A Land-Based Thalassia testudinum Nursery Near Tampa Bay, Florida

An experimental, land-based seagrass nursery, built near Tampa Bay, FL, produced cultivars of Thalassia testudinum Banks and Solander ex König (turtle grass). The nursery was a rectangular basin measuring 6.1 X 12.2 m that graded from 1.5 to 2.0 m in depth constructed inside a fiberglass-covered pole building. The basin had a vinyl liner covered with 10–20 cm of sand and 1.0–1.3 m of water. The nursery ran for 26 mo and focused on producing cultivars of T. testudinum using differing planting techniques. Survival rates were 84% after 3–12 mo in the first planting and 91% after 4 mo in the second planting because early harvesting was required as a result of leaks in the vinyl liner. The planting method that resulted in the highest survival rate was bare rhizomes with two or more short shoots. The cultivars from the two nursery experiments were used in two mitigation projects in Tampa Bay. The nonrecurring cost of the nursery was $12,081.45 over a 3-yr period, and recurring costs are estimated at$22,280.00, with a potential production of 2,500 turf-like 20-cm2 units of T. testudinum that could be sold at $20.00 per planting unit

An Economic Framework for User Financial Incentives for Health Behaviour Change

Background: Diseases such as stroke and heart disease are chiefly caused by unhealthy behaviours and are a major societal burden. User financial incentives are being explored as a way to encourage healthier lifestyles. This research developed a framework to provide information on pricing and cost-effectiveness of incentives and guide design of future incentive schemes. Methods: The workstreams were: a) structured, configurative literature review to identify neo-classical/behavioural economic explanations for behaviour change and incentives; b) contingent valuation survey to identify willingness to accept (WTA) and incentive pricing; c) systematic review and meta-analysis of incentives for weight loss; d) development of decision-analytic model to estimate cost-effectiveness of incentives for weight loss. Results: The reviews identified a number of factors important for understanding the effect of incentives including internal motivation, self-control and time preference. A theoretical framework of incentive impact was developed to facilitate WTA survey design. The WTA survey was completed by 112 people (n=56 at 3 months). 57% strongly disagreed with incentive use. The mean incentive required per month depended on behaviour, ranging £103.69 for smoking cessation to £45.43 for reducing alcohol intake. The most important predictors of WTA were self-control, perceived difficulty of change and attitudes to incentives. There was some evidence that WTA incentives increased over time. Review and meta-regression provided efficacy parameters for the decision-analytic model which comprised the following health states: healthy, type II diabetes, stroke, myocardial infarction and dead. Analyses from NHS and employer perspectives indicated incentives for weight loss are cost-effective over a lifetime as they dominated usual care. Discussion: Incentives may be most powerful if they are personalised to account for individual factors and attitudes and are dynamic in response to these. Incentives may be cost-effective in a number of scenarios. Further research is required on the long term outcomes of incentives and financing models

Equity and the financial costs of informal caregiving in palliative care: a critical debate.

BACKGROUND: Informal caregivers represent the foundation of the palliative care workforce and are the main providers of end of life care. Financial pressures are among the most serious concerns for many carers and the financial burden of end of life caregiving can be substantial. METHODS: The aim of this critical debate paper was to review and critique some of the key evidence on the financial costs of informal caregiving and describe how these costs represent an equity issue in palliative care. RESULTS: The financial costs of informal caregiving at the end of life can be significant and include carer time costs, out of pocket costs and employment related costs. Financial burden is associated with a range of negative outcomes for both patient and carer. Evidence suggests that the financial costs of caring are not distributed equitably. Sources of inequity are reflective of those influencing access to specialist palliative care and include diagnosis (cancer vs non-cancer), socio-economic status, gender, cultural and ethnic identity, and employment status. Effects of intersectionality and the cumulative effect of multiple risk factors are also a consideration. CONCLUSIONS: Various groups of informal end of life carers are systematically disadvantaged financially. Addressing these, and other, determinants of end of life care is central to a public health approach to palliative care that fully recognises the value of carers. Further research exploring these areas of inequity in more depth and gaining a more detailed understanding of what influences financial burden is required to take the next steps towards meeting this aspiration. We will address the conclusions and recommendations we have made in this paper through the work of our recently established European Association of Palliative Care (EAPC) Taskforce on the financial costs of family caregiving

