Current Standard Of Care Research Articles

A cost analysis of upscaling access to continuity of midwifery carer: Population-based microsimulation in Queensland, Australia

ObjectiveTo quantify the economic impact of upscaling access to continuity of midwifery carer, compared with current standard maternity care, from the perspective of the public health care system. MethodsWe created a static microsimulation model based on a whole-of-population linked administrative data set containing all public hospital births in one Australian state (Queensland) between July 2017 to June 2018 (n = 37,701). This model was weighted to represent projected State-level births between July 2023 and June 2031. Woman and infant health service costs (inpatient, outpatient and emergency department) during pregnancy and birth were summed. The base model represented current standard maternity care and a counterfactual model represented two hypothetical scenarios where 50% or 65% of women giving birth would access continuity of midwifery carer. Costs were reported in 2021/22 AUD. ResultsThe estimated cost savings to Queensland public hospital funders per pregnancy were $336 in 2023/24 and $546 with 50% access. With 65% access, the cost savings were estimated to be $534 per pregnancy in 2023/24 and $839 in 2030/31. A total State-level annual cost saving of $12 million in 2023/24 and $19 million in 2030/31 was estimated with 50% access. With 65% access, total State-level annual cost savings were estimated to be $19 million in 2023/24 and $30 million in 2030/31. ConclusionEnabling most childbearing women in Australia to access continuity of midwifery carer would realise significant cost savings for the public health care system by reducing the rate of operative birth.

Beyond Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer: New Frontiers, New Challenges.

Chemoimmunotherapy is currently the preferred first-line treatment option for the majority of patients with advanced non-small cell lung cancer without driver genetic alterations. Most of these patients, however, will experience disease progression within the first year after treatment initiation and both patients and their physicians will be confronted with the dilemma of the optimal second-line treatment. Identification of molecular targets, such as KRASG12C, BRAFV600X, METexon14, and human epidermal growth factor receptor 2 mutations, and RET rearrangements offer therapeutic opportunities in pretreated patients with corresponding alterations. For those tumors that do not harbor oncogenic drivers, second-line treatment with docetaxel remains the current standard of care despite modest efficacy. Strategies to challenge docetaxel include the combination of immune checkpoint inhibitors (ICIs) with tyrosine inhibitors of multiple kinases or with DNA damage response inhibitors, antibody-drug conjugates, and locoregional treatments for oligoprogressive disease. Next-generation immunotherapy strategies, such as T-cell engagers, immune-mobilizing monoclonal T-cell receptors, chimeric antigen receptor cell therapy, tumor infiltrating lymphocytes, and T-cell receptor cell therapy are being currently investigated in the quest to reverse resistance to ICIs. Importantly, the advent of these new agents heralds a novel spectrum of toxicities that require both the physician's and the patient's education. Herein, we review current and future strategies aiming to outperform docetaxel after chemoimmunotherapy failure, and we provide practical information on how to best communicate to our patients the unique toxicity aspects associated with immunotherapy.

Current surgical approaches to pediatric renal tumors.

Pediatric renal tumors are among the most common pediatric solid malignancies. Surgical resection is a key component in the multidisciplinary therapy for children with kidney tumors. Therefore, it is imperative that surgeons caring for children with renal tumors fully understand the current standards of care in order to provide appropriate surgical expertise within this multimodal framework. Fortunately, the last 60years of international, multidisciplinary pediatric cancer cooperative group studies have enabled high rates of cure for these patients. This review will highlight the international surgical approaches to pediatric patients with kidney cancer to help surgeons understand the key differences and similarities between the European (International Society of Pediatric Oncology) and North American (Children's Oncology Group) recommendations.

Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer

Triple negative breast cancer (TNBC) accounts for 15–20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.

