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1.
Nat Commun ; 15(1): 4004, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734697

The current thyroid ultrasound relies heavily on the experience and skills of the sonographer and the expertise of the radiologist, and the process is physically and cognitively exhausting. In this paper, we report a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nod- ules. In this system, human skeleton point recognition, reinforcement learning, and force feedback are used to deal with the difficulties in locating thyroid targets. The orientation of the ultrasound probe is adjusted dynamically via Bayesian optimization. Experimental results on human participants demonstrated that this system can perform high-quality ultrasound scans, close to manual scans obtained by clinicians. Additionally, it has the potential to detect thyroid nodules and provide data on nodule characteristics for American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) calculation.


Robotics , Thyroid Gland , Thyroid Nodule , Ultrasonography , Humans , Thyroid Gland/diagnostic imaging , Ultrasonography/methods , Ultrasonography/instrumentation , Robotics/methods , Robotics/instrumentation , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/pathology , Bayes Theorem , Female , Adult , Male , Thyroid Neoplasms/diagnostic imaging
4.
Small Methods ; : e2400119, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639023

Surface-enhanced Raman scattering (SERS) sensors typically employ nanophotonic structures that support high-field confinement and enhancement in hotspots to increase the Raman scattering from target molecules by orders of magnitude. In general, high field and SERS enhancement can be achieved by reducing the critical dimensions and mode volumes of the hotspots to nanoscale. To this end, a multitude of SERS sensors employing photonic structures with nanometric hotspots have been demonstrated. However, delivering analyte molecules into nanometric hotspots is challenging, and the trade-off between field confinement/enhancement and analyte delivery efficiency is a critical limiting factor for the performance of many nanophotonic SERS sensors. Here, a new type of SERS sensor employing solid-metal nanoparticles and bulk liquid metal is demonstrated to form nanophotonic resonators with a nanoparticle-on-liquid-mirror (NPoLM) architecture, which effectively resolves this trade-off. In particular, this unconventional sensor architecture allows for the convenient formation of nanometric hotspots by introducing liquid metal after analyte molecules are efficiently delivered to the surface of gold nanoparticles. In addition, a cost-effective and reliable process is developed to produce gold nanoparticles on a substrate suitable for forming NPoLM structures. These NPoLM structures achieve two orders of magnitude higher SERS signals than the gold nanoparticles alone.

5.
Sci Rep ; 14(1): 8892, 2024 04 17.
Article En | MEDLINE | ID: mdl-38632335

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.


Myocardial Infarction , Percutaneous Coronary Intervention , Adult , Humans , Holidays , Taiwan , Time Factors , Risk Factors , Hospital Mortality , Patient Admission , Retrospective Studies
6.
medRxiv ; 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38645067

Background: Sex differences are related to both biological factors and the gendered environment. To untangle sex-related effects on health and disease it is important to model sex-related differences better. Methods: Data came from the baseline visit of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a longitudinal cohort study following 16,415 individuals recruited at baseline from four study sites: Bronx NY, Miami FL, San Diego CA, and Chicago IL. We applied LASSO penalized logistic regression of male versus female sex over sociodemographic, acculturation, and psychological factors jointly. Two "gendered indices", GISE and GIPSE, summarizing the sociodemographic environment (GISE, primary) and psychosocial and sociodemographic environment (GIPSE, secondary) associated with sex, were calculated by summing these variables, weighted by their regression coefficients. We examined the association of these indices with insomnia derived from self-reported symptoms assessed via the Women Health Initiative Insomnia Rating Scale (WHIIRS), a phenotype with strong sex differences, in sex-adjusted and sex-stratified analyses. All analyses were adjusted for age, Hispanic/Latino background, and study center. Results: The distribution of GISE and GIPSE differed by sex with higher values in male individuals, even when constructing and validating them on separate, independent, subsets of HCHS/SOL individuals. In an association model with insomnia, male sex was associated with lower likelihood of insomnia (odds ratio (OR)=0.60, 95% CI (0.53, 0.67)). Including GISE in the model, the association was slightly weaker (OR=0.63, 95% CI (0.56, 0.70)), and weaker when including instead GIPSE in the association model (OR=0.78, 95% CI (0.69, 0.88)). Higher values of GISE and of GIPSE, more common in male sex, were associated with lower likelihood of insomnia, in analyses adjusted for sex (per 1 standard deviation of the index, GISE OR= 0.92, 95% CI (0.87, 0.99), GIPSE OR=0.65, 95% CI (0.61, 0.70)). Conclusions: New measures such as GISE and GIPSE capture sex-related differences beyond binary sex and have the potential to better model and inform research studies of health. However, such indices do not account for gender identity and may not well capture the environment experienced by intersex and non-binary persons.

