Surgeon preference for treatment allocation in older people facing major gastrointestinal surgery: an application of the discrete choice experiment methodology.

AIM: Variation in major gastrointestinal surgery rates in the older population suggests heterogeneity in surgical management. A higher prevalence of comorbidities, frailty and cognitive impairments in the older population may account for some variation. The aim of this study was to determine surgeon preference for major surgery versus conservative management in hypothetical patient scenarios based on key attributes. METHOD: A survey was designed according to the discrete choice methodology guided by a separate qualitative study. Questions were designed to test for associations between key attributes (age, comorbidity, urgency of presentation, pathology, functional and cognitive status) and treatment preference for major gastrointestinal surgery versus conservative management. The survey consisting of 18 hypothetical scenarios was disseminated electronically to UK gastrointestinal surgeons. Binomial logistic regression was used to identify associations between the attributes and treatment preference. RESULTS: In total, 103 responses were received after 256 visits to the questionnaire site (response rate 40.2%). Participants answered 1847 out of the 1854 scenarios (99.6%). There was a preference for major surgery in 1112/1847 (60.2%) of all scenarios. Severe comorbidities (OR 0.001, 95% CI 0.000-0.030; P = 0.000), severe cognitive impairment (OR 0.001, 95% CI 0.000-0.033; P = 0.000) and age 85 years and above (OR 0.028, 95% CI 0.005-0.168; P = 0.000) were all significant in the decision not to offer major gastrointestinal surgery. CONCLUSION: This study has demonstrated variation in surgical treatment preference according to key attributes in hypothetical scenarios. The development of fitness-stratified guidelines may help to reduce variation in surgical practice in the older population.

Healthcare professional preferences in the health and fitness assessment and optimization of older patients facing colorectal cancer surgery.

AIM: There are few age- and fitness-specific, evidence-based guidelines for colorectal cancer surgery. The uptake of different assessment and optimization strategies is variable. The aim of this study was to explore healthcare professional opinion about these issues using a mixed methods design. METHODS: Semi-structured qualitative interviews were undertaken with healthcare professionals from a single UK region involved in the treatment, assessment and optimization of colorectal surgery patients. Interviews were analysed using the framework approach. An online questionnaire survey was subsequently designed and disseminated to UK surgeons to quantitatively assess the importance of interview themes. Descriptive statistics were used to analyse questionnaire data. RESULTS: Thirty-seven healthcare professionals out of 42 approached (response rate 88%) were interviewed across five hospitals in the south Yorkshire region. Three broad themes were developed: attitudes towards treatment of the older patient, methods of assessment of suitability and optimization strategies. The questionnaire was completed by 103 out of an estimated 256 surgeons (estimated response rate 40.2%). There was a difference in opinion regarding the role of major surgery in older patients, particularly when there is coexisting dementia. Assessment was not standardized. Access to optimization strategies was limited, particularly in the emergency setting. CONCLUSION: There is wide variation in the process of assessment and provision of optimization strategies in UK practice. Lack of evidence-based guidelines, cost and time constraints restrict the development of services and pathways. Differences in opinion between surgeons towards patients with frailty or dementia may account for some of the variation in colorectal cancer outcomes.

Protocol for a multi-centre observational and mixed methods pilot study to identify factors predictive of poor functional recovery after major gastrointestinal surgery and strategies to enhance uptake of perioperative optimization: Optimizing the care and treatment pathways for older patients facing major gastrointestinal surgery (OCTAGON).

INTRODUCTION: National datasets report large variations in outcomes from older people (≥65 years) between different UK surgical units. This implies that not all patients receive the same level of care or access to resources, such as rehabilitation or allied health professional input. This might impact functional decline. AIMS: Our aim is to evaluate the baseline status of older patients facing major gastrointestinal surgery and the impact of variation in perioperative assessment and provision of perioperative support on functional outcomes. Patients' experiences and views of assessment and optimization will be explored via integrated qualitative semi-structured interviews. METHODS AND ANALYSIS: This multi-centre, pilot cohort study will include patients ≥65 years presenting via both elective and emergency pathways at three to five South Yorkshire NHS hospitals (Clinical Trials registration NCT04545125). The primary outcome is functional recovery measured using the World Health Organization Disability Assessment Schedule 2.0 at 6 weeks post-operation. Secondary outcomes include feasibility, quality of life, length of stay and complication rate. An opportunistic sample size of 120 has been estimated and will inform the design of a future, adequately powered study. For the qualitative study, 20-30 semi-structured patient interviews will be undertaken with patients from the cohort study to explore experiences of assessment and optimization. Interviews will be digitally recorded, transcribed verbatim and analysed according to the framework approach. ETHICS AND DISSEMINATION: This study has been approved by the National Health Service Research Ethics Committee and is registered centrally with Health Research Authority. It has been adopted by the National Institute for Health Research Portfolio scheme. Dissemination will be via international and national surgical and geriatric conferences.

Charge Density in Enzyme Active Site as a Descriptor of Electrostatic Preorganization.

Large protein macromolecules in enzymatic catalysis have been shown to exert a specific electric field that reduces the reorganization energy upon barrier crossing and thus reduces the reaction free energy barrier. In this work we suggest that the charge density in the active site of an enzyme investigated using formalisms embodied by the quantum theory of atoms in molecules (QTAIM) provides a sensitive and quantum mechanically rigorous probe of electrostatic preorganization. We focus on the active site of ketosteroid isomerase, a well-studied enzyme for which electrostatic preorganization has been modeled theoretically and studied experimentally. We study the charge density in the active site and the reaction mechanism in the presence of small external electric fields of various directions and magnitudes. We show that the geometry of the full charge density is a sensitive reporter on the external field experienced by the active site. Changes are observed in the relative positions of critical points and amount of charge at critical points as a function of the field. At the same time, a subset of these features correlates linearly with the barrier of the first reaction step in catalysis. Small changes in the barrier, within 1-2 kcal/mol, are reflected in the charge density, suggesting the existence of a field - reactant state charge density - reaction barrier correlation. Hence, QTAIM can be used for the analysis of electric field in enzyme active sites, and further investigations and exploitations of the found correlations may prove useful in enzyme design where preorganization is optimized.