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.

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.

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.

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.

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.

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.

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.

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.

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.

Plasmonic Photothermal Gold Bipyramid Nanoreactors for Ultrafast Real-Time Bioassays.

Nucleic acid amplification techniques have been among the most powerful tools for biological and biomedical research, and the vast majority of the bioassays rely on thermocycling that uses time-consuming and expensive Peltier-block heating. Here, we introduce a plasmonic photothermal method for quantitative real-time PCR, using gold bipyramids and light to achieve ultrafast thermocycling. Moreover, we successfully extend our photothermal system to other biological assays, such as isothermal nucleic acid amplification and restriction enzyme digestion.

Improvement in functional performance with high-speed power training in older adults is optimized in those with the highest training velocity.

PURPOSE: To identify whether variability in limb movement velocity during high-speed power training (HSPT) may impact physical functioning in older adults. METHODS: 42 older men and women (71.3 ± 6.6 years) were randomized to lower extremity HSPT (n = 28) or control (CON; n = 14) (Analysis 1) for 12 weeks. A second analysis (Analysis 2) allocated HSPT into high-velocity (n = 14) or low-velocity (n = 14) based on a limb movement speed above or below the median average velocity during the 12-week HSPT intervention. Habitual gait speed, maximal gait speed, timed up-and-go, and the short physical performance battery were measured at baseline and 12 weeks. Change scores were compared between HSPT and CON (Analysis 1), and high-velocity, low-velocity, and CON (Analysis 2) using ANCOVA. Statistical significance was accepted at p < 0.05. RESULTS: Analysis 1 There were no group differences in habitual gait speed, maximal gait speed, or timed up-and-go between HSPT and CON (all p > 0.05). Short physical performance battery was greater in HSPT (0.96 ± 0.19) compared to CON (0.10 ± 0.26; p = 0.01). Analysis 2 There were no group differences in the change in habitual GS (p = 0.33) among high-velocity, low-velocity and CON. There were significant group differences in the change in maximal GS (p = 0.007), timed up-and-go (p = 0.03), and short physical performance battery (p = 0.03). CONCLUSIONS: There is considerable variation in self-selected maximal limb velocity during HSPT in older adults. In the present cohort, an average limb velocity of 0.88 m/s during HSPT was necessary to ensure optimal improvement in functional performance for older adults, but this threshold will need further investigation.

Junior doctor-led 'near-peer' prescribing education for medical students.

AIMS: Prescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor-led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tutorials on students and tutors. METHODS: One hundred and ninety-six tutorials were delivered to 183 students during 2010-2011. Each student completed a questionnaire after tutorial attendance which explored their previous prescribing experiences and the perceived benefits of tutorial attendance. Tutors completed a questionnaire which evaluated their teaching experiences and the impact on their prescribing practice. Student tutorial attendance was compared with end-of-year examination performance using linear regression analysis. RESULTS: The students reported increased confidence in their prescribing knowledge and skills after attending tutorials. Students who attended more tutorials also tended to perform better in end-of-year examinations (Drug prescribing: r = 0.16, P = 0.015; Fluid prescribing: r = 0.18, P = 0.007). Tutors considered that participation enhanced their own prescribing knowledge and skills. Although they were occasionally unable to address student uncertainties, 80% of tutors reported frequently correcting misconceptions and deficits in student knowledge. Ninety-five percent of students expressed a preference for prescribing training delivered by junior doctors over more senior doctors. CONCLUSIONS: A 'near-peer' junior doctor-led approach to delivering prescribing training to medical students was highly valued by both students and tutors. Although junior doctors have relatively less clinical experience of prescribing, we believe that this can be addressed by training and academic supervision and is outweighed by the benefits of these tutorials.

Endogenous tissue plasminogen activator enhances fibrinolysis and limits thrombus formation in a clinical model of thrombosis.

OBJECTIVE: Using a clinical model of deep arterial injury, we assessed the ability of exogenous and endogenous tissue plasminogen activator (t-PA) to limit acute in situ thrombus formation. APPROACH AND RESULTS: Ex vivo thrombus formation was assessed in the Badimon chamber at low and high shear rates in 2 double-blind randomized cross-over studies of 20 healthy volunteers during extracorporeal administration of recombinant t-PA (0, 40, 200, and 1000 ng/mL) or during endogenous t-PA release stimulated by intra-arterial bradykinin infusion in the presence or absence of oral enalapril. Recombinant t-PA caused a dose-dependent reduction in thrombus area under low and high shear conditions (P<0.001 for all). Intra-arterial bradykinin increased plasma t-PA concentrations in the chamber effluent (P<0.01 for all versus saline) that was quadrupled in the presence of enalapril (P<0.0001 versus placebo). These increases were accompanied by an increase in plasma D-dimer concentration (P<0.005 for all versus saline) and, in the presence of enalapril, a reduction in thrombus area in the low shear (16±5; P=0.03) and a trend toward a reduction in the high shear chamber (13±7%; P=0.07). CONCLUSIONS: Using a well-characterized clinical model of coronary arterial injury, we demonstrate that endogenous t-PA released from the vascular endothelium enhances fibrinolysis and limits in situ thrombus propagation. These data support a crucial role for the endogenous fibrinolytic system in vivo and suggest that continued exploration and manipulation of its therapeutic potential are warranted.

High-speed power training in older adults: a shift of the external resistance at which peak power is produced.

Studies have shown that power training increases peak power (PP) in older adults. Evaluating the external resistance (% 1 repetition maximum [1RM]) at which PP is developed is critical given that changes in the components of PP (force and velocity) are dependent on the %1RM at which PP occurs. The purpose of this study was to compare the changes in PP (and the external resistance at which PP occurred) after 12 weeks of high-speed power training (HSPT) vs. traditional slow-speed strength training (SSST). Seventy-two older men and women were randomized to HSPT at 40% of the 1RM (HSPT: n = 24 [70.8 ± 6.8 years]); traditional resistance training at 80% 1RM (SSST: n = 22 [68.6 ± 7.8 years]); or control (CON: n = 18 [71.5 ± 6.1 years]). Measures of muscle performance were obtained at baseline and after the 12-week training intervention. Changes in muscle power and 1RM strength improved similarly with both HSPT and SSST, but HSPT shifted the external resistance at which PP was produced to a lower external resistance (from 67% 1RM to 52% 1RM) compared with SSST (from 65% 1RM to 62% 1RM) (p ≤ 0.05), thus increasing the velocity component of PP (change: HSPT = 0.18 ± 0.21 m·s; SSST = -0.03 ± 0.15 m·s) (p ≤ 0.05). Because sufficient speed of the lower limb is necessary for functional tasks related to safety (crossing a busy intersection, fall prevention), HSPT should be implemented in older adults to improve power at lower external resistances, thus increasing the velocity component of power and making older adults safer in their environment. These data provide clinicians with the necessary information to tailor exercise programs to the individual needs of the older adult, affecting the components of power.

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.

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.

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.