Improving outcomes in older vascular surgical patients

Older people commonly develop conditions that require definitive management with emergency or planned surgical procedures. Adverse postoperative outcomes are more common in these older patients in comparison to younger cohorts. This can be attributed in part to the pathophysiological profile of older people, who often present for surgery with coexisting physiological decline, multimorbidity and geriatric syndromes. The risk factors for vascular disease may put the vascular surgical population at particularly high risk of adverse postoperative outcomes. Preoperative Comprehensive Geriatric Assessment (CGA) and optimisation has not yet been studied in vascular surgical patients as a method to improve postoperative outcomes. The overall programme of research presented in this thesis aims to design and evaluate an intervention to improve postoperative outcomes in older vascular patients, according to the Medical Research Council framework for ‘Developing and Evaluating Complex Interventions’. First, a systematic review and narrative synthesis of existing literature found that preoperative CGA and optimisation may improve postoperative outcomes in older patients undergoing elective surgery. Second, a national UK wide survey identified only three trusts providing CGA and optimisation-based input throughout the perioperative pathway for older surgical patients. Geriatricians who responded to the survey cited funding and workforce issues as the main barriers to developing such services. Third, an observational study described a high prevalence of frailty and cognitive impairment in older vascular surgical patients and showed that the combination of frailty and cognitive impairment contributes to postoperative morbidity and length of hospital stay. The use of brief assessment tools was shown to be acceptable and feasible in the preoperative setting in this study. Fourth, a randomised controlled trial demonstrated that preoperative CGA and optimisation reduced length of stay in older patients undergoing vascular surgery by 40% when compared with standard preoperative assessment. This was predominantly due to fewer medical complications with a trend towards fewer delayed discharges. Finally, an observational study described distress related to postoperative delirium in patients and their relatives. The degree and recall of distress was found to be associated with the severity of delirium and specific phenotypic features of the delirious episode. In conclusion, the work presented in this thesis demonstrates that postoperative outcomes for older vascular surgical patients can be improved using a CGA based intervention. This programme of research sets the scene for ongoing work to further investigate patient reported postoperative outcomes and to study the implementation of CGA based perioperative services on a wider scale

Brazilian Maize Yields Negatively Affected by climate after Land Clearing

To date, over 50% of the Brazilian Cerrado has been cleared predominantly for 11 agropastoral purposes. Here, we use the Weather Research and Forecasting model to run 15- 12 year climate simulations across Brazil with six land-cover scenarios: 1) before extensive land 13 clearing; 2) observed in 2016; 3) Cerrado replaced with single-cropped (soy) agriculture; 4) 14 Cerrado replaced with double-cropped (soy-maize) agriculture; 5) eastern Amazon replaced 15 with single-cropped agriculture; and 6) eastern Amazon replaced with double-cropped 16 agriculture. All land-clearing scenarios (2-6) contain significantly more growing season days 17 with temperatures that exceed critical temperature thresholds for maize. Evaporative fraction 18 significantly decreases across all land-clearing scenarios. Altered weather reduces maize yields 19 between 6–8%, when compared to the before extensive land clearing scenario; however, soy 20 yields were not significantly affected. Our findings provide evidence that land clearing has 21 degraded weather in the Brazilian Cerrado, undermining one of the main reasons for land 22 clearing: rainfed crop production

The isolated muscle fibre as a model of disuse atrophy: characterization using PhAct, a method to quantify f-actin

Research into muscle atrophy and hypertrophy is hampered by limitations of the available experimental models. Interpretation of in vivo experiments is confounded by the complexity of the environment while in vitro models are subject to the marked disparities between cultured myotubes and the mature myofibres of living tissues. Here we develop a method (PhAct) based on ex vivo maintenance of the isolated myofibre as a model of disuse atrophy, using standard microscopy equipment and widely available analysis software, to measure f-actin content per myofibre and per nucleus over two weeks of ex vivo maintenance. We characterize the 35% per week atrophy of the isolated myofibre in terms of early changes in gene expression and investigate the effects on loss of muscle mass of modulatory agents, including Myostatin and Follistatin. By tracing the incorporation of a nucleotide analogue we show that the observed atrophy is not associated with loss or replacement of myonuclei. Such a completely controlled investigation can be conducted with the myofibres of a single muscle. With this novel method we can identify those features and mechanisms of atrophy and hypertrophy that are intrinsic to the muscle fibre from those that include activities of other tissues and systemic agents

