BRAVEHeart: a randomised trial comparing the accuracy of Breathe Well and RPM for deep inspiration breath hold breast cancer radiotherapy.

BACKGROUND: Deep inspiration breath hold (DIBH) reduces radiotherapy cardiac dose for left-sided breast cancer patients. The primary aim of the BRAVEHeart (Breast Radiotherapy Audio Visual Enhancement for sparing the Heart) trial is to assess the accuracy and usability of a novel device, Breathe Well, for DIBH guidance for left-sided breast cancer patients. Breathe Well will be compared to an adapted widely available monitoring system, the Real-time Position Management system (RPM). METHODS: BRAVEHeart is a single institution prospective randomised trial of two DIBH devices. BRAVEHeart will assess the DIBH accuracy for Breathe Well and RPM during left-sided breast cancer radiotherapy. After informed consent has been obtained, 40 patients will be randomised into two equal groups, the experimental arm (Breathe Well) and the control arm (RPM with in-house modification of an added patient screen). The primary hypothesis of BRAVEHeart is that the accuracy of Breathe Well in maintaining the position of the chest during DIBH is superior to the RPM system. Accuracy will be measured by comparing chest wall motion extracted from images acquired of the treatment field during breast radiotherapy for patients treated using the Breathe Well system and those using the RPM system. DISCUSSION: The Breathe Well device uses a depth camera to monitor the chest surface while the RPM system monitors a block on the patient's abdomen. The hypothesis of this trial is that the chest surface is a better surrogate for the internal chest wall motion used as a measure of treatment accuracy. The Breathe Well device aims to deliver an easy-to-use implementation of surface monitoring. The findings from the study will help inform the technology choice for other centres performing DIBH. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881203 . Registered on 26 August 2016.

Big Data Readiness in Radiation Oncology: An Efficient Approach for Relabeling Radiation Therapy Structures With Their TG-263 Standard Name in Real-World Data Sets.

PURPOSE: To prepare for big data analyses on radiation therapy data, we developed Stature, a tool-supported approach for standardization of structure names in existing radiation therapy plans. We applied the widely endorsed nomenclature standard TG-263 as the mapping target and quantified the structure name inconsistency in 2 real-world data sets. METHODS AND MATERIALS: The clinically relevant structures in the radiation therapy plans were identified by reference to randomized controlled trials. The Stature approach was used by clinicians to identify the synonyms for each relevant structure, which was then mapped to the corresponding TG-263 name. We applied Stature to standardize the structure names for 654 patients with prostate cancer (PCa) and 224 patients with head and neck squamous cell carcinoma (HNSCC) who received curative radiation therapy at our institution between 2007 and 2017. The accuracy of the Stature process was manually validated in a random sample from each cohort. For the HNSCC cohort we measured the resource requirements for Stature, and for the PCa cohort we demonstrated its impact on an example clinical analytics scenario. RESULTS: All but 1 synonym group ("Hydrogel") was mapped to the corresponding TG-263 name, resulting in a TG-263 relabel rate of 99% (8837 of 8925 structures). For the PCa cohort, Stature matched a total of 5969 structures. Of these, 5682 structures were exact matches (ie, following local naming convention), 284 were matched via a synonym, and 3 required manual matching. This original radiation therapy structure names therefore had a naming inconsistency rate of 4.81%. For the HNSCC cohort, Stature mapped a total of 2956 structures (2638 exact, 304 synonym, 14 manual; 10.76% inconsistency rate) and required 7.5 clinician hours. The clinician hours required were one-fifth of those that would be required for manual relabeling. The accuracy of Stature was 99.97% (PCa) and 99.61% (HNSCC). CONCLUSIONS: The Stature approach was highly accurate and had significant resource efficiencies compared with manual curation.

Do acamprosate or naltrexone have an effect on daily drinking by reducing craving for alcohol?

