The impact of health disparities on peripheral vascular access outcomes in hospitalized patients: an observational study.

BACKGROUND: Placement of peripheral intravenous catheters (PIVC) is a routine procedure in hospital settings. The primary objective is to explore the relationship between healthcare inequities and PIVC outcomes. METHODS: This study was a multicenter, observational analysis of adults with PIVC access established in the emergency department requiring inpatient admission between January 1st, 2021, and January 31st, 2023, in metro Detroit, Michigan, United States. Epidemiological, demographic, therapeutic, clinical, and outcomes data were collected. Health disparities were defined by the National Institute on Minority Health and Health Disparities. The primary outcome was the proportion of PIVC dwell time to hospitalization length of stay, expressed as the proportion of dwell time (hours) to hospital stay (hours) x 100%. Multivariable linear regression and a machine learning model were used for variable selection. Subsequently, a multivariate linear regression analysis was utilized to adjust for confounders and best estimate the true effect of each variable. RESULTS: Between January 1st, 2021, and January 31st, 2023, our study analyzed 144,524 ED encounters, with an average patient age of 65.7 years and 53.4% female. Racial demographics showed 67.2% White, and 27.0% Black, with the remaining identifying as Asian, American Indian Alaska Native, or other races. The median proportion of PIVC dwell time to hospital length of stay was 0.88, with individuals identifying as Asian having the highest ratio (0.94) and Black individuals the lowest (0.82). Black females had a median dwell time to stay ratio of 0.76, significantly lower than White males at 0.93 (p < 0.001). After controlling for confounder variables, a multivariable linear regression demonstrated that Black males and White males had a 10.0% and 19.6% greater proportion of dwell to stay, respectively, compared to Black females (p < 0.001). CONCLUSIONS: Black females face the highest risk of compromised PIVC functionality, resulting in approximately one full day of less reliable PIVC access than White males. To comprehensively address and rectify these disparities, further research is imperative to improve understanding of the clinical impact of healthcare inequities on PIVC access. Moreover, it is essential to formulate effective strategies to mitigate these disparities and ensure equitable healthcare outcomes for all individuals.

Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis.

BACKGROUND: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease. METHODS: Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins in the plasma, and the coagulation factor prekallikrein (PK; encoded by the KLKB1 gene) was revealed. The correlation between serum PK protein content and lipid levels in young Chinese Han people was then analyzed. To investigate the effects of PK ablation on LDLR and lipid levels in vivo, we genetically deleted Klkb1 in hamsters and heterozygous Ldlr knockout mice and knocked down Klkb1 using adeno-associated virus-mediated shRNA in rats. The additive effect of PK and proprotein convertase subtilisin/kexin 9 inhibition also was evaluated. In addition, we applied the anti-PK neutralizing antibody that blocked the PK and LDLR interaction in mice. Mice lacking both PK and apolipoprotein e (Klkb1-/-Apoe-/-) were generated to assess the role of PK in atherosclerosis. RESULTS: PK directly bound LDLR and induced its lysosomal degradation. The serum PK concentrations positively correlated with LDL cholesterol levels in 198 young Chinese Han adults. Genetic depletion of Klkb1 increased hepatic LDLR and decreased circulating cholesterol in multiple rodent models. Inhibition of proprotein convertase subtilisin/kexin 9 with evolocumab further decreased plasma LDL cholesterol levels in Klkb1-deficient hamsters. The anti-PK neutralizing antibody could similarly lower plasma lipids through upregulating hepatic LDLR. Ablation of Klkb1 slowed the progression of atherosclerosis in mice on Apoe-deficient background. CONCLUSIONS: PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol, and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat atherosclerotic cardiovascular disease.

An ultrasensitive electrochemical sensing platform based on silver nanoparticle-anchored 3D reduced graphene oxide for rifampicin detection.

A facile strategy has been reported to anchor silver nanoparticles (Ag NPs) onto three-dimensional reduced graphene oxide (3D rGO) via a green and simple method. An accurate and reliable electrochemical sensing platform based on Ag NPs/3D rGO was designed for the ultrasensitive detection of rifampicin (RIF). The morphology and features of Ag NPs/3D rGO were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Raman spectroscopy and electrochemical measurements. The interface of the modified electrode presented effective electrical activity for the analysis of RIF due to the large electrochemically active surface area and excellent electron transport ability. The sensor exhibited a good linear relationship in the range of 0.01 nM-45 µM and a low detection limit of 0.810 nM (S/N = 3). Crucially, the fabricated Ag NPs/3D rGO sensor was successfully utilized to assess RIF in human blood, drug and aquatic product samples. This sensing platform exhibited outstanding electrochemical performance for RIF detection and showed great potential application in clinical diagnosis, pharmaceutical and food-related fields.

