US Guidelines Research Articles

QUICK‐B‐WIM: Large scale application of a moving force identification method on a railway bridge

AbstractGlobally, infrastructure faces the challenge of aging bridges and increasing traffic loads. Extended operational availability and safety of the bridge structures can be enabled by Structural Health Monitoring (SHM) methods. For this, knowledge of the actual vehicle loads is of crucial importance for evaluation of the remaining service life. Direct measurement of the moving loads, however, is either very cumbersome and requires considerable financial effort or in some cases even impossible. Bridge Weigh‐In‐Motion (B‐WIM) methods use the structural responses of bridge structures to determine the external vehicle loads. The present contribution deals with the testing of a novel moving force identification (MFI) method, denoted as Quick‐BWIM (QBWIM) under real operating conditions. In this study, 43 train crossings within 18 hours were investigated and compared with a nearby axle load measurement point. QBWIM achieves an average error of only 1.1% with a standard deviation of 7.5% for individual axles and an average error of 2.1% with a standard deviation of 1.5% for the identification of gross vehicle weights (GVW). This study shows that QBWIM can meet European and US guidelines even under poor conditions and is able to reliably determine axle loads in real time.

Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Abstract P435: Barriers For Secondary Hypertension Screening In The Us: A National Physician Survey

Background: Although US and international expert guidelines recommend screening for secondary hypertension in patients with treatment-resistant hypertension (RHTN) and other high-risk groups, screening is conducted in <3% of candidates. Objective: To determine barriers for secondary hypertension screening across US practices. Participants and Measurements: Internists, family practitioners, cardiologists, nephrologists, and endocrinologists, randomly selected from active members of the American Medical Association were surveyed on barriers for secondary hypertension screening. Results: Response rate was 67% (425 of 633 response-eligible physicians). The leading reported barriers preventing secondary hypertension screening included visit time constraints (43.5%), poor ancillary support (29.4%), and testing-related logistics (27.5%). Physicians practicing in large medical groups or staff-model HMO were more likely than physicians in private practice to not have access to specialists (adjusted OR, 95% CI: 4.01 [1.19-13.47]), and to be unfamiliar with screening results interpretation and next steps (2.11 [1.03-4.32]), but less likely to report poor ancillary support (0.47 [0.28-0.79]) or reimbursement concerns (0.29 [0.13-0.63]). Primary care physicians were more likely than endocrinologists (16.67 [2.04-100.00]) and nephrologists (10.00 [1.32-100.00] to lack familiarity with testing interpretation and subsequent steps. Physicians in practices covered primarily by Medicare were more likely to report poor ancillary support (2.02 [1.16-3.53]), and lack of access to specialists (4.96 [1.04-23.52]) as compared to physicians in practices covered primarily by private health insurance. Conclusions: Our findings suggest an urgent need to address major barriers to secondary hypertension screening, including ensuring adequate clinic visit time, ancillary support, and timely access to specialists.

Implementation Strategies to Improve Blood Pressure Control in the United States: A Scientific Statement From the American Heart Association and American Medical Association.

Hypertension is one of the most important risk factors that contribute to incident cardiovascular events. A multitude of US and international hypertension guidelines, scientific statements, and policy statements have recommended evidence-based approaches for hypertension management and improved blood pressure (BP) control. These recommendations are based largely on high-quality observational and randomized controlled trial data. However, recent published data demonstrate troubling temporal trends with declining BP control in the United States after decades of steady improvements. Therefore, there is a widening disconnect between what hypertension experts recommend and actual BP control in practice. This scientific statement provides information on the implementation strategies to optimize hypertension management and to improve BP control among adults in the United States. Key approaches include antiracism efforts, accurate BP measurement and increased use of self-measured BP monitoring, team-based care, implementation of policies and programs to facilitate lifestyle change, standardized treatment protocols using team-based care, improvement of medication acceptance and adherence, continuous quality improvement, financial strategies, and large-scale dissemination and implementation. Closing the gap between scientific evidence, expert recommendations, and achieving BP control, particularly among disproportionately affected populations, is urgently needed to improve cardiovascular health.