AIM: To explore the effect of acamprosate and naltrexone on craving and alcohol consumption in the treatment of alcohol dependence. DESIGN: A randomized, double-blind, single-dummy, placebo-controlled trial. SETTING: Three treatment centres in Sydney, Australia. PARTICIPANTS: A total of 169 alcohol-dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day) or placebo for 12 weeks, in conjunction with manualized medication compliance therapy. INTERVENTION: During the course of the trial, participants kept a daily diary which included the number of standard drinks they consumed and their peak craving for alcohol that day rated on a 0-10 scale. MEASUREMENTS: Subjective ratings of daily craving and daily drinking for the first 6 weeks of treatment. FINDINGS: Mixed/hierarchical linear models were employed on an intention-to-treat basis. Analyses revealed that craving was a significant predictor of daily drinking and baseline levels of depression were the best predictor of daily craving. There was no significant improvement in model fit when treatment group was added both in models of daily craving and daily drinking. Daily alcohol consumption was best predicted by a model incorporating baseline dependence and depression scores, and daily craving, entered as a time-varying covariate. However, there was a significant craving x time x treatment interaction (t = -3.365, df = 4413.712, P < 0.001), suggesting that at higher levels of craving drinking was reduced at a significantly greater rate with naltrexone compared to acamprosate. CONCLUSIONS: Naltrexone had a greater effect on drinking when craving was high. These results support the role of naltrexone in reducing craving when that craving is highly salient. The role of acamprosate in reducing craving was not supported by these findings.

Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial.

AIM: To compare the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence. DESIGN: A double-blind, placebo-controlled trial. SETTING: Three treatment centres in Australia. PARTICIPANTS: A total of 169 alcohol dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day) or placebo for 12 weeks. INTERVENTION: All subjects were offered manualized compliance therapy, a brief intervention that targets problems that may affect treatment compliance such as ambivalence and misperceptions about medication. MEASUREMENTS: Time to the first drink, time to first relapse, drinks per drinking day and cumulative abstinence. FINDINGS: In intention-to-treat analyses, there were no differences between groups on outcome measures of drinking, craving or biochemical markers. Similarly, analyses of the 94 subjects that completed the study in full and demonstrated 80% compliance, revealed no significant treatment effects. Differential treatment effects were identified after stratification according to scores on the Alcohol Dependence Scale (ADS) and Depression Anxiety and Stress Scale (DASS). A significant beneficial treatment effect on time to first relapse was revealed for subjects with 'no depression' allocated to naltrexone (n = 56; P < 0.01). In addition, a significant beneficial treatment effect was revealed in subjects with 'low dependence' allocated to naltrexone (n = 34; P < 0.05). CONCLUSIONS: The results of this study support the efficacy of naltrexone in the relapse prevention of alcoholism amongst those with low levels of clinical depression and alcohol dependence severity. No effect of acamprosate was found in our sample.

The crystal structures of dystrophin and utrophin spectrin repeats: implications for domain boundaries.

Dystrophin and utrophin link the F-actin cytoskeleton to the cell membrane via an associated glycoprotein complex. This functionality results from their domain organization having an N-terminal actin-binding domain followed by multiple spectrin-repeat domains and then C-terminal protein-binding motifs. Therapeutic strategies to replace defective dystrophin with utrophin in patients with Duchenne muscular dystrophy require full-characterization of both these proteins to assess their degree of structural and functional equivalence. Here the high resolution structures of the first spectrin repeats (N-terminal repeat 1) from both dystrophin and utrophin have been determined by x-ray crystallography. The repeat structures both display a three-helix bundle fold very similar to one another and to homologous domains from spectrin, α-actinin and plectin. The utrophin and dystrophin repeat structures reveal the relationship between the structural domain and the canonical spectrin repeat domain sequence motif, showing the compact structural domain of spectrin repeat one to be extended at the C-terminus relative to its previously defined sequence repeat. These structures explain previous in vitro biochemical studies in which extending dystrophin spectrin repeat domain length leads to increased protein stability. Furthermore we show that the first dystrophin and utrophin spectrin repeats have no affinity for F-actin in the absence of other domains.