisation processes and skill-biased technological change. Although these are most commonly considered as independent influences, after critically outlining views about these factors, this article argues that strong interdependence exists between them. The article then examines potential policy responses to this growing inequality.

Saving, productivity and national income: a discrete-time geometric framework

This paper proposes an alternative geometric framework for analysing the inter-relationship between domestic saving, productivity and income determination in discrete time. The framework provides a means of understanding how low saving economies like the United States sustained high growth rates in the 1990s whereas high saving Japan did not. It also illustrates how the causality between saving and economic activity runs both ways and that discrete changes in national output and income depend on both current and previous accumulation behaviour. The open economy analogue reveals how international capital movements can create external account imbalances that enhance income growth for both borrower and lender economies. (C) 2002 Elsevier Science B.V. All rights reserved.