Developing an intervention to optimise the outcome of cardiac surgery in people with diabetes: the OCTOPuS pilot study.

BACKGROUND: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to improved postoperative outcomes. The aim of this study was to develop and pilot a specialist diabetes team-led intervention to improve surgical outcomes in people with diabetes. DESIGN: Open pilot feasibility study SETTING: Diabetes and cardiothoracic surgery departments, University Hospital Southampton NHS Foundation Trust PARTICIPANTS: Seventeen people with diabetes undergoing cardiothoracic surgery INTERVENTION: Following two rapid literature reviews, a prototype intervention was developed based on a previously used nurse-led outpatient intervention and tested. PRIMARY OUTCOME: Feasibility and acceptability of delivering the intervention SECONDARY OUTCOMES: Biomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In depth qualitative interviews with participants and healthcare professionals were used to explore perceptions and experiences of the intervention and how it might be improved. RESULTS: Thirteen of the 17 people recruited completed the study and underwent cardiothoracic surgery. All components of the OCTOPuS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention as a result of feedback from the participants and healthcare professionals. Median (IQR) HbA1c was 10 mmol/mol (3, 13) lower prior to surgery than at baseline. CONCLUSION: This study has shown that it is possible to develop a clinical pathway to improve diabetes management prior to admission. The clinical and cost-effectiveness of this intervention will now be tested in a multicentre randomised controlled trial in cardiothoracic centres across the UK. TRIAL REGISTRATION: ISRCTN; ISRCTN10170306 . Registered 10 May 2018.

The INTRABEAM® Photon Radiotherapy System for the adjuvant treatment of early breast cancer: a systematic review and economic evaluation.

BACKGROUND: Initial treatment for early breast cancer is usually either breast-conserving surgery (BCS) or mastectomy. After BCS, whole-breast external beam radiotherapy (WB-EBRT) is the standard of care. A potential alternative to post-operative WB-EBRT is intraoperative radiation therapy delivered by the INTRABEAM(®) Photon Radiotherapy System (Carl Zeiss, Oberkochen, Germany) to the tissue adjacent to the resection cavity at the time of surgery. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of INTRABEAM for the adjuvant treatment of early breast cancer during surgical removal of the tumour. DATA SOURCES: Electronic bibliographic databases, including MEDLINE, EMBASE and The Cochrane Library, were searched from inception to March 2014 for English-language articles. Bibliographies of articles, systematic reviews, clinical guidelines and the manufacturer's submission were also searched. The advisory group was contacted to identify additional evidence. METHODS: Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were conducted. Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to full texts of retrieved papers by one reviewer and checked by a second reviewer. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, and differences in opinion were resolved through discussion at each stage. Clinical effectiveness studies were included if they were carried out in patients with early operable breast cancer. The intervention was the INTRABEAM system, which was compared with WB-EBRT, and study designs were randomised controlled trials (RCTs). Controlled clinical trials could be considered if data from available RCTs were incomplete (e.g. absence of data on outcomes of interest). A cost-utility decision-analytic model was developed to estimate the costs, benefits and cost-effectiveness of INTRABEAM compared with WB-EBRT for early operable breast cancer. RESULTS: One non-inferiority RCT, TARGeted Intraoperative radioTherapy Alone (TARGIT-A), met the inclusion criteria for the review. The review found that local recurrence was slightly higher following INTRABEAM than WB-EBRT, but the difference did not exceed the 2.5% non-inferiority margin providing INTRABEAM was given at the same time as BCS. Overall survival was similar with both treatments. Statistically significant differences in complications were found for the occurrence of wound seroma requiring more than three aspirations (more frequent in the INTRABEAM group) and for a Radiation Therapy Oncology Group toxicity score of grade 3 or 4 (less frequent in the INTRABEAM group). Cost-effectiveness base-case analysis indicates that INTRABEAM is less expensive but also less effective than WB-EBRT because it is associated with lower total costs but fewer total quality-adjusted life-years gained. However, sensitivity analyses identified four model parameters that can cause a switch in the treatment option that is considered cost-effective. LIMITATIONS: The base-case result from the model is subject to uncertainty because the disease progression parameters are largely drawn from the single available RCT. The RCT median follow-up of 2 years 5 months may be inadequate, particularly as the number of participants with local recurrence is low. The model is particularly sensitive to this parameter. CONCLUSIONS AND IMPLICATIONS: A significant investment in INTRABEAM equipment and staff training (clinical and non-clinical) would be required to make this technology available across the NHS. Longer-term follow-up data from the TARGIT-A trial and analysis of registry data are required as results are currently based on a small number of events and economic modelling results are uncertain. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006720. FUNDING: The National Institute for Health Research Health Technology Assessment programme. Note that the economic model associated with this document is protected by intellectual property rights, which are owned by the University of Southampton. Anyone wishing to modify, adapt, translate, reverse engineer, decompile, dismantle or create derivative work based on the economic model must first seek the agreement of the property owners.

An economic model of school-based behavioral interventions to prevent sexually transmitted infections.

OBJECTIVES: Reducing sexually transmitted infections (STI) and teenage pregnancy through effective health education is a high priority for health policy. Behavioral interventions which teach skills to practice safer sex may reduce the incidence of STIs. We evaluated the cost-effectiveness of school-based behavioral interventions in young people. METHODS: We developed an economic model to estimate the total number of STI cases averted, consequent gain in health related quality of life (HRQoL) and savings in medical costs, based on changes in sexual behavior. The parameters for the model were derived from a systematic literature search on the intervention effectiveness, epidemiology of STIs, sexual behavior and lifestyles, HRQoL and health service costs. RESULTS: The costs of providing teacher-led and peer-led behavioral interventions were €5.16 and €18 per pupil, respectively. For a cohort of 1000 boys and 1000 girls aged 15 years, the model estimated that the behavioral interventions would avert two STI cases and save 0.35 Quality Adjusted Life Years (QALYs). Compared to standard education, the incremental cost-effectiveness of the teacher-led and peer-led interventions was €24,268 and €96,938 per QALY gained, respectively. CONCLUSIONS: School-based behavioral interventions which provide information and teach young people sexual health skills can bring about improvements in knowledge and increased self-efficacy, though these may be limited in terms of impact on sexual behavior. There was uncertainty around the results due to the limited effect of the intervention on behavioral outcomes and paucity of data for other input parameters.

Characterization of NO-sensitive guanylyl cyclase: expression in an identified interneuron involved in NO-cGMP-dependent memory formation.

In a number of neuronal models of learning signalling by endogenous nitric oxide (NO), produced by the enzyme NO synthase (NOS), is essential for the formation of long-term memory (LTM). For example, in the molluscan model system Lymnaea, NO is required for LTM formation in the first few hours after one-trial reward conditioning. Furthermore, conditioning leads to transient up-regulation of the NOS gene in identified modulatory neurons, the cerebral giant cells (CGCs), which are known to be involved in LTM formation. In Lymnaea nothing is known however about the structure and localization of the major receptor for NO, the soluble guanylyl cyclase (sGC). Here we report on the cloning and characterization of both alpha and beta subunits of NO-sensitive sGC and show that they are coexpressed in the CGCs. Furthermore, our electrophysiological experiments on isolated CGCs show that these neurons respond to NO by generating a prolonged depolarization of the membrane potential. Moreover, we demonstrate that this depolarization is blocked by ODQ, supporting our hypothesis that it is mediated by sGC.