Dehydration among the Elderly: A Comparison between Nine Different Clinical and Metabolic Criteria

Background: Dehydration, as a common problem in older adults, plays a significant role in morbidity and mortality. The elderly are more susceptible to dehydration and fluid deficiency due to age-related factors. There is not much literature concerning fluid intake in older adults. This study aims to investigate fluid intake and dehydration prevalence in older people and compare the accuracy of potential markers in the detection of dehydration.
 Methods: This cross-sectional study was done on 127 old people (48 males and 79 females) selected from a nursing home in Shiraz, Iran. Socioeconomic status was assessed via interview. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), urine specific gravity (USG), urine color (UC) and bioelectrical impedance analysis (BIA), extracellular water (ECW), intracellular water (ICW), and total body water (TBW) were measured. The fluid intakes were recorded using a beverage and fluid intake questionnaire. Total fluid intakes were compared using two fluid intake guidelines (European guidelines and US guidelines) as well. Furthermore, anthropometric indices were measured.
 Results: The mean age of participants was 73.01± 5.70 year. Fluid intake was 2.32 ± 0.48 liter/day. Based on urine specific gravity (USG) (˃1.020) and SBP (SBP ˂ 100 mmHg), 9.4% and 14.2% of the participants were dehydrated respectively. Among all hydration criteria, ECW had the highest potential for detection which identified 72.4% of participants as dehydrated. Among fluid intake guidelines, US guidelines were the best in dehydration diagnosis (112 individuals out of 127).
 Conclusions: Although urinary markers and physical indexes (SBP and HR) could not be used to determine hydration status, BIA measurements, especially ECW, have the potential to detect dehydration. In addition, daily fluid intakes are still practical for assessment of hydration status.

Activated PI3Kδ syndrome - reviewing challenges in diagnosis and treatment.

Activated PI3Kδ syndrome (APDS) is a rare inborn error of immunity (IEI) characterized primarily by frequent infections, lymphoproliferation and autoimmunity. Since its initial description in 2013, APDS has become part of the growing group of nearly 500 IEIs affecting various components of the immune system. The two subtypes of APDS - APDS1 and APDS2 - are caused by variants in the PIK3CD and PIK3R1 genes, respectively. Due to the rarity of the disease and the heterogeneous clinical picture, many patients are not diagnosed until years after symptom onset. Another challenge is the large number of PIK3CD and PIK3R1 variants whose functional significance for developing APDS is inconclusive. Treatment of APDS has so far been mostly symptom-oriented with immunoglobulin replacement therapy, immunosuppressive therapies and antibiotic or antiviral prophylaxes. Additionally, allogeneic stem cell transplantation as well as new targeted therapies are options targeting the root cause that may improve patients' quality of life and life expectancy. However, the clinical course of the disease is difficult to predict which complicates the choice of appropriate therapies. This review article discusses diagnostic procedures and current and future treatment options, and highlights the difficulties that physicians, patients and their caretakers face in managing this complex disease. This article is based on cohort studies, the German and US guidelines on the management of primary immunodeficiencies as well as on published experience with diagnosis and compiled treatment experience for APDS.

Physical activity is inversely associated with overall cancer risk among college students in the United States: Results from the National College Health Assessment.

To our knowledge, this is the first epidemiologic study to examine the association between physical activity (PA) and cancer using data from the American College Health Association-National College Health Assessment (ACHA-NCHA). The goal of the study was to understand the dose-response relation between PA and cancer, as well as the associations between meeting US PA guidelines and overall cancer risk in US college students. The ACHA-NCHA provided self-reported information on demographic characteristics, PA, body mass index, smoking status, and overall cancer during 2019-2022 (n = 293,682; 0.08% cancer cases). To illustrate the dose-response relationship, a restricted cubic spline logistic regression analysis was used to evaluate the association of overall cancer with moderate-to-vigorous PA (MVPA) on a continuous basis. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals for the associations between meeting the three U.S. PA guidelines and overall cancer risk. The cubic spline observed that MVPA was inversely associated with the odds of overall cancer risk after adjusting for covariates; a one hour/week increase in moderate and vigorous PA was associated with a 1% and 5% reduced overall cancer risk, respectively. Multivariable-adjusted logistic regression analyses showed that meeting the US guidelines for aerobic PA for adults (≥150 minutes/week of moderate aerobic PA or ≥75 minutes of vigorous PA) (OR: 0.85), for PA for adults (≥2 days of muscle strengthening activity in addition to aerobic MVPA) (OR: 0.90), and for highly active adults (≥2 days of muscle strengthening activity and ≥300 minutes/week of aerobic moderate PA or 150 minutes/week of vigorous PA) (OR: 0.89) were statistically significant and inversely associated with cancer risk. MVPA, especially meeting US guidelines, may be inversely associated with overall cancer among college students in the US. To reduce cancer risks, multilevel interventions to promote US physical activity guidelines among college students are warranted.

Comparison of the European and US guidelines for lipid-lowering therapy in primary prevention of cardiovascular disease.

