Adherence to the Eatwell Guide and cardiometabolic, cognitive and neuroimaging parameters: an analysis from the PREVENT dementia study.

BACKGROUND: The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. METHODS: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer's disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. RESULTS: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG ß: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG ß: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic ß: -0.24, 95% CI: -0.45, -0.03; diastolic ß: -0.16, 95% CI: -0.29, -0.03; BMI ß: -0.09, 95% CI: -0.16, -0.01). CONCLUSIONS: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Improving hip fracture care: A five-year review of the early contributors to the Australian and New Zealand Hip Fracture Registry.

OBJECTIVE: The aim of this study was to examine temporal trends (2016-2020) in hip fracture care in Australian and New Zealand (ANZ) hospitals that started providing patient-level data to the ANZ Hip Fracture Registry (ANZHFR) on/before 1 January 2016 (early contributors). METHODS: Retrospective cohort study of early contributor hospitals (n = 24) to the ANZHFR. The study cohort included patients aged ≥50 years admitted with a low trauma hip fracture between 1 January 2016 and 31 December 2020 (n = 26,937). Annual performance against 11 quality indicators and 30- and 365-day mortality were examined. RESULTS: Compared to 2016/2017, year-on-year improvements were demonstrated for preoperative cognitive assessment (2020: OR 3.57, 95% confidence interval [95% CI] 3.29-3.87) and nerve block use prior to surgery (2020: OR 4.62, 95% CI 4.17-5.11). Less consistent improvements over time from 2016/2017 were demonstrated for emergency department (ED) stay of <4 h (2017; 2020), pain assessment ≤30 min of ED presentation (2020), surgery ≤48 h (2020) and bone protection medication prescribed on discharge (2017-2020; 2020 OR 2.22, 95% CI 2.03-2.42). The odds of sustaining a hospital-acquired pressure injury increased in 2019-2020 compared to 2016. The odds of receiving an orthogeriatric model of care and being offered the opportunity to mobilise on Day 1 following surgery fluctuated. There was a reduction in 365-day mortality in 2020 compared to 2016 (OR 0.86, 95% CI 0.74-0.98), whereas 30-day mortality did not change. CONCLUSIONS: Several quality indicators improved over time in early contributor hospitals. Indicators that did not improve may be targets for future care improvement activities, including considering incentivised hip fracture care, which has previously been shown to improve care/outcomes. COVID-19 and reporting practices may have impacted the study findings.

Adherence to the Eatwell Guide and population and planetary health: A Rank Prize Forum report.

This report summarises a Forum conducted in June 2023 to explore the current state of the knowledge around the Eatwell Guide, which is the UK government's healthy eating tool, in relation to population and planetary health. The 1.5-day Forum highlighted the limited, albeit promising evidence linking higher adherence to the Eatwell Guide with favourable health outcomes, including reduced overall mortality risk, lower abdominal obesity in post-menopausal women and improved cardiometabolic health markers. Similarly, evidence was presented to suggest that higher adherence to the Eatwell Guide is associated with reduced greenhouse gas emissions. Presentations were given around cultural adaptations of the Eatwell Guide, including African Heritage and South Asian versions, which are designed to increase the acceptability and uptake of the Eatwell Guide in these communities in the United Kingdom. Presentations highlighted ongoing work relevant to the applications of the Eatwell Guide in randomised controlled trials and public health settings, including the development of a screening tool to quantify Eatwell Guide adherence. The Forum ended with a World Café-style event, in which the strengths and limitations of the Eatwell Guide were discussed, and directions for future research were identified. This Forum report serves as a primer on the current state of the knowledge on the Eatwell Guide and population and planetary health and will be of interest to researchers, healthcare professionals and public health officials.

Effects of PROtein enriched MEDiterranean Diet and EXercise on nutritional status and cognition in adults at risk of undernutrition and cognitive decline: the PROMED-EX Randomised Controlled Trial.