The Potential for mHealth Interventions to Support Women with Breast Cancer after Active Treatment

Breast cancer is the most commonly diagnosed cancer among women worldwide. Chances of living one-year after diagnosis are high (~98%), and health self-management is essential to reduce risks of recurrence. Mobile health (mHealth) has emerged as a wide-reaching and cost-effective way of providing health information and support. Therefore, we conducted a narrative review of the currently available mHealth literature and synthesised the literature according to the impacts of mHealth interventions on patient outcomes, the potential mechanism for behaviour change and innovative approaches to developing future mHealth interventions. Results found a small amount of evidence for the value of mHealth interventions (text message programs, smartphone applications and activity trackers) for supporting women after breast cancer treatment. However, accessibility, cost and gender inequities may pose barriers to implementation. Developing consumer-led mHealth interventions based on lived-experiences will be essential to improving user outcomes. In conclusion, mHealth interventions are widely available and have the potential to support women after breast cancer treatment and further robust research will determine effectiveness in specific subgroups and populations

Atmospheric oxygen tension slows myoblast proliferation via mitochondrial activation

Mitochondrial activity inhibits proliferation and is required for differentiation of myoblasts. Myoblast proliferation is also inhibited by the ~20% oxygen level used in standard tissue culture. We hypothesize that mitochondrial activity would be greater at hyperoxia (20% O(2)) relative to more physiological oxygen (5% O(2)).Murine primary myoblasts from isolated myofibres and conditionally immortalized H-2K myoblasts were cultured at 5% and 20% oxygen. Proliferation, assayed by cell counts, EdU labeling, and CFSE dilution, was slower at 20% oxygen. Expression of MyoD in primary myoblasts was delayed at 20% oxygen, but myogenicity, as measured by fusion index, was slightly higher. FACS-based measurement of mitochondrial activity indicators and luminometric measurement of ATP levels revealed that mitochondria exhibited greater membrane potential and higher levels of Reactive Oxygen Species (ROS) at 20% oxygen with concomitant elevation of intracellular ATP. Mitochondrial mass was unaffected. Low concentrations of CCCP, a respiratory chain uncoupler, and Oligomycin A, an ATP synthase inhibitor, each increased the rate of myoblast proliferation. ROS were investigated as a potential mechanism of mitochondrial retrograde signaling, but scavenging of ROS levels by N-acetyl-cysteine (NAC) or α-Phenyl-N-tert-butylnitrone (PBN) did not rescue the suppressed rate of cell division in hyperoxic conditions, suggesting other pathways. Primary myoblasts from older mice showed a slower proliferation than those from younger adult mice at 20% oxygen but no difference at 5% oxygen.These results implicate mitochondrial regulation as a mechanistic explanation for myoblast response to oxygen tension. The rescue of proliferation rate in myoblasts of aged mice by 5% oxygen suggests a major artefactual component to age-related decline of satellite cell proliferation in standard tissue culture at 20% oxygen. It lends weight to the idea that these age-related changes result at least in part from environmental factors rather than characteristics intrinsic to the satellite cell

Smart Drugs “As Common As Coffee”: Media Hype about Neuroenhancement

Background: The use of prescription drugs to improve cognitive functioning in normal persons -"neuroenhancement" - has gained recent attention from bioethicists and neuroscientists. Enthusiasts claim that the practice is widespread and increasing, and has many potential benefits; however recent evidence provides weak support for these claims. In this study we explored how the newsprint media portrays neuroenhancement

Dopaminergic medication impairs feedback-based stimulus-response learning but not response selection in Parkinson\u27s disease.