The Evolving Scenario of ES-SCLC Management: From Biology to New Cancer Therapeutics

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease (ES-SCLC) has been marked by incorporating immune checkpoint inhibitors (ICIs) into platinum-based chemotherapy, leading to modest improvements. Moreover, few second-line-and-beyond treatment options are currently available. The main limitation for the molecular study of SCLC has been the scarcity of samples, because only very early diseases are treated with surgery and biopsies are not performed when the disease progresses. Despite all these difficulties, in recent years we have come to understand that SCLC is not a homogeneous disease. At the molecular level, in addition to the universal loss of retinoblastoma (RB) and TP53 genes, a recent large molecular study has identified other mutations that could serve as targets for therapy development or patient selection. In recent years, there has also been the identification of new genetic subtypes which have shown us how intertumor heterogeneity exists. Moreover, SCLC can also develop intratumoral heterogeneity linked mainly to the concept of cellular plasticity, mostly due to the development of resistance to therapies. The aim of this review is to quickly present the current standard of care of ES-SCLC, to focus on the molecular landscapes and subtypes of SCLC, subsequently present the most promising therapeutic strategies under investigation, and finally recap the future directions of ongoing clinical trials for this aggressive disease which still remains a challenge.

INJEX50 could improve the success rate of local anesthesia for arterial cannulation in the pediatric intensive care unit: Arandomized, double-blind, single-center study.

Quick arterial cannulation is required in pediatric emergency situation, which require effective local anesthesia to avoid withdrawal movement. However, pediatric local anesthesia could be difficult because of withdrawal movement. Jet injectors, which are needleless and provide local anesthesia quickly, could be helpful for pediatric local anesthesia during arterial cannulation. This study aimed to examine whether new jet injector "INJEX50" could improve the success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with the current standard of care, infiltration using a 26-gauge needle. This study was a randomized, double-blind, single-center study. Participants were infants and young children in the pediatric intensive care unit, who required an arterial line. Local anesthesia was performed with either a 26-gauge needle (group C) or INJEX50 (group I) before arterial cannulation. The primary outcome (success of local anesthesia) was the presence of withdrawal movement at the time of skin puncture for arterial cannulation. The secondary outcomes included rescue sedation during arterial cannulation. Data were analyzed using Fisher's exact test and the Mann-Whitney U-test, with values of p < .05 considered statistically significant. Seventy patients were randomly assigned to groups C and I. The local anesthesia success rate in group I (30/35 [86%]) was significantly higher than that in group C (15/35 [43%], odds ratio, 8.00; 95% confidence interval, 2.51-25.5; p = .0005). In conclusion, INJEX50 could improve success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with 26-gauge needle.

Innovative technologies in thoracolumbar and lumbar spine surgery failing to reach standard of care: state-of-art review.

To evaluate previously popular technologies in the field of spine surgery, and to better understand their advantages and limitations to the current standards of care. Spine surgery is an ever-evolving field that serves to resolve various spinal pathologies in patients of all ages. While there are established treatments for various conditions, such as lumbar spinal stenosis, idiopathic scoliosis, and degenerative lumbar disease, there is always further research and development in these areas to produce innovative technologies that can lead to better outcomes. As this process progresses, we must remind ourselves of previously tried and tested inventions and their outcomes that have fallen short of becoming a standard to ensure we are able to learn lessons from the past. A thorough literature review was conducted with the aim of compiling literature of previously utilized technologies in spine surgery. Biomedical databases were utilized to gather relevant articles including PubMed, MEDLINE, and EMBASE. Emphasis was placed on gathering articles with technologies or therapeutics aimed at treating common spinal pathologies including lumbar spinal stenosis (LSS), adolescent idiopathic scoliosis (AIS), and other degenerative lumbar spine diseases. The keywords used were: "failed technologies", "historical technologies", "spine surgery", "spinal stenosis", "adolescent idiopathic scoliosis", and "degenerative lumbar spine disease". A total of 47 articles were gathered after initial review. Different technologies pertaining to spine surgery were identified and critically evaluated. Some of these technologies included X-STOP, Vertiflex, Vertebral Body Stapling, and Dynesys. These technologies were evaluated for their strengths and limitations across their spinal pathology applications. While each type of technology had their benefits, the data tended to be mixed with various limitations across studies. These technologies have been trialed in the field of spine surgery across various spinal pathologies, but still prove of limited efficacy and shortcomings to the current standards of care.

