Cross-sectional study of the provision of interventional oncology services in the UK

Objective: To map out the current provision of interventional oncology (IO) services in the UK. Design: Cross-sectional multicentre study. Setting: All National Health Service (NHS) trusts in England and Scottish, Welsh and Northern Ireland health boards. Participants: Interventional radiology (IR) departments in all NHS trusts/health boards in the UK. Results: A total of 179 NHS trusts/health boards were contacted. We received a 100% response rate. Only 19 (11%) institutions had an IO lead. 144 trusts (80%) provided IO services or had a formal pathway of referral in place for patients to a recipient trust. 21 trusts (12%) had plans to provide an IO service or formal referral pathway in the next 12 months only. 14 trusts (8%) did not have a pathway of referral and no plans to implement one. 70 trusts (39%) offered supportive and disease-modifying procedures. One trust had a formal referral pathway for supportive procedures. 73 trusts (41%) provided only supportive procedures (diagnostic or therapeutic). Of these, 43 (59%) had a referral pathway for disease-modifying IO procedures, either from a regional cancer network or through IR networks and 30 trusts (41%) did not have a referral pathway for disease-modifying procedures. Conclusion: The provision of IO services in the UK is promising; however, collaborative networks are necessary to ensure disease-modifying IO procedures are made accessible to all patients and to facilitate larger registry data for research with commissioning of new services

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

Background: Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20–30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.Objectives: To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.Data sources: Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.Review methods: Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.Results: The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of –£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ? 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.Conclusions: There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.Source of funding: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research

The Carina Nebula and Gum 31 molecular complex: II. The distribution of the atomic gas revealed in unprecedented detail

We report high spatial resolution observations of the HI 21cm line in the Carina Nebula and the Gum 31 region obtained with the Australia Telescope Compact Array. The observations covered $\sim$ 12 deg$^2$ centred on $l= 287.5\deg,b = -1\deg$, achieving an angular resolution of $\sim$ 35 arcseconds. The HI map revealed complex filamentary structures across a wide range of velocities. Several "bubbles" are clearly identified in the Carina Nebula Complex, produced by the impact of the massive star clusters located in this region. An HI absorption profile obtained towards the strong extragalactic radio source PMN J1032--5917 showed the distribution of the cold component of the atomic gas along the Galactic disk, with the Sagittarius-Carina and Perseus spiral arms clearly distinguishable. Preliminary calculations of the optical depth and spin temperatures of the cold atomic gas show that the HI line is opaque ($\tau \gtrsim$ 2) at several velocities in the Sagittarius-Carina spiral arm. The spin temperature is $\sim100$ K in the regions with the highest optical depth, although this value might be lower for the saturated components. The atomic mass budget of Gum 31 is $\sim35 \%$ of the total gas mass. HI self absorption features have molecular counterparts and good spatial correlation with the regions of cold dust as traced by the infrared maps. We suggest that in Gum 31 regions of cold temperature and high density are where the atomic to molecular gas phase transition is likely to be occurring.Comment: 20 pages, 1 table, 16 Figures, Accepted for Publication in the Monthly Notices of the Royal Astronomical Society Journa

Focused Ion Beam induced hydride formation does not affect Fe, Ni, Cr-clusters in irradiated Zircaloy-2

Room temperature focused ion beam (FIB) milling is known to potentially promote the formation of hydrides in zirconium and its alloys. We used atom probe tomography (APT) to determine the composition of irradiated and as-produced Zircaloy-2 fuel cladding. We consistently found ∼ 50 at% hydrogen in all room temperature FIB-milled specimens run in voltage pulsing APT measurements. Crystallographic analysis of APT data however showed slightly better agreement with δ-hydride (ZrH2, FCC, ∼ 60–66.7 at% H) than γ-hydride (ZrH, FCT, ∼ 50 at% H). Electron energy loos spectroscopy (EELS) measurements prior to APT analyses confirmed the presence of δ-hydride. Hence, APT gives a systematic underestimation of hydrogen for Zr-hydride. Milling at cryogenic temperatures was found to not cause such hydride formation. However, we did not find significant differences in the clusters formed by segregation of the alloying elements Fe, Cr and Ni to irradiation induced a-loops whether the material was identified as α-Zr or hydride. Therefore, analyzing irradiation-induced redistribution of alloying elements in Zr fuel cladding using APT does not rely on FIB preparation at cryogenic temperatures. However, in conjunction with voltage pulsing APT cryo-FIB can be worthwhile if one aims at investigating hydrogen distribution or hydrides

Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease.

BACKGROUND: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group. METHODS: A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays. RESULTS: PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients. CONCLUSION: Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.The authors would like to acknowledge the study funders: the Big Lottery Fund (C498A738) and Parkinson’s UK (J-0802). The research was supported by a National Institute of Health Research Biomedical Research Award (to Addenbrooke’s Hospital/University of Cambridge), the Wellcome Trust (103838, 100333/Z/12/Z) and a Raymond and Beverly Sackler Studentship (to DPB). We would like to thank staff at the Wellcome Trust Clinical Research Facility in Addenbrooke’s Hospital, Cambridge for performing the melatonin blood sampling.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/mds.2659

Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors

RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies

Receiving the news of a diagnosis of motor neurone disease: what does it take to make it better?

Our objectives were to identify the experiences of people with MND in receiving the diagnosis and to determine which aspects of breaking this bad news were associated with greater satisfaction with the way the diagnosis was delivered to them. An anonymous postal survey was facilitated by all MND associations in Australia, in 2014, and centred on the SPIKES protocol for communicating bad news. Of the patients (n?=?248, response rate 29%), 36% were dissatisfied with the delivery of the diagnosis and gave low ratings on the ability/skills of their neurologists to deliver the diagnosis. It was evident that the longer the patients spent with their neurologists during breaking such bad news, the more they were satisfied and the higher they rated the neurologists' abilities/skills. The largest significant differences between neurologists rated as having high or low skills in delivering the diagnosis were in four domains: 1) responding empathically to the feelings of patient/family; 2) sharing the information and suggesting realistic goals; 3) exploring what patient/family are expecting or hoping for; and 4) making a plan and following through. In conclusion, with over one-third of patients dissatisfied with their experience, there is room for improvement in the practice of neurologists in specified areas that could form the basis for changing practice, and the development of standards and protocols likely to have implications at the international level