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BMJ Open Jun 2024Diagnostic imaging is vital in emergency departments (EDs). Accessibility and reporting impacts ED workflow and patient care. With radiology workforce shortages,...
Assessing the effectiveness of artificial intelligence (AI) in prioritising CT head interpretation: study protocol for a stepped-wedge cluster randomised trial (ACCEPT-AI).
INTRODUCTION
Diagnostic imaging is vital in emergency departments (EDs). Accessibility and reporting impacts ED workflow and patient care. With radiology workforce shortages, reporting capacity is limited, leading to image interpretation delays. Turnaround times for image reporting are an ED bottleneck. Artificial intelligence (AI) algorithms can improve productivity, efficiency and accuracy in diagnostic radiology, contingent on their clinical efficacy. This includes positively impacting patient care and improving clinical workflow. The ACCEPT-AI study will evaluate Qure.ai's qER software in identifying and prioritising patients with critical findings from AI analysis of non-contrast head CT (NCCT) scans.
METHODS AND ANALYSIS
This is a multicentre trial, spanning four diverse sites, over 13 months. It will include all individuals above the age of 18 years who present to the ED, referred for an NCCT. The project will be divided into three consecutive phases (pre-implementation, implementation and post-implementation of the qER solution) in a stepped-wedge design to control for adoption bias and adjust for time-based changes in the background patient characteristics. Pre-implementation involves baseline data for standard care to support the primary and secondary outcomes. The implementation phase includes staff training and qER solution threshold adjustments in detecting target abnormalities adjusted, if necessary. The post-implementation phase will introduce a notification (prioritised flag) in the radiology information system. The radiologist can choose to agree with the qER findings or ignore it according to their clinical judgement before writing and signing off the report. Non-qER processed scans will be handled as per standard care.
ETHICS AND DISSEMINATION
The study will be conducted in accordance with the principles of Good Clinical Practice. The protocol was approved by the Research Ethics Committee of East Midlands (Leicester Central), in May 2023 (REC (Research Ethics Committee) 23/EM/0108). Results will be published in peer-reviewed journals and disseminated in scientific findings (ClinicalTrials.gov: NCT06027411) TRIAL REGISTRATION NUMBER: NCT06027411.
Topics: Humans; Artificial Intelligence; Tomography, X-Ray Computed; Emergency Service, Hospital; Head; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Algorithms
PubMed: 38885990
DOI: 10.1136/bmjopen-2023-078227 -
JMIR Research Protocols Jun 2024Vascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients' quality of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients' quality of life. Previous studies have reported that disorders of serum iron metabolism and iron deposition in the brain can lead to inflammation, abnormal protein aggregation and degeneration, and massive neuronal apoptosis in the central nervous system, which in turn leads to a progressive decline in cognitive processes. Our previous clinical studies have found acupuncture to be a safe and effective intervention for treating VCI, but the specific mechanisms require further exploration.
OBJECTIVE
The objective of the trial is to evaluate the clinical efficacy of Tongdu Xingshen acupuncture and to investigate whether it can improve VCI by regulating brain iron deposition and body iron metabolism.
METHODS
In total, 42 patients with VCI and 21 healthy individuals will participate in this clinical trial. The 42 patients with VCI will be randomized into acupuncture and control groups, while the 21 healthy individuals will be in the healthy control group. Both the control and acupuncture groups will receive conventional medical treatment and cognitive rehabilitation training. In addition, the acupuncture group will receive electroacupuncture treatment with Tongdu Xingshen for 30 minutes each time, 6 times a week for 4 weeks. Meanwhile, the healthy control group will not receive any intervention. All 3 groups will undergo baseline assessments of brain iron deposition, serum iron metabolism, and neuropsychological tests after enrollment. The acupuncture and control groups will be evaluated again at the end of 4 weeks of treatment, as described earlier. By comparing neuropsychological test scores between groups, we will examine the efficacy of Tongdu Xingshen acupuncture in treating VCI. Additionally, we will test the correlations between neuropsychological test scores, brain iron deposition, and body iron metabolism indexes to explore the possible mechanisms of Tongdu Xingshen acupuncture in treating VCI.
RESULTS
Participants are currently being recruited. The first participant was enrolled in June 2023, which marked the official start of the experiment. As of the submission of the paper, there were 23 participants. The recruitment process is expected to continue until June 2025, at which point the processing and analysis of data will begin. As of May 15, 2024, up to 30 people have been enrolled in this clinical trial.
CONCLUSIONS
This study will provide data on the effects of Tongdu Xingshen acupuncture on cerebral iron deposition as well as somatic iron metabolism in patients with VCI. These results will help to prove whether Tongdu Xingshen acupuncture can improve VCI by regulating brain iron deposition and body iron metabolism, which will provide the clinical and theoretical basis for the wide application of acupuncture therapy in VCI rehabilitation.
TRIAL REGISTRATION
China Clinical Registration Agency ChiCTR2300072188; https://tinyurl.com/5fcydtkv.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/56484.
Topics: Humans; Acupuncture Therapy; Iron; Brain; Cognitive Dysfunction; Male; Female; Middle Aged; Aged; Adult
PubMed: 38885500
DOI: 10.2196/56484 -
The Journal of Clinical Investigation Jun 2024Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes...
Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes in addition to bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in IFITM5. Here, we generated a conditional Rosa26 knock-in mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in OI type V patients. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with increase in the skeletal progenitor population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 showed decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupts early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.
PubMed: 38885336
DOI: 10.1172/JCI170369 -
JCI Insight Jun 2024Interferon signaling gene (ISG) expression scores are potential markers of inflammation with significance from cancer to genetic syndromes. In Aicardi Goutières...
Interferon signaling gene (ISG) expression scores are potential markers of inflammation with significance from cancer to genetic syndromes. In Aicardi Goutières Syndrome (AGS), a disorder of abnormal DNA and RNA metabolism, this score has potential as a diagnostic biomarker, although the approach to ISG calculation has not been standardized or validated. To optimize ISG calculation and validate ISG as a diagnostic biomarker, mRNA levels of 36 type I interferon response genes were quantified from 997 samples (including 334 AGS), and samples were randomized into training and test datasets. An independent validation cohort (n = 122) was also collected. ISGs were calculated using all potential combinations up to 6 genes. A 4-gene approach (IFI44L, IFI27, USP18, IFI6) was the best-performing model [area under the curve (AUC) of 0.8872 (training dataset), 0.9245 (test dataset)]. The majority of top performing gene combinations included IFI44L. Performance of IFI44L-alone was 0.8762 (training dataset) and 0.9580 (test dataset) by AUC. The top approaches were able to discriminate cases of genetic interferonopathy from control samples. This study validates the context of use for the ISG score as a diagnostic biomarker and underscores the importance of IFI44L in diagnosis of genetic interferonopathies.
PubMed: 38885315
DOI: 10.1172/jci.insight.178456 -
PloS One 2024Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions....
Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions. The possibility that genetic risk, in the form of polygenic risk scores (PGS), could be integrated into prediction of risk of diLQTS has great potential, although it is unknown how genetic risk is related to clinical risk factors as might be applied in clinical decision-making. In this study, we examined the PGS for QT interval in 2500 subjects exposed to a known QT-prolonging drug on prolongation of the QT interval over 500ms on subsequent ECG using electronic health record data. We found that the normalized QT PGS was higher in cases than controls (0.212±0.954 vs. -0.0270±1.003, P = 0.0002), with an unadjusted odds ratio of 1.34 (95%CI 1.17-1.53, P<0.001) for association with diLQTS. When included with age and clinical predictors of QT prolongation, we found that the PGS for QT interval provided independent risk prediction for diLQTS, in which the interaction for high-risk diagnosis or with certain high-risk medications (amiodarone, sotalol, and dofetilide) was not significant, indicating that genetic risk did not modify the effect of other risk factors on risk of diLQTS. We found that a high-risk cutoff (QT PGS ≥ 2 standard deviations above mean), but not a low-risk cutoff, was associated with risk of diLQTS after adjustment for clinical factors, and provided one method of integration based on the decision-tree framework. In conclusion, we found that PGS for QT interval is an independent predictor of diLQTS, but that in contrast to existing theories about repolarization reserve as a mechanism of increasing risk, the effect is independent of other clinical risk factors. More work is needed for external validation in clinical decision-making, as well as defining the mechanism through which genes that increase QT interval are associated with risk of diLQTS.
Topics: Humans; Male; Female; Long QT Syndrome; Middle Aged; Electrocardiography; Multifactorial Inheritance; Risk Factors; Aged; Adult; Torsades de Pointes; Case-Control Studies; Phenethylamines; Genetic Risk Score; Sulfonamides
PubMed: 38885227
DOI: 10.1371/journal.pone.0303261 -
PloS One 2024Monitoring in highway projects is significant for the safety, efficiency and quality of construction. This paper proposes a detailed method for monitoring soft-soil...
Monitoring in highway projects is significant for the safety, efficiency and quality of construction. This paper proposes a detailed method for monitoring soft-soil roadbed and high-slope, and the layered settlement gauge and total station are employed to carry out experimental monitoring. The law and stability of soft-soil roadbed settlement and deformation under high-slope are further analyzed. The results show that the cumulative values of roadbed settlement and slope platform deformation in general both increase with the increase of monitoring time. However, near 180 days, an abnormal settlement phenomenon was monitored on both sides of the highway with a maximum value of 9.44 mm. This phenomenon was captured at gauge #1, #3, and #4 on observation stake 3, and exact oppositely, it was also observed at gauge #2 on observation stake 4. Moreover, unusual deformations of the high-slope platforms occurred over a period of 10 to 30 days, and these unusual settlements and deformations are indicative of the highway's instability. Therefore, the monitoring on soft-soil roadbed settlement and high-slope deformation can provide reference for highway construction.
