Assessing fatigue in persons with cancer: an instrument development and testing study

BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent, subjective experience of patients with and survivors of cancer. Effective assessment of the attributes of CRF from the patient's perspective is essential. The current study developed a measure of CRF from the patient's perspective and determined its psychometric properties for patients with cancer undergoing chemotherapy. METHODS: Chemotherapy outpatients in a free-standing metropolitan area cancer clinic participated in the current multiphase study. In the instrument development phase, 42 items were generated from a qualitative study with 10 semistructured individual interviews and 6 daily fatigue diaries. These items were revised based on content evaluation by 20 cancer patient content experts. In the instrument analysis phase, the 30 content-validated items were pilot tested by 30 patients with breast carcinoma using cognitive interview techniques. The psychometric properties of the resulting 16-item, 5-point CRF rating scale were tested with 82 patients with breast carcinoma. RESULTS: Principal axis factoring gave a one-factor solution accounting for 59% variance. Coefficient alpha reliability was 0.95 for the final 15-item scale. Convergent validity with the Schwartz Cancer Fatigue Scale was 0.84, concurrent validity with the Geriatric Depression Scale was 0.61, and predictive validity with the Cancer-Related Fatigue Distress Scale was 0.83. CONCLUSIONS: This newly developed instrument to assess the subjective fatigue symptoms of patients with cancer demonstrated effective use of diary and interview methods in instrument development and both cognitive interviewing and traditional psychometric techniques in instrument analysis. The instrument has promising psychometric properties, but confirmatory testing is needed.     

Small margin excision of periocular basal cell carcinoma: 5 year results

BACKGROUND: The traditional surgical management of nodular adnexal basal cell carcinomas (BCC) involves excision with 3-4 mm margins and primary repair. This may remove a significant area of healthy tissue, often necessitating a complicated reconstruction, without the confirmation that tumour excision is complete. METHODS: Nodular adnexal BCCs were excised with 2 mm margins, and the repair delayed for 2 days, providing time for histological confirmation of complete excision with formal paraffin sections. Any incompletely excised tumours underwent further resection, which was facilitated by the undisturbed wound edges. Repair was again delayed until further histological examination had confirmed complete excision. RESULTS: 5 year follow up data were available for 55 patients who had undergone small margin BCC excision with delayed repair. 10 patients required more than one excision to achieve clear margins. There were no recurrences. CONCLUSION: Small margin excision of nodular adnexal BCCs with delayed repair is a safe and efficient method. Delayed repair allows histological confirmation of complete excision and assists further resection if required. Preservation of healthy tissue is maximised allowing less radical reconstructive surgery without resorting to Mohs' labour intensive technique.     

An evaluation of the impact of computer-based prompts on screen readers' interpretation of mammograms

The NHS Breast Screening Programme is changing working practices in response to increased workload and manpower shortages. Radiographers are being trained as film readers. Computer aids are being considered. We have evaluated the impact of prompts placed by the R2 ImageChecker 1000 on the sensitivity and specificity of film readers, including non-radiologist film readers. 30 radiologists, 5 breast clinicians and 15 radiographers each read 180 films, including 60 cancers (20 false negative interval cases and 40 screen detected cancers). Each reader read each case twice, once with and once without computer prompts. The order in which the reading sessions were carried out was randomized separately for each reader. 36 out of 40 screen-detected cases were prompted by the ImageChecker, a sensitivity of 90%. Eight out of 20 interval cases were prompted, a sensitivity of 40%. No significant difference was found for readers' sensitivity or specificity between the prompted and unprompted conditions. No significant difference was found between the sensitivity and specificity of the different groups of film reader. No difference in impact of prompts was found for well or poorly performing film readers. The result suggests that this version of the ImageChecker would not have a significant impact on the UK screening programme.     

Assessing the impact of CAD on the sensitivity and specificity of film readers

AIM: To assess the impact of computer-aided detection (CAD) prompts on film readers' sensitivity and specificity. MATERIAL AND METHODS: Thirty-five readers read 120 films, including 44 cancers, 40 of which were prompted. All readers looked at all cases with and without prompts. The sensitivity and specificity were calculated for each reader under each condition. RESULTS: The sensitivity improved when CAD prompts were used (0.80 from 0.77). The difference was slightly below the threshold for statistical significance (95% CI for the difference is -0.0027-0.064). The specificity also improved (0.86 from 0.85), but not significantly. There was a significant improvement in sensitivity when readers' judgements were combined to simulate double reading, from 0.77 to 0.81. (95% CI for the difference is 0.014-0.077). CONCLUSIONS: Analysis of prompted cancers that readers did and did not recall, found that cases were more likely to be correctly recalled if there were emphasized prompts, more prompts or if the case was harder. There was no statistically significant effect for type of abnormality or tumour size or for the performance, attitude or experience of the reader.     