7.
Bioconjug Chem ; 35(5): 593-603, 2024 May 15.
Article En | MEDLINE | ID: mdl-38592684

Ferritin is a multivalent, self-assembling protein scaffold found in most human cell types, in addition to being present in invertebrates, higher plants, fungi, and bacteria, that offers an attractive alternative to polymer-based drug delivery systems (DDS). In this study, the utility of the ferritin cage as a DDS was demonstrated within the context of T cell agonism for tumor killing. Members of the tumor necrosis factor receptor superfamily (TNFRSF) are attractive targets for the development of anticancer therapeutics. These receptors are endogenously activated by trimeric ligands that occur in transmembrane or soluble forms, and oligomerization and cell-surface anchoring have been shown to be essential aspects of the targeted agonism of this receptor class. Here, we demonstrated that the ferritin cage could be easily tailored for multivalent display of anti-OX40 antibody fragments on its surface and determined that these arrays are capable of pathway activation through cell-surface clustering. Together, these results confirm the utility, versatility, and developability of ferritin as a DDS.


Ferritins , Humans , Ferritins/chemistry , Ferritins/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Drug Delivery Systems
8.
JAMA Netw Open ; 7(2): e2354734, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38335002

Importance: Denosumab, a humanized monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is a widely used antiresorptive medication for osteoporosis treatment. Recent preclinical studies indicate that inhibition of RANKL signaling improves insulin sensitivity, glucose tolerance, and ß-cell proliferation, suggesting that denosumab may improve glucose homeostasis; however, whether denosumab reduces the risk of incident diabetes remains unclear. Objective: To evaluate whether denosumab use is associated with a lower risk of developing diabetes in patients with osteoporosis. Design, Setting, and Participants: This nationwide, propensity score-matched cohort study used administrative data from Taiwan's National Health Insurance Research Database. Adult patients who received denosumab for osteoporosis therapy in Taiwan between 2012 and 2019 were included. To eliminate the inherent bias from confounding by indication, the patients were categorized into a treatment group (34 255 patients who initiated denosumab treatment and adhered to it) and a comparison group (34 255 patients who initiated denosumab treatment but discontinued it after the initial dose) according to the administration status of the second dose of denosumab. Propensity score matching was performed to balance patient characteristics and to control for confounders. Exposure: Treatment with denosumab. Main Outcomes and Measures: The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. A Cox proportional hazards model was used to estimate the hazard ratio (HR) for incident diabetes. Data were analyzed from January 1 to November 30, 2023. Results: After propensity score matching, 68 510 patients were included (mean [SD] age, 77.7 [9.8] years; 57 762 [84.3%] female). During a mean (SD) follow-up of 1.9 (1.6) years, 2016 patients developed diabetes in the treatment group and 3220 developed diabetes in the comparison group (incidence rate, 35.9 vs 43.6 per 1000 person-years). Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90). Several sensitivity analyses also demonstrated similar results of lower diabetes risk associated with denosumab treatment. Conclusions and relevance: The results from this cohort study indicating that denosumab treatment was associated with lower risk of incident diabetes may help physicians choose an appropriate antiosteoporosis medication for patients with osteoporosis while also considering the risk of diabetes.


