Global DNA and p53 region-specific hypomethylation in human colonic cells is induced by folate depletion and reversed by folate supplementation.

There is increasing evidence to suggest that reduced folate status may be a causative factor in carcinogenesis, particularly colorectal carcinogenesis. Folate is essential for the synthesis of S-adenosylmethionine, the methyl donor required for all methylation reactions in the cell, including the methylation of DNA. Global DNA hypomethylation appears to be an early, and consistent, molecular event in carcinogenesis. We have examined the effects of folate depletion on human-derived cultured colon carcinoma cells using 2 novel modifications to the Comet (single cell gel electrophoresis) assay to detect global DNA hypomethylation and gene region–specific DNA hypomethylation. Colon cells cultured in folate-free medium for 14 d showed a significant increase in global DNA hypomethylation compared with cells grown in medium containing 3µmol/L folic acid. This was also true at a gene level, with folate-deprived cells showing significantly more DNA hypomethylation in the region of the p53 gene. In both cases, the effects of folate depletion were completely reversed by the reintroduction of folic acid to the cells. These results confirm that decreased folate levels are capable of inducing DNA hypomethylation in colon cells and particularly in the region of the p53 gene, suggesting that a more optimal folate status in vivo may normalize any DNA hypomethylation, offering potential protective effects against carcinogenesis. This study also introduces 2 novel functional biomarkers of DNA hypomethylation and demonstrates their suitability to detect folate depletion–induced molecular changes.

α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans

Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.

Blue sky thinking : using projective techniques to stimulate discussion, reflection and insight

The prime purpose of this session is to share a new use of projective techniques to stimulate discussion, reflection and insight with students. The session will provide an introduction to the nature and use of projective techniques and an explanation why images of the sky were chosen as the stimuli. Then, the majority of the session will consist of an opportunity to experience this new technique in a simulated session. The session will end with a plenary discussion and a review of the effectiveness and applicability of the technique.

Using internet technology within the organization : a structurational analysis of intranets

Many organizations are implementing Internet technology, specifically Word Wide Web technology, inside the organization in the form of an “organizational Internet” or irttrunet. Intranet technology can unify dispersed computer based information systems in the organization into one rich “system”. Thus, intranets can have a major impact on organizational processes, for example cross-functional information sharing and collaboration. We focus on the social aspects surrounding intranet implementation. We seek to answer how intranet implementations shape and how they are shaped by ‘social structures employed by organizational agents. We adapt structuration theory into an explanatory device to analyze inhanet implementation and we apply it to four cases. We conclude that, intranets are initially more shaped by, rather than shaping social structures, but that this may change over time. The following learning points are condensed: Firstly, intranets are socially constructed and implementers need to be cautious when seeking to transplanting Web technology into an organizational context. Secondly, intranets typically evolve in sophistication over time. Finally, institutionalization is isolated as the key challenge in intranet implementation.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians : a model process

Background
The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients.

Methods
The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug.

Results
Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug.

Conclusions
Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.

Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Transfer of electronic commerce trust between brick-and-mortar and online business environments

Through experimentation, we establish a causal relationship between trust and the expansion of a retailer from online to brick-and-mortar and vice versa. Trust is multidimensional and contingent on the distribution path first chosen. Vendor trustworthiness (knowledge-based) and technological trustworthiness (institution-based) have different effects depending on the initial and new distribution channel. Expanding from brick-and-mortar to online negatively affects technology-based trust, while transfers from an online to a physical location maintain the same level of technology-based trust. Vendor-based trust is positively affected by transfer from online to the brick-and-mortar location, and is not significantly unaffected by transfers from brick and-mortar to online locations. The perceived “permanence” of a physical location influences consumer beliefs about the location’s trustworthiness.

BMI and healthcare cost impact of eliminating tax subsidy for advertising unhealthy food to youth