An adaptable implementation package targeting evidence-based indicators in primary care: a pragmatic cluster-randomised evaluation

Background In primary care, multiple priorities and system pressures make closing the gap between evidence and practice challenging. Most implementation studies focus on single conditions, limiting generalisability. We compared an adaptable implementation package against an implementation control and assessed effects on adherence to four different evidence-based quality indicators. Methods and findings We undertook two parallel, pragmatic cluster-randomised trials using balanced incomplete block designs in general practices in West Yorkshire, England. We used ‘opt-out’ recruitment, and we randomly assigned practices that did not opt out to an implementation package targeting either diabetes control or risky prescribing (Trial 1); or blood pressure (BP) control or anticoagulation in atrial fibrillation (AF) (Trial 2). Within trials, each arm acted as the implementation control comparison for the other targeted indicator. For example, practices assigned to the diabetes control package acted as the comparison for practices assigned to the risky prescribing package. The implementation package embedded behaviour change techniques within audit and feedback, educational outreach, and computerised support, with content tailored to each indicator. Respective patient-level primary endpoints at 11 months comprised the following: achievement of all recommended levels of haemoglobin A1c (HbA1c), BP, and cholesterol; risky prescribing levels; achievement of recommended BP; and anticoagulation prescribing. Between February and March 2015, we recruited 144 general practices collectively serving over 1 million patients. We stratified computer-generated randomisation by area, list size, and pre-intervention outcome achievement. In April 2015, we randomised 80 practices to Trial 1 (40 per arm) and 64 to Trial 2 (32 per arm). Practices and trial personnel were not blind to allocation. Two practices were lost to follow-up but provided some outcome data. We analysed the intention-to-treat (ITT) population, adjusted for potential confounders at patient level (sex, age) and practice level (list size, locality, pre-intervention achievement against primary outcomes, total quality scores, and levels of patient co-morbidity), and analysed cost-effectiveness. The implementation package reduced risky prescribing (odds ratio [OR] 0.82; 97.5% confidence interval [CI] 0.67–0.99, p = 0.017) with an incremental cost-effectiveness ratio of £1,359 per quality-adjusted life year (QALY), but there was insufficient evidence of effect on other primary endpoints (diabetes control OR 1.03, 97.5% CI 0.89–1.18, p = 0.693; BP control OR 1.05, 97.5% CI 0.96–1.16, p = 0.215; anticoagulation prescribing OR 0.90, 97.5% CI 0.75–1.09, p = 0.214). No statistically significant effects were observed in any secondary outcome except for reduced co-prescription of aspirin and clopidogrel without gastro-protection in patients aged 65 and over (adjusted OR 0.62; 97.5% CI 0.39–0.99; p = 0.021). Main study limitations concern our inability to make any inferences about the relative effects of individual intervention components, given the multifaceted nature of the implementation package, and that the composite endpoint for diabetes control may have been too challenging to achieve. Conclusions In this study, we observed that a multifaceted implementation package was clinically and cost-effective for targeting prescribing behaviours within the control of clinicians but not for more complex behaviours that also required patient engagement. Trial registration The study is registered with the ISRCTN registry (ISRCTN91989345)

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research

Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo

Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironrnent. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-beta II and the subsequent activation of NF-kappa B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-beta knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-beta II-NF-kappa B signaling pathway in the tumor microenvironment. Upregulated stromal PKG-beta II in biopsies from patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies

Prevention of bone metastases and management of bone health in early breast cancer

Treatment options for women with early-stage breast cancer have never been better, and the addition of bisphosphonates to adjuvant therapy is a valuable new tool capable of substantially improving clinical outcomes for these women. Several recent studies demonstrated that the anticancer activity of bisphosphonates is not limited to bone, and can translate into a reduction in disease recurrence, including reductions in locoregional and distant metastases. In addition, bisphosphonates maintain bone health during adjuvant therapy; this may be especially important for women who are at high risk for fracture

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution