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Purpose: The Exercise for Health trials were randomised, controlled trials designed to evaluate an 8-month pragmatic exercise intervention, commencing 6 weeks post-surgery for women with newly diagnosed breast cancer residing in urban or rural/regional Australia. For these exploratory analyses, the primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively.Methods: Consenting urban- (n = 194) and rural/regional-residing women (n = 143) were randomised to exercise (intervention delivered face-to-face or by telephone) or usual care. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for survival outcomes (exercise group, n = 207, 65% urban women; usual care group, n = 130, 46% urban women).Results: After a median follow-up of 8.3 years, there were 11 (5.3%) deaths in the exercise group compared with 15 (11.5%) deaths in the usual care group (OS HR for the exercise group: 0.45, 95% CI 0.20–0.96; p = 0.04). DFS events for the exercise versus usual care group were 25 (12.1%) and 23 (17.7%), respectively (HR: 0.66, 95% CI 0.38–1.17; p = 0.16). HRs for OS favoured exercise irrespective of age, body mass index, stage of disease, intervention compliance, and physical activity levels at 12 months post-diagnosis, although were stronger (p < 0.05) for younger women, women with stage II + disease, women with 1 + comorbidity at time of diagnosis, higher intervention compliance and for those who met national physical activity guidelines at 12 months post-diagnosis.Conclusion: An exercise intervention delivered during and beyond treatment for breast cancer, and that was designed to cater for all women irrespective of place of residence and access to health services, has clear potential to benefit survival. Trial numbers: ACT RN: 012606000233527; ACT RN: 12609000809235. [ABSTRACT FROM AUTHOR]

Adverse changes in nutrition-related outcomes including quality of life (QoL) occur after PBSC transplantation. This randomised controlled trial aims to evaluate the impact of nutrition and exercise counselling provided at hospital discharge on nutritional status, body composition and QoL post transplantation. Usual care (UC) (n=19) received no intervention after discharge; extended care (EC) (n=18) received fortnightly telephone counselling from a dietitian and exercise physiologist up to 100 days post transplantation. Nutritional status (patient-generated subjective global assessment, and diet history), QoL (EORTC QLQ-C30 version 3) and body composition (air displacement plethysmography) were assessed at pre-admission, discharge and 100 days post transplantation. Intervention groups were compared using two-sample t-tests of changes in the outcomes; results were adjusted using analysis of covariance. EC exhibited clinically important but not statistically significant increases in protein intake (14.7 g; confidence interval (CI) 95% −6.5, 35.9, P=0.165), cognitive functioning (7.2; CI 95% −7.9, 22.2, P=0.337) and social functioning (16.5; CI 95% −7.3, 40.3, P=0.165) compared with UC. Relative to pre-admission, EC experienced less weight loss than UC (−3.3 kg; CI 95% −6.7, 0.2, P=0.062). Physical activity was not significantly different between the groups. Ongoing nutrition and exercise counselling may prevent further weight loss and improve dietary intake and certain QoL components in autologous PBSC transplantation patients following hospitalisation. [ABSTRACT FROM AUTHOR]

We investigate the sequence-dependent behaviour of localised excitations in a toy, nonlinear model of DNA base-pair opening originally proposed by Salerno. Specifically we ask whether “breather” solitons could play a role in the facilitated location of promoters by RNA polymerase (RNAP). In an effective potential formalism, we find excellent correlation between potential minima and Escherichia coli promoter recognition sites in the T7 bacteriophage genome. Evidence for a similar relationship between phage promoters and downstream coding regions is found and alternative reasons for links between AT richness and transcriptionally-significant sites are discussed. Consideration of the soliton energy of translocation provides a novel dynamical picture of sliding: steep potential gradients correspond to deterministic motion, while “flat” regions, corresponding to homogeneous AT or GC content, are governed by random, thermal motion. Finally we demonstrate an interesting equivalence between planar, breather solitons and the helical motion of a sliding protein “particle” about a bent DNA axis. [ABSTRACT FROM AUTHOR]

Summary:In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n=43) or not receive (n=47) amifostine 910?mg/m2 prior to melphalan 200?mg/m2. Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65%of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P=0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P=0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14%of the amifostine and control groups, respectively (P=0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to high-dose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis.Bone Marrow Transplantation (2005) 35, 971-977. doi:10.1038/sj.bmt.1704946 Published online 21 March 2005 [ABSTRACT FROM AUTHOR]

Summary:The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P<0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P<0.01) and nonexercising transplant patients (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.Bone Marrow Transplantation (2004) 33, 553-558. doi:10.1038/sj.bmt.1704378 Published online 12 January 2004 [ABSTRACT FROM AUTHOR]