Emerging roles for the ER stress sensor IRE1α in metabolic regulation and disease.

Inositol-requiring enzyme 1 (IRE1) is an endoplasmic reticulum (ER)-resident transmembrane protein that senses ER stress and is evolutionarily conserved from yeast to humans. IRE1 possesses both Ser/Thr protein kinase and endoribonuclease (RNase) activities within its cytoplasmic domain and is activated through autophosphorylation and dimerization/oligomerization. It mediates a critical arm of the unfolded protein response to manage ER stress provoked by lumenal overload of unfolded/misfolded proteins. Emerging lines of evidence have revealed that in mammals, IRE1α functions as a multifunctional signal transducer that responds to metabolic cues and nutrient stress conditions, exerting profound and broad effects on metabolic homeostasis. In this review, we cover recent advances in our understanding of how IRE1α integrates a variety of metabolic and stress signals and highlight its tissue-specific or context-dependent metabolic activities. We also discuss how dysregulation of this metabolic stress sensor during handling of excessive nutrients in cells contributes to the progression of obesity and metabolic disorders.

Efficacy of different dose of dexmedetomidine combined with remifentanil in colonoscopy: a randomized controlled trial.

BACKGROUND: Dexmedetomidine has advantages during colonoscopy as it allows the patient to cooperate during the procedure. Few studies examined the dexmedetomidine-remifentanil combination. This study was to evaluate the effects of different doses of the dexmedetomidine-remifentanil combination in colonoscopy. METHODS: This was a prospective trial carried out at the Fourth Hospital of Hebei Medical University between 02/2018 and 10/2018. The patients were randomized: group I (dexmedetomidine 0.2 µg·kg- 1), group II (dexmedetomidine 0.3 µg·kg- 1), and group III (dexmedetomidine 0.4 µg·kg- 1), all combined with remifentanil. The primary outcomes were the patient's body movements during the procedure and adverse events. RESULTS: Compared with at admission (T0), the SBP, HR, and RR at immediately after giving DEX (T1), at the beginning of the examination (T2), 5 min after the beginning of the examination (T3), 10 min after the beginning of the examination (T4), and at the end of the examination (T5) in the three groups were all reduced (all P < 0.05), but all were within the clinically normal range. SpO2 remained > 98% in all patients during the examination. Compared with T0, the BIS values of the three groups were decreased at T1 and T2 (all P < 0.05). There were no significant differences in BIS among the three groups (all P > 0.05). The minimum BIS value in group III was lower than in groups I and II (P < 0.05). The degree of satisfaction with the anesthesia effect was higher in groups II and III that in group I (P < 0.05). No hypotension occurred, seven patients had bradycardia, and four patients had nausea/vomiting. CONCLUSIONS: Dexmedetomidine 0.3 µg·kg- 1 combined with remifentanil was effective for colonoscopy and had few adverse reactions. Chinese Clinical Trial Registry: ChiCTR2000029105 , Registered 13 January 2020 - Retrospectively registered.

Antihypertensive prescription is associated with improved 30-day outcomes for discharged hypertensive emergency department patients.

Background: Hypertension (HTN) is common in discharged emergency department (ED) patients, yet the short-term outcomes of treating HTN at ED discharge are unclear. This study aimed to investigate whether emergency physician (EP) prescription of oral antihypertensive therapy at ED discharge for hypertensive patients is associated with a decreased 30-day risk of the severe adverse events (AEs), death, and revisits to the ED. Methods: We conducted an observational cohort study assessing the 30-day outcomes of discharged ED patients with HTN, comparing outcomes based on whether antihypertensive therapy was prescribed. All discharged adult ED patients from an eight-hospital system with a diagnosis of HTN from January 2016 to February 2020 were screened, and consisted of a mix of suburban and urban patients with broad ethnic and socioeconomic backgrounds. Patients were categorized into the treatment group if they received a prescription for antihypertensive medication at ED discharge. The primary outcome was severe composite AEs from HTN (aortic catastrophe, heart failure, myocardial infarction, hemorrhagic and ischemic stroke, or hypertensive encephalopathy) within 30 days of ED discharge. The secondary outcomes were death or ED revisit over the same period. Results: The study sample consisted of 93,512 ED visits; 57.5% were female, and mean age was 59.3 years. 4.7% of patients were prescribed antihypertensive treatment at ED discharge. Within 30 days, 0.7% of patients experienced an AE, 0.1% died, and 15.2% had an ED revisit. The treatment group had significantly lower odds of AE (adjusted odds ratio [aOR]: 0.224, 95%CI 0.106-0.416, p < 0.001), and ED revisits (aOR: 0.610, 95%CI 0.547-0.678, p < 0.001), adjusting for age, race, degree of HTN, ED treatment for elevated HTN, Elixhauser comorbidity index, and heart failure history. There was no difference in odds of death 30 days after discharge. Conclusion and relevance: Prescription antihypertensive therapy for discharged ED patients is associated with a 30-day decrease in severe adverse events and ED revisit rate.

