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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Ten years survival benefit and appropriateness of surgical versus percutaneous revascularization in synergy between percutaneous coronary intervention with taxus and cardiac surgery randomized trial.
OBJECTIVES: Average treatment effects from randomized trials do not reflect the heterogeneity of an individual's response to treatment. This study evaluates the appropriate proportions of patients for coronary artery bypass grafting, or percutaneous intervention based on the predicted/observed ratio of 10-year all-cause mortality in the SYNTAX population. METHODS: The study included 1800 randomized patients and 1275 patients in the nested percutaneous (n = 198) or surgical (n = 1077) registries. The primary end-point was 10-year all-cause mortality. The SYNTAX score II-2020 was validated internally in the randomized cohort and externally in the registry cohort. Proportions of patients with survival benefits from coronary artery bypass grafting or percutaneous intervention were determined using SYNTAX score II-2020. RESULTS: Ten-year mortality was 23.8% for coronary artery bypass grafting 28.6% for percutaneous intervention in the randomized cohort, 27.6% for coronary artery bypass grafting, and 55.4% for percutaneous intervention in the registries. In the coronary artery bypass grafting registry, the SYNTAX score II-2020 predicted 10-year mortality with helpful calibration and discrimination (C-index : 0.70, intercept : 0.00, slope : 0.76). The proportion of patients deriving a predicted survival benefit from coronary artery bypass grafting over percutaneous intervention was 82.4% (2143/2602) and 17.7% (459/2602) for the entire SYNTAX trial population; translating into a 4.7 to 1 appropriate ratio of treatment allocation to coronary artery bypass grafting and percutaneous intervention. CONCLUSIONS: Choosing a revascularization modality should depend on an individual's long-term prognosis rather than average treatment effects. Additionally, patients should be informed about their predicted prognosis. TRIAL REGISTRATION: Registered on clinicaltrial.govSYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050);SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).
Muscarinic receptors mediate motivation via preparatory neural activity in humans.
Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson's disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using electroencephalography (EEG). We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivational effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation [CNV]) was strengthened by high incentives and by muscarinic blockade, although THP reduced the incentive effect. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions; frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. The incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug's effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.
Muscarinic receptors mediate motivation via preparatory neural activity in humans
Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson’s disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using electroencephalography (EEG). We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivational effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation [CNV]) was strengthened by high incentives and by muscarinic blockade, although THP reduced the incentive effect. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions; frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. The incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug’s effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.
A narrative review of the current available literature on the intersection between the climate crisis and paediatric surgical care.
The climate crisis exacerbates health inequities, including in paediatric surgery, creating a vicious cycle. We sought to review (a) existing evidence on the connection between paediatric surgery and climate and (b) how this addresses the vicious cycle. A PubMed search was conducted on 23-08-2023. Articles not commenting on "climate change" and "paediatric surgery" were excluded. Included papers were categorised into emerging themes. Out of 151 search results, seven articles were included. The emerging themes related to "Effect of climate on paediatric surgical illness" (n = 3), "Effect of surgery on climate" (n = 2), and "Mitigating impact of paediatric surgery" (n = 2). Five articles were observational studies, and two were literature reviews, all papers published after 2020. We found limited primary research focusing on the intersection between climate change and paediatric surgery. Articles tend to focus on quantifying impact and mitigation, which does not lend itself to climate justice. The syndemic model of health focuses on the complex interconnections and pathways through which health conditions interact within populations to exacerbate adverse health outcomes. We suggest future research needs to be reframed, with the interconnection between health inequities, the climate crisis, and the wider health system addressed together.
The Use of Virtual Patients to Provide Feedback on Clinical Reasoning: A Systematic Review.
PURPOSE: Virtual patients (VPs) are increasingly used in health care professions education to support clinical reasoning (CR) development. However, the extent to which feedback is given across CR components is unknown, and guidance is lacking on how VPs can optimize CR development. This systematic review sought to identify how VPs provide feedback on CR. METHOD: Seven databases (MEDLINE, EMBASE, CINAHL, ERIC, PsycINFO, Scopus, and ProQuest Dissertations) were searched in March 2023 using terms (e.g., medical education, virtual patient, case-based learning, computer simulation) adapted from a previous systematic review. All studies that described VP use for developing CR in medical professionals and provided feedback on at least 1 CR component were retrieved. Screening, data extraction, and quality assessment were performed. Narrative synthesis was performed to describe the approaches used to measure and provide feedback on CR. RESULTS: A total of 6,526 results were identified from searches, of which 72 met criteria, but only 35 full-text articles were analyzed because the reporting of interventions in abstracts (n = 37) was insufficient. The most common CR components developed by VPs were leading diagnosis (23 [65.7%]), management or treatment plan (23 [65.7%]), and information gathering (21 [60%]). The CR components were explored by various approaches, from redefined questions to free text and concept maps. CONCLUSIONS: Studies describing VP use for giving CR feedback have mainly focused on easy-to-assess CR components, whereas few studies have described VPs designed for assessing CR components, such as problem representation, hypothesis generation, and diagnostic justification. Despite feedback being essential for learning, few VPs provided information on the learner's use of self-regulated learning processes. Educators designing or selecting VPs for CR use must consider the needs of learner groups and how different CR components can be explored and should make the instructional design of VPs explicit in published work.
