The economic burden of cancer, coronary heart disease, dementia, and stroke in England in 2018, with projection to 2050: an evaluation of two cohort studies.

BACKGROUND: Cancer, coronary heart disease, dementia, and stroke are major contributors to morbidity and mortality in England. We aimed to assess the economic burden (including health-care, social care, and informal care costs, as well as productivity losses) of these four conditions in England in 2018, and forecast this cost to 2050 using population projections. METHODS: We used individual patient-level data from the Clinical Practice Research Datalink (CPRD) Aurum, which contains primary care electronic health records of patients from 738 general practices in England, to calculate health-care and residential and nursing home resource use, and data from the English Longitudinal Study on Ageing (ELSA) to calculate informal and formal care costs. From CPRD Aurum, we included patients registered on Jan 1, 2018, in a CPRD general practice with Hospital Episode Statistics (HES)-linked records, omitting all children younger than 1 year. From ELSA, we included data collected from wave 9 (2018-19). Aggregate English resource use data on morbidity, mortality, and health-care, social care, and informal care were obtained and apportioned, using multivariable regression analyses, to cancer, coronary heart disease, dementia, and stroke. FINDINGS: We included 4 161 558 patients from CPRD Aurum with HES-linked data (mean age 41 years [SD 23], with 2 079 679 [50·0%] men and 2 081 879 [50·0%] women) and 8736 patients in ELSA (68 years [11], with 4882 [55·9 %] men and 3854 [44·1%] women). In 2018, the total cost was £18·9 billion (95% CI 18·4-19·4) for cancer, £12·7 billion (12·3-13·0) for coronary heart disease, £11·7 billion (9·6-12·7) for dementia, and £8·6 billion (8·2-9·0) for stroke. Using 2050 English population projections, we estimated that costs would rise by 40% (39-41) for cancer, 54% (53-55) for coronary heart disease, 100% (97-102) for dementia, and 85% (84-86) for stroke, for a total of £26·5 billion (25·7-27·3), £19·6 billion (18·9-20·2), £23·5 billion (19·3-25·3), and £16·0 billion (15·3-16·6), respectively. INTERPRETATION: This study provides contemporary estimates of the wide-ranging impact of the most important chronic conditions on all aspects of the economy in England. The data will help to inform evidence-based polices to reduce the impact of chronic disease, promoting care access, better health outcomes, and economic sustainability. FUNDING: Alzheimer's Research UK.

Examining the Impact of Structural Uncertainty Across 10 Type 2 Diabetes Models: Results From the 2022 Mount Hood Challenge.

OBJECTIVES: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes. METHODS: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences. RESULTS: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially-by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB. CONCLUSIONS: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling.

Associations between BMI and hospital resource use in patients hospitalised for COVID-19 in England: a community-based cohort study.

BACKGROUND: Excess weight is a major risk factor for severe disease after infection with SARS-CoV-2. However, the effect of BMI on COVID-19 hospital resource use has not been fully quantified. This study aimed to identify the association between BMI and hospital resource use for COVID-19 admissions with the intention of informing future national hospital resource allocation. METHODS: In this community-based cohort study, we analysed patient-level data from 57 415 patients admitted to hospital in England with COVID-19 between April 1, 2020, and Dec 31, 2021. Patients who were aged 20-99 years, had been registered with a general practitioner (GP) surgery that contributed to the QResearch database for the whole preceding year (2019) with at least one BMI value measured before April 1, 2020, available in their GP record, and were admitted to hospital for COVID-19 were included. Outcomes of interest were duration of hospital stay, transfer to an intensive care unit (ICU), and duration of ICU stay. Costs of hospitalisation were estimated from these outcomes. Generalised linear and logit models were used to estimate associations between BMI and hospital resource use outcomes. FINDINGS: Patients living with obesity (BMI >30·0 kg/m2) had longer hospital stays relative to patients in the reference BMI group (18·5-25·0 kg/m2; IRR 1·07, 95% CI 1·03-1·10); the reference group had a mean length of stay of 8·82 days (95% CI 8·62-9·01). Patients living with obesity were more likely to be admitted to ICU than the reference group (OR 2·02, 95% CI 1·86-2·19); the reference group had a mean probability of ICU admission of 5·9% (95% CI 5·5-6·3). No association was found between BMI and duration of ICU stay. The mean cost of COVID-19 hospitalisation was £19 877 (SD 17 918) in the reference BMI group. Hospital costs were estimated to be £2736 (95% CI 2224-3248) higher for patients living with obesity. INTERPRETATION: Patients admitted to hospital with COVID-19 with a BMI above the healthy range had longer stays, were more likely to be admitted to ICU, and had higher health-care costs associated with hospital treatment of COVID-19 infection as a result. This information can inform national resource allocation to match hospital capacity to areas where BMI profiles indicate higher demand. FUNDING: National Institute for Health Research.

