Background: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use, but cost-effectiveness data on interventions to improve antibiotic use are limited. Beginning in September 2017, an antibiotic stewardship intervention was launched in within 10 outpatient Veterans Healthcare Administration clinics. The intervention was based on the Core Elements and used an academic detailing (AD) and an audit and feedback (AF) approach to encourage appropriate use of antibiotics. The objective of this analysis was to evaluate the cost-effectiveness of the intervention among patients with uncomplicated acute respiratory tract infections (ARI). Methods: We developed an economic simulation model from the VA’s perspective for patients presenting for an index outpatient clinic visit with an ARI (Fig. 1). Effectiveness was measured as quality-adjusted life-years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug reactions (ADRs), and healthcare utilization were obtained from the published literature. Probability parameters for antibiotic treatment, appropriateness of treatment, antibiotic ADRs, hospitalization, and return ARI visits were estimated using VA Corporate Data Warehouse data from a total of 22,137 patients in the 10 clinics during 2014–2019 before and after the intervention. Detailed cost data on the development of the AD and AF materials and electronically captured time and effort for the National AD Service activities by specific providers from a national ARI campaign were used as a proxy for the cost estimate of similar activities conducted in this intervention. We performed 1-way and probabilistic sensitivity analyses (PSAs) using 10,000 second-order Monte Carlo simulations on costs and utility values using their means and standard deviations. Results: The proportion of uncomplicated ARI visits with antibiotics prescribed (59% vs 40%) was lower and appropriate treatment was higher (24% vs 32%) after the intervention. The intervention was estimated to cost $110,846 (2018 USD) over a 2-year period. Compared to no intervention, the intervention had lower mean costs ($880 vs $517) and higher mean QALYs (0.837 vs 0.863) per patient because of reduced inappropriate treatment, ADRs, and subsequent healthcare utilization, including hospitalization. In threshold analyses, the antibiotic stewardship strategy was no longer dominant if intervention cost was >$64,415,000 or the number of patients cared for was <3,672. In the PSA, the antibiotic stewardship intervention was dominant in 100% of the 10,000 Monte Carlo iterations (Fig. 2). Conclusions: In every scenario, the VA outpatient AD and AF antibiotic stewardship intervention was a dominant strategy compared to no intervention.

Funding: None

Disclosures: None

Within the Biostatistics, Epidemiology, and Research Design (BERD) component of the Northwestern University Clinical and Translational Sciences Institute, we created a mentoring program to complement training provided by the associated Multidisciplinary Career Development Program (KL2). Called Research design Analysis Methods Program (RAMP) Mentors, the program provides each KL2 scholar with individualized, hands-on mentoring in biostatistics, epidemiology, informatics, and related fields, with the goal of building multidisciplinary research teams. From 2015 to 2019, RAMP Mentors paired 8 KL2 scholars with 16 individually selected mentors. Mentors had funded/protected time to meet at least monthly with their scholar to provide advice and instruction on methods for ongoing research, including incorporating novel techniques. RAMP Mentors has been evaluated through focus groups and surveys. KL2 scholars reported high satisfaction with RAMP Mentors and confidence in their ability to establish and maintain methodologic collaborations. Compared with other Northwestern University K awardees, KL2 scholars reported higher confidence in obtaining research funding, including subsequent K or R awards, and selecting appropriate, up-to-date research methods. RAMP Mentors is a promising partnership between a BERD group and KL2 program, promoting methodologic education and building multidisciplinary research teams for junior investigators pursuing clinical and translational research.

Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring. Micro 3D computed tomography examination at fetal stages Embryonic day E14.5 and E17.4, reflecting early and late stages of bone formation, demonstrated LPD treatment caused increased bone formation of relative high mineral density quality in males, but not females, at E14.5, disproportionate to fetal growth, with bone quality maintained at E17.5. In contrast, Emb-LPD caused a late increase in male fetal bone growth, proportionate to fetal growth, at E17.5, affecting central and peripheral skeleton and of reduced mineral density quality relative to controls. These altered dynamics in bone growth coincide with increased placental efficiency indicating compensatory responses to dietary treatments. Overall, our data show fetal bone formation and mineral quality is dependent upon maternal nutritional protein content and is sex-specific. In particular, we find the duration and timing of poor maternal diet to be critical in the outcomes with periconceptional protein restriction leading to male offspring with increased bone growth but of poor mineral density, thereby susceptible to later disease risk.