Bone Density Conservation Agents , Diabetes Mellitus , Osteoporosis , Adult , Humans , Female , Aged , Male , Denosumab/therapeutic use , Cohort Studies , Osteoporosis/drug therapy , Osteoporosis/epidemiology , Bone Density Conservation Agents/therapeutic use , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Glucose
9.
Nat Commun ; 15(1): 1845, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38418471

Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we apply principal component analysis (PCA) to seven SDB-related measures. We estimate the associations of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint penalized regression analysis. The discovery analysis includes 3299 individuals, with validation in a separate dataset of 1522 individuals. Five metabolite associations with SDB PCs are discovered and replicated. SDB PC1, characterized by frequent respiratory events common in older and male adults, is associated with pregnanolone and progesterone-related sulfated metabolites. SDB PC2, characterized by short respiratory event length and self-reported restless sleep, enriched in young adults, is associated with sphingomyelins. Metabolite risk scores (MRSs), representing metabolite signatures associated with the two SDB PCs, are associated with 6-year incident hypertension and diabetes. These MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.


Diabetes Mellitus , Hypertension , Sleep Apnea Syndromes , Young Adult , Humans , Male , Aged , Hypertension/complications , Risk Factors , Regression Analysis
10.
Korean Circ J ; 54(3): 126-137, 2024 Mar.
Article En | MEDLINE | ID: mdl-38324232

BACKGROUND AND OBJECTIVES: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. METHODS: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. RESULTS: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14-1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. CONCLUSIONS: Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

11.
Eur Heart J Digit Health ; 5(1): 69-76, 2024 Jan.
Article En | MEDLINE | ID: mdl-38264699

Aims: Social robots are arriving to the modern healthcare system. Whether patients with heart failure, a prevalent chronic disease with high health and human costs would derive benefit from a social robot intervention has not been investigated empirically. Diverse healthcare provider's perspectives are needed to develop an acceptable and feasible social robot intervention to be adopted for the clinical benefit of patients with heart failure. Using a qualitative research design, this study investigated healthcare providers' perspectives of social robot use in heart failure patient care. Methods and results: Interdisciplinary healthcare providers from a tertiary care cardiac hospital completed a structured individual interview and a supplemental questionnaire. The framework method was used to analyse the qualitative data. Respondents (n = 22; saturation was reached with this sample; 77% female; 52% physicians) were open to using social robots to augment their practice, particularly with collecting pertinent data and providing patient and family education and self-management prompts, but with limited responsibility for direct patient care. Prior to implementation, providers required robust evidence of: value-added beyond current remote patient monitoring devices, patient and healthcare provider partnerships, streamlined integration into existing practice, and capability of supporting precision medicine goals. Respondents were concerned that social robots did not address and masked broader systemic issues of healthcare access and equity. Conclusion: The adoption of social robots is a viable option to assist in the care of patients with heart failure, albeit in a restricted capacity. The results inform the development of a social robotic intervention for patients with heart failure, including improving social robot efficiencies and increasing their uptake, while protecting patients' and providers' best interest.

12.
Syst Rev ; 13(1): 17, 2024 01 05.
Article En | MEDLINE | ID: mdl-38183086

PURPOSE: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews. METHODS: To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case-control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes. DISCUSSION: The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).


Hypertension , Adult , Humans , Prospective Studies , Retrospective Studies , Canada , Systematic Reviews as Topic , Hypertension/diagnosis , Hypertension/prevention & control , Meta-Analysis as Topic
13.
ISA Trans ; 144: 133-144, 2024 Jan.
Article En | MEDLINE | ID: mdl-37977885

This paper studies the exponential synchronization problem for a class of delayed coupled neural networks with delay-compensatory impulsive control. A Razumikhin-type inequality involving some destabilizing delayed impulse gains and a new idea of delay-compensatory that shows two critical roles for system stability are presented, respectively. Based on the constructed inequality and the presented delay-compensatory idea, sufficient stability and synchronization criteria for globally exponential synchronization (GES) of coupled neural networks (CNNs) are presented. Compared with existing results, the uniqueness of the presented results lies in that impulse delays can be fetched and integrated to compensate for instantaneous unstable impulse dynamics caused by destabilizing gains. Moreover, constraints between system delay and impulsive delay are relaxed, and the interval of impulses no longer constrains the system delay. Comparisons and a practical application are given to demonstrate the superior performance of the presented novel control methods.