INTRODUCTION: Undernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade or more, providing a unique opportunity for early intervention to correct undernutrition and potentially prevent or delay cognitive impairment. The combined effects of diet and exercise on undernutrition have not yet been evaluated. The objective of this trial is to determine the effect of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline. METHODS: One hundred and five participants aged 60 years and over at risk of undernutrition and with subjective cognitive decline will be recruited to participate in a 6-month, single-blind, parallel-group randomised controlled trial. Participants will be block randomised into one of three groups: group 1-PROMED-EX (diet+exercise), group 2-PROMED (diet only) and group 3-standard care (control). The primary outcome is nutritional status measured using the Mini Nutritional Assessment. Secondary outcomes include cognitive function, nutritional intake, body composition, physical function and quality of life. Mechanistic pathways for potential diet and exercise-induced change in nutritional status and cognition will be explored by measuring inflammatory, metabolic, nutritional and metabolomic biomarkers. ETHICS AND DISSEMINATION: The study is approved by the UK Office for Research Ethics Committee (ref: 21/NW/0215). Written informed consent will be obtained from participants prior to recruitment. Research results will be disseminated to the public via meetings and media and the scientific community through conference presentations and publication in academic journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05166564).

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery.

A preclinical evaluation using a regenerative medicine methodology comprising an additively manufactured medical-grade ε-polycaprolactone ß-tricalcium phosphate (mPCL-TCP) scaffold with a corticoperiosteal flap was undertaken in eight sheep with a tibial critical-size segmental bone defect (9.5 cm3, M size) using the regenerative matching axial vascularization (RMAV) approach. Biomechanical, radiological, histological, and immunohistochemical analysis confirmed functional bone regeneration comparable to a clinical gold standard control (autologous bone graft) and was superior to a scaffold control group (mPCL-TCP only). Affirmative bone regeneration results from a pilot study using an XL size defect volume (19 cm3) subsequently supported clinical translation. A 27-year-old adult male underwent reconstruction of a 36-cm near-total intercalary tibial defect secondary to osteomyelitis using the RMAV approach. Robust bone regeneration led to complete independent weight bearing within 24 months. This article demonstrates the widely advocated and seldomly accomplished concept of "bench-to-bedside" research and has weighty implications for reconstructive surgery and regenerative medicine more generally.

Protocol for the BONE-RECON trial: a single-arm feasibility trial for critical sized lower limb BONE defect RECONstruction using the mPCL-TCP scaffold system with autologous vascularised corticoperiosteal tissue transfer.

INTRODUCTION: Reconstruction of critical bone defects is challenging. In a substantial subgroup of patients, conventional reconstructive techniques are insufficient. Biodegradable scaffolds have emerged as a novel tissue engineering strategy for critical-sized bone defect reconstruction. A corticoperiosteal flap integrates the hosts' ability to regenerate bone and permits the creation of a vascular axis for scaffold neo-vascularisation (regenerative matching axial vascularisation-RMAV). This phase IIa study evaluates the application of the RMAV approach alongside a custom medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold (Osteopore) to regenerate bone sufficient to heal critical size defects in lower limb defects. METHODS AND ANALYSIS: This open-label, single-arm feasibility trial will be jointly coordinated by the Complex Lower Limb Clinic (CLLC) at the Princess Alexandra Hospital in Woolloongabba (Queensland, Australia), the Australian Centre for Complex Integrated Surgical Solutions (Queensland, Australia) and the Faculty of Engineering, Queensland University of Technology in Kelvin Grove (Queensland, Australia). Aiming for limb salvage, the study population (n=10) includes any patient referred to the CLLC with a critical-sized bone defect not amenable to conventional reconstructive approaches, after discussion by the interdisciplinary team. All patients will receive treatment using the RMAV approach using a custom mPCL-TCP implant. The primary study endpoint will be safety and tolerability of the reconstruction. Secondary end points include time to bone union and weight-bearing status on the treated limb. Results of this trial will help shape the role of scaffold-guided bone regenerative approaches in complex lower limb reconstruction where current options remain limited. ETHICS AND DISSEMINATION: Approval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12620001007921.

Two-country comparison of the prescription of bone protection medication before and early after hip fracture.