INTRODUCTION: Food and beverage TV advertising contributes to childhood obesity. The current tax treatment of advertising as an ordinary business expense in the U.S. subsidizes marketing of nutritionally poor foods and beverages to children. This study models the effect of a national intervention that eliminates the tax subsidy of advertising nutritionally poor foods and beverages on TV to children aged 2-19 years. METHODS: We adapted and modified the Assessing Cost Effectiveness framework and methods to create the Childhood Obesity Intervention Cost Effectiveness Study model to simulate the impact of the intervention over the 2015-2025 period for the U.S. population, including short-term effects on BMI and 10-year healthcare expenditures. We simulated uncertainty intervals (UIs) using probabilistic sensitivity analysis and discounted outcomes at 3% annually. Data were analyzed in 2014. RESULTS: We estimated the intervention would reduce an aggregate 2.13 million (95% UI=0.83 million, 3.52 million) BMI units in the population and would cost $1.16 per BMI unit reduced (95% UI=$0.51, $2.63). From 2015 to 2025, the intervention would result in $352 million (95% UI=$138 million, $581 million) in healthcare cost savings and gain 4,538 (95% UI=1,752, 7,489) quality-adjusted life-years. CONCLUSIONS: Eliminating the tax subsidy of TV advertising costs for nutritionally poor foods and beverages advertised to children and adolescents would likely be a cost-saving strategy to reduce childhood obesity and related healthcare expenditures.

Cost effectiveness of a sugar-sweetened beverage excise tax in the U.S.

INTRODUCTION: Reducing sugar-sweetened beverage consumption through taxation is a promising public health response to the obesity epidemic in the U.S. This study quantifies the expected health and economic benefits of a national sugar-sweetened beverage excise tax of $0.01/ounce over 10 years. METHODS: A cohort model was used to simulate the impact of the tax on BMI. Assuming ongoing implementation and effect maintenance, quality-adjusted life-years gained and disability-adjusted life-years and healthcare costs averted were estimated over the 2015-2025 period for the 2015 U.S. POPULATION: Costs and health gains were discounted at 3% annually. Data were analyzed in 2014. RESULTS: Implementing the tax nationally would cost $51 million in the first year. The tax would reduce sugar-sweetened beverage consumption by 20% and mean BMI by 0.16 (95% uncertainty interval [UI]=0.06, 0.37) units among youth and 0.08 (95% UI=0.03, 0.20) units among adults in the second year for a cost of $3.16 (95% UI=$1.24, $8.14) per BMI unit reduced. From 2015 to 2025, the policy would avert 101,000 disability-adjusted life-years (95% UI=34,800, 249,000); gain 871,000 quality-adjusted life-years (95% UI=342,000, 2,030,000); and result in $23.6 billion (95% UI=$9.33 billion, $54.9 billion) in healthcare cost savings. The tax would generate $12.5 billion in annual revenue (95% UI=$8.92, billion, $14.1 billion). CONCLUSIONS: The proposed tax could substantially reduce BMI and healthcare expenditures and increase healthy life expectancy. Concerns regarding the potentially regressive tax may be addressed by reduced obesity disparities and progressive earmarking of tax revenue for health promotion.

Cost effectiveness of an elementary school active physical education policy

INTRODUCTION: Many American children do not meet recommendations for moderate to vigorous physical activity (MVPA). Although school-based physical education (PE) provides children with opportunities for MVPA, less than half of PE minutes are typically active. The purpose of this study is to estimate the cost effectiveness of a state "active PE" policy implemented nationally requiring that at least 50% of elementary school PE time is spent in MVPA. METHODS: A cohort model was used to simulate the impact of an active PE policy on physical activity, BMI, and healthcare costs over 10 years for a simulated cohort of the 2015 U.S. population aged 6-11 years. Data were analyzed in 2014. RESULTS: An elementary school active PE policy would increase MVPA per 30-minute PE class by 1.87 minutes (95% uncertainty interval [UI]=1.23, 2.51) and cost $70.7 million (95% UI=$51.1, $95.9 million) in the first year to implement nationally. Physical activity gains would cost $0.34 per MET-hour/day (95% UI=$0.15, $2.15), and BMI could be reduced after 2 years at a cost of $401 per BMI unit (95% UI=$148, $3,100). From 2015 to 2025, the policy would cost $235 million (95% UI=$170 million, $319 million) and reduce healthcare costs by $60.5 million (95% UI=$7.93 million, $153 million). CONCLUSIONS: Implementing an active PE policy at the elementary school level could have a small impact on physical activity levels in the population and potentially lead to reductions in BMI and obesity-related healthcare expenditures over 10 years.