Hyperkalemia in chronic kidney disease patients with and without heart failure: an Italian economic modelling study

BackgroundHyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin–angiotensin–aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting.MethodsA lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF.ResultsPatiromer was associated with an incremental discounted cost of €4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of €24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions.ConclusionPatiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.

Enhancing drug and cell line representations via contrastive learning for improved anti-cancer drug prioritization

Due to cancer’s complex nature and variable response to therapy, precision oncology informed by omics sequence analysis has become the current standard of care. However, the amount of data produced for each patient makes it difficult to quickly identify the best treatment regimen. Moreover, limited data availability has hindered computational methods’ abilities to learn patterns associated with effective drug-cell line pairs. In this work, we propose the use of contrastive learning to improve learned drug and cell line representations by preserving relationship structures associated with drug mechanisms of action and cell line cancer types. In addition to achieving enhanced performance relative to a state-of-the-art method, we find that classifiers using our learned representations exhibit a more balanced reliance on drug- and cell line-derived features when making predictions. This facilitates more personalized drug prioritizations that are informed by signals related to drug resistance.

Omega-3 fatty acid diglyceride emulsions as a novel injectable acute therapeutic in neonatal hypoxic-ischemic brain injury

Hypoxic-ischemic encephalopathy (HIE), resulting from a lack of blood flow and oxygen before or during newborn delivery, is a leading cause of cerebral palsy and neurological disability in children. Therapeutic hypothermia (TH), the current standard of care in HIE, is only beneficial in 1 of 7–8 cases. Therefore, there is a critical need for more efficient treatments. We have previously reported that omega-3 (n-3) fatty acids (FA) carried by triglyceride (TG) lipid emulsions provide neuroprotection after experimental hypoxic-ischemic (HI) injury in neonatal mice. Herein, we propose a novel acute therapeutic approach using an n-3 diglyceride (DG) lipid emulsions. Importantly, n-3 DG preparations had much smaller particle size compared to commercially available or lab-made n-3 TG emulsions. We showed that n-3 DG molecules have the advantage of incorporating at substantially higher levels than n-3 TG into an in vitro model of phospholipid membranes. We also observed that n-3 DG after parenteral administration in neonatal mice reaches the bloodstream more rapidly than n-3 TG. Using neonatal HI brain injury models in mice and rats, we found that n-3 DG emulsions provide superior neuroprotection than n-3 TG emulsions or TH in decreasing brain infarct size. Additionally, we found that n-3 DGs attenuate microgliosis and astrogliosis. Thus, n-3 DG emulsions are a superior, promising, and novel therapy for treating HIE.

Immunomodulatory extracellular matrix hydrogel induces tissue regeneration in a model of partial glossectomy

While oropharyngeal cancer treatment regimens, including surgical resection, irradiation, and chemotherapy, are effective at removing tumors, they lead to muscle atrophy, denervation, and fibrosis, contributing to the pathogenesis of oropharyngeal dysphagia – difficulty swallowing. Current standard of care of rehabilitative tongue strengthening and swallowing exercises is ineffective. Here, we evaluate an alternative approach utilizing an acellular and injectable biomaterial to preserve muscle content and reduce fibrosis of the tongue after injury. Skeletal muscle extracellular matrix (SKM) hydrogel is fabricated from decellularized porcine skeletal muscle tissue. A partial glossectomy injury in the rat is used to induce tongue fibrosis, and SKM hydrogels along with saline controls are injected into the site of scarring two weeks after injury. Tissues are harvested at 3 and 7 days post-injection for gene expression and immunohistochemical analyses, and at 4 weeks post-injection to evaluate histomorphological properties. SKM hydrogel reduces scar formation and improves muscle regeneration at the site of injury compared to saline. SKM additionally modulates the immune response towards an anti-inflammatory phenotype. This study demonstrates the immunomodulatory and tissue-regenerative capacity of an acellular and minimally invasive ECM hydrogel in a rodent model of tongue injury.

Cost Effectiveness of Adding Fenfluramine to Standard of Care for Patients with Dravet Syndrome in Sweden.