Pharmacological management of bone health warrants investigation into factors influencing initiation of bone protection medication (BPM) at discharge after a hip fracture. This sprint audit identified reasons attributed to low BPM treatment levels at hospital discharge which can guide improvement in the prevention of future fractures. PURPOSE: To compare patient characteristics and Australian and New Zealand approaches to prescribing bone protection medication (BPM) pre- or post-hip fracture, determine reasons why BPM was not prescribed earlier post-fracture, and assess the generalisability of sprint audit and the Australian and New Zealand Hip Fracture Registry (ANZHFR) patient cohorts. METHODS: A retrospective cohort study of hip fracture patients from the ANZHFR aged ≥ 50 years (2016-2020) and consecutive patients from the 2021 BPM sprint audit. Multivariable logistic regression was used to examine factors associated with not prescribing BPM. RESULTS: Of 55,618 patients admitted with a hip fracture in the ANZHFR, less than 10% of patients in Australia and New Zealand were taking BPM on admission, increasing to 22.4% in Australia and 27.8% in New Zealand on discharge. Registry patients who were younger (50-69 years), healthy (ASA grade 1), lived in a residential aged care facility, had impaired cognition, delirium identified, or were awaiting a specialist falls assessment were less likely to take BPM. Within the audit, 46.2% of patients in Australia and 39.2% in New Zealand did not have BPM in their discharge prescription. The most common reason for not prescribing BPM in Australia was low level of vitamin D (13.3%), and in New Zealand, renal impairment (14.8%). Sprint and registry patient characteristics were comparable in terms of patient age, sex, usual place of residence, and ASA grade. CONCLUSIONS: BPM prescription early after hip fracture is low. Opportunities exist to increase the rate of prescription of medications known to prevent future fractures in this high-risk population.

Research priorities in pernicious anaemia: James Lind Alliance Priority Setting Partnership.

OBJECTIVES: To form a James Lind Alliance (JLA) Priority Setting Partnership (PSP) to determine research priorities related to the cause, diagnosis, treatment and management of pernicious anaemia (PA) from the perspectives of patients, carers and clinicians. DESIGN: The PSP conducted two surveys and a workshop to identify the Top 10 questions for research. A first survey identified questions relating to the cause, diagnosis, treatment and management of PA. A literature search checked whether any of these questions had already been answered. A second survey asked respondents to identify and rank their top 10 questions from the list of questions from the first survey. An online workshop used an adapted nominal group technique to agree a final Top 10. RESULTS: In the first survey, 933 people submitted 3480 responses that were categorised and summarised to generate a long list of 40 questions. None had been answered by previous research. The combined rankings from the 1068 patients, carers and clinicians who took part in the second survey identified a short list of 16 questions. These were discussed at the final workshop to agree the final Top 10. The number one question was about an accurate and reliable diagnostic test for PA. The other nine questions were about making treatment safe and effective, understanding why people with PA vary in their need for treatment, links to other conditions, and how to encourage clinicians to take PA seriously and provide long-term care. CONCLUSIONS: This JLA PSP enabled patients, carers and clinicians to work together to agree the Top 10 uncertainties relating to the cause, diagnosis, management and treatment of PA. Addressing any of these questions will greatly benefit the end-users of research, the people whose daily lives and decisions will be directly affected by generating high quality research evidence.

Experience of a systematic approach to care and prevention of fragility fractures in New Zealand.

This narrative review describes efforts to improve the care and prevention of fragility fractures in New Zealand from 2012 to 2022. This includes development of clinical standards and registries to benchmark provision of care, and public awareness campaigns to promote a life-course approach to bone health. PURPOSE: This review describes the development and implementation of a systematic approach to care and prevention for New Zealanders with fragility fractures, and those at high risk of first fracture. Progression of existing initiatives and introduction of new initiatives are proposed for the period 2022 to 2030. METHODS: In 2012, Osteoporosis New Zealand developed and published a strategy with objectives relating to people who sustain hip and other fragility fractures, those at high risk of first fragility fracture or falls and all older people. The strategy also advocated formation of a national fragility fracture alliance to expedite change. RESULTS: In 2017, a previously informal national alliance was formalised under the Live Stronger for Longer programme, which includes stakeholder organisations from relevant sectors, including government, healthcare professionals, charities and the health system. Outputs of this alliance include development of Australian and New Zealand clinical guidelines, clinical standards and quality indicators and a bi-national registry that underpins efforts to improve hip fracture care. All 22 hospitals in New Zealand that operate on hip fracture patients currently submit data to the registry. An analogous approach is ongoing to improve secondary fracture prevention for people who sustain fragility fractures at other sites through nationwide access to Fracture Liaison Services. CONCLUSION: Widespread participation in national registries is enabling benchmarking against clinical standards as a means to improve the care of hip and other fragility fractures in New Zealand. An ongoing quality improvement programme is focused on eliminating unwarranted variation in delivery of secondary fracture prevention.

Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series.

BACKGROUND: We describe the first clinical series of a novel bone replacement technique based on regenerative matching axial vascularisation (RMAV). This was used in four cases: a tibial defect after treatment of osteomyelitis; a calvarial defect after trauma and failed titanium cranioplasty; a paediatric tibial defect after neoadjuvant chemotherapy and resection of Ewing sarcoma; and a paediatric mandibular deficiency resulting from congenital hemifacial microsomia. METHOD: All patients underwent reconstruction with three-dimensional (3D)-printed medical-grade polycaprolactone and tricalcium phosphate (mPCL-TCP) scaffolds wrapped in vascularised free corticoperiosteal flaps. OUTCOME: Functional volumes of load-sharing regenerate bone have formed in all cases after a moderate duration of follow-up. At 36 cm, case 1 remains the longest segment of load bearing bone ever successfully reconstructed. This technique offers an alternative to existing methods of large volume bone defect reconstruction that may be safe, reliable, and give predictable outcomes in challenging situations. It achieves this by using a bioresorbable scaffold to support and direct the growth of regenerate bone, driven by RMAV. CONCLUSION: This technique may facilitate the reconstruction of bone defects previously thought unreconstructable, reduce the risk of long-term implant-related complications and achieve these outcomes in a hostile environment. These potential benefits must now be formally tested in prospective clinical trials.

Seasonality of hip fracture and vitamin D deficiency persists in a sub-tropical climate.

Both hip fractures and vitamin D (25-hydroxyvitamin D (25-OHD)) deficiency are more common in winter in regions with temperate climates, but few data exist for a sub-tropical climate. In a South East Queensland tertiary hospital over a 7-year period, there were significantly more hip fractures in winter than the other three seasons (analysis of variance P = 0.003), with associated higher frequency of 25-OHD deficiency - 42.5% in winter compared to 28.5% in summer, odds ratio 1.86 (95% confidence interval 1.35-2.56), P = 0.0001. Seasonality of hip fracture and 25-OHD deficiency occurs even in a sub-tropical climate.

'E' therapy in the community: Examination of the uptake and effectiveness of BRAVE (a self-help computer programme for anxiety in children and adolescents) in primary care.

OBJECTIVE: Recognizing and treating anxiety early is an important public mental health objective. There is clinical trial evidence that 'e' therapies are appealing, engaging and effective and have the potential to improve access to treatment. However, their implementation and effectiveness in real world settings is still emerging. Following a major natural disaster in NZ, an online therapist assisted CBT programme for children with anxiety, (BRAVE_TA) was made available in primary care. METHODS: Uptake and feasibility of BRAVE_TA delivery was assessed by examining referral patterns, non-engagement rates and programme progression within a geographic region of NZ (Canterbury population of around 500,000). Effectiveness of BRAVE_TA was measured by the extent of change in the primary outcome measure of anxiety, the CAS8, between baseline and last completed session. RESULTS: There were 1361 referrals to BRAVE_TA over 2014-2018, mostly from primary care doctors and nurses in primary schools. After attrition due to triage and family withdrawal, 75% (N = 1026) were enrolled. Around half of children/adolescents completed 4 sessions with moderate effect sizes achieved Children/adolescents who completed more sessions, had lower anxiety after their last session, with most of the improvement occurring within the first three to four sessions. CONCLUSION: BRAVE_TA has shown to be an acceptable and effective 'e' therapy tool in a 'real world' primary care setting for children/adolescents with anxiety. This study supports the role of 'e' therapy as part of a stepped-care model within primary care in improving access to treatment and thus improving public mental health in children.Trial registry: ACTRN12612000063819.

Using Care Bundles to Improve Surgical Outcomes and Reduce Variation in Care for Fragility Hip Fracture Patients.

