NUTRITIONAL, HORMONAL, AND PSYCHOLOGICAL RISK FACTORS FOR BREAST CANCER

Over the course of a lifetime, one in eight women will develop breast cancer. To date, 30-40% of breast cancer cases can be attributed to established risk factors, which supports the need for identification of additional modifiable risk factors. Therefore, we conducted three epidemiologic studies to examine the associations between nutritional, hormonal, and psychological risk factors and breast cancer risk. In our first study, we examined the relationship between urinary melatonin levels and the risk of breast cancer in a nested-case control study within the Nurses’ Health Study II. While limited in some respects, experimental and epidemiologic evidence support the potential relationship between melatonin as a protective factor against breast cancer risk. In this updated analysis of our previously published results with longer follow-up time and a greater sample size, adding cases that occurred more distant from urine collection, we did not observe a significant association between urinary melatonin levels and breast cancer risk. In our second study, we investigated the associations between dairy consumption (overall and by specific dairy products) and circulating hormone levels in the Nurses’ Health Study. In this study, we observed a significant positive association between low-fat dairy intake and plasma levels of IGF-I that persisted after adjustment for IGFBP-3, and a significant decrease in SHBG; however, no significant associations emerged between dairy intake and prolactin or sex steroid hormone levels. In our third study, we examined the associations between depressive symptoms, antidepressant (AD) use, and breast cancer risk in the Women’s Health Initiative Observational Study. Depressive symptoms and AD use were associated with a significant increased risk of total breast cancer; however, no association was observed with invasive breast cancer. Depressive symptoms and AD use were each associated with a non-significant increased risk of in situ breast cancer. However, this association appeared due largely to a positive association with in situ breast cancer that was based, at least in part, on increased mammographic screening among exposed women. In summary, these studies add to the growing literature of potentially modifiable risk factors and their relationships with breast cancer risk

Examining the feasibility of an economic analysis of dyadic developmental psychotherapy for children with maltreatment associated psychiatric problems in the United Kingdom

Background: Children with maltreatment associated psychiatric problems are at increased risk of developing behavioural or mental health disorders. Dyadic Developmental Psychotherapy (DDP) was proposed as treatment for children with maltreatment histories in the USA, however, being new to the UK little is known of its effectiveness or cost-effectiveness. As part of an exploratory study, this paper explores the feasibility of undertaking economic analysis of DDP in the UK. Methods: Feasibility for economic analysis was determined by ensuring such analysis could meet key criteria for economic evaluation. Phone interviews were conducted with professionals (therapists trained and accredited or in the process of becoming accredited DDP practitioners). Three models were developed to represent alternative methods of DDP service delivery. Once appropriate comparators were determined, economic scenarios were constructed. Cost analyses were undertaken from a societal perspective. Finally, appropriate outcome measurement was explored through clinical opinion, literature and further discussions with clinical experts. Results: Three DDP models were constructed: DDP Full-Basic, DDP Home-Based and DDP Long-Term. Two potential comparator interventions were identified and defined as Consultation with Carers and Individual Psychotherapy. Costs of intervention completion per case were estimated to be: £6,700 (DDP Full-Basic), £7,100 (Consultations with Carers), £7,200 (DDP Home-Based), £11,400 (Individual Psychotherapy) and £14,500 (DDP Long-Term). None of the models of service delivery were found to currently measure effectiveness consistently. The Strengths and Difficulties Questionnaire (SDQ) was deemed an appropriate primary outcome measure, however, it does not cover all disorders DDP intends to treat and the SDQ is not a direct measure of health gain. Inclusion of quality of life measurement is required for comprehensive economic analysis. Conclusions: Economic analysis of DDP in the UK is feasible if vital next steps are taken to measure intervention outcomes consistently, ideally with a quality of life measurement. An economic analysis using the models constructed could determine the potential cost-effectiveness of DDP in the UK and identify the most efficient mode of service delivery

