ACCERT: Auckland's cancer cachexia evaluating resistance training study

Background: Cancer Cachexia (CC) is a common problem seen in many advanced malignancies including Non- Small-Cell Lung Cancer (NSCLC). In CC there is a significant loss of adipose tissue and skeletal muscle mass. Muscle wasting is the main cause of impaired function, leading to respiratory complications and fatigue. The optimal treatment for CC is the complete removal of the tumour; unfortunately with advanced NSCLC this is unachievable. The next best options are to increase nutritional intake to counteract weight loss, address the anorexia, inflammation, and metabolic alterations i.e. loss of body fat and the skeletal muscle wasting. This requires the need to utilise a multi-targeted approach to decrease the inflammation and to stimulate the skeletal anabolic pathways with the use of progressive resistance training (PRT). PRT has shown acceptability and benefits in other cancer populations. This study aims to identify a novel multi-targeted treatment regimen that will alleviate and/or stabilise CC weight loss. Methods: This is a randomised, open-label study to investigate whether 2 sessions each week of PRT followed by essential amino acids (EAA's) high in leucine, when administered in addition to Eicosapentaenoic Acid (EPA) and a Cox-2 inhibitor is acceptable to NSCLC cachectic patients for a period of 20 weeks (primary endpoint). Secondary endpoints include Lean Body Mass, MRI thigh skeletal muscle values, QoL and Fatigue questionnaires, serum pro-inflammatory cytokine profiles, and hand and leg strength. Safety data will also be collected. Outcome measures to power a future study will be determined from the trend in difference between the two groups. 21 patients are planned to be randomised in a 1:2 ratio Arm A EPA and Cox-2 inhibitor vs. Arm B EPA, Cox-2 inhibitor, PRT followed by EAA's. All patients are offered to continue with the study medications and/or PRT sessions on compassionate use. Main inclusion criteria include: histological proven NSCLC patients who have at least 5% weight loss and fulfil the following cachectic definition (Evans Clin Nut 2008 27). A guest patient was enrolled in May 2012, followed by study participants in June 201

Contamination in trials of educational interventions

Objectives: To consider the effects of contamination on the magnitude and statistical significance (or precision) of the estimated effect of an educational intervention, to investigate the mechanisms of contamination, and to consider how contamination can be avoided. Data sources: Major electronic databases were searched up to May 2005. Methods: An exploratory literature search was conducted. The results of trials included in previous relevant systematic reviews were then analysed to see whether studies that avoided contamination resulted in larger effect estimates than those that did not. Experts’ opinions were elicited about factors more or less likely to lead to contamination. We simulated contamination processes to compare contamination biases between cluster and individually randomised trials. Statistical adjustment was made for contamination using Complier Average Causal Effect analytic methods, using published and simulated data. The bias and power of cluster and individually randomised trials were compared, as were Complier Average Causal Effect, intention-to-treat and per protocol methods of analysis. Results: Few relevant studies quantified contamination. Experts largely agreed on where contamination was more or less likely. Simulation of contamination processes showed that, with various combinations of timing, intensity and baseline dependence of contamination, cluster randomised trials might produce biases greater than or similar to those of individually randomised trials. Complier Average Causal Effect analyses produced results that were less biased than intention-to-treat or per protocol analyses. They also showed that individually randomised trials would in most situations be more powerful than cluster randomised trials despite contamination. Conclusions: The probability, nature and process of contamination should be considered when designing and analysing controlled trials of educational interventions in health. Cluster randomisation may or may not be appropriate and should not be uncritically assumed always to be a solution. Complier Average Causal Effect models are an appropriate way to adjust for contamination if it can be measured. When conducting such trials in future, it is a priority to report the extent, nature and effects of contamination.We are grateful to the National Health Service Research and Development National Coordinating Centre for Research Methodology for funding this research

Nucleosome conformation dictates the histone code

Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' that are read by specialized regions (reader domains) in chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP: histone PTM] specificities, and thus decipher the histone code and guide epigenetic therapies. However, this has largely been done using the reductive approach of isolated reader domains and histone peptides, which cannot account for any higher-order factors. Here, we show that the [BPTF PHD finger and bromodomain: histone PTM] interaction is dependent on nucleosome context. The tandem reader selectively associates with nucleosomal H3K4me3 and H3K14ac or H3K18ac, a combinatorial engagement that despite being in cis is not predicted by peptides. This in vitro specificity of the BPTF tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. We propose that regulatable histone tail accessibility and its impact on the binding potential of reader domains necessitates we refine the 'histone code' concept and interrogate it at the nucleosome level

The Cholecystectomy As A Day Case (CAAD) score: a validated score of preoperative predictors of successful day-case cholecystectomy using the CholeS data set

Background: Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods: Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results: Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions: The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Acute Physiological Responses to Strongman Training Compared to Traditional Strength Training

Harris, NK, Woulfe, CJ, Wood, MR, Dulson, DK, Gluchowski, AK, and Keogh, JB. Acute physiological responses to strongman training compared to traditional strength training. J Strength Cond Res 30(5): 1397–1408, 2016—Strongman training (ST) has become an increasingly popular modality, but data on physiological responses are limited. This study sought to determine physiological responses to an ST session compared to a traditional strength exercise training (RST) session. Ten healthy men (23.6 6 27.5 years, 85.8 6 10.3 kg) volunteered in a crossover design, where all participants performed an ST session, an RST session, and a resting session within 7 days apart. The ST consisted of sled drag, farmer’s walk, 1 arm dumbbell clean and press, and tire flip at loads eliciting approximately 30 seconds of near maximal effort per set. The RST consisted of squat, deadlift, bench press, and power clean, progressing to 75% of 1 repetition maximum. Sessions were equated for approximate total set duration. Blood lactate and salivary testosterone were recorded immediately before and after training sessions. Heart rate, caloric expenditure, and substrate utilization were measured throughout the resting session, both training protocols and for 80 minutes after training sessions. Analyses were conducted to determine differences in physiological responses within and between protocols. No significant changes in testosterone occurred at any time point for either session. Lactate increased significantly immediately after both sessions. Heart rate, caloric expenditure, and substrate utilization were all elevated significantly during ST and RST. Heart rate and fat expenditure were significantly elevated compared to resting in both sessions’ recovery periods; calorie and carbohydrate expenditures were not. Compared to RST, ST represents an equivalent physiological stimulus on key parameters indicative of potential training-induced adaptive responses. Such adaptations could conceivably include cardiovascular conditioning

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts: an economic decision model

Objectives: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. Data sources: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. Review methods: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GPprescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. Results: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 £/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 £/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 £/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 £/% cured for OTC duct tape and 0.76 £/% cured for OTC cryotherapy to 1.12 £/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. Conclusions: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more costeffective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts: an economic decision model

Objectives: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. Data sources: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. Review methods: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GPprescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. Results: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 £/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 £/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 £/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 £/% cured for OTC duct tape and 0.76 £/% cured for OTC cryotherapy to 1.12 £/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. Conclusions: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more costeffective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public\ud awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care