Cognitive dysfunction is a feature of Parkinson\u27s Disease (PD). Some cognitive functions are impaired by dopaminergic medications prescribed to address the movement symptoms that typify PD. Learning appears to be the cognitive function most frequently worsened by dopaminergic therapy. However, this result could reflect either impairments in learning (i.e., acquisition of associations among stimuli, responses, and outcomes) or deficits in performance based on learning (e.g., selecting responses). We sought to clarify the specific effects of dopaminergic medication on (a) stimulus-response association learning from outcome feedback and (b) response selection based on learning, in PD. We tested 28 PD patients on and/or off dopaminergic medication along with 32 healthy, age- and education-matched controls. In Session 1, participants learned to associate abstract images with specific key-press responses through trial and error via outcome feedback. In Session 2, participants provided specific responses to abstract images learned in Session 1, without feedback, precluding new feedback-based learning. By separating Sessions 1 and 2 by 24 h, we could distinguish the effect of dopaminergic medication on (a) feedback-based learning and response selection processes in Session 1 as well as on (b) response selection processes when feedback-based learning could not occur in Session 2. Accuracy achieved at the end of Session 1 were comparable across groups. PD patients on medication learned stimulus-response associations more poorly than PD patients off medication and controls. Medication did not influence decision performance in Session 2. We confirm that dopaminergic therapy impairs feedback-based learning in PD, discounting an alternative explanation that warranted consideration

Development and implementation of Heart Team: a Facebook support group for cardiac patients

Improving adherence to cardiac rehabilitation programs should reduce the risk of repeat cardiac events and improve quality of life. We present the process of developing and piloting a Facebook support group, Heart Team, which other cardiac health professionals could adapt and trial at their hospital, rehabilitation or community service.Cardiovascular Disease Research Network Project Grant by the Australia Heart Foundatio

Digital behaviour change interventions to increase vegetable intake in adults: A systematic review

Background: Digital interventions may help address low vegetable intake in adults, however there is limited understanding of the features that make them effective. We systematically reviewed digital interventions to increase vegetable intake to 1) describe the effectiveness of the interventions; 2) examine links between effectiveness and use of co-design, personalisation, behavioural theories, and/or a policy framework; and 3) identify other features that contribute to effectiveness. Methods: A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Scopus, CINAHL, Cochrane Library, INFORMIT, IEEE Xplore and Clinical Trial Registries, published between January 2000 and August 2022. Digital interventions to increase vegetable intake were included, with effective interventions identified based on statistically significant improvement in vegetable intake. To identify policy-action gaps, studies were mapped across the three domains of the NOURISHING framework (i.e., behaviour change communication, food environment, and food system). Risk of bias was assessed using Cochrane tools for randomized, cluster randomized and non-randomized trials. Results: Of the 1,347 records identified, 30 studies were included. Risk of bias was high or serious in most studies (n = 25/30; 83%). Approximately one quarter of the included interventions (n = 8) were effective at improving vegetable intake. While the features of effective and ineffective interventions were similar, embedding of behaviour change theories (89% vs 61%) and inclusion of stakeholders in the design of the intervention (50% vs 38%) were more common among effective interventions. Only one (ineffective) intervention used true co-design. Although fewer effective interventions included personalisation (67% vs 81%), the degree of personalisation varied considerably between studies. All interventions mapped across the NOURISHING framework behaviour change communication domain, with one ineffective intervention also mapping across the food environment domain. Conclusion: Few digital interventions identified in this review were effective for increasing vegetable intake. Embedding behaviour change theories and involving stakeholders in intervention design may increase the likelihood of success. The under-utilisation of comprehensive co-design methods presents an opportunity to ensure that personalisation approaches better meet the needs of target populations. Moreover, future digital interventions should address both behaviour change and food environment influences on vegetable intake