Comparison of surgical or non-surgical management for non-acute anterior cruciate ligament injury: the ACL SNNAP RCT.

Background: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. Objective(s): To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). Design: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out. Setting: Twenty-nine NHS orthopaedic units in the United Kingdom. Participants: Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Interventions: Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. Main outcome measures: The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Results: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively. Limitations: Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. Conclusions: Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation. Future work: Confirmatory studies and those to explore the influence of fidelity and compliance will be useful. Trial registration: This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367. Funding: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.

The study aimed to find out whether it is better to offer surgical reconstruction or rehabilitation first to patients with a more long-standing injury of their anterior cruciate ligament in their knee. This injury causes physical giving way of the knee and/or sensations of it being wobbly (instability). The instability can affect daily activities, work, sport and can lead to arthritis. There are two main treatment options for this problem: non-surgical rehabilitation (prescribed exercises and advice from physiotherapists) or an operation by a surgeon to replace the damaged ligament (anterior cruciate ligament reconstruction). Although studies have highlighted the best option for a recently injured knee, the best management was not known for patients with a long-standing injury, perhaps occurring several months previously. Because the surgery is expensive to the NHS (around £100 million per year), it was also important to look at the costs involved. We carried out a study recruiting 316 non-acute anterior cruciate ligament-injured patients from 29 different hospitals and allocated each patient to either surgery or rehabilitation as their treatment option. We measured how well they did with special function and activity scores, patient satisfaction and costs of treatment. Patients in both groups improved substantially. It was expected that some patients in the rehabilitation group would want surgery if non-surgical management was unsuccessful. Forty-one per cent of patients who initially underwent rehabilitation subsequently elected to have reconstructive surgery. Overall, the patients allocated to the surgical reconstruction group had better results in terms of knee function and stability, activity level and satisfaction with treatment than patients allocated to the non-operative rehabilitation group. There were few problems or complications with either treatment option. Although the surgery was a more expensive treatment option, it was found to be cost-effective in the UK setting. The evidence can be discussed in shared decision-making with anterior cruciate ligament-injured patients. Both strategies of management led to improvement. Although a rehabilitation strategy can be beneficial, especially for recently injured patients, it is advised that later-presenting non-acute and more long-standing anterior cruciate ligament-injured patients undergo surgical reconstruction without necessarily delaying for a period of rehabilitation.

Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management.

OBJECTIVES: Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. AIMS: (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. METHODS: Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. RESULTS: All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. DISCUSSION: Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT01144338 and NCT00790205.

Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91).

BACKGROUND: The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years. METHODS: 5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan-Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837. FINDINGS: Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3-26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2-17; p=0·015) for death from any cause, 17% (6-26; p=0·002) for myocardial infarction, and 26% (14-36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5-32; p=0·010) for death from any cause and 31% (12-46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy. INTERPRETATION: Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible. FUNDING: University of Oxford Nuffield Department of Population Health Pump Priming.

Trajectories of clinical characteristics, complications and treatment choices in data-driven subgroups of type 2 diabetes.

AIMS/HYPOTHESIS: This study aimed to explore the added value of subgroups that categorise individuals with type 2 diabetes by k-means clustering for two primary care registries (the Netherlands and Scotland), inspired by Ahlqvist's novel diabetes subgroups and previously analysed by Slieker et al. METHODS: We used two Dutch and Scottish diabetes cohorts (N=3054 and 6145; median follow-up=11.2 and 12.3 years, respectively) and defined five subgroups by k-means clustering with age at baseline, BMI, HbA1c, HDL-cholesterol and C-peptide. We investigated differences between subgroups by trajectories of risk factor values (random intercept models), time to diabetes-related complications (logrank tests and Cox models) and medication patterns (multinomial logistic models). We also compared directly using the clustering indicators as predictors of progression vs the k-means discrete subgroups. Cluster consistency over follow-up was assessed. RESULTS: Subgroups' risk factors were significantly different, and these differences remained generally consistent over follow-up. Among all subgroups, individuals with severe insulin resistance faced a significantly higher risk of myocardial infarction both before (HR 1.65; 95% CI 1.40, 1.94) and after adjusting for age effect (HR 1.72; 95% CI 1.46, 2.02) compared with mild diabetes with high HDL-cholesterol. Individuals with severe insulin-deficient diabetes were most intensively treated, with more than 25% prescribed insulin at 10 years of diagnosis. For severe insulin-deficient diabetes relative to mild diabetes, the relative risks for using insulin relative to no common treatment would be expected to increase by a factor of 3.07 (95% CI 2.73, 3.44), holding other factors constant. Clustering indicators were better predictors of progression variation relative to subgroups, but prediction accuracy may improve after combining both. Clusters were consistent over 8 years with an accuracy ranging from 59% to 72%. CONCLUSIONS/INTERPRETATION: Data-driven subgroup allocations were generally consistent over follow-up and captured significant differences in risk factor trajectories, medication patterns and complication risks. Subgroups serve better as a complement rather than as a basis for compressing clustering indicators.