The feasibility of a randomised controlled trial of Dyadic Developmental Psychotherapy

Background: Maltreated children have significant and complex problems which clinicians find difficult to diagnose and treat. Previous US pilot work suggests that Dyadic Developmental Psychotherapy (DDP) may be effective; however, rigorous evidence from a randomised controlled trial (RCT) is lacking. The purpose of this study is to establish the feasibility of an RCT of DDP by exploring the ways that DDP is operating across different UK sites and the impacts of current practice on the potential set-up of an RCT. Methods: Qualitative methods (interviews, focus groups and teleconferences) were used to explore trial feasibility with therapists and service managers from teams implementing both DDP and possible control interventions. Data were analysed thematically and related to various aspects of trial design. Results: DDP was commonly regarded as having a particular congruence with the complexity of maltreatment-associated problems and a common operating model of DDP was evident across sites. A single control therapy was harder to establish, however, and it is likely to be a non-specific and context-dependent intervention/s offered within mainstream Child and Adolescent Mental Health Services (CAMHS). Because a ‘gold standard’ Treatment as Usual (TAU) does not currently exist, randomisation between DDP and TAU (CAMHS) therefore looks feasible and ethical. The nature of family change during DDP was regarded as multi-faceted, non-linear and relationship-based. Assessment tools need to be carefully considered in terms of their ability to capture change that covers both individual child and family-based functioning. Conclusions: An RCT of DDP is feasible and timely. This study has demonstrated widespread interest, support and engagement regarding an RCT and permissions have been gained from sites that have shown readiness to participate. As maltreated children are among the most vulnerable in society, and as there are currently no treatments with RCT evidence, such a trial would be a major advance in the field

Effectiveness of mycorrhizae and vermicompost seed inoculation for germination, vegetative growth, cannabinoid content, and cured flower weight of CBD-rich hemp (Cannabis sativa L.)

Effective germination and vigorous growth of hemp cultivars is paramount to cultivators’ ability to produce high-quality hemp products. Beneficial bacteria and fungi are known symbionts to plants and are used in regenerative agriculture to increase plant health and crop yield. This pilot study investigated the effect of microbial seed inoculation on germination rate, plant height, cured flower weight, and cannabinoid content of cannabidiol (CBD)-rich hemp (Cannabis sativa L). The experiment included a control and the following treatments: 1) seed inoculation of Great White â Premium Mycorrhizae (GW), 2) seed inoculation of vermicompost (V), and 3) seed inoculation of Great White â Premium Mycorrhizae and vermicompost (GW+V). There were no significant differences for germination rate or plant height across treatments. For cured flower weight, the GW+V and V groups had increased cured flower weight by 29.0% and 43.0%, respectively, while the GW treatment had 4.4% more weight than the control group. Preliminary results indicate that the GW+V and V treatments had higher total tetrahydrocannabinol (THC) and CBD content than the control at 17.6% and 19.0%, and 17.6% and 12.1%, respectively. These results suggest further investigation is needed to determine if seed inoculation is advantageous for hemp cultivators

Protocol for the economic evaluation of a complex intervention to improve the mental health of maltreated infants and children in foster care in the UK (The BeST? services trial)