INTRODUCTION: Fragility hip fractures constitute a large proportion of orthogeriatric admissions to orthopedic wards. This study looked at reducing variation in care in fragility hip fracture patients using a novel approach with care bundles. The care bundle comprises 5 elements targeted at providing adequate analgesia, early mobilization, improving recognition of delirium, and decreasing rates of urinary infections. METHODS: A total of 198 patients who sustained a fragility hip fracture during the intervention period were included in the study. The primary outcome measure was compliance in applying the bundle to the study population, and secondary outcome measures were in-hospital mortality, acute length of stay, delirium and duration of delirium, and urinary tract infections. RESULTS: During the 12-month intervention period, compliance to the bundle of care was 47% (n = 92) based on the "all-or-none" approach. This was 28% higher than the preintervention rate. Overall, there was an increased rate of compliance across all individual elements of the bundle in the intervention group when compared to the preintervention group (P = .01). The most significant clinical result was a 10.5% reduction in "in-hospital mortality" in the intervention group (P < .001). CONCLUSION: This study demonstrated that the implementation of specific care bundle in patients with fragility hip fracture significantly reduces variation in care.

Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. WHAT THIS STUDY ADDS: Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role. AIMS: To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. METHODS: A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. RESULTS: No significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as 'solubility limited' displayed an overall reduction as compared with 'freely soluble' compounds, as well as an unaltered and increased ppR. CONCLUSION: Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance.

The impact of intestinal failure on oral drug absorption: a review.

INTRODUCTION: Intestinal failure is a complex gastroenterological condition that occurs as a result of reduced intestinal absorption of nutrients and/or water and electrolytes. Without treatment, nutritional depletion and/or dehydration will result. It can be acute or chronic and occurs secondary to a variety of causes, including massive bowel resection, inflammatory bowel diseases of the bowel, and small bowel dysfunction. RESULTS AND DISCUSSION: Resection of the small bowel results in a range of physiological changes that affect the absorption of nutrients, water, and electrolytes. In addition, these changes may also affect the absorption of orally administered medication. However, there is only minimal published literature regarding this, with the publications limited to case reports of failure or efficacy of certain medicines such as digoxin and warfarin in individual patients. Due to the highly heterogeneous nature of intestinal failure patients, there is little generalizability of the information within these articles to other patients. Only one article seeks to provide limited practical advice regarding prescribing in this complex patient group. CONCLUSION: The input of specialist pharmacists is necessary in the management of these patients to ensure that appropriate drugs and formulations are prescribed in a timely manner to optimize absorption and resultant efficacy.

Nutrition support to patients undergoing gastrointestinal surgery.

Nutritional depletion has been demonstrated to be a major determinant of the development of post-operative complications. Gastrointestinal surgery patients are at risk of nutritional depletion from inadequate nutritional intake, surgical stress and the subsequent increase in metabolic rate. Fears of postoperative ileus and the integrity of the newly constructed anastomosis have led to treatment typically entailing starvation with administration of intravenous fluids until the passage of flatus. However, it has since been shown that prompt postoperative enteral feeding is both effective and well tolerated. Enteral feeding is also associated with specific clinical benefits such as reduced incidence of postoperative infectious complications and an improved wound healing response. Further research is required to determine whether enteral nutrition is also associated with modulation of gut function. Studies have indicated that significant reductions in morbidity and mortality associated with perioperative Total Parenteral Nutrition (TPN) are limited to severely malnourished patients with gastrointestinal malignancy. Meta-analyses have shown that enteral nutrition is associated with fewer septic complications compared with parenteral feeding, reduced costs and a shorter hospital stay, so should be the preferred option whenever possible. Evidence to support pre-operative nutrition support is limited, but suggests that if malnourished individuals are adequately fed for at least 7-10 days preoperatively then surgical outcome can be improved. Ongoing research continues to explore the potential benefits of the action of glutamine on the gut and immune system for gastrointestinal surgery patients. To date it has been demonstrated that glutamine-enriched parenteral nutrition results in reduced length of stay and reduced costs in elective abdominal surgery patients. Further research is required to determine whether the routine supplementation of glutamine is warranted. A limitation for targeted nutritional support is the lack of a standardised, validated definition of nutritional depletion. This would enable nutrition support to be more readily targeted to those surgical patients most likely to derive significant clinical benefit in terms of improved post-operative outcome.

Galls on thistles.

Plant galls - the more we learn, the more there is to know! Approximately 15000 insect species ( c. 2% of all known insects) form galls, and this habit is extremely common over a range of floras and latitudes. Yet, there is still no general consensus on why they exist. Thistle-galling insects are relatively well known and are used as biological control agents (of thistles) and model ecological systems.