Premature ventricular complexes after catheter ablation for atrial fibrillation: Accounting for regression to the mean.

INTRODUCTION: Prior studies have indicated that the frequency of premature ventricular complexes (PVC) increases after catheter ablation for atrial fibrillation (AF). However, these studies have primarily focused on patients whose PVC burden increased rather than including the full spectrum of outcomes. METHODS AND RESULTS: We performed a single-center retrospective cohort study of consecutive patients who underwent first-time AF ablation from 1/2018 to 12/2022 for paroxysmal or persistent AF and had both preablation and postablation rhythm monitoring within 6 months of the procedure. Patients were excluded if they had prior AF or PVC ablation or were prescribed a class I or III antiarrhythmic medication. Among 2945 patients who underwent AF ablation during the study period, 130 patients underwent first-time AF ablation and received both pre and post ambulatory monitoring. The median PVC burden before ablation was <1%. Most patients (63%) had no change in PVC burden after AF ablation compared with preablation, and patients who had an increase in PVC burden were offset by those with reductions in PVCs. A paired analysis pre- and post-AF ablation showed no significant change in PVC burden (p = .495). CONCLUSION: Although an elevated PVC burden after AF ablation may be seen clinically, the majority of patients have no change in burden. Studies that suggest an increase in PVC burden after AF ablation may suffer from incomplete sample selection and thus omit the important effect of regression to the mean.

Exome sequence analysis identifies rare coding variants associated with a machine learning-based marker for coronary artery disease.

Coronary artery disease (CAD) exists on a spectrum of disease represented by a combination of risk factors and pathogenic processes. An in silico score for CAD built using machine learning and clinical data in electronic health records captures disease progression, severity and underdiagnosis on this spectrum and could enhance genetic discovery efforts for CAD. Here we tested associations of rare and ultrarare coding variants with the in silico score for CAD in the UK Biobank, All of Us Research Program and BioMe Biobank. We identified associations in 17 genes; of these, 14 show at least moderate levels of prior genetic, biological and/or clinical support for CAD. We also observed an excess of ultrarare coding variants in 321 aggregated CAD genes, suggesting more ultrarare variant associations await discovery. These results expand our understanding of the genetic etiology of CAD and illustrate how digital markers can enhance genetic association investigations for complex diseases.

Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications.

Studies have shown that drug targets with human genetic support are more likely to succeed in clinical trials. Hence, a tool integrating genetic evidence to prioritize drug target genes is beneficial for drug discovery. We built a genetic priority score (GPS) by integrating eight genetic features with drug indications from the Open Targets and SIDER databases. The top 0.83%, 0.28% and 0.19% of the GPS conferred a 5.3-, 9.9- and 11.0-fold increased effect of having an indication, respectively. In addition, we observed that targets in the top 0.28% of the score were 1.7-, 3.7- and 8.8-fold more likely to advance from phase I to phases II, III and IV, respectively. Complementary to the GPS, we incorporated the direction of genetic effect and drug mechanism into a directional version of the score called the GPS with direction of effect. We applied our method to 19,365 protein-coding genes and 399 drug indications and made all results available through a web portal.

Ketamine for Traumatic Assault-Induced Depression: A Case Report.

BACKGROUND: This case report describes the use of ketamine as a rapid, effective treatment of depression in a 68-year-old female patient with no significant medical history of psychiatric disorders. Patients who experience intentional or unintentional traumas are at an increased risk for developing depression or posttraumatic stress disorder, and emerging evidence has supported the use of ketamine as an alternative treatment of depression. CASE PRESENTATION: This is the case of a 68-year-old female patient who was assaulted, resulting in multiple stab wounds to both hands and the right upper quadrant. She underwent placement of a chest tube and surgical repair of the liver and was subsequently admitted to the intensive care unit. These events led to the development of severe depression symptoms, as evidenced by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 37. As treatment of her acute depression, the patient received a single intravenous dose of ketamine (0.5 mg/kg) infused over 40 min and was monitored for side effects. The MADRS is a 10-item depression screening tool that assesses symptoms and changes over time. Within 4 hr of receiving ketamine, the patient reported a significant improvement in her mood and her MADRS score decreased to 16, classifying this patient as experiencing mild depression. The patient continued to improve, and 24 hr after receiving ketamine, her MADRS score was 4, indicating remission of her depression symptoms. CONCLUSION: This case report aims to provide an account of the potential benefits of ketamine as a rapid treatment of depression in an adult trauma patient.

