Combined atrial fibrillation ablation and left atrial appendage occlusion procedure in the United States: a propensity score matched analysis from 2016-2019 national readmission database.

AIMS: The safety and feasibility of combining percutaneous catheter ablation (CA) for atrial fibrillation with left atrial appendage occlusion (LAAO) as a single procedure in the USA have not been investigated. We analyzed the US National Readmission Database (NRD) to investigate the incidence of combined LAAO + CA and compare major adverse cardiovascular events (MACEs) with matched LAAO-only and CA-only patients. METHODS AND RESULTS: In this retrospective study from NRD data, we identified patients undergoing combined LAAO and CA procedures on the same day in the USA from 2016 to 2019. A 1:1 propensity score match was performed to identify patients undergoing LAAO-only and CA-only procedures. The number of LAAO + CA procedures increased from 28 (2016) to 119 (2019). LAAO + CA patients (n = 375, mean age 74 ± 9.2 years, 53.4% were males) had non-significant higher MACE (8.1%) when compared with LAAO-only (n = 407, 5.3%) or CA-only patients (n = 406, 7.4%), which was primarily driven by higher rate of pericardial effusion (4.3%). All-cause 30-day readmission rates among LAAO + CA patients (10.7%) were similar when compared with LAAO-only (12.7%) or CA-only (17.5%) patients. The most frequent primary reason for readmissions among LAAO + CA and LAAO-only cohorts was heart failure (24.6 and 31.5%, respectively), while among the CA-only cohort, it was paroxysmal atrial fibrillation (25.7%). CONCLUSION: We report an 63% annual growth (from 28 procedures) in combined LAAO and CA procedures in the USA. There were no significant difference in MACE and all-cause 30-day readmission rates among LAAO + CA patients compared with matched LAAO-only or CA-only patients.

Outcomes and predictors of readmission after implantation of a percutaneous left atrial appendage occlusion device in the United States: A propensity score-matched analysis from The National Readmission Database.

BACKGROUND: Left atrial appendage occlusion (LAAO) devices have become a favorable alternative option among nonvalvular atrial fibrillation (AF) patients with long-term contraindication to anticoagulation. Real-world experience with postprocedural readmission rates and predictors of readmission in LAAO patients is limited. OBJECTIVE: To assess all-cause 30-day readmission rate and predictors of readmission after LAAO procedure in the United States. METHOD: This retrospective observational study included all AF patients undergoing percutaneous LAAO procedures in the United States from January 1, 2016, and December 31, 2017, in the National Readmission Database. The primary outcome measure was all-cause 30-day readmission. A propensity score-matched analysis compared outcomes with a non-LAAO AF cohort. RESULT: Among 14 024 LAAO procedures (age: 76 ± 8 years; 60.5% males), 9.4% were readmitted within 30-days and, 0.2% died during their index hospitalization. The most frequent primary diagnosis during readmission among LAAO was gastrointestinal bleeding (12%). The incidence of LAAO procedures increased by 102%. In the multivariate model, gender and CHA2 DS2 -VASc failed to predict readmission. Age 55-64 years had lower odds (adjusted odds ratios [aOR]: 0.41; 95% confidence interval [CI]: 0.18-0.94), while drug abuse (aOR: 4.1; 95% CI: 1.34-12.54), and deficiency anemia (aOR: 1.88; 95% CI: 1.12-3.18) had higher odds of readmission. In propensity-matched cohort, compared to non-LAAO AF, LAAO patients had lower 30-day readmission (9.4% vs. 10.98%, p = .002) and all-cause in-hospital mortality (0.19% vs. 0.57%, p < .001). CONCLUSION: The readmission rate following the LAAO procedure is substantial (approximately 10%), and largely attributable to gastrointestinal bleeding. Factors such as drug abuse and anemia must be explored further to minimize readmission risk.

Development of a Library of Thiophene-Based Drug-Like Lego Molecules: Evaluation of Their Anion Binding, Transport Properties, and Cytotoxicity.

The anion-binding and transport properties of an extensive library of thiophene-based molecules are reported. Seventeen bis-urea positional isomers, with different binding conformations and lipophilicities, have been synthesized by appending α- or ß-thiophene or α-, ß-, or γ-benzo[b]thiophene moieties to an ortho-phenylenediamine central core, yielding six subsets of positional isomers. Through 1 H NMR, X-ray crystallography, molecular modelling, and anion efflux studies, it is demonstrated that the most active transporters adopt a pre-organized binding conformation capable of promoting the recognition of chloride, using urea and C-H binding groups in a cooperative fashion. Additional large unilamellar vesicle-based assays, carried out under electroneutral and electrogenic conditions, together with N-methyl-d-glucamine chloride assays, have indicated that anion efflux occurs mainly through an H+ /Cl- symport mechanism. On the other hand, the most efficient anion transporter displays cytotoxicity against tumor cell lines, while having no effects on a cystic fibrosis cell line.