CD86 blockade in genetically modified porcine cells delays xenograft rejection by inhibiting T-cell and NK-cell activation

Porcine xenografts transplanted into primates are rejected in spite of immunosuppression. Identification of the triggering mechanisms and the strategies to overcome them is crucial to achieve long-term graft survival. We hypothesized that porcine CD86 (pCD86) contributes to xenograft rejection by direct activation of host T cells and NK cells. Formerly, we designed the human chimeric molecule hCD152-hCD59 to block pCD86 in cis. To test the efficacy in vivo, we have utilized a pig-to-mouse xenotransplant model. First, we showed that hCD152-hCD59 expression prevents the binding of murine CD28Ig to pCD86 on porcine aortic endothelial cells (PAEC) and dramatically reduces IL-2 secretion by Con A-stimulated mouse splenocytes in coculture. Moreover, IFN-gamma secretion by IL-12-stimulated mouse NK cells was averted after coculture with hCD152-hCD59 PAEC. In vivo, control PAEC implanted under the kidney capsule were rapidly rejected (2-4 weeks) in BALB/c and BALB/c SCID mice. Rejection of hCD152-hCD59 PAEC was significantly delayed in both cases. Signs of immune modulation in the hCD152-hCD59-PAEC BALB/c recipients were identified such as early hyporesponsiveness and diminished antibody response. Thus, simply modifying the donor xenogeneic cell can diminish both T cell and NK cell immune responses. We specifically demonstrate that pCD86 contributes to rejection of porcine xenografts.     

Computerized diagnosis of breast lesions on ultrasound

We present a computer-aided diagnosis (CAD) method for breast lesions on ultrasound that is based on the automatic segmentation of lesions and the automatic extraction of four features related to the lesion shape, margin, texture, and posterior acoustic behavior. Using a database of 400 cases (94 malignant lesions, 124 complex cysts, and 182 benign solid lesions), we investigate the marginal benefit of each feature in our CAD method and the performance of our CAD method in distinguishing malignant lesions from various classes of benign lesions. Finally, independent validation is performed on our CAD method. Eleven independent trials yielded an average Az value of 0.87 in the task of distinguishing malignant from benign lesions.     

Mini Monoka silicone monocanalicular lacrimal stents: Subjective and objective outcomes

BACKGROUND. Canalicular injuries and anomalies are relatively common. Despite this, controversy still exists regarding the indications for surgery and best surgical methods. The most favourable intervention would be one that is simple, associated with a high level of subjective and objective outcome, and does not threaten the uninjured or unaffected part of the lacrimal drainage system. This study assesses outcomes of intervention with the Mini Monoka silicone monocanalicular lacrimal stent. METHOD. A single cohort, hospital-based study with retrospective and prospective components. Participants were all identifiable patients at Bristol Eye Hospital in whom the Mini Monoka silicone monocanalicular stent was used for any indication. Retrospective analysis of patient records for all related pre-operative, operative and postoperative data was performed. Prospective analysis of subjective outcome via confidential patient questionnaire and objective outcome via clinical examination was performed. RESULTS. Complete data were obtainable in 13 patients (14 canaliculi) of the identified 22 patients (23 canaliculi). Follow-up was from 12 to 70 months (mean 39 months). A high level of subjective outcome was noted with no patients experiencing significant or disabling symptoms. In terms of objective outcome, 79% achieved canalicular patency. The main complications with this technique were premature stent loss (29%) and stent migration (14%). CONCLUSIONS. The Mini Monoka monocanalicular stent is a safe, effective and simple surgical technique that, unlike bicanalicular procedures, does not threaten the uninjured / unaffected part of the lacrimal drainage system.     

Health issues among Filipino women in remote Queensland

ABSTRACT: This paper discusses health issues among Filipinas (women born in the Philippines) living in remote and rural environments in Queensland. The sample was recruited as part of the University of Queensland component of the Australian Longitudinal Study of Women's Health (ALSWH). Most of the women lived in an urban or semi-urban area (391), whereas 90 lived in rural or remote areas. Community perceptions had a much greater impact on health service utilisation in rural and remote areas than in urban areas. The transition between newcomer and old-timer is more difficult for Filipinas than for other rural women because they are visibly different from other members of the community and suffer from stigmatisation associated with perceptions of Filipinas as mail order brides. For these women, concerns about confidentiality and a reluctance to ask for support are major barriers to health service utilisation. The area of greatest concern is mental health, particularly in relation to parenting issues. Improving access may involve providing a greater awareness of what services are available and allowing women to access services in a way that does not require them to label themselves or be labelled by others.     

Liquid chromatography-mass spectrometry and liquid chromatography-NMR characterization of in vitro metabolites of a potent and irreversible peptidomimetic inhibitor of rhinovirus 3C protease.

In vitro metabolism of AG7088 [trans-(4S,2'R,5'S,3"'S)-4-[2'-4-(4-fluorobenzyl)-6'-methyl-5'-[(5"-methylisoxazole-3"-carbonylamino]-4-oxoheptanoylamino]-5-(2"'-oxopyrrolidin-3-"'-yl)pent-2-enoic acid ethyl ester] was studied in liver microsomes isolated from mice, rats, rabbits, dogs, monkeys, and humans. The structures of the metabolites were characterized by liquid chromatography (LC)-tandem mass spectrometry and LC-NMR methods. Hydrolysis of the ethyl ester to produce metabolite M4 (AG7185) is the predominant pathway in all species, with the greatest activity observed in rodents and rabbits, followed by monkeys, dogs, and humans. Several hydroxylation products were identified as minor metabolites, including diastereomers M1 and M2, with a hydroxy group at the P1-lactam moiety, and M3, with a hydroxy group at the methyl position of the methylisoxazole ring. Rodent and rabbit liver microsomes formed almost exclusively the acid metabolite M4 (AG7185), with very little hydroxylated metabolites, whereas monkey liver microsomes formed more secondary metabolites (i.e., acid analogs of the hydroxylated metabolites). The overall metabolic profile of AG7088 formed in dog liver microsomes closely resembled that of human liver microsomes; therefore, this species may be the most appropriate animal model relative to humans for exposure to AG7088 and its metabolites.