Streamlining care in two neurosurgical practices in a rural trauma center.

ABSTRACT: To maximize cost-effective care and evaluate the use of physician associates/assistants (PAs) and NPs in an academic inpatient setting, we investigated the effect of streamlining care by using a common PA position between two neurosurgery groups. Trauma registry data were obtained and analyzed to gain insight into hospital length of stay (LOS) and clinical outcomes before and after implementing this new position. The average hospital LOS was reduced for less severely injured patients, and the time to initiation of venous thromboembolism prophylaxis decreased for injured neurosurgical patients. These results indicate the successful facilitation of time-sensitive, value-based healthcare for this specific clinical population at our Level 2 trauma center.

Collaborative Approach to Organ Donation in a Level II Trauma Center.

BACKGROUND: Although a shortage of organ donors is a continuing global problem in health care, obtaining authorization for donation after an individual experiences a traumatic nonsurvivable event can be difficult. OBJECTIVE: To improve organ donation practices at a level II trauma center. METHODS: After reviewing trauma mortality cases and performance improvement metrics with their organ procurement organization's hospital liaison, leaders at the trauma center implemented a multidisciplinary performance improvement initiative to engage the facility's donation advisory committee, provide education for staff members, and increase program visibility to create a more donation-friendly culture for the facility. RESULTS: The initiative led to an improved donation conversion rate and a greater number of organs procured. Continued education increased staff and provider awareness of organ donation, contributing to the positive outcomes. CONCLUSION: A multidisciplinary initiative that includes continuing staff education can improve organ donation practices and program visibility, ultimately benefiting patients in need of organ transplantation.

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group.

BACKGROUND: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. METHODS: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. RESULTS: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. CONCLUSIONS: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.

Evaluating the Effect of a Dosing and Titration Protocol on Dexmedetomidine-Induced Hypotension in Trauma Patients.

BACKGROUND: Dexmedetomidine is an α-2 receptor agonist commonly used as a continuous infusion for sedation and analgesia; however, dose-dependent hypotension may limit its utility. Despite its widespread use, there is no consensus on appropriate dosing and titration. OBJECTIVE: The objective of this study was to determine whether a dexmedetomidine dosing and titration protocol is associated with decreased rates of hypotension in trauma patients. METHODS: This pre-post intervention study took place at a Level II trauma center in the Southeastern United States from August 2021 to March 2022 and included patients admitted by the trauma service to either the surgical trauma intensive care unit or intermediate care unit and received dexmedetomidine for greater than or equal to 6 hours. Patients were excluded if they were hypotensive or on vasopressors at baseline. The primary outcome was incidence of hypotension. Secondary outcomes included dosing and titration practices, initiation of a vasopressor, incidence of bradycardia, and time to goal Richmond Agitation Sedation Scale (RASS) score. RESULTS: Fifty-nine patients met inclusion criteria: 30 in the pre-intervention group and 29 in the post-intervention group. Protocol adherence in the post group was 34% with a median of one violation per patient. Rates of hypotension were similar between the groups (60% vs. 45%, p = .243) but significantly lower in the post group patients with zero protocol violations (60% vs. 20%, p = .029). The post group also had a significantly lower maximal dose (1.1 vs. 0.7 µg/kg/hr, p < .001). There were no significant differences in the initiation of a vasopressor, incidence of bradycardia, or time to goal RASS. CONCLUSION: Adherence to a dexmedetomidine dosing and titration protocol significantly decreased incidence of hypotension and maximal dexmedetomidine dose without increasing time to goal RASS score in critically ill trauma patients.