Bioelectronic Direct Current Stimulation at the Transition Between Reversible and Irreversible Charge Transfer.

Many biological processes rely on endogenous electric fields (EFs), including tissue regeneration, cell development, wound healing, and cancer metastasis. Mimicking these biological EFs by applying external direct current stimulation (DCS) is therefore the key to many new therapeutic strategies. During DCS, the charge transfer from electrode to tissue relies on a combination of reversible and irreversible electrochemical processes, which may generate toxic or bio-altering substances, including metal ions and reactive oxygen species (ROS). Poly(3,4-ethylenedioxythiophene) (PEDOT) based electrodes are emerging as suitable candidates for DCS to improve biocompatibility compared to metals. This work addresses whether PEDOT electrodes can be tailored to favor reversible biocompatible charge transfer. To this end, different PEDOT formulations and their respective back electrodes are studied using cyclic voltammetry, chronopotentiometry, and direct measurements of H2O2 and O2. This combination of electrochemical methods sheds light on the time dynamics of reversible and irreversible charge transfer and the relationship between capacitance and ROS generation. The results presented here show that although all electrode materials investigated generate ROS, the onset of ROS can be delayed by increasing the electrode's capacitance via PEDOT coating, which has implications for future bioelectronic devices that allow longer reversibly driven pulse durations during DCS.

Analytical validation and algorithm improvement of HepatoPredict kit to assess hepatocellular carcinoma prognosis before a liver transplantation.

Objectives: To verify the analytical performance of the HepatoPredict kit, a novel tool developed to stratify Hepatocellular Carcinoma (HCC) patients according to their risk of relapse after a Liver Transplantation (LT). Methods: The HepatoPredict tool combines clinical variables and a gene expression signature in an ensemble of machine-learning algorithms to forecast the benefit of a LT in HCC patients. To ensure the accuracy and reliability of this method, extensive analytical validation was conducted to verify its specificity and robustness. The experiments were designed following the guidelines for multi-target genomic assays such as ISO201395-2019, MIQE, CLSI-MM16, CLSI-MM17, and CLSI-EP17-A. The validation process included reproducibility between operators and between RNA extractions and RT-qPCR runs, and interference of input RNA levels or varying reagent levels. A recently retrained version of the HepatoPredict algorithms was also tested. Results: The validation process demonstrated that the HepatoPredict kit met the required standards for robustness (p > 0.05), analytical specificity (inclusivity of 95 %), and sensitivity (LoB, LoD, linear range, and amplification efficiency between 90 and 110 %). The operator, equipment, input RNA, and reagents used had no significant effect on the HepatoPredict results. Additionally, the testing of a recently retrained version of the HepatoPredict algorithm, showed that this new version further improved the accuracy of the kit and performed better than existing clinical criteria in accurately identifying HCC patients who are more likely to benefit LT. Conclusions: Even with the introduced variations in molecular and clinical variables, the HepatoPredict kit's prognostic information remains consistent. It can accurately identify HCC patients who are more likely to benefit from a LT. Its robust performance also confirms that it can be easily integrated into standard diagnostic laboratories.

Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.

Cost-effectiveness analysis of a pragmatic randomized trial evaluating surgical reconstruction versus rehabilitation in patients with long-standing anterior cruciate ligament injury.