Peripartum management of patient with long QT3 after successful implantable cardioverter defibrillator device discharge resulting in device failure: a case report.

BACKGROUND: Long QT3 syndrome type 3 (LQT3) is a gain of function mutation of the SCN5A gene that is inherited in an autosomal dominant fashion. Long QT3 syndrome type 3 results in an increase in arrhythmic events during rest, sleep, and bradycardia by extending the QT interval and inducing Torsades de pointes and sudden cardiac death. Attempting to block the sodium channel with Class I anti-arrhythmics or blocking adrenergic tone with beta-blockers especially in women has shown to be beneficial. There have been few large-scale studies on treating patients with LQT3 due to its lethality and underreported number of cases. Specifically, the safety and efficacy of pharmacologic treatment in pregnant LQT3 patients are unknown. CASE SUMMARY: This case demonstrates the safe use of Mexiletine and Propranolol in a 3rd-trimester pregnant LQT3 patient after a presumed ventricular arrhythmia and device-lead electrical short from therapy rendered her implantable cardioverter defibrillator inoperable in a VVI mode (venticular demand pacing). With appropriate medications, the patient was safely monitored through the remainder of her pregnancy and safely delivered at 36 weeks of pregnancy a healthy baby girl. The daughter, heterozygous for LQT3, showed no evidence of intrauterine growth restriction or other side effects from the medications. DISCUSSION: There are many variants of the SCN5A gene mutations that can lead to different phenotypes and not all mutations are responsive to the same medications. In this case, Mexiletine and Propranolol, both of which have only recently shown to benefit certain variants or LQT3 respectively, were safely started during the 3rd trimester of pregnancy without harming the foetus.

Effectiveness of the Ophthalmological Training Component of the STOMP (Simulation Training for Operational Medical Providers) Curriculum.

INTRODUCTION: Simulation has been used in medicine to train clinicians to manage a variety of clinical scenarios. A key adaptation of the use of simulation in military healthcare occurred in 2015 with the development of the STOMP (Simulation Training for Operational Medical Providers) curriculum, a specific curriculum designed for the intern (PGY-1) trained physicians being sent into the military to practice primary care. Despite showing the curriculum's influence on self-perceived comfort scores, no study has determined whether simulation is an effective means of improving general medical officer (GMO) physicians' skills compared to other traditional styles of education. Specifically, this study sought to determine whether simulation-based education (SBE) of ophthalmologic skills improves GMO physicians' clinical performance, as compared to traditional didactic-based instruction. METHODS: The study, conducted at Naval Medical Center Portsmouth, included GMO physicians who were enrolled in the 2019 STOMP class. Following a brief overview of the study, GMO physicians who elected to participate in the study were randomized to either SBE or lecture-based training for three commonly used ophthalmological procedures: slit lamp exam, tonometry, and corneal foreign body removal. After completing the simulation and lecture-based education training sessions, participants' procedural performance was evaluated utilizing a locally developed performance checklist, and completion time for each of the three procedures was recorded. Data were analyzed using the t-test and Mann-Whitney test. A significance level of 0.05 was considered to be statistically significant. RESULTS: Of the 50 consented participants, 46 completed the study. The mean overall completion scores for the performance checklists were significantly higher for the SBE group (n=26) compared to the lecture group (n=20) [80% (95% CI 78-82%) vs 41% (95% CI 35-47%), respectively]. Time to completion of the individual tasks was also significantly shorter for the SBE group compared to the lecture group (with mean differences ranging from 27 to 126 seconds, all p<.05). CONCLUSIONS: Simulation-based training appeared to be more effective at teaching three ophthalmological procedures (slit lamp exam, tonometry, and corneal foreign body removal) to GMO physicians compared to didactic-based instruction alone.

Simulation Training for Operational Medicine Providers (STOMP): Impact of a Comprehensive Skills-Based Curriculum for Military General Medical Officers.