Adult golf cart injuries: A rising hazard off the course.

OBJECTIVE: Golf carts are increasingly being used as a means of transportation for travel in neighborhoods, city areas, and unpaved surfaces. The catchment area of our regional trauma center has seen an increase in golf cart use for transportation. In fact, Georgia has recently changed legislation to support the growing need for more defined laws around golf cart use. This study aims to further evaluate injury and outcome patterns in the adult population of northeast Georgia. METHODS: We performed a retrospective review of adult golf cart injured patients from 2018 to 2022. We evaluated key demographics, such as age and gender, along with the length of stay, Glasgow Coma Scale (GCS), and Injury Severity Score (ISS). Outcomes included the injury type. RESULTS: The results showed that orthopedic injuries were the most common (n = 24). Most patients were in the driver's seat (76%). Ejection from the golf cart was common (82%). Geriatric patients, 65 and older, had an increased length of stay compared to patients under the age of 65 (10 vs 3.9 days). CONCLUSION: Based on these results, future work includes injury prevention, increased awareness of injury patterns in prehospital and hospital settings, and communities updating their ordinances.

Programming Nucleation and Growth in Colloidal Crystals Using DNA.

Colloidal crystal engineering with DNA has advanced beyond controlling the lattice symmetry and parameters of ordered crystals to now tuning crystal habit and size. However, the predominately used slow-cooling procedure that enables faceted crystal habits also limits control over crystal size and uniformity because nucleation and growth cannot be separated. Here, we explore how DNA sequence design can be used to deliberately separate nucleation and growth in a given crystallization process. Specifically, two batches of complementary particles are created with one batch exhibiting perfectly complementary base pairs while the other has a strategically introduced mismatch. This design enables the weaker binding "growth" particles to participate in heterogeneous growth on the nucleates formed from the stronger binding "seed" particles, effectively eliminating secondary nucleation pathways. By eliminating secondary nucleation events, this approach improves crystal uniformity, as measured by polydispersity (from PDI = 0.201 to 0.091). By using this approach with two different particle cores (gold and silver), we show how core-shell colloidal crystals can be synthesized in a one-pot fashion. This work shows how tuning DNA interaction strength can profoundly impact crystal size, uniformity, and structure, parameters central to using such materials as device components.

Changing the Playing Field: A Prehospital Blood Product Pilot Project in Rural North Georgia.

BACKGROUND: In Georgia, the paramedic's scope of practice prohibited the initiation of blood products. Due to the rural landscape in Georgia, one region's Regional Trauma Advisory Committee (RTAC) advocated expanding the scope of practice for Georgia's paramedics to allow them to initiate blood products in the prehospital environment. This study evaluated the safety and feasibility of allowing paramedics to initiate blood products for hemorrhaging patients utilizing a regionally established prehospital blood pilot program. MATERIALS AND METHODS: Approval was obtained from the state medical directors and the Office of EMS and Trauma. The project team addressed product selection, equipment, prehospital service selection, education, policies and procedures, monitoring, and performance improvement. Four EMS services were identified to participate. Liquid plasma was selected due to cost and availability. Equipment was secured for blood storage and temperature monitoring to ensure the hospital's blood bank could maintain standards for exchange. A transfusion guideline was created, an administrative policy was developed, and an education plan was developed. A process with the trauma center's blood bank was also instituted to minimize waste and reduce costs. RESULTS AND DISCUSSION: The pilot project began in spring of 2020, and as of January 2023, there have been 100 field initiations and no adverse effects, demonstrating the safety of paramedics to initiate blood products in the field. A post-licensure skill for paramedics is now available in Georgia for the initiation of blood products. The repeatability of a similar project depends on the resources available, the stakeholder commitment, and the partnerships across disciplines.

Symmetry-Breaking Dendrimer Synthons in Colloidal Crystal Engineering with DNA.