Aims: The aim of this study was to estimate the incremental use of resources, costs, and quality of life outcomes associated with surgical reconstruction compared to rehabilitation for long-standing anterior cruciate ligament (ACL) injury in the NHS, and to estimate its cost-effectiveness. Methods: A total of 316 patients were recruited and randomly assigned to either surgical reconstruction or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment). Healthcare resource use and health-related quality of life data (EuroQol five-dimension five-level health questionnaire) were collected in the trial at six, 12, and 18 months using self-reported questionnaires and medical records. Using intention-to-treat analysis, differences in costs, and quality-adjusted life years (QALYs) between treatment arms were estimated adjusting for baseline differences and following multiple imputation of missing data. The incremental cost-effectiveness ratio (ICER) was estimated as the difference in costs divided by the difference in QALYs between reconstruction and rehabilitation. Results: At 18 months, patients in the surgical reconstruction arm reported higher QALYs (0.052 (95% confidence interval (CI) -0.012 to 0.117); p = 0.177) and higher NHS costs (£1,017 (95% CI 557 to 1,476); p < 0.001) compared to rehabilitation. This resulted in an ICER of £19,346 per QALY with the probability of surgical reconstruction being cost-effective of 51% and 72% at a willingness-to-pay threshold of £20,000 and £30,000 per QALY, respectively. Conclusion: Surgical reconstruction as a management strategy for patients with long-standing ACL injury is more effective, but more expensive, at 18 months compared to rehabilitation management. In the UK setting, surgical reconstruction is cost-effective.

Randomised controlled trial of automated VR therapy to improve positive self-beliefs and psychological well-being in young people diagnosed with psychosis: a study protocol for the Phoenix VR self-confidence therapy trial.

INTRODUCTION: The confidence of young people diagnosed with psychosis is often low. Positive self-beliefs may be few and negative self-beliefs many. A sense of defeat and failure is common. Young people often withdraw from many aspects of everyday life. Psychological well-being is lowered. Psychological techniques can improve self-confidence, but a shortage of therapists means that very few patients ever receive such help. Virtual reality (VR) offers a potential route out of this impasse. By including a virtual coach, treatment can be automated. As such, delivery of effective therapy is no longer reliant on the availability of therapists. With young people with lived experience, we have developed a staff-assisted automated VR therapy to improve positive self-beliefs (Phoenix). The treatment is based on established cognitive behavioural therapy and positive psychology techniques. A case series indicates that this approach may lead to large improvements in positive self-beliefs and psychological well-being. We now aim to conduct the first randomised controlled evaluation of Phoenix VR. METHODS AND ANALYSIS: 80 patients with psychosis, aged between 16 and 30 years old and with low levels of positive self-beliefs, will be recruited from National Health Service (NHS) secondary care services. They will be randomised (1:1) to the Phoenix VR self-confidence therapy added to treatment as usual or treatment as usual. Assessments will be conducted at 0, 6 (post-treatment) and 12 weeks by a researcher blind to allocation. The primary outcome is positive self-beliefs at 6 weeks rated with the Oxford Positive Self Scale. The secondary outcomes are psychiatric symptoms, activity levels and quality of life. All main analyses will be intention to treat. ETHICS AND DISSEMINATION: The trial has received ethical approval from the NHS Health Research Authority (22/LO/0273). A key output will be a high-quality VR treatment for patients to improve self-confidence and psychological well-being. TRIAL REGISTRATION NUMBER: ISRCTN10250113.

Automated Identification of Cutaneous Leishmaniasis Lesions Using Deep-Learning-Based Artificial Intelligence.

The polymorphism of cutaneous leishmaniasis (CL) complicates diagnosis in health care services because lesions may be confused with other dermatoses such as sporotrichosis, paracocidiocomycosis, and venous insufficiency. Automated identification of skin diseases based on deep learning (DL) has been applied to assist diagnosis. In this study, we evaluated the performance of AlexNet, a DL algorithm, to identify pictures of CL lesions in patients from Midwest Brazil. We used a set of 2458 pictures (up to 10 of each lesion) obtained from patients treated between 2015 and 2022 in the Leishmaniasis Clinic at the University Hospital of Brasilia. We divided the picture database into training (80%), internal validation (10%), and testing sets (10%), and trained and tested AlexNet to identify pictures of CL lesions. We performed three simulations and trained AlexNet to differentiate CL from 26 other dermatoses (e.g., chromomycosis, ecthyma, venous insufficiency). We obtained an average accuracy of 95.04% (Confidence Interval 95%: 93.81-96.04), indicating an excellent performance of AlexNet in identifying pictures of CL lesions. We conclude that automated CL identification using AlexNet has the potential to assist clinicians in diagnosing skin lesions. These results contribute to the development of a mobile application to assist in the diagnosis of CL in health care services.