INTRODUCTION: A standardized training curriculum designed for general medical officers (GMO) titled Simulation Training for Operational Medicine Providers (STOMP) was recently developed to educate and improve GMOs' procedural skills through directed feedback prior to assuming duties in an operational environment. This study aimed to determine the impact this novel curriculum had on GMOs'confidence levels in 21 core privileges covering eight different subspecialties while stationed at Naval Medical Center Portsmouth (NMCP). MATERIALS AND METHODS: A cohort study from 2015 to 2017 was designed to address our specific aim to examine if the implementation of the STOMP curriculum increased GMOs' confidence levels. Fifty-seven participants enrolled in the study. The GMO case group completed the STOMP curriculum (n = 22), while the control or GMO self-study group (n = 35) did not complete the curriculum. Six months after starting clinical practice at NMCP, both groups completed an online survey that assessed their confidence level in performing each core privilege using a 5-point Likert scale. Scores were analyzed using a Wilcoxon Mann-Whitney test. Research data were derived from an approved Naval Medical Center, Portsmouth, Virginia IRB, protocol number: NMCP.2016.0010. RESULTS: Participants demonstrated a statistically significant increase in self-rated confidence scores (p < 0.05) in nine core privilege skills: punch biopsy, shave biopsy, excisional biopsy, removal of otic foreign body, removal of nasal foreign body, removal of ocular foreign body, tonometry, incision and drainage of a thrombosed hemorrhoid, and reduction of simple closed fractures and dislocations. CONCLUSIONS: These findings suggest that a novel and recently developed standardized simulation training curriculum entitled STOMP improves the confidence levels of early career physicians' in several primary care procedural skills and is an ideal adjunct to traditional lecture-based teaching prior to independent practice in a primary care environment.

Fluorinated synthetic anion carriers: experimental and computational insights into transmembrane chloride transport.

A series of fluorinated tripodal tris-thioureas function as highly active anion transporters across lipid bilayers and cell membranes. Here, we investigate their mechanism of action using anion transport assays in cells and synthetic vesicles and molecular modelling of transporter-lipid interactions. When compared with non-fluorinated analogues, fluorinated compounds demonstrate a different mechanism of membrane transport because the free transporter cannot effectively diffuse through the membrane. As a result, in H+/Cl- cotransport assays, fluorinated transporters require the presence of oleic acid to form anionic oleate complexes for recycling of the transporter, whereas non-fluorinated analogues readily diffuse through the membrane as free transporters and show synergistic transport with the proton transporter gramicidin. Molecular dynamics simulations revealed markedly stronger transporter-lipid interactions for fluorinated compounds compared with non-fluorinated analogues and hence, higher energy barriers for fluorinated compounds to cross the membrane as free transporters. With use of appropriate proton transporters to ensure measurement of the correct rate-limiting steps, the transport rates determined in synthetic vesicle assays show excellent agreement with the anion transport rates determined in cell-based assays. We conclude that integration of computational and experimental methods provides a strategy to optimise transmembrane anion transporter design for biomedical applications.

Simulation Training for Operational Medicine Providers (STOMP): Design and Implementation of a Novel Comprehensive Skills-Based Curriculum for Military General Medical Officers.

Background: Fifty percent of graduating U.S. Navy post-graduate year (PGY)-1 physicians will practice in the operational environment before returning to residency training. However, current internship structure is less rotational and focuses more on specialty-specific training. Therefore, these physicians may not be fully prepared for this primary care role. Methods: Based on the U.S. Navy privileges for General Medical Officers, a comprehensive didactic and simulation curriculum was developed. Twenty-three procedural skill competencies (SK) and five validated standardized patient (SP) scenarios were identified. During the SK portion, learners reviewed instructional videos, read reference materials, and practiced with partial task trainers before small-group sessions with subject matter experts (SME). Separate SP round-robin sessions were conducted and feedback provided by SMEs and SPs. Learners demonstrated competency or were remediated. Results: One hundred and three PGY-1 trainees participated over 2 yr. All trainees met requirements during the SK phase. During the SP phase, seven learners required remediation. All learners ultimately met requirements for privileging. Conclusion: The Simulation Training for Operational Medicine Providers curriculum for future General Medical Officers is an effective tool for primary care skill training and credentialing. Plans for export to other Graduate Medical Education sites are underway and further evaluation of skills retention is warranted.

Anion transport across varying lipid membranes--the effect of lipophilicity.

The anion transport properties of a range of alkyl-substituted phenylthioureas were tested in vesicles of different lipid composition. Although changes in the bilayer affected the rate of transport for all compounds in the series, the 'ideal' log P for peak activity did not change depending on the composition of the bilayers tested.