This study evaluated, in a Swedish setting, the cost effectiveness of fenfluramine (FFA) as an add-on to standard of care (SoC) for reducing seizure frequency in Dravet syndrome, a severe developmental epileptic encephalopathy. Cost effectiveness of FFA+SoC compared with SoC only was evaluated using a patient-level simulation model with a lifetime horizon. Patient characteristics and treatment effects, including convulsive seizures, seizure-free days and mortality, were derived from FFA clinical trials. Resource use and costs included cost of drug acquisition, routine care and monitoring, as well as ongoing and emergency resources. Quality of life (QoL) estimates for patients and their caregivers were derived from clinical trial data. Robustness was evaluated by one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analyses. Lifetime cost of FFA+SoC was ~3 million SEK per patient compared with ~1.5 million SEK for SoC only. FFA+SoC generated 15% more QALYs than SoC only (21.2 vs 18.5 over a lifetime), resulting in an incremental cost-effectiveness ratio (ICER) of ~540,000SEK. Moreover, FFA+SoC had a higher probability of being cost effective than SoC only from a willingness-to-pay threshold of 710,000SEK. Results remained generally consistent across scenario analyses, with only few exceptions (exclusions of carer utility or FFA effect on sudden unexpected death in epilepsy). Due to better seizure control, FFA is a clinically meaningful add-on therapy and was estimated to be a cost-effective addition to current SoC for patients with this rare disease in Sweden at a willingness-to-pay threshold of 1,000,000 SEK.

Overall Survival in Patients with Esophageal Cancer and Clinical Complete Response after Radio Chemotherapy: Should a Watchful Waiting Strategy be the new Standard of Care?

Abstract Background The current standard of care for curative treatment of esophageal cancer (EC) consists of neoadjuvant radio chemotherapy (RCT) followed by resection. However, an organ-sparing approach with a watchful waiting (WW) strategy and resection only in case of cancer recurrence is gaining importance in patients with clinical complete response (cCR) after RCT. Nevertheless, data on overall survival, particularly in subgroups with and without tumor recurrence, is limited. Aims To compare overall survival (OS) rates in patients with cCR based on initial management and at time of recurrence. Methods We retrospectively analyzed data from all patients with EC and cCR to RCT between 01/2014 and 12/2021. OS- and disease-free survival was calculated using Kaplan-Meier survival analysis. Results Of 96 patients with cCR after RCT, 45 underwent resection (47%), and 51 (53%) a WW approach. There were no significant differences in baseline patient or tumor characteristics. In the WW group, 28 patients (55%) had cancer recurrence. Of those, 11 patients (of 28, 39%) underwent either salvage esophagectomy or endoscopic submucosal dissection in curative intent. No significant difference in OS could be detected in patients with WW and either no recurrence or recurrence treated in curative intention (p=0.716). Further, OS was significantly longer in those patients than in patients with primary resection (p=0.031) and WW patients with recurrence and palliative treatment (p&amp;lt;0.001). (Fig 1). Conclusion In a WW concept for patients with EC and cCR after RCT, patients with cancer recurrence can achieve the same OS as patients without recurrence if treated in curative intention. Moreover, OS in both those patient groups was superior to that of patients undergoing direct resection after RCT, supporting a WW approach as at least safe and applicable in clinical practice. Further prospective data are needed to determine the value of WW as standard of care for patients with cCR following neoadjuvant RCT.

Pathological Complete Response after Radio Chemotherapy and Esophagectomy – false Sense of Security?