Topics: Soil; Environmental Monitoring
PubMed: 38885204
DOI: 10.1371/journal.pone.0303860 -
Epilepsia Open Jun 2024The blood-brain barrier (BBB) is a barrier protecting the brain and a milieu of continuous exchanges between blood and brain. There is emerging evidence that the BBB... (Review)
Review
The blood-brain barrier (BBB) is a barrier protecting the brain and a milieu of continuous exchanges between blood and brain. There is emerging evidence that the BBB plays a major role in epileptogenesis and drug-resistant epilepsy, through several mechanisms, such as water homeostasis dysregulation, overexpression of drug transporters, and inflammation. Studies have shown abnormal water homeostasis in epileptic tissue and altered aquaporin-4 water channel expression in animal epilepsy models. This review focuses on abnormal water exchange in epilepsy and describes recent non-invasive MRI methods of quantifying water exchange. PLAIN LANGUAGE SUMMARY: Abnormal exchange between blood and brain contribute to seizures and epilepsy. The authors describe why correct water balance is necessary for healthy brain functioning and how it is impacted in epilepsy. This review also presents recent MRI methods to measure water exchange in human brain. These measures would improve our understanding of factors leading to seizures.
PubMed: 38884502
DOI: 10.1002/epi4.12994 -
The Israel Medical Association Journal... Jun 2024
Topics: Humans; ST Elevation Myocardial Infarction; Heart Septal Defects, Ventricular; Male; Electrocardiography; Treatment Outcome
PubMed: 38884315
DOI: No ID Found -
The Israel Medical Association Journal... Jun 2024Gram-negative bloodstream infections (GN-BSI) are life threatening. Appropriate antimicrobial therapy and source control when indicated improve survival. Dementia is an...
BACKGROUND
Gram-negative bloodstream infections (GN-BSI) are life threatening. Appropriate antimicrobial therapy and source control when indicated improve survival. Dementia is an independent risk factor for death and is associated with increased risk for infections, especially in advanced stages. Data about the best diagnostic and therapeutic approaches for patients with dementia and GN-BSI are lacking.
OBJECTIVES
To evaluate patients with dementia and GN-BSI and determine whether diagnostic imaging improves clinical outcomes.
METHODS
We performed a retrospective cohort study of adult patients with GN-BSI, during 2019-2022. Patients with or without a diagnosis of dementia were compared. Outcomes were in-hospital mortality and recurrent bacteremia. Demographic, clinical, diagnostic, and therapeutic data were collected and analyzed.
RESULTS
A total of 87 patients with dementia and 130 without were included. Patients with dementia received appropriate empirical antimicrobial therapy in 38% of cases compared to 62% of patients without dementia, P < 0.001. Imaging studies were performed in half of patients in both groups. In the dementia group, 17% had abnormal findings that required source control versus 30% in the control group (P = 0.049). Source control was performed in 15% of patients with dementia versus 28% of patients without dementia (P = 0.032). Mortality was 27.6% in the dementia group versus 22.3% in the control group (P = 0.42).
CONCLUSIONS
In patients with dementia and GN-BSI, imaging studies have lower effect on clinical outcomes. Imaging studies should be performed in selected cases only and not conducted routinely.
Topics: Humans; Retrospective Studies; Male; Female; Dementia; Bacteremia; Aged; Gram-Negative Bacterial Infections; Hospital Mortality; Aged, 80 and over; Anti-Bacterial Agents; Risk Factors; Cohort Studies; Middle Aged
PubMed: 38884312
DOI: No ID Found -
F1000Research 2022Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations...
BACKGROUND
Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of -infected erythrocytes in the placenta. However, the pathomechanism of placental infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality.
METHODS
This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique.
RESULTS
In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby's body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p<0.05), but not for VEGF and VEGFR-2 in the plasma.
CONCLUSION
This study indicated that sequestration may promote LBW through alterations and imbalances in angiogenic factors led by HIF-1α.
Topics: Humans; Female; Hypoxia-Inducible Factor 1, alpha Subunit; Malaria, Vivax; Pregnancy; Infant, Low Birth Weight; Placenta; Adult; Plasmodium vivax; Infant, Newborn; Angiogenesis Inducing Agents; Vascular Endothelial Growth Factor A; Pregnancy Complications, Parasitic; Cross-Sectional Studies; Vascular Endothelial Growth Factor Receptor-1
PubMed: 38884107
DOI: 10.12688/f1000research.73820.3