This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34+ yield 0.5-1.9 x 106/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20?ug/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20?ug/kg/day plus filgrastim 5-10?ug/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of ?3 x 106 CD34+ cells/kg. In both groups, CD34+ yield (x 106/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 106/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 106/kg BW in the prior mobilization as in those with 0.76-1.99 x 106/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34+ cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.Bone Marrow Transplantation (2003) 31, 371-378. doi:10.1038/sj.bmt.1703860 [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to assess changes in total energy expenditure (TEE), body weight (BW) and body composition following a peripheral blood stem cell transplant and following participation in a 3-month duration, moderate-intensity, mixed-type exercise programme. The doubly labelled and singly labelled water methods were used to measure TEE and total body water (TBW). Body weight and TBW were then used to calculate percentage body fat (%BF), and fat and fat-free mass (FFM). TEE and body composition measures were assessed pretransplant (PI), immediately post-transplant (PII) and 3 months post-PII (PIII). Following PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). While there was no change in TEE between pre- and post-transplant, BW (P<0.01) and FFM (P<0.05) significantly decreased during the same period. Participation in the exercise programme led to increases in TEE to levels that were both higher than pre- and post-transplant measures (P<0.01). By PIII, the exercising patients also showed gains in FFM (P<0.01) in association with a reduction in %BF (P<0.05). Exercise has a functionally important role in preserving and increasing skeletal mass in the rehabilitation phase of cancer patients.Bone Marrow Transplantation (2003) 31, 331-338. doi:10.1038/sj.bmt.1703867 [ABSTRACT FROM AUTHOR]

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects. [ABSTRACT FROM AUTHOR]

2-Chlorodeoxyadenosine (2-CdA) was studied as initial therapy in patients with advanced and/or progressive chronic lymphocytic leukaemia using a shortened dosage schedule of 0.14 mg/kg/day by 2 hour IV infusion on 5 consecutive days. Thirty-four patients were treated, 25 males and 9 females (M:F = 2.7:1), with a median age of 58.8 years (range 3979). Distribution by Rai stage was I-2; II-16; III-9 and IV-7; and Binet: A-4; B-16; and C-14. ECOG performance status was 0-24; 1-9; 2-0; 3-1. All patients have completed study and have a minimum of 12 months follow-up. Patients came off study as follows: completed 3 or more cycles of treatment 26; progressive disease 1; toxicity 5; other 1; early death 1. Thirty-one patients remain alive with three deceased; one at day 4 (ECOG 3), while the other two occurred off-study. Thirty-three patients received at least one full cycle of treatment and a decrease of > 50% in the lymphocyte count occurred in all 33 (mean pre- and post-treatment of 89.0 and 7.9 × 109/L, respectively). Responses were evaluable in 32 and classified according to the National Cancer Institute Criteria (1988) as follows: complete remission (CR) 8 (25%); partial response (PR) 20 (62.5%); non-response (NR) 3; progressive disease (PD) 1. A majority of CRs showed residual CLL cells by histologic (nodules in 7/8) or phenotypic (6/8) criteria. The 32 evaluable patients had an overall response rate of 87.5% and a failure rate of 12.5%. Toxicity included infection 12; grade III or IV thrombocytopenia 2; and autoimmune haemolysis 1. Analysis with duration of response, at average 20 months (minimum 12 months) follow-up, will be presented. 2-CdA given by a shortened infusion schedule over 5 days results in a high response rate. [ABSTRACT FROM AUTHOR]

In the original publication of the article, under the heading Discussion, 1st paragraph, the sentence that reads as, “Nonetheless, our observed improvements of over 50% for OS and over 30% for DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies” should read as “Nonetheless, our observed improvements of over 50% for OS and DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies.” Under the heading Discussion, 3rd paragraph, the sentence that reads as “We cannot discount the possibility …such as education, income and access to care [1, 7]” should read as “We cannot discount the possibility…such as education, income and access to care, which ultimately have on survival outcomes [1, 7].” [ABSTRACT FROM AUTHOR]

In recent years the ratio of inhaled corticosteroid:bronchodilator (C:B) prescribing has been promoted as a quality marker for asthma treatment and cross-sectional data indicate an association with hospital admissions. If prescribing advice has been followed then it can be hypothesised that the C:B ratio will have increased and hospitalisation decreased. The West Midlands General Practice Research Database was used to monitor changes in the C:B ratio and hospital referrals for asthma between 1993 and 1996. The C:B ratio increased from 0.5 to 0.6 (P<0.001) and hospital referrals decreased from 7% to 4% per annum (P<0.001). Overall, 38% of the variation in hospital referrals was explained by the C:B ratio. This is higher than previous studies, perhaps because the study was longitudinal and the ratio assessed accurately in terms of volume rather than prescription items. When measured in defined daily doses, the C:B ratio does appear to have validity as an indicator of good prescribing in primary care. The General Practice Research Database offers an opportunity for assessing the validity of prescribing indicators before they are considered for wider use by Primary Care Groups and Health Authorities. [ABSTRACT FROM AUTHOR]