Introduction: Children who have experienced abuse and neglect are at increased risk of mental and physical health problems throughout life. This places an enormous burden on individuals, families and society in terms of health services, education, social care and judiciary sectors. Evidence suggests that early intervention can mitigate the negative consequences of child maltreatment, exerting long-term positive effects on the health of maltreated children entering foster care. However, evidence on cost-effectiveness of such complex interventions is limited. This protocol describes the first economic evaluation of its kind in the UK. Methods and analysis: An economic evaluation alongside the Best Services Trial (BeST?) has been prospectively designed to identify, measure and value key resource and outcome impacts arising from the New Orleans intervention model (NIM) (an infant mental health service) compared with case management (CM) (enhanced social work services as usual). A within-trial economic evaluation and long-term model from a National Health Service/Personal Social Service and a broader societal perspective will be undertaken alongside the National Institute for Health Research (NIHR)–Public Health Research Unit (PHRU)-funded randomised multicentre BeST?. BeST? aims to evaluate NIM compared with CM for maltreated children entering foster care in a UK context. Collection of Paediatric Quality of Life Inventory (PedsQL) and the recent mapping of PedsQL to EuroQol-5-Dimensions (EQ-5D) will facilitate the estimation of quality-adjusted life years specific to the infant population for a cost–utility analysis. Other effectiveness outcomes will be incorporated into a cost-effectiveness analysis (CEA) and cost-consequences analysis (CCA). A long-term economic model and multiple economic evaluation frameworks will provide decision-makers with a comprehensive, multiperspective guide regarding cost-effectiveness of NIM. The long-term population health economic model will be developed to synthesise trial data with routine linked data and key government sector parameters informed by literature. Methods guidance for population health economic evaluation will be adopted (lifetime horizon, 1.5% discount rate for costs and benefits, CCA framework, multisector perspective). Ethics and dissemination: Ethics approval was obtained by the West of Scotland Ethics Committee. Results of the main trial and economic evaluation will be submitted for publication in a peer-reviewed journal as well as published in the peer-reviewed NIHR journals library (Public Health Research Programme). Trial registration number: NCT02653716; Pre-results

Economic evaluation of population health interventions aimed at children and delivered at school

Background: Population health interventions by their nature affect an entire population and are typically delivered outwith of health services and within the community, such as in schools. An example of such interventions are those that aim to improve children’s social and emotional wellbeing, which have demonstrated effectiveness in the short-term and potentially the long-term. However, challenges arise when conducting economic evaluations of population health interventions, most notably the difficulties of identifying, measuring, and valuing broader intersectoral costs, health, and non-health outcomes. Economic evaluation in an education context is relatively novel, but could provide decision-makers with information to help them make transparent and consistent decisions about how to allocate limited funds. This thesis examined the role for economic evaluation in school-based interventions and sought to determine appropriate methods for its implementation in addition to examining appropriate child-focused outcome measures. Thus, the overarching research question asked, ‘How should the cost-effectiveness of school-based, population health interventions aimed at children be determined?’ Methods: A mixed methods approach to this thesis was used: (i) a systematic literature review and narrative synthesis to determine which evaluation methods (economic and non-economic) are currently being used in school-based population health interventions; (ii) a case study to illustrate an economic evaluation (including cost-utility and cost-effectiveness analysis) of a school-based intervention to reflect on the advantages and disadvantages for decision making in this context; and (iii) an exploration of outcome measures (through mapping validation) for valuing child health and social and emotional wellbeing in school-based programmes to support future evaluation work in this context. Data for the economic evaluation and mapping validation study were available from a cluster randomised controlled trial of the Roots of Empathy programme in Northern Ireland (Ref: 10/3006/02). Results: The systematic review found that the methods currently being utilised to evaluate school programmes are varied (including economic evaluation, cost only, and effectiveness only studies), with poor quality reporting for the economic evaluations. Of the few cost-utility analyses in school-based settings identified, none had directly measured health-related quality of life using child measures or values. The case study cost-utility analysis using Child Health Utility 9D of a school-based intervention was found to be cost-effective from the National Health Service perspective with an incremental cost-effectiveness ratio of £11,000 per quality-adjusted life year (confidence interval: -£95,500 to £147,000), however the wide confidence interval demonstrates considerable uncertainty. This uncertainty is likely due to a lack of statistically significant effect that remained at the 36-month follow-up. Cost-effectiveness analysis using child behavioural descriptive measure, the Strengths and Difficulties Questionnaire, resulted in an incremental cost-effectiveness ratio of £197 per unit decrease in total difficulties score (confidence interval: £77 to £471). The Strengths and Difficulties Questionnaire is suitable for measuring social and emotional wellbeing, but is less advantageous for cost-effectiveness decision-making as no consensus has been reached as to what a clinically meaningful change in score represents, nor has a cost-effectiveness threshold been defined. It remains uncertain how these cost-effectiveness results will be interpreted in an education decision-making context where cost-effectiveness thresholds have not been set up. The mapping validation study validated a mapping algorithm to convert the Strengths and Difficulties Questionnaire into child health utility. Using this algorithm provides an option for valuing incremental changes in health-related quality of life against a generally accepted cost-effectiveness threshold from a health service perspective. Conclusions: Given the findings from the various aspects of work undertaken for this thesis to address population health issues, this thesis identified cost-benefit analysis as currently the most comprehensive method for determining the value for money of school-based public health interventions. Cost-benefit analysis incorporates monetary valuation of multisector outcomes in a final net benefit/loss result allowing clear, consistent, decision-making criteria to be set. Other methods such as cost-consequence analysis, cost-utility analysis, and multi-criteria decision analysis may also be suitable depending on the decision-making context and problem. This thesis demonstrates a lack of clear decision-making criteria in place for funding allocation decisions in education (e.g. education specific cost-effectiveness thresholds). Furthermore, there is no equitable method currently in place for apportioning the cost of funding public health interventions that generate benefits for multiple sectors. From a health service perspective, directly measuring child health utility using the Child Health Utility 9D is preferred as it is the only preference-based measure developed specifically for children and valued by young people. Mean child health utility can be predicted by mapping from the Strengths and Difficulties Questionnaire. This affords the opportunity to estimate longer-term utility by utilising long-term cohort data that routinely collects the Strengths and Difficulties Questionnaire, as long-term cost-effectiveness of school-based preventive programmes is an area in need of further research. The school setting plays an important role in shaping our young people’s futures. Economic evaluation of school-based population health interventions is justified, as schools need to maximise their existing resources in order to give children the best start in life

