Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial.

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate [ß (standard deviation difference vs. placebo): 0.69; 95% CI = 0.24, 1.15; p = 0.003], valine (ß: -0.62; -1.03, -0.02; p = 0.004), pyruvate (ß: -0.56; -0.95, -0.16; p = 0.006) and docosahexaenoic acid (ß: -0.50; -085, -0.14; p = 0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (ß: -0.65; -1.04, -0.26; p = 0.001 and ß: -0.59; -1.01, -0.18; p = 0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p = 0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.

Is a preoperative group and save necessary for enhanced recovery joint replacement patients?

AIM: To consider the financial benefit to the authors' trust of omitting a preoperative group and save in enhanced recovery arthroplasty patients, and to estimate the scope for national savings. Patient safety was considered to determine acceptability for routine practice. METHODS: A total of 121 patients receiving a total knee replacement or total hip replacement on the authors' enhanced recovery protocol were selected. Pre- and postoperative haemoglobin levels were obtained. The transfusion team were contacted when the postoperative haemoglobin level was ≤8 g/dl to determine whether blood products had been issued. Costs for group and save were obtained from the pathology department. RESULTS: Mean postoperative reduction in haemoglobin level was 2.6 g/dl (P≤0.001) and 2.1 g/dl (P≤0.001) for total hip replacement and total knee replacement respectively. No patients were transfused. One group and save costs £12.00, and omission of this test in these patients would have saved £1452.00. Potentially, £1 605 408 could have been saved in the 133 784 patients undergoing NHS arthroplasty in 2012. Group and save omission would not affect management of intraoperative haemorrhage where O negative blood would be available. If a transfusion is required postoperatively it would take 100 minutes to issue crossmatched blood - a time delay unlikely to compromise patient safety. CONCLUSIONS: These results suggest that a preoperative group and save could be omitted in arthroplasty patients on this enhanced recovery programme to prevent needless expenditure, but more long-term follow up is required to ensure patients are not put at risk.

Predicting response to rhDNase and hypertonic saline in children with cystic fibrosis.

Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). Alternate-day rhDNase and hypertonic saline (HS) represent potential cheaper alternative therapies. However, not all patients improve on treatment. To assess response, many CF centers have developed formal n-of-1 trials of treatment to find out who benefits. Response to daily rhDNase at 3 months has been shown to be a good predictor of response at 1 year. There are no data correlating individual response at a shorter time period with 3-month response. We assessed whether individual responses to daily rhDNase, alternate-day rhDNase, and HS could be predicted from lung function response at 6 weeks, thus shortening the n-of-1 trial, or from baseline patient characteristics, therefore avoiding the need for an n-of-1 trial. In a randomized crossover trial, 48 CF children were allocated consecutively to 12 weeks of once-daily 2.5-mg rhDNase, alternate-day 2.5-mg rhDNase, and twice-daily 5 ml of 7% HS. Forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were measured at baseline and then at 6 and 12 weeks into each treatment period. Lung function response to the drugs at 6 weeks was highly predictive of response at 3 months. There was some evidence that response to HS was worse in patients with lower baseline lung function. However, there was no association between response to alternate-day or daily rhDNase and baseline characteristics. In conclusion, response to rhDNase and HS at 6 weeks was highly predictive of response at 3 months. For daily and alternate-day rhDNase, at least, the drug needs to be administered for at most 6 weeks initially to assess long-term response to treatment. Response to treatment could not be reliably predicted from baseline characteristics.