Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood.

Animal fibre: the forgotten nutrient in strict carnivores? First insights in the cheetah.

As wild felids are obligate carnivores, it is likely that poorly enzymatically digestible animal tissues determine hindgut fermentation, instead of plant fibre. Therefore, faecal concentrations of short-chain fatty acids (SCFA, including branched-chain fatty acids, BCFA), indole and phenol were evaluated in 14 captive cheetahs, fed two different diets differing in proportion of poorly enzymatically digestible animal tissue. Using a cross-over design, the cheetahs were fed exclusively whole rabbit or supplemented beef for 1 month each. Feeding whole rabbit decreased faecal propionic (p < 0.001) and butyric (p = 0.013) acid concentrations, yet total SCFA was unaltered (p = 0.146). Also, a remarkably higher acetic acid to propionic acid ratio (p = 0.013) was present when fed whole rabbit. Total BCFA (p = 0.011) and putrefactive indole (p = 0.004) and phenol (p = 0.002) were lower when fed whole rabbit. Additionally, serum indoxyl sulphate, a toxic metabolite of indole, was analysed and showed a quadratic decrease (p = 0.050) when fed whole rabbit. The divergent SCFA ratios and the decrease in putrefaction when fed whole rabbit could be caused by the presence of undigested tissue, such as skin, bone and cartilage, that might have fibre-like functions. The concept of animal fibre is an unexplored area of interest relevant to gastrointestinal health of captive cheetahs and likely other felids.

Fermentation of animal components in strict carnivores: a comparative study with cheetah fecal inoculum.

The natural diet of felids contains highly digestible animal tissues but also fractions resistant to small intestinal digestion, which enter the large intestine where they may be fermented by the resident microbial population. Little information exists on the microbial degradability of animal tissues in the large intestine of felids consuming a natural diet. This study aimed to rank animal substrates in their microbial degradability by means of an in vitro study using captive cheetahs fed a strict carnivorous diet as fecal donors. Fresh cheetah fecal samples were collected, pooled, and incubated with various raw animal substrates (chicken cartilage, collagen, glucosamine-chondroitin, glucosamine, rabbit bone, rabbit hair, and rabbit skin; 4 replicates per substrate) for cumulative gas production measurement in a batch culture technique. Negative (cellulose) and positive (casein and fructo-oligosaccharides; FOS) controls were incorporated in the study. Additionally, after 72 h of incubation, short-chain fatty acids (SCFA), including branched-chain fatty acids (BCFA), and ammonia concentrations were determined for each substrate. Glucosamine and glucosamine-chondroitin yielded the greatest organic matter cumulative gas volume (OMCV) among animal substrates (P < 0.05), whereas total SCFA production was greatest for collagen (P < 0.05). Collagen induced an acetate production comparable with FOS and a markedly high acetate-to-propionate ratio (8.41:1) compared with all other substrates (1.67:1 to 2.97:1). Chicken cartilage was rapidly fermentable, indicated by a greater maximal rate of gas production (R(max)) compared with all other substrates (P < 0.05). In general, animal substrates showed an earlier occurrence for maximal gas production rate compared with FOS. Rabbit hair, skin, and bone were poorly fermentable substrates, indicated by the least amount of OMCV and total SCFA among animal substrates (P < 0.05). The greatest amount of ammonia production among animal substrates was measured after incubation of collagen and rabbit bone (P < 0.05). This study provides the first insight into the potential of animal tissues to influence large intestinal fermentation in a strict carnivore, and indicates that animal tissues have potentially similar functions as soluble or insoluble plant fibers in vitro. Further research is warranted to assess the impact of fermentation of each type of animal tissue on gastro-intestinal function and health in the cheetah and other felid species.

Assessment of health status and health-related quality of life in survivors of Hodgkin's disease in childhood.

Although the great majority of children with Hodgkin's disease survive with modern treatment strategies, the list of late sequelae is long, yet there is no published information on the comprehensive health status and health-related quality of life (HRQL) in this population. In the experience of a single institution, survivors of Hodgkin's disease in childhood were invited to self-report on their health status using a 15-item questionnaire connected to the Health Utilities Index, a series of multi-attribute health status classification systems that, in turn, are linked to preference functions which provide single-attribute and global utility scores for HRQL. The mean global utility score was 0.85 (on a 0 = dead to 1. 0 = perfect health scale), a figure less than that in survivors of acute lymphoblastic leukemia (ALL) but comparable to that in survivors of brain tumors (0.84) or extremely low birthweight (ELBW 0.82). The burden of morbidity is emphasized by the ratio of the numbers of health states per patient:0.67 for survivors of Hodgkin's disease, 0.66 for survivors of brain tumors, 0.39 for survivors of ELBW, 0.47 for survivors of high-risk ALL and 0.28 for survivors of standard-risk ALL. In Hodgkin's disease survivors, the attributes affected most commonly and severely were pain, cognition and emotion. This experience demands exploration of the health status and HRQL in a much larger cohort of such survivors, perhaps in the context of co-operative group studies.

Preliminary translation and cultural adaptation of Health Utilities Index questionnaires for application in Argentina.

Quality-of-life assessment is being used increasingly in clinical research. This is true particularly in the case of survivors of cancer in childhood, where improving survival rates have raised concern regarding the long-term effects of medical cure. Health-status assessment and quality-of-life instruments have been developed for the most part in the English language, thus necessitating their translation and cultural adaptation for use in non-English-speaking countries. Our purpose was to develop a set of Spanish-language questionnaires for application with a population of children with cancer in a tertiary-care center in Buenos Aires, Argentina. The Health Utilities Index (HUI), a conceptual framework for assessing health status, was chosen for this study. Three distinct questionnaires, based on the HUI, were used: a self-completed one for health professionals and teachers (15Q) to report assessments of children and 2 interviewer-administered ones, for child survivors (42Q) to report assessments about their own health status and parents (45Q) to report assessments about their children's health status. The original translations and reviews were accomplished with direct oversight by members of the HUI Group, to ensure conceptual equivalence. The instruments were then tested in Buenos Aires by application to staff of the hematology-oncology service, childhood cancer patients and the parents of childhood cancer patients. Several modifications were made based on these tests. We concluded that the translation and cultural adaptation of these instruments was adequate for use with the groups tested in a pilot survey of survivors of childhood cancer in Argentina.

A randomized trial comparing 12 weeks versus 36 weeks of adjuvant chemotherapy in stage II breast cancer.

A randomized trial has been performed in which women with axillary node-positive breast cancer were allocated to either a short intensive 12-week chemohormonal treatment consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and tamoxifen (CMFVP plus AT) or 36 weeks of CMFVP. The median follow-up is 37 months. Of the 222 women randomized to the 12-week treatment, 113 (50.9%) have experienced either recurrence or death as compared with 90 patients (41.9%) in the 36-week treatment group. The corresponding 3-year relapse-free survivals are 55% and 64%, respectively, P = .003. Fifty-nine (26.6%) of the patients in the 12-week group have died compared with 46 (21.4%) of the 36-week group. The corresponding 3-year survival rates are 78% and 85%, respectively, P = .04. A Cox regression analysis showed an associated increased risk ratio for recurrence or death of 1.7, P = .003, and for death of 1.8, P = .017 in the 12-week treatment group compared with the 36-week group. Thus, this 12-week regimen of adjuvant chemohormonal therapy is inadequate treatment for women with axillary node-positive breast cancer; possible explanations for this inferiority are its shorter duration and/or a negative interaction of tamoxifen on the chemotherapy.