Cost effectiveness of childhood obesity interventions: Evidence and methods for CHOICES

INTRODUCTION: The childhood obesity epidemic continues in the U.S., and fiscal crises are leading policymakers to ask not only whether an intervention works but also whether it offers value for money. However, cost-effectiveness analyses have been limited. This paper discusses methods and outcomes of four childhood obesity interventions: (1) sugar-sweetened beverage excise tax (SSB); (2) eliminating tax subsidy of TV advertising to children (TV AD); (3) early care and education policy change (ECE); and (4) active physical education (Active PE). METHODS: Cost-effectiveness models of nationwide implementation of interventions were estimated for a simulated cohort representative of the 2015 U.S. population over 10 years (2015-2025). A societal perspective was used; future outcomes were discounted at 3%. Data were analyzed in 2014. Effectiveness, implementation, and equity issues were reviewed. RESULTS: Population reach varied widely, and cost per BMI change ranged from $1.16 (TV AD) to $401 (Active PE). At 10 years, assuming maintenance of the intervention effect, three interventions would save net costs, with SSB and TV AD saving $55 and $38 for every dollar spent. The SSB intervention would avert disability-adjusted life years, and both SSB and TV AD would increase quality-adjusted life years. Both SSB ($12.5 billion) and TV AD ($80 million) would produce yearly tax revenue. CONCLUSIONS: The cost effectiveness of these preventive interventions is greater than that seen for published clinical interventions to treat obesity. Cost-effectiveness evaluations of childhood obesity interventions can provide decision makers with information demonstrating best value for the money.

Modeling the cost effectiveness of child care policy changes in the U.S.

INTRODUCTION: Child care facilities influence diet and physical activity, making them ideal obesity prevention settings. The purpose of this study is to quantify the health and economic impacts of a multi-component regulatory obesity policy intervention in licensed U.S. child care facilities. METHODS: Two-year costs and BMI changes resulting from changes in beverage, physical activity, and screen time regulations affecting a cohort of up to 6.5 million preschool-aged children attending child care facilities were estimated in 2014 using published data. A Markov cohort model simulated the intervention's impact on changes in the U.S. population from 2015 to 2025, including short-term BMI effects and 10-year healthcare expenditures. Future outcomes were discounted at 3% annually. Probabilistic sensitivity analyses simulated 95% uncertainty intervals (UIs) around outcomes. RESULTS: Regulatory changes would lead children to watch less TV, get more minutes of moderate and vigorous physical activity, and consume fewer sugar-sweetened beverages. Within the 6.5 million eligible population, national implementation could reach 3.69 million children, cost $4.82 million in the first year, and result in 0.0186 fewer BMI units (95% UI=0.00592 kg/m(2), 0.0434 kg/m(2)) per eligible child at a cost of $57.80 per BMI unit avoided. Over 10 years, these effects would result in net healthcare cost savings of $51.6 (95% UI=$14.2, $134) million. The intervention is 94.7% likely to be cost saving by 2025. CONCLUSIONS: Changing child care regulations could have a small but meaningful impact on short-term BMI at low cost. If effects are maintained for 10 years, obesity-related healthcare cost savings are likely.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process

BACKGROUND: The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. METHODS: The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. RESULTS: Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. CONCLUSIONS: Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Discordant age and sex-specific trends in the incidence of a first coronary heart disease event in Western Australia from 1996 to 2007

OBJECTIVE: To determine age- and sex-specific population trends in fatal and non-fatal first coronary heart disease (CHD) events in Western Australia from 1996 to 2007. DESIGN: Longitudinal retrospective population study. SETTING: State-wide population. PATIENTS: All residents aged 35-84 years during 1996-2007 who died or were hospitalised with a principal diagnosis of acute CHD. DATA SOURCES: Person-linked file of mortality and morbidity records. MAIN OUTCOME MEASURES: Age-standardised (35-84 years) and age-specific (35-54, 55-69, 70-84 years) rates by gender for a first CHD event were calculated with a 10-year lead-in period to define first events. RESULTS: From 1996 to 2007 there were 36 631 first CHD events, including 8518 (23%) fatal cases in those aged 35-84 years. Overall, age-adjusted rates for fatal first CHD declined 5.3%/year in men (95% CI -6.1% to -4.6%) and 6.5%/year in women (95% CI -7.5% to -5.5%). However, age-specific fatal first CHD rates were neutral in both men aged 35-54 years (0.1%/year; 95% CI -1.8% to 2.1%) and women of the same age, (-1.6%/year; 95% CI -5.6% to 2.5%). Age-specific trends in non-fatal CHD rates reflected the same trends in fatal CHD events in men and women, with rates reportedly increasing in women aged 35-54 years (2.5%/year (95% CI 1.1% to 3.9%). CONCLUSION: The age-specific decline in fatal and non-fatal first CHD rates in older men and women was not observed in those aged 35-54 years. These novel findings provide evidence for a levelling in the CHD incidence rates in younger adults and puts renewed importance on primary prevention in this group.