Tumores Neuroendocrinos: un desafío transversal / Update on neuroendocrine tumors

Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.

Problemas éticos en la asignación de recursos escasos y cuidado intensivo en la atención de la pandemia por SARS-CoV-2 Una reflexión desde los principios, criterios, derechos y deberes / Ethical problems in the assignment of scarce resources and intensive care in SARS-CoV-2 pandemic healthcare Thoughts based on principles, criteria, rights and responsibilities

Resumen Este documento tiene como finalidad identificar algunos problemas éticos de los procesos de atención en el contexto de la pandemia por SARS-CoV-2 en Colombia, y proponer un conjunto de principios y criterios éticos que permitan a las instituciones y los trabajadores de la salud la toma de decisiones éticamente sustentables y jurídicamente factibles, con un especial enfoque en la protección del núcleo de los derechos fundamentales de pacientes y trabajadores, en un contexto extraordinario caracterizado por la inequidad estructural y la discrepancia entre la oferta y la demanda de bienes, recursos y servicios de salud, con el objetivo de mitigar el estrés moral, maximizar los beneficios derivados de la utilización de los recursos escasos y modular los riesgos éticos y jurídicos asociados.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1952).

Abstract The purpose of this document is to identify some ethical problems in healthcare processes within the context of the SARS-CoV-2 pandemic in Colombia, and propose a collection of ethical principles and criteria which will allow healthcare institutions and workers to make ethically supported and legally feasible decisions. These decisions should especially focus on protecting the core of the fundamental rights of patients and workers, in an extraordinary context characterized by structural inequity and a discrepancy between the supply and demand of healthcare goods, resources and services. Ultimately, this will mitigate moral stress, maximize the benefits derived from the use of scarce resources, and modulate the associated ethical and legal risks.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1952).

Incidencia de infección y trombosis asociadas a catéter central de inserción periférica (PICC) colocado por Radiología Intervencionista / Incidence of infection and thrombosis associated with peripheral insertion central catheter (PICC) placed by Interventional Radiology / Incidência de infecção e trombose associada a cateteres centrais de inserção periférica (linhas PICC) implantados pelo Serviço de Radiologia Intervencionista

Resumen: Objetivo general: Determinar la incidencia de la trombosis venosa (TV) e infección asociada con el catéter central de inserción periférica (PICC). Material y métodos: Se realizó un estudio retrospectivo, replicativo y descriptivo, cuya duración fue de 38 meses. Los catéteres centrales de inserción periférica se colocaron por el Servicio de Radiología Intervencionista con la misma técnica en las extremidades superiores. Se guardó una imagen del procedimiento con el nombre y diámetro de la vena usada. En el estudio se incluyó a partir del primer catéter PICC colocado en marzo de 2015 hasta el último en abril de 2018. Se registraron las trombosis venosas demostradas por ultrasonido Doppler, la duración del catéter y las bacteriemias relacionadas con el PICC (BRC-PICC). Resultados: Se colocaron 448 PICC y, de éstos, se excluyeron 78. Los 370 catéteres restantes sumaron 3,363 días-catéter. El 99.45% de los procedimientos resultaron exitosos. La incidencia de trombosis encontrada fue de 0.016% (n = 6) y la de infección de 0.03% (n = 12). El vaso más frecuentemente utilizado fue la vena basílica derecha. Conclusiones: La incidencia tanto de trombosis como de infección se mantiene por debajo de las reportadas en la literatura. Las venas mayores a 3.8 mm de diámetro tienen una probabilidad muy baja de presentar trombosis venosa.

Abstract: Objective: To determine the incidence of venous thrombosis (VT) and infection associated with PICC lines. Material and methods: A retrospective, replicative and descriptive study was conducted over 38 months. The PICC line was inserted in the upper extremities by the Interventional Radiology Service with the same technique. An image of the procedure with the name and diameter of the selected vein was saved. Venous thrombosis, demonstrated by Doppler ultrasound, the duration of the catheter and bacteremia related to the PICC line (BRC-PICC) were recorded. Results: 448 PICCs were placed and 78 were excluded. The remaining 370 catheters added 3,363 catheter days. 99.45% of the procedures were technically successful. The incidence of thrombosis was 0.016% (n = 6) and that of infection 0.03% (n = 12). The most frequently selected vessel was the right basilic vein. Conclusions: The incidence of thrombosis and infection were below the reported in the literature. Veins greater than 3.8 mm have a very low probability of having TV.