Abstract Background Esophageal cancer (EC) is associated with a high morbidity and mortality, even in a curative treatment approach. The current standard of care for curative treatment of EC consists of neoadjuvant radio chemotherapy (RCT) followed by resection. Pathological response in the resected tissue is a well-known predictor of disease-free (DFS) and overall survival (OS). Yet, even in a pathological complete response (pCR), cancer recurrence is not infrequent. Aims To analyze DFS and OS in patients with pCR after trimodal therapy and identify risk factors for recurrence. Methods We retrospectively analyzed all patients with pathological complete response after RCT and esophagectomy treated for EC between 01/2014 and 12/2021. Clinical data such as demographic data, tumor characteristics at staging and restaging and postoperative follow-up, were extracted from electronic medical records. Results Of 28 patients, 10 (35.7%) developed cancer recurrence. There were no statistically significant differences in patient or tumor characteristics between patients with or without recurrence. Recurrence occurred after a median 21 months (IQR 30). Median OS was 40.5 months (IQR 40) in patients with and 48.5 months (IQR 32) in patients without recurrence (p=0.121). Recurrence was mostly distant (n = 9, 90%). 4 (of 10, 40%) patients were then addressed in curative, 6 (60%) in palliative intention. Predictive factors for cancer recurrence were persistent tumor in endosonography and/or computed tomography during restaging. Conclusion Even in patients with pCR after RCT and esophagectomy, around one third develops cancer recurrence. A tight follow-up with special attention to distant rather than local recurrence seems beneficial. Patients with an aspect of only partial response at restaging are at higher risk for recurrence and should be monitored even closer.

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Porphyromonas gingivalis, a bridge between oral health and immune evasion in gastric cancer.

Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis' virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.

Recent Translational Research Models of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p&amp;lt;0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected &amp;gt;90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Effectiveness of a mindfulness and acceptance-based intervention for improving the mental health of adolescents with HIV in Uganda: An open-label trial.

Adolescents with HIV (AWH) face the double burden of dealing with challenges presented by their developmental phase while coping with stigma related to HIV, affecting their mental health. Poor mental health complicates adherence to daily treatment regimens, requiring innovative psychosocial support strategies for use with adolescents. We assessed the effectiveness of a mindfulness and acceptance-based intervention on the mental health of AWH in Uganda. One hundred and twenty-two AWH, mean age 17 ±1.59 (range 15 to 19 years), 57% female, receiving care at a public health facility in Kampala were enrolled in an open-label randomized trial (ClinicalTrials.gov: NCT05010317) with assessments at pre-and post-intervention. The mindfulness and acceptance-based intervention involved weekly 90-minute group sessions for four consecutive weeks facilitated by two experienced trainers. Sessions involved clarifying values, skillfully relating to thoughts, allowing and becoming aware of experiences non-judgmentally, and exploring life through trial and error. The control group received the current standard of care. Three mental health domains (depression, anxiety, and internalized stigma) were compared between the intervention and control groups. A linear mixed effects regression was used to analyze the effect of the intervention across the two time points. Results showed that the intervention was associated with a statistically significant reduction in symptoms of depression (β = -10.72, 95%CI: 6.25, -15.20; p < .0001), anxiety (β = -7.55, 95%CI: 2.66, -12.43; p = .0003) and stigma (β = -1.40, 95%CI: 0.66 to -2.15; p = .0004) over time. Results suggest that mindfulness and acceptance-based interventions have the potential to improve the mental health of AWH.

Segmentation of mature human oocytes provides interpretable and improved blastocyst outcome predictions by a machine learning model

Within the medical field of human assisted reproductive technology, a method for interpretable, non-invasive, and objective oocyte evaluation is lacking. To address this clinical gap, a workflow utilizing machine learning techniques has been developed involving automatic multi-class segmentation of two-dimensional images, morphometric analysis, and prediction of developmental outcomes of mature denuded oocytes based on feature extraction and clinical variables. Two separate models have been developed for this purpose—a model to perform multiclass segmentation, and a classifier model to classify oocytes as likely or unlikely to develop into a blastocyst (Day 5–7 embryo). The segmentation model is highly accurate at segmenting the oocyte, ensuring high-quality segmented images (masks) are utilized as inputs for the classifier model (mask model). The mask model displayed an area under the curve (AUC) of 0.63, a sensitivity of 0.51, and a specificity of 0.66 on the test set. The AUC underwent a reduction to 0.57 when features extracted from the ooplasm were removed, suggesting the ooplasm holds the information most pertinent to oocyte developmental competence. The mask model was further compared to a deep learning model, which also utilized the segmented images as inputs. The performance of both models combined in an ensemble model was evaluated, showing an improvement (AUC 0.67) compared to either model alone. The results of this study indicate that direct assessments of the oocyte are warranted, providing the first objective insights into key features for developmental competence, a step above the current standard of care—solely utilizing oocyte age as a proxy for quality.