Spinal Cord Stimulation Improves Quality of Life for Patients With Chronic Pain-Data From the UK and Ireland National Neuromodulation Registry.
INTRODUCTION: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications. MATERIALS AND METHODS: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures. RESULTS: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions. CONCLUSIONS: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements.
Figure 1 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Sequential stratification/adjustments to the model comparing the risk of incident colorectal cancer associated with DP1 and DP2. Top, sequential changes to the HRs for quintiles 5 versus 1 for DP1 and DP2. Bottom, sequential changes to the HRs for DP1 and DP2 <i>z</i>-scores in continuous form. The <i>X</i>-axis represents HRs on the log-scale. CIs were obtained using the floating absolute risk method (<a href="#bib34" target="_blank">34</a>). χ<sup>2</sup> and <i>P</i> values were calculated by likelihood ratio tests to assess the heterogeneity in the associations with sequential adjustments for covariates. Behavioral factors included smoking status, physical activity level (MET-hours/week), and total energy intake (ln-kJ). SES* comprises TDI and educational attainment. Models were stratified by covariates violating the proportional hazards assumption: physical activity, family history of colorectal cancer, education, and BMI. SES, socioeconomic status.</p>
Supplementary Table S8 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Table S8 Hazard ratios and 95% confidence intervals of all variables in the fully-adjusted model for DP2</p>
Supplementary Figure S4 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Figure S4 DP2 associations with CRC by anatomic subsite</p>
Supplementary Table S6 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Table S6 Subgroup analysis of the association between DP1 and incident CRC by anatomic subgroup, fully adjusted and stratified model.</p>
Supplementary Figure S3 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Figure S3 Hazard ratios and 95% confidence intervals for interactions of DP1 and DP2 with age and sex</p>
Supplementary Table S11 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Table S11. Comparison of incident colorectal cancer cases and baseline characteristics between those completing 2 vs. 3+ WebQs</p>
Supplementary Figure S1 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Figure S1 Directed acyclic graph of variables used in the model.</p>
Supplementary Table S9 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Table S9 Sensitivity analyses of the fully adjusted and stratified model for the association between dietary pattern 1 and incident overall CRC</p>
Supplementary Table S3 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Table S3. Univariable associations with colorectal cancer</p>
Supplementary Figure S5 from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<p>Figure S5 DP2 Sensitivity analyses</p>
Data from Associations between Dietary Patterns and Incident Colorectal Cancer in 114,443 Individuals from the UK Biobank: A Prospective Cohort Study
<div>AbstractBackground:<p>Diet–disease association studies increasingly use dietary patterns (DP) to account for the complexity of the exposure. We assessed if a DP associated with type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality is also associated with colorectal cancer.</p>Methods:<p>We used reduced rank regression on 24-hour recall data to identify DPs, explaining the maximum variation in four nutrient-response variables: energy density, saturated fatty acids, free sugars, and fiber density. Cox proportional hazards models examined prospective associations between DP adherence (coded in a continuous scale as <i>z</i>-scores as well as in quintiles) and incident colorectal cancer. Subgroup analyses were conducted for tumor site, age, and sex.</p>Results:<p>After exclusions, 1,089 colorectal cancer cases occurred in 114,443 participants over a median follow-up of 8.0 years. DP1 was characterized by increased intake of chocolate and confectionery; butter; low-fiber bread; red and processed meats; and alcohol, as well as low intake of fruits, vegetables, and high-fiber cereals. After accounting for confounders, including body mass, there were positive linear associations between DP1 and incident overall colorectal cancer (HR of quintile 5 vs. 1, 1.34; 95% confidence interval, 1.16–1.53, <i>P</i><sub>trend</sub> = 0.005) and rectal cancer (HR of quintile 5 vs. 1, 1.58; 95% confidence interval, 1.27–1.96, <i>P</i><sub>trend</sub> = 0.009) but not for proximal or distal colon cancers. No DP2–colorectal cancer association was observed.</p>Conclusions:<p>A DP previously associated with cardiometabolic disease is also associated with incident colorectal cancer, especially rectal cancers.</p>Impact:<p>These consistent associations of particular food groups with both cardiometabolic disease and this diet-related cancer strengthen the evidence base for holistic population dietary guidelines to prevent ill-health.</p></div>