Population-wide impacts of new guidelines in the primary prevention of atherosclerotic cardiovascular disease (ASCVD) should be explored in independent cohorts. Assess and compare the lipid-lowering therapy eligibility and predictive classification performance of 2016 and 2021 European Society of Cardiology (ESC), 2019 American Heart Association/American College of Cardiology (AHA/ACC), and 2022 US Preventive Services Task Force (USPSTF) guidelines. Participants from the CoLaus|PsyCoLaus study, without ASCVD and not taking lipid-lowering therapy at baseline. Derivation of 10-year risk for ASCVD using Systematic COronary Risk Evaluation (SCORE1), SCORE2 [including SCORE2-Older Persons (SCORE2-OP)], and pooled cohort equation. Computation of the number of people eligible for lipid-lowering therapy based on each guideline and assessment of discrimination and calibration metrics of the risk models using first incident ASCVD as an outcome. Among 4,092 individuals, 158 (3.9%) experienced an incident ASCVD during a median follow-up of 9 years (interquartile range, 1.1). Lipid-lowering therapy was recommended or considered in 40.2% (95% confidence interval, 38.2-42.2), 26.4% (24.6-28.2), 28.6% (26.7-30.5), and 22.6% (20.9-24.4) of women and in 62.1% (59.8-64.3), 58.7% (56.4-61.0), 52.6% (50.3-54.9), and 48.4% (46.1-50.7) of men according to the 2016 ESC, 2021 ESC, 2019 AHA/ACC, and 2022 USPSTF guidelines, respectively. 43.3 and 46.7% of women facing an incident ASCVD were not eligible for lipid-lowering therapy at baseline according to the 2021 ESC and 2022 USPSTF, compared with 21.7 and 38.3% using the 2016 ESC and 2019 AHA/ACC, respectively. Both the 2022 USPSTF and 2021 ESC guidelines particularly reduced lipid-lowering therapy eligibility in women. Nearly half of women who faced an incident ASCVD were not eligible for lipid-lowering therapy.

Enteral nutrition management in critically ill adult patients and its relationship with intensive care unit-acquired muscle weakness: A national cohort study.

To assess the incidence and determinants of ICU-acquired muscle weakness (ICUAW) in adult patients with enteral nutrition (EN) during the first 7 days in the ICU and mechanical ventilation for at least 48 hours. A prospective, nationwide, multicentre cohort study in a national ICU network of 80 ICUs. ICU patients receiving invasive mechanical ventilation for at least 48 hours and EN the first 7 days of their ICU stay were included. The primary outcome was incidence of ICUAW. The secondary outcome was analysed, during days 3-7 of ICU stay, the relationship between demographic and clinical data to contribute to the onset of ICUAW, identify whether energy and protein intake can contribute independently to the onset of ICUAW and degree of compliance guidelines for EN. 319 patients were studied from 69 ICUs in our country. The incidence of ICUAW was 153/222 (68.9%; 95% CI [62.5%-74.7%]). Patients without ICUAW showed higher levels of active mobility (p = 0.018). The logistic regression analysis showed no effect on energy or protein intake on the onset of ICUAW. Overfeeding was observed on a significant proportion of patient-days, while more overfeeding (as per US guidelines) was found among patients with obesity than those without (42.9% vs 12.5%; p<0.001). Protein intake was deficient (as per US/European guidelines) during ICU days 3-7. The incidence of ICUAW was high in this patient cohort. Early mobility was associated with a lower incidence of ICUAW. Significant overfeeding and deficient protein intake were observed. However, energy and protein intake alone were insufficient to explain ICUAW onset. Low mobility, high incidence of ICUAW and low protein intake suggest the need to train, update and involve ICU professionals in nutritional care and the need for early mobilization of ICU patients.

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.

Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Sex Differences in Epidemiology, Morphology, Mechanisms, and Treatment of Mitral Valve Regurgitation.

Sex-related disparities have been recognized in incidence, pathological findings, pathophysiological mechanisms, and diagnostic pathways of non-rheumatic mitral regurgitation. Furthermore, access to treatments and outcomes for surgical and interventional therapies among women and men appears to be different. Despite this, current European and US guidelines have identified common diagnostic and therapeutic pathways that do not consider patient sex in decision-making. The aim of this review is to summarize the current evidence on sex-related differences in non-rheumatic mitral regurgitation, particularly regarding incidence, imaging modalities, surgical-derived evidence, and outcomes of transcatheter edge-to-edge repair, with the goal of informing clinicians about sex-specific challenges to consider when making treatment decisions for patients with mitral regurgitation.

Management of suspected and known eosinophilic esophagitis-anationwide survey in Austria.