Characterizing non-lethal damage within dry seeds may allow us to detect early signs of ageing and accurately predict longevity. We compared RNA degradation and viability loss in seeds exposed to stressful conditions to quantify relationships between degradation rates and stress intensity or duration. We subjected recently harvested (‘fresh’) ‘Williams 82’ soya bean seeds to moisture, temperature and oxidative stresses, and measured time to 50% viability (P50) and rate of RNA degradation, the former using standard germination assays and the latter using RNA Integrity Number (RIN). RIN values from fresh seeds were also compared with those from accessions of the same cultivar harvested in the 1980s and 1990s and stored in the refrigerator (5°C), freezer (−18°C) or in vapour above liquid nitrogen (−176°C). Rates of viability loss (P50−1) and RNA degradation (RIN⋅d−1) were highly correlated in soya bean seeds that were exposed to a broad range of temperatures [holding relative humidity (RH) constant at about 30%]. However, the correlation weakened when fresh seeds were maintained at high RH (holding temperature constant at 35°C) or exposed to oxidizing agents. Both P50−1 and RIN⋅d−1 parameters exhibited breaks in Arrhenius behaviour near 50°C, suggesting that constrained molecular mobility regulates degradation kinetics of dry systems. We conclude that the kinetics of ageing reactions at RH near 30% can be simulated by temperatures up to 50°C and that RNA degradation can indicate ageing prior to and independent of seed death.

Microalgal blooms are a natural part of the seasonal cycle of photosynthetic organisms in marine ecosystems. They are key components of the structure and dynamics of the oceans and thus sustain the benefits that humans obtain from these aquatic environments. However, some microalgal blooms can cause harm to humans and other organisms. These harmful algal blooms (HABs) have direct impacts on human health and negative influences on human wellbeing, mainly through their consequences to coastal ecosystem services (fisheries, tourism and recreation) and other marine organisms and environments. HABs are natural phenomena, but these events can be favoured by anthropogenic pressures in coastal areas. Global warming and associated changes in the oceans could affect HAB occurrences and toxicity as well, although forecasting the possible trends is still speculative and requires intensive multidisciplinary research. At the beginning of the 21st century, with expanding human populations, particularly in coastal and developing countries, mitigating HABs impacts on human health and wellbeing is becoming a more pressing public health need. The available tools to address this global challenge include maintaining intensive, multidisciplinary and collaborative scientific research, and strengthening the coordination with stakeholders, policymakers and the general public. Here we provide an overview of different aspects of the HABs phenomena, an important element of the intrinsic links between oceans and human health and wellbeing.

Background: Humor therapy is a non-pharmacological intervention with potential to improve mood and quality of life for institutionalized older persons, including those with dementia. The primary aims of the Sydney Multisite Intervention of LaughterBosses and ElderClowns (SMILE) are to examine the effects of humor therapy on residents’ mood, quality of life, social engagement, and agitation.

Methods: SMILE is a single-blinded cluster-randomized controlled trial where 398 consented residents in 35 residential aged care facilities will be allocated to receive humor therapy or usual care. Residents allocated to the intervention group will engage in humor therapy with professional performers (ElderClowns) and trained facility staff (LaughterBosses) for a minimum of nine two-hour sessions over 12 weeks as well as engaging humorously with LaughterBosses during the course of daily care. The usual care control group will not engage in any formal humor therapy. Researchers, blind to treatment allocation, will assess residents at baseline (week 0), post-intervention (week 13), and follow-up (week 26). The measurement suite includes the Cornell Scale for Depression in Dementia, the Dementia Quality of Life Scale, the Multidimensional Observation Scale for Elderly Subjects, the Cohen-Mansfield Agitation Inventory, and the Neuropsychiatric Inventory. Observations of residents’ engagement will be recorded at each humor therapy session.

Conclusions: SMILE is the first large rigorous study of humor therapy in aged care.

Background: A large and growing number of people with dementia are being cared for in long-term care. The empirical literature on the design of environments for people with dementia contains findings that can be helpful in the design of these environments. A schema developed by Marshall in 2001 provides a means of reviewing the literature against a set of recommendations. The aims of this paper are to assess the strength of the evidence for these recommendations and to identify those recommendations that could be used as the basis for guidelines to assist in the design of long term care facilities for people with dementia.

