Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.

BACKGROUND: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. METHODS: Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). FINDINGS: After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%. INTERPRETATION: Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of developing cognitive and motor impairments compared with infants born at term. Early developmental interventions have been used in the clinical setting with the aim of improving the overall functional outcome for these infants. However, the benefit of these programs remains unclear. OBJECTIVES: To review the effectiveness of early developmental intervention post-discharge from hospital for preterm (< 37 weeks) infants on motor or cognitive development. SEARCH STRATEGY: The Cochrane Neonatal Review group search strategy was used to identify randomised and quasi-randomised controlled trials of early developmental interventions post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE Advanced, CINAHL, PsychINFO and EMBASE (1966 through February 2006). SELECTION CRITERIA: Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programs that commenced within the first 12 months of life for infants born at < 37 weeks with no major congenital abnormalities. Intervention could commence as an inpatient; however, a post discharge component was necessary to be included in this review. The outcome measures were not pre-specified other than that they had to assess cognitive and/or motor ability. The rates of intellectual impairment, cerebral palsy and development co-ordination disorder were also documented. DATA COLLECTION AND ANALYSIS: Data were extracted and entered by two independent review authors. Cognitive and motor outcomes were pooled in three age groups - infant (0 to 2 years), preschool (3 to < 5 years) or school age (5 to 17 years). Meta-analysis was carried out using RevMan 4.2 to determine the effects of early developmental intervention in the short (0 to 2 years), medium (3 to < 5 years) and long term (5 to 17 years). Subgroup analysis was carried out in relation to; gestational age, birthweight, brain injury, commencement of intervention, focus of intervention and study quality. MAIN RESULTS: Sixteen studies met the inclusion criteria (2379 randomised patients). Six of these studies were RCTs and had strong methodological quality. There was variability with regard to the focus and intensity of the intervention, and in length of follow-up. Meta-analysis concluded that intervention improved cognitive outcomes at infant age (developmental quotient [DQ]: standard mean difference [SMD] 0.46 SD; 95% CI 0.36 0.57; P < 0.0001), and at preschool age (intelligence quotient [IQ]; SMD 0.46 SD; 95%CI 0.33, 0.59; P < 0.0001). However, this effect was not sustained at school age (IQ; SMD 0.02 SD; 95% CI -0.10, 0.14; P = 0.71). There was significant heterogeneity between studies for cognitive outcomes at infant and school ages. There was little evidence of an effect of early intervention on motor outcomes in the short, medium or long-term, but there were only two studies reporting outcomes beyond 2 years. AUTHORS' CONCLUSIONS: Early intervention programs for preterm infants have a positive influence on cognitive outcomes in the short to medium term. However, there was significant heterogeneity between the interventions included in this review. Further research is needed to determine which early developmental interventions are the most effective at improving cognitive and motor outcomes, and on the longer-term effects of these programs. Cost-effectiveness and access to services should also be evaluated since they are important factors when considering implementation of an early developmental intervention program for a preterm infant.

Influence of ventilatory mode on target concentrations required for anaesthesia using a 'Diprifusor' TCI system.

This study examined the influence of mode of ventilation (spontaneous or controlled) on the target blood concentrations required to maintain anaesthesia with 'Diprifusor' (a target controlled infusion system for propofol) in 40 healthy, unpremedicated, adult patients undergoing knee arthroscopy. All patients were given alfentanil (10 micrograms.kg-1) and ketorolac (10 mg) immediately before induction and all received a 2:1 mixture of nitrous oxide:oxygen. An initial target blood concentration of propofol of 6.0 micrograms.ml-1 was used in most patients to induce anaesthesia. The blood target concentration required to produce acceptable anaesthetic conditions was not significantly influenced by the mode of ventilation. The mean maintenance target concentration for propofol was 3.9 (SD 0.83) micrograms.ml-1 in the ventilated group and 3.5 (SD 0.82) micrograms.ml-1 in the group of patients breathing spontaneously.

Practical optoelectronic neural network realizations based on the fault tolerance of the backpropagation algorithm.

This paper describes how the fault tolerance of the backpropagation algorithm can be used to accommodate the realistic (nonideal) transfer characteristics of the optical communication links used, between neural layers, in optoelectronic neural networks. In particular the authors demonstrate that networks, utilizing MSM (metal-semiconductor-metal) photodiodes (PDs) and either LED (light emitting diode) or MQW (multiple quantum well) laser transmitters within these intraneural links, are capable of performing satisfactorily even in the presence of such nonideal device phenomena as: 60% optical crosstalk, 50% optoelectronic device variation, or a thresholded (I(th)=0.5*I(max)) laser output characteristic. Subsequent to this, the authors then show how it is possible to use this fault tolerance to simplify the neuron architecture, to the extent that it consists only of MSM PDs a current amplifier, and an MQW laser. The overall neuron transfer function is then a first-order approximation to the original sigmoidal function.

Weight and neuron output resolution requirements in optoelectronic neural networks.

We demonstrate that the resolution requirements of the optoelectronic devices used in the communication links of an analog multiperceptron neural network, trained with the standard backpropagation algorithm, can be simultaneously reduced to 8 bits (receiver) and 4 bits (transmitter), respectively, without any significant effect on the network's learning or generalization performances. In addition, we also show that a simple modification to the sigmoidal function, used within each neuron architecture, permits the resolution requirements of the optoelectronic receiver to be further reduced to 4 bits without any additional effect on network performance other than a reduction in learning rate. Both of these limited device resolution performances, however, can be achieved only provided that the weight-storage and the weight-updating procedures are maintained at 14 bits or greater.

Detecting awareness during general anaesthetic caesarean section. An evaluation of two methods.

Seventy-four patients received general anaesthesia for Caesarean section. Seven percent of the elective group and 28% of the emergency patients reported dreaming or recall of voices during the procedure (p less than 0.05) at postoperative interview. One patient from each group reported feeling pain or suffocation. All patients were monitored for awareness using the isolated forearm technique and lower oesophageal contractility. Provoked lower oesophageal contractility was the most effective of the different indices. A value greater than 35 mmHg on at least one occasion had a false negative rate of 33%, a false positive rate of 28% and a predictive value of 25%. A value greater than 13 mmHg picked up all patients who dreamed, with a false positive rate of 68%. Both of the 'aware' patients had provoked lower oesophageal contractility response of greater than 70 mmHg, an attribute shared by only 8% of the rest. The isolated forearm was particularly ineffective.

Medical problems of recreational diving.

The commonly encountered clinical disorders including emergencies confronting the recreational diver are described in this article. The quality of early management critically alters the outcome and with appropriate treatment complete recovery is possible. Serious disability and death can result from inadequate care before the patient reaches hospital.