Eosinophilic esophagitis (EoE) is achronic immune-mediated disease of the esophagus with increasing incidence and dysphagia as the main symptom. The management of suspected or known EoE by Austrian endoscopists has not been investigated yet. Aweb-based survey with 13questions about the management of EoE was sent to endoscopists via the Austrian Society of Gastroenterology and Hepatology (ÖGGH). Atotal of 222 endoscopists (74% gastroenterologists, 23% surgeons, and 2% pediatricians; 68% working in ahospital) from all 9states participated. In patients with dysphagia but anormal appearing esophagus, 85% of respondents reported always taking biopsies; however, surgeons were less likely to obtain biopsies compared to gastroenterologists ("always" 69% vs. 90%, "sometimes" 29% vs. 10%, "never" 2% vs. 0%, p < 0.001). The approved budesonide orodispersible tablet is the preferred first-line drug used in EoE, ahead of proton pump inhibitors (PPI). Only 65% of participants monitor the patients by endoscopy and histology after 12weeks of induction therapy, 26% do not continue maintenance therapy, and 22% monitor patients only when symptomatic. The vast majority of Austrian endoscopists adhere to the European and US guidelines in cases of suspected EoE. In contrast, despite the chronic disease course, asignificant percentage of providers indicate not to use maintenance therapy and monitor the patients routinely.

Pregnancy and Labor Epidural Effects on Gastric Emptying: A Prospective Comparative Study

(Anesthesiology. 2022;136:542–550) Strict fasting during labor has been practiced for more than 70 years in the United States. During that time, the incidence of peripartum aspiration pneumonia has significantly decreased, in part due to advances in anesthesia. Some European guidelines allow patients to consume low-residue food during labor, while US guidelines only allow for clear fluids. There is a lack of strong data concerning gastric emptying in labor. This study compared gastric emptying after a light meal in laboring patients with epidural analgesia, laboring patients without epidural analgesia, pregnant nonlaboring women, and nonpregnant women.

Leisure-time and competitive sport participation: a changing paradigm for HCM patients.

HCM has long been considered the most frequent cause of death in athletes, and reason for disqualification from sport. However, our perception of the impact of sports on HCM is largely based on anecdotal evidence. In this review, we provide a reappraisal of current knowledge relative to 1) the impact of sport on LV remodeling, and 2) on the clinical outcome of HCM in athletes. 1) The limited available evidence argues against the hypothesis that intensive exercise conditioning may trigger and/or worsen the development of LV hypertrophy or cause changes in LV function in adult HCM athletes. 2) Recent observations challenge the concept of a detrimental effect of sport on HCM clinical course. The Reset-HCM study showed that 16-week moderate-intensity exercise resulted in a small, significant increase in exercise capacity and no adverse events. In a cohort of 88 low-risk HCM athletes followed for a 7-year period, survival analyses showed no difference in mortality between HCM who discontinued or pursued vigorous exercise programmes. Further reassurance was provided by the ICD Sports Safety Registry. Clinical implications: At present, patients' attitude to sport participation is highly variable, based on social and legal backgrounds surrounding medical practice in different countries. The shared-decision-making as suggested by current US and European guidelines allows the physician to deliver a tailored and more liberal advice. Physicians should be aware of the changing paradigm relative to exercise and sport prescription for HCM and promote active lifestyle as an integral component of modern management of HCM patients.

Clinical and Public Health Considerations for HPV Vaccination in Midadulthood: A Narrative Review.

Human papillomavirus (HPV) is an important cause of anogenital and oropharyngeal cancers, anogenital warts, and recurrent respiratory papillomatosis. Beginning in 2019, US guidelines recommended shared clinical decision-making (SCDM) for HPV vaccination among midadults (27-45 years). We conducted a narrative review of existing literature on HPV vaccination in midadults. The available evidence demonstrates that HPV vaccination in midadults is safe, efficacious, and likely to benefit both HPV-naïve midadults and those with previous infections. However, gaps in knowledge related to HPV vaccination have been identified among clinicians and midadult patients. Universal midadult HPV vaccination in the United States could avert 20 934-37 856 cancer cases over 100 years, costing $141 000-$1 471 000 per quality-adjusted life-year gained. Wide variation in these estimates reflects uncertainties in sexual behavior, HPV natural history, and naturally acquired immunity. Greater awareness among clinicians and midadult patients and broad implementation of SCDM may accelerate progress toward eliminating HPV-associated cancers and other diseases.

Incorporating Health Policy and Advocacy Curricula Into Undergraduate Medical Education in the United States.

Physicians serve as crucial advocates for their patients. Undergraduate medical education (UME) must move beyond the biomedical model, built upon the perception that health is defined purely