A standardized educational program to improve peripheral vascular access outcomes in the emergency department: A quasi-experimental pre-post trial.

OBJECTIVE: Difficult intravenous access (DIVA) patients are known to have disproportionately poorer vascular access outcomes. The impact of education and training on vascular access outcomes in this vulnerable population is unclear. We aim to demonstrate the success of a program (Operation (O) STICK) on improving vascular access outcomes in DIVA patients. METHODS: This was a quasi-experimental pre-post interventional study conducted at a tertiary care emergency department (ED) with 120,000 annual visits and 1100 hospital beds. Adult patients requiring an ultrasound-guided (US) peripheral intravenous catheter (PIVC) in the ED were eligible participants. Traditional (palpation method) insertions were excluded. Using multivariable linear regression and inverse probability weighted (IPW) linear regression, the standard group inclusive of PIVCs inserted by staff without formalized OSTICK training were compared to the interventional group inclusive of PIVCs inserted by staff with training and competency in the OSTICK training model. RESULTS: Data were collected over two time intervals: 4/1/21-9/30/21 (pre; non-OSTICK) and 10/1/22-3/31/23 (post; OSTICK). 2375 DIVA patients included 1035 (43.6%) non-OSTICK and 1340 (56.4%) OSTICK PIVCs. Overall, OSTICK PIVCs had a higher proportion of upper arm or forearm placements (94.6% vs 57.4%; p < 0.001), 20 gauge catheters (97.1% vs 92.3%; p < 0.001), and left-sided placements (54.4% vs 43.5%; p < 0.001). 62.7% of OSTICK PIVCs were placed by ED technicians, compared to 25.5% in the non-OSTICK group (p < 0.001). OSTICK PIVCs were placed on the first attempt 86.2% of the time and by the second attempt 95.4% of the time. In a subanalysis of 1343 hospitalized patients (689 (51.3%) OSTICK vs 654 (48.7%) non-OSTICK), OSTICK PIVCs survived for a median of 92% of the patient's hospital length of stay, compared to non-OSTICK PIVCs at 74% (p < 0.001). CONCLUSIONS: Formalized vascular access training in the ED leads to improved adherence to best practices for PIVC insertion, high success of cannulation with minimal attempts, and improved PIVC functionality during hospitalization for DIVA patients. Importantly, these outcomes are sustainable as they were captured 12 months after implementation of the program.

Risk of midline catheter-related thrombosis due to catheter diameter: An observational cohort study.

OBJECTIVE: Deep vein thrombosis is a common and serious complication associated with midline catheters (MC). The aim of this investigation was to determine if catheter diameter is related to development of thrombosis. METHODS: This was an observational cohort study conducted at a tertiary care academic center in Southeastern Michigan. Hospitalized adults that required a MC were eligible participants. Primary outcome was symptomatic MC associated upper extremity deep vein thrombosis (DVT) comparing three catheter diameters. Secondary outcomes included complications based on size and DVT comparing catheter to vein ratio. RESULTS: Between January 1, 2017, and December 31, 2021, 3088 MCs met inclusion criteria; the distribution of 3 French (Fr), 4 Fr, and 5 Fr MCs was 35.1 %, 57.0 %, and 7.9 %, respectively. The majority of the population was female (61.2 %) and the average age was 64.2 years old. DVT occurred in 4.4 %, 3.9 %, and 11.9 % of 3 Fr, 4 Fr, and 5 Fr MCs, respectively (p < 0.001). In multivariable regression analysis, there was no difference in the odds of developing DVT for the 4 Fr MC compared to the 3 Fr (aOR 0.88; 95 % CI 0.59-1.31; p = 0.5243), however, there was significantly higher odds for the 5 Fr (aOR 2.72; 95 % CI 1.62-4.51; p = 0.001). Additionally, for every additional day the MC was in place, the odds of DVT increased by 3 % (aOR 1.03; 95 % CI 1.01-1.05; p = 0.0039). When comparing accuracy of the size model versus catheter to vein ratio model for predicting DVT, receiver operating characteristic curve analysis demonstrated the area under the curve for size was 73.70 % (95 % CI 68.04 %-79.36 %) compared to 73.01 % (95 % CI: 66.88 %-79.10 %) for catheter-to-vein ratio. CONCLUSIONS: Smaller diameter catheters should be preferentially chosen to mitigate the risk of thrombosis when therapy via midline catheters is required. Choosing a catheter based on reduced size or 1:3 catheter to vein ratio threshold has similar accuracy in predicting DVT.