Breaking symmetry in colloidal crystals is challenging due to the inherent chemical and structural isotropy of many nanoscale building blocks. If a non-particle component could be used to anisotropically encode such building blocks with orthogonal recognition properties, one could expand the scope of structural and compositional possibilities of colloidal crystals beyond what is thus far possible with purely particle-based systems. Herein, we report the synthesis and characterization of novel DNA dendrimers that function as symmetry-breaking synthons, capable of programming anisotropic and orthogonal interactions within colloidal crystals. When the DNA dendrimers have identical sticky ends, they hybridize with DNA-functionalized nanoparticles to yield three distinct colloidal crystals, dictated by dendrimer size, including a structure not previously reported in the field of colloidal crystal engineering, Si2Sr. When used as symmetry-breaking synthons (when the sticky ends deliberately consist of orthogonal sequences), the synthesis of binary and ternary colloidal alloys with structures that can only be realized through directional interactions is possible. Furthermore, by modulating the extent of shape anisotropy within the DNA dendrimers, the local distribution of the nanoparticles within the crystals can be directed.

Adverse event reviews in healthcare: what matters to patients and their family? A qualitative study exploring the perspective of patients and family.

OBJECTIVES: Explore what 'good' patient and family involvement in healthcare adverse event reviews may involve. DESIGN: Data was collected using semi-structured telephone interviews. Interview transcripts were analysed using an inductive thematic approach. SETTING: NHS Scotland. PARTICIPANTS: 19 interviews were conducted with patients who had experienced an adverse event during the provision of their healthcare or their family member. RESULTS: Four key themes were derived from these interviews: trauma, communication, learning and litigation. CONCLUSIONS: There are many advantages of actively involving patients and their families in adverse event reviews. An open, collaborative, person-centred approach which listens to, and involves, patients and their families is perceived to lead to improved outcomes. For the patient and their family, it can help with reconciliation following a traumatic event and help restore their faith in the healthcare system. For the health service, listening and involving people will likely enhance learning with subsequent improvements in healthcare provision with reduction in risk of similar events occurring for other patients. This study suggests eight recommendations for involving patients and families in adverse event reviews using the APICCTHS model (table 3) which includes an apology, person-centred inclusive communication, closing the loop, timeliness, putting patients and families at the heart of the review with appropriate support for staff involved. Communicating in a compassionate manner could also decrease litigation claims following an adverse event.

Programming "Atomic Substitution" in Alloy Colloidal Crystals Using DNA.

Although examples of colloidal crystal analogues to metal alloys have been reported, general routes for preparing 3D analogues to random substitutional alloys do not exist. Here, we use the programmability of DNA (length and sequence) to match nanoparticle component sizes, define parent lattice symmetry and substitutional order, and achieve faceted crystal habits. We synthesized substitutional alloy colloidal crystals with either ordered or random arrangements of two components (Au and Fe3O4 nanoparticles) within an otherwise identical parent lattice and crystal habit, confirmed via scanning electron microscopy and small-angle X-ray scattering. Energy dispersive X-ray spectroscopy reveals information regarding composition and local order, while the magnetic properties of Fe3O4 nanoparticles can direct different structural outcomes for different alloys in an applied magnetic field. This work constitutes a platform for independently defining substitution within multicomponent colloidal crystals, a capability that will expand the scope of functional materials that can be realized through programmable assembly.

The JAK-Inhibitor Tofacitinib Rescues Human Intestinal Epithelial Cells and Colonoids from Cytokine-Induced Barrier Dysfunction.