Resumo: Objetivo: Determinar a incidência de trombose venosa (TV) e infecção associada ao PICC. Material e métodos: Foi realizado um estudo retrospectivo, replicativo e descritivo, durante 38 meses. Os cateteres PICC foram colocados nas extremidades superiores pelo serviço de Radiologia Intervencionista com a mesma técnica. Guardou-se uma imagem do procedimento com o nome e o diâmetro da veia utilizada. Incluíu-se desde o primeiro cateter PICC colocado em março de 2015 até abril de 2018. Registraram-se as tromboses venosas por ultrassom Doppler, duração do cateter e bacteremias relacionadas ao PICC (BRC-PICC). Resultados: Colocaram-se 448 PICC e foram excluídos 78. Os 370 cateteres restantes somaram 3363 dias de cateter. 99.45% dos procedimentos foram bem sucedidos. A incidência de trombose encontrada foi de 0.016% (n = 6) e a de infecção de 0.03% (n = 12). O vaso mais utilizado foi a veia basílica direita. Conclusões: A incidência de trombose e infecção permanece abaixo da relatada na literatura. Veias com diâmetro superior a 3.8 mm têm uma probabilidade muito baixa de apresentar trombose venosa.

Relação entre índice de massa corporal e a funcionalidade/incapacidade de mulheres obesas / Relationship between body mass index and the functionality/disability of obese women

O objetivo do estudo foi avaliar a relação entre o Índice de Massa Corporal (IMC) de mulheres com obesidade tipo I e II com os domínios "Funções do Corpo" e "Atividades e Participação", que compõe o core set resumido da Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) desenvolvido para obesidade. Participaram do estudo 72 mulheres, com idades entre 20 e 40 anos. O IMC foi determinado e, em seguida, utilizou-se o core set. Os resultados demonstram que o IMC não se relacionou com o escore de "Funções do Corpo" independentemente do tipo de obesidade, contudo, em mulheres obesas do tipo II, o IMC se correlacionou significativamente e positivamente com o escore de "Atividade e Participação" (r = 0,51; p = 0,002). A análise intergrupos demonstrou diferença significativa entre as obesas do tipo I (1,75 ± 0,23 pontos) e II (3,00 ± 0,23 pontos) no que se refere ao escore de "Atividades e Participação" (p = 0,013). Os achados demonstram que o grau de obesidade está relacionado com maiores índices de limitação/restrição funcional, o que pode direcionar a tomada de decisão clínica no que tange ações de prevenção, promoção e recuperação da saúde. (AU)

The objective of the study was to evaluate the relationship between the Body Mass Index (BMI) of women with type I and II obesity with the "Functions of the Body" and "Activities and Participation" domains, which compose the core set summarized from the International Classification of Functioning, Disability and Health (CIF) developed for obesity. 72 women, aged between 20 and 40, participated in the study. The BMI was determined and then the core set was used. The results showed that BMI was not related to the "Body Functions" score regardless of the obesity type; however, in type II obese women, the BMI correlated significantly and positively with the "Activity and Participation" (r = 0.51, p = 0.002). The intergroup analysis showed a significant difference between type I (1.75 ± 0.23 points) and II (3.00 ± 0.23 points) with respect to the "Activities and Participation" score (p = 0.013 ). The findings show that the degree of obesity is related to higher functional limitation/restriction indexes, which may lead to clinical decisionmaking regarding prevention, promotion and recovery of health. (AU)

Epidemiología del mixoma cardiaco en una población española. Una serie quirúrgica de 30 años / Epidemiology of cardiac myxoma in a Spanish population. A 30-year surgical series

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Prevalence of hypoalbuminemia in outpatients with HIV/AIDS

Abstract INTRODUCTION: Hypoalbuminemia may predict progression of disease and mortality in patients with human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS). This study was conducted to investigate the risk factors associated with hypoalbuminemia in outpatients with HIV/AIDS. METHODS: A cross-sectional study was performed in 196 outpatients with HIV/AIDS. RESULTS: The prevalence of hypoalbuminemia was 11.7%. The only risk factor associated with hypoalbuminemia was current antiretroviral therapy (no exposure: odds ratio=3.46, 95% confidence interval=1.20-10.02). CONCLUSIONS: The monitoring of plasma albumin is key to determine when antiretroviral therapy should be initiated in individuals not exposed to antiretroviral medicines.