Bridging the Gap in Traditional PIVC Placement: An Evaluation of Operation STICK Vascular Access Outcomes.

Objective: Education and training is core to improving peripheral intravenous access outcomes. This study aimed to show that a vascular access training program (Operation STICK) in the emergency department (ED) improves the outcomes of traditionally placed peripheral intravenous catheters (PIVC). Methods: This was a pre-post quasi-experimental study of traditionally placed PIVCs at a large ED in southeastern Michigan, United States. A control group (non-OSTICK) was compared to an experimental group (OSTICK) using a 3:1 propensity score matched analysis. Groups were comprised of ED patients with traditional PIVC placements in two separate six-month periods: non-OSTICK PIVCs from April to September 2021 and OSTICK PIVCs (placed by an OSTICK graduate) from October 2022 to March 2023. The primary outcome was PIVC functionality. The secondary outcome was adherence to best practices. Results: A total of 6512 PIVCs were included in the study; 4884 (75.0%) were in the non-OSTICK group, while 1628 (25.0%) were in the OSTICK group. 68.1% of OSTICK PIVCs and 59.7% of non-OSTICK PIVCs were placed by ED technicians (p < 0.001). 91.3% of OSTICK PIVCs were placed on the first attempt, and 98.5% were placed within two attempts. A subgroup analysis of admitted patients (2540 PIVCs; 553 (21.8%) OSTICK-trained and 1987 (78.2%) non-OSTICK-trained) revealed 87.6% of OSTICK PIVCs and 80.3% of non-OSTICK PIVCs were 20 gauge (p < 0.001). The median proportion of dwell time to hospital length of stay was 94% for OSTICK PIVCs, compared to 88% for non-OSTICK PIVCs (p < 0.001). Conclusion: This study underscores the value of education and training in enhancing vascular access outcomes. Implementing Operation STICK, a comprehensive vascular access training program, at a large ED has led to high first-stick success, adherence to best practice recommendations for site and device selection, and improved PIVC functionality for traditionally placed catheters.

Advances of Protein Palmitoylation in Tumor Cell Deaths.

In this comprehensive survey, we delve into the multifaceted role of palmitoylation across various cell death modalities in the oncological context, from its intricate correlations with tumorigenesis, steered by the Asp-His-His-Cys tetrapeptide motif (DHHC) family, to the counter-process of depalmitoylation mediated by enzymes like Palmitoyl protein thioesterase-1 (PPT1). Innovations in detection methodologies have paralleled our growing understanding, transitioning from rudimentary techniques to sophisticated modern methods. Central to our discourse are agents like Ezurpimtrostat (GNS561) and dimeric chloroquine (DC661), promising heralds in palmitoylation-targeted cancer therapy. Collectively, this review accentuates palmitoylation's transformative potential in oncology, foreshadowing groundbreaking therapeutic strategies and deepening our molecular comprehension of cancer dynamics.

Multiview Multi-Instance Multilabel Active Learning.

Multiview multi-instance multilabel learning (M3L) is a framework for modeling complex objects. In this framework, each object (or bag) contains one or more instances, is represented with different feature views, and simultaneously annotated with a set of nonexclusive semantic labels. Given the multiplicity of the studied objects, traditional M3L methods generally demand a large number of labeled bags to train a predictive model to annotate bags (or instances) with semantic labels. However, annotating sufficient bags is very expensive and often impractical. In this article, we present an active learning-based M3L approach (M3AL) to reduce the labeling costs of bags and to improve the performance as much as possible. M3AL first adapts the multiview self-representation learning to evacuate the shared and individual information of bags and to learn the shared/individual similarities between bags across/within views. Next, to avoid scrutinizing all the possible labels, M3AL introduces a new query strategy that leverages the shared and individual information, and the diverse instance distribution of bags across views, to select the most informative bag-label pair for the query. Experimental studies on benchmark data sets show that M3AL can significantly reduce the query costs while achieving a better performance than other related competitive methods at the same cost.