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.

Pectenotoxins - an issue for public health - A review of their comparative toxicology and metabolism

Pectenotoxins (PTXs) are a group of toxins associated with diarrhetic shellfish poisoning (DSP) and isolated from DSP toxin-producing dinoflagellate algae. Consumption of shellfish contaminated with PTXs has been associated with incidences of severe diarrhetic illness resulting in hospitalisation. Concern has been raised for public health following the discovery that these toxins are not only hepatotoxic and can cause diarrhetic effects in mammals, but that they are potently cytotoxic to human cancer cell lines and have been found to be tumour promoters in animals. With advances in knowledge and technology, more PTXs are being identified, but little is known of their toxicology and the potential impact these toxins may have on public health in the long term. Without such information, adequate health-risk assessments for the consumption of shellfish contaminated with PTXs cannot be performed. This review gives a brief introduction to diarrhetic shellfish toxins, details the known toxicology and metabolism of PTXs in animals, and discusses known incidences of PTX poisoning in humans. (C) 2001 Elsevier Science Ltd. All rights reserved.

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.

Analysis of the study design and manuscript deficiencies in research articles submitted to Emergency Medicine

Objective: To describe and analyse the study design and manuscript deficiencies in original research articles submitted to Emergency Medicine. Methods: This was a retrospective, analytical study. Articles were enrolled if the reports of the Section Editor and two reviewers were available. Data were extracted from these reports only. Outcome measures were the mean number and nature of the deficiencies and the mean reviewers’ assessment score. Results: Fifty-seven articles were evaluated (28 accepted for publication, 19 rejected, 10 pending revision). The mean (± SD) number of deficiencies was 18.1 ± 6.9, 16.4 ± 6.5 and 18.4 ± 6.7 for all articles, articles accepted for publication and articles rejected, respectively (P = 0.31 between accepted and rejected articles). The mean assessment scores (0–10) were 5.5 ± 1.5, 5.9 ± 1.5 and 4.7 ± 1.4 for all articles, articles accepted for publication and articles rejected, respectively. Accepted articles had a significantly higher assessment score than rejected articles (P = 0.006). For each group, there was a negative correlation between the number of deficiencies and the mean assessment score (P > 0.05). Significantly more rejected articles ‘… did not further our knowledge’ (P = 0.0014) and ‘… did not describe background information adequately’ (P = 0.049). Many rejected articles had ‘… findings that were not clinically or socially significant’ (P = 0.07). Common deficiencies among all articles included ambiguity of the methods (77%) and results (68%), conclusions not warranted by the data (72%), poor referencing (56%), inadequate study design description (51%), unclear tables (49%), an overly long discussion (49%), limitations of the study not described (51%), inadequate definition of terms (49%) and subject selection bias (40%). Conclusions: Researchers should undertake studies that are likely to further our knowledge and be clinically or socially significant. Deficiencies in manuscript preparation are more frequent than mistakes in study design and execution. Specific training or assistance in manuscript preparation is indicated.

Improving pain management by nurses: A pilot peer intervention program

Significant pain continues to be reported by many hospitalized patients despite the numerous and varied educational programs developed and implemented to improve pain management. A theoretically based Peer Intervention Program was designed from a predictive model to address nurses' beliefs, attitudes, subjective norms, self-efficacy, perceived control and intentions in the management of pain with p.r.n. (as required) narcotic analgesia. The pilot study of this program utilized a quasi-experimental pre-post test design with a patient intervention, nurse and patient intervention and control conditions consisting of 24, 18 and 19 nurses, respectively. One week after the intervention, significant differences were found between the nurse and patient condition and the two other conditions in beliefs, self-efficacy, perceived control, positive trend in attitudes, subjective norms and intentions. The most positive aspects of the program were supportive interactive discussions with peers and an awareness and understanding of beliefs and attitudes and their roles in behavior.

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.

Knowledge and markets

An economy is a coordinated system of distributed knowledge. Economic evolution occurs as knowledge grows and the structure of the system changes. This paper is about the role of markets in this process. Traditionally, the theory of markets has not been a central feature of evolutionary economics. This seems to be due to the orthodox view of markets as information-processing mechanisms for finding equilibria. But in economic evolution markets are actually knowledge-structuring mechanisms. What then is the relation between knowledge, information, markets and mechanisms? I argue that an evolutionary theory of markets, in the manner of Loasby (1999), requires a clear formulation of these relations. I suggest that a conception of knowledge and markets in terms of a graphical theory of complex systems furnishes precisely this.

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.