Methods: The literature was searched for articles published after 1980, evaluating an intervention utilizing the physical environment, focused on the care of people with dementia and incorporating a control group, pre-test-post-test, cross sectional or survey design. A total of 156 articles were identified as relevant and subjected to an evaluation of their methodological strength. Of these, 57 articles were identified as being sufficiently strong to be reviewed.

Results: Designers may confidently use unobtrusive safety measures; vary ambience, size and shape of spaces; provide single rooms; maximize visual access; and control levels of stimulation. There is less agreement on the usefulness of signage, homelikeness, provision for engagement in ordinary activities, small size and the provision of outside space.

Conclusions: There is sufficient evidence available to come to a consensus on guiding principles for the design of long term environments for people with dementia.

Dementia has been identified as a national health priority in Australia. National programs in the areas of research, education and training have been established. The Dementia Care Skills for Aged Care Workers program is a three-year project that commenced in 2006. It has the goal of providing training in the essentials of dementia care to 17,000 staff of aged care services across Australia. Successful completion of the training results in the award of a nationally recognized qualification. Although the delivery of the training has been difficult in some areas – because of the long distances to be covered by trainers and trainees, a wide range of cultural backgrounds, and difficulties in finding staff to cover for people attending the training – the seven training organizations providing this training are on target to meet the goal. The project is being evaluated independently. The anecdotal reports available to date strongly suggest that the training is being well received and is making a difference to practice.

A surprisingly large proportion of attendees (9%) have been registered nurses, which demonstrates the need among this group of staff for training in the care of people with dementia.

Recent studies have suggested that untreated coeliac disease is associated with lower total cholesterol than in the general population while the effect of treatment with a gluten-free diet on the cholesterol profile of clinically apparent coeliac disease is not known. We measured the cholesterol profile at diagnosis, and compared this with Health Survey for England figures, and again following 12 months treatment with a gluten-free diet in 100 consecutive adults with coeliac disease attending the Royal Hallamshire Hospital, Sheffield, UK. The mean total cholesterol was 4·84 (sd 1·2) mmol/l in adults (mean age 51 (sd 16) years) newly diagnosed with coeliac disease. At diagnosis of coeliac disease, men had 21 % lower and women had 9 % lower mean total cholesterol in comparison to the general population (difference in age-adjusted mean total cholesterol − 1·09 mmol/l (95 % CI − 0·97, − 1·21); − 0·46 mmol/l (95 % CI − 0·24, − 0·68), respectively). There was no change in mean total cholesterol following treatment. However, there was a small but statistically significant increase of 0·12 mmol/l (95 % CI 0·05, 0·18) in the mean HDL-cholesterol. Total cholesterol was lower at diagnosis in coeliac patients than in the general population and did not increase with 1 year of a gluten-free diet while HDL-cholesterol increased following treatment. Any increase in risk of IHD or stroke in people with coeliac disease is unlikely due to an adverse cholesterol profile either before diagnosis or after treatment with a gluten-free diet.

We have investigated the effect of Si3N4 content in (Ti(Hf)O2)x(Si3N4)y(SiO2)1-x-y pseudo-ternary alloys by tracking systematic changes of electrical properties, including electrically active defects. Results from Soft x-ray photoelectron spectroscopy (SXPS) studies indicate no detectable hole traps for Ti/Hf Si oxynitrides with Si3N4 content >35%; these alloys have equal concentrations of Ti(Hf)O2 and SiO2, ~30-32%, and additionally are stable for annealing in Ar ambients to temperatures of 1100°C. Derivative near edge x-ray absorption spectroscopy (NEXAS) comparisons for the O K1 edges of TiO2 and optimized Ti Si oxynitride alloys provides a significantly reduced average crystal field d-state splitting from 1.9 to 1.6eV, as well as decreased electron trapping, and is correlated with a four-fold coordination of Ti in the Ti Si oxynitride alloys. The flat band voltage shift with varying frequency from 10 kHz to 1MHz in these alloys is less than 12 mV and the compositional dependence of current-voltage characteristics on Si3N4 composition results in the lowest leakage current at a Si3N4 content of ~40 % with the smallest equivalent oxide thickness (EOT) as well. Based on these studies, Transition Metal (TM) Si oxynitride alloys are anticipated to yield EOT <1 nm for scaled CMOS devises.