A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia.

Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35-44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50-0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01-2.21), P=0.04) due to lower NRM (34 vs 14%, P=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57-0.97), P=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35-44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (P=0.3).

Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness.

OBJECTIVE: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. DESIGN: A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. SETTING: Two large obstetric units in the UK. PARTICIPANTS: Women booked for delivery at the participating units other than those electing for a Caesarean delivery. INTERVENTIONS: Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. MAIN OUTCOME MEASURES: The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. RESULTS: PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79-88%); vaginal swab 58% (52-64%); rectal swab 71% (66-76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85-89%); vaginal swab 92% (90-94%); rectal swab 92% (90-93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35-37 weeks' gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. CONCLUSIONS: Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35-37 weeks' gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.

Comparison of the adjoint and influence coefficient methods for solving the inverse hyperthermia problem.

An adjoint formulation is derived and used to determine the elements in the Jacobian matrix associated with the inverse problem of estimating the blood perfusion and temperature fields during hyperthermia cancer treatments. This method and a previously developed influence coefficient method for obtaining that matrix are comparatively evaluated by solving a set of numerically simulated inverse hyperthermia problems. The adjoint method has the advantage of requiring fewer solutions of the bioheat transfer equation to estimate the Jacobian than does the influence coefficient method when the number of measurement sensors is significantly smaller than the number of unknown parameters. Thus, it could be a preferable method to use in hyperthermia applications where the number of sensors is strictly limited by patient considerations. However, the adjoint method requires that CPU time intensive convolutions be numerically evaluated. Comparisons of the performance of the adjoint formulation and the influence coefficient method show that, first, there is a critical ratio of the number of measurement sensors to the number of unknown parameters at which the CPU time per iteration required to calculate the Jacobian matrix is the same for both methods. The adjoint method is faster than the influence coefficient method only when the value of the ratio is less than that critical value. For the hyperthermia problems investigated in the present study, this only occurs for cases with a very small number of measurement sensors. This presents a potential problem for clinical applications because the fewer measurement sensors used, the less information that can be gathered to correctly solve the inverse problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled comparison of short-wave diathermy treatment with osteopathic treatment in non-specific low back pain.

The effectiveness of spinal manipulation carried out by a non-medical qualified osteopath was compared with that of short-wave diathermy (SWD) and a placebo (detuned SWD) in 109 patients with low back pain. More than half the subjects in each of the 3 treatment groups benefited immediately from therapy. Significant improvements were observed in the 3 groups at the end of 2 weeks' treatment, and these were still apparent at 12 weeks. The outcome of treatment was unrelated to the initial severity or duration of pain or to the trend of pain towards deterioration or improvement. It is, therefore, unlikely that the results simply reflect the natural history of low back pain. Benefits obtained with osteopathy and SWD in this study may have been achieved through a placebo effect.