Changes in plasma membrane fluidity of Bryonia dioica internodes during thigmomorphogenesis

AbstractFluidity changes in plasma membrane (PM) lipid extracts or native membranes isolated from Bryonia dioica internodes after a mechanical stimulation were monitored by steady-state fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene as a probe. The signal was shown to rapidly induce an increase in the bulk lipid fluidity. This event was closely related to a relative enrichment in some phospholipid species (PC, PG and PS) as well as a significant increase in the unsaturation index of total fatty acyl chains. Free sterols and protein content did not appear to be involved into this process. After 48 h, lipids from rubbed internodes became less fluid than PM lipids from control internodes

Effets maternels d'un système sanguin sur le nombre d'œufs et conséquences sur la sélection dans une souche expérimentale

International audienc

Optimizing Real-Time Wellness Intervention Studies in Healthcare Shift Workers: Outcomes from a Prospective, Single-subject Design Study of a Digital Sleep Aid

Sleep disorders associated with shift work impair alertness and increase risk of chronic physical and mental health disease. Though studying sleep aids in at-risk populations such as shift workers is critical to improving wellness, implementing robust studies to evaluate wellness interventions in live populations can be particularly challenging. We performed a prospective, single-subject design study in which we assessed the effect of noise-masking earbuds on sleep quality, sleepiness, and stress level in health care shift workers. Despite being gifted the technology at the end of the study, we faced poor participant accrual and study retention. Additionally, robust analysis of our intervention’s impact on post-shift alertness was underpowered due to variable participant scheduling. In order to make meaningful advances in improving wellness among such groups, studies emphasizing objective outcome measures while minimizing participant obligation to study protocols are ideal. Here, we discuss our experience studying a digital sleep intervention in a real-time setting and propose solutions for improving subject accrual, retention and methods for objective data collection in studies performed in a live shift worker population