14.
Diabetes Metab Res Rev ; 40(2): e3739, 2024 Feb.
Article En | MEDLINE | ID: mdl-37862117

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). MATERIALS AND METHODS: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted. RESULTS: Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p < 0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p = 0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p < 0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p = 0.43), suggesting the robustness of our retrospective analysis. CONCLUSIONS: In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA.


Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Symporters , Venous Thromboembolism , Humans , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Hypoglycemic Agents/adverse effects , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Venous Thromboembolism/chemically induced , Venous Thromboembolism/epidemiology , Retrospective Studies , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Glucose , Sodium , Glucagon-Like Peptide-1 Receptor/agonists
16.
Radiographics ; 44(1): e230061, 2024 Jan.
Article En | MEDLINE | ID: mdl-38060424

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.


Digestive System Surgical Procedures , Laparoscopy , Pancreatic Neoplasms , Humans , Postoperative Complications/diagnostic imaging , Postoperative Complications/surgery , Laparoscopy/methods , Pancreas/diagnostic imaging , Pancreas/surgery , Diagnostic Imaging , Pancreatic Neoplasms/pathology
17.
IEEE Trans Cybern ; 54(2): 776-786, 2024 Feb.
Article En | MEDLINE | ID: mdl-38127614

In this article, the adaptive tracking control problem is considered for high-order stochastic nonlinear time-delay systems in fixed-time. Being different from existing results, an improved Lyapunov-Krasovskii function is designed, which can not only compensate for the time-delay term but also remove the obstacle from the high-order term. Due to the introduction of the Lyapunov-Krasovskii function into the total Lyapunov function, it makes it difficult to stabilize the controlled system within a fixed-time interval. L'Hopital's rule is used to determine the boundedness of the Lyapunov-Krasovskii function, and the fixed-time boundedness of the integral functions can be inferred. By utilizing the fixed-time Lyapunov stability theorem, it is proved that the controlled system is semi-globally practical fixed-time stable (SGPFS), all the closed-loop signals (CLSs) are bounded within the fixed-time interval, and the tracking error converges into a small region around zero. The validity of the designed scheme is substantiated via simulation results.

18.
J Am Coll Radiol ; 20(11S): S471-S480, 2023 11.
Article En | MEDLINE | ID: mdl-38040465

The differential diagnosis for left lower quadrant pain is wide and conditions range from the benign and self-limited to life-threatening surgical emergencies. Along with patient history, physical examination, and laboratory tests, imaging is often critical to limit the differential diagnosis and identify life-threatening abnormalities. This document will discuss the guidelines for the appropriate use of imaging in the initial workup for patients who present with left lower quadrant pain, patients with suspected diverticulitis, and patients with suspected complications from diverticulitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Diverticulitis , Societies, Medical , Humans , Abdominal Pain , Diagnostic Imaging , Evidence-Based Medicine , United States
19.
BMJ Open ; 13(11): e074463, 2023 11 10.
Article En | MEDLINE | ID: mdl-37949621

BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.


Arteritis , Atherosclerosis , Diabetes Mellitus, Type 2 , Ischemic Attack, Transient , Prediabetic State , Stroke , Humans , Fluorodeoxyglucose F18 , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Radiopharmaceuticals , C-Reactive Protein , Prospective Studies , Interleukin-6 , Positron Emission Tomography Computed Tomography , Canada , Atherosclerosis/drug therapy , Tomography, X-Ray Computed , Inflammation/drug therapy , Biomarkers , Anti-Inflammatory Agents/therapeutic use , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
20.
Cardiovasc Diabetol ; 22(1): 227, 2023 08 28.
Article En | MEDLINE | ID: mdl-37641086

BACKGROUND: Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada. METHODS: We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014-2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death. RESULTS: We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63-0.69) and mortality (0.68, 0.64-0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77-0.88) and mortality (0.71, 0.66-0.78) outcomes than a result in the normoglycemic range. CONCLUSIONS: Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults.


Diabetes Mellitus , Myocardial Infarction , Young Adult , Humans , Female , Male , Outpatients , Cohort Studies , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Ontario/epidemiology
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