BACKGROUND: Alterations to epithelial tight junctions can compromise the ability of the epithelium to act as a barrier between luminal contents and the underlying tissues, thereby increasing intestinal permeability, an early critical event in inflammatory bowel disease (IBD). Tofacitinib (Xeljanz), an orally administered pan-Janus kinase (JAK) inhibitor, was recently approved for the treatment of moderate to severe ulcerative colitis. Nevertheless, the effects of tofacitinib on intestinal epithelial cell functions are largely unknown. The aim of this study was to determine if JAK inhibition by tofacitinib can rescue cytokine-induced barrier dysfunction in intestinal epithelial cells (IECs). METHODS: T84 IECs were used to evaluate the effects of tofacitinib on JAK-signal transducer and activator of transcription (STAT) activation, barrier permeability, and expression and localization of tight junction proteins. The impact of tofacitinib on claudin-2 promoter activity was assessed in HT-29 IECs. Tofacitinib rescue of barrier function was also tested in human colonic stem cell-derived organoids. RESULTS: Pretreatment with tofacitinib prevented IFN-γ-induced decreases in transepithelial electrical resistance (TER) and increases in 4 kDa FITC-dextran permeability (FD4), partly due to claudin-2 transcriptional regulation and restriction of ZO-1 rearrangement at tight junctions. Although tofacitinib administered after IFN-γ challenge only partially normalized TER and claudin-2 levels, FD4 permeability and ZO-1 localization were fully recovered. The IFN-γ-induced FD4 permeability in primary human colonoids was fully rescued by tofacitinib. CONCLUSIONS: These data suggest differential therapeutic efficacy of tofacitinib in the rescue of pore vs leak-tight junction barrier defects and indicate a potential contribution of improved epithelial barrier function to the beneficial effects of tofacitinib in IBD patients.

Regioselective surface encoding of nanoparticles for programmable self-assembly.

Surface encoding of colloidal nanoparticles with DNA is fundamental for fields where recognition interaction is required, particularly controllable material self-assembly. However, regioselective surface encoding of nanoparticles is still challenging because of the difficulty associated with breaking the identical chemical environment on nanoparticle surfaces. Here we demonstrate the selective blocking of nanoparticle surfaces with a diblock copolymer (polystyrene-b-polyacrylic acid). By tuning the interfacial free energies of a ternary system involving the nanoparticles, solvent and copolymer, controllable accessibilities to the nanoparticles' surfaces are obtained. Through the modification of the polymer-free surface region with single-stranded DNA, regioselective and programmable surface encoding is realized. The resultant interparticle binding potential is selective and directional, allowing for an increased degree of complexity of potential self-assemblies. The versatility of this regioselective surface encoding strategy is demonstrated on various nanoparticles of isotropic or anisotropic shape and a total of 24 distinct complex nanoassemblies are fabricated.

Publisher Correction: Regioselective surface encoding of nanoparticles for programmable self-assembly.

In the version of this Article originally published, the diblock copolymer structure in Fig. 2a showed a single bond between the carbon and the oxygen atoms; it should have been a double bond. This has been corrected in all versions of the Article.

Integrated clinical experience with concurrent problem-based learning is associated with increased clinical reasoning of physical therapy students in the United States.

Clinical reasoning (CR) is a key learning domain for physical therapy educators and core skill for entry level practitioners. Integrated clinical experiences (ICE) and problem-based learning (PBL) are each reported to improve interpersonal and social domains, while promoting knowledge acquisition and clinical reasoning. Unfortunately, studies monitoring CR during ICE with concurrent PBL in physical therapy education are sparse. We hypothesize that an ICE with concurrent PBL is associated with increased self-reported CR in third year student physical therapists (PTs) in the United States. The Self-Assessment of Clinical Reflection and Reasoning (SACRR) survey was administered to 42 student PTs at the beginning, and end of their third and final year of didactic training. Between pretest and posttest analyses, participants completed a faculty-led ICE and PBL coursework for 16 weeks. The SACRR overall and 26 individual item scores were examined. Wilcoxon ranked-signed test and paired t-test were used with statistical significance accepted at P< 0.05. Significant improvements observed in SACRR overall score (P< 0.001), including six of the 26 survey items centered around decision-making based on experience and evidence as well as self-reflection and reasoning. An ICE with PBL is associated with increased self-assessed CR and reflection in third year student PTs in the United States. Monitoring the impact of curricular design on CR may improve educators' ability to improve cognitive and psychomotor skills, with a call for increased explicit use of theoretical frameworks and teaching techniques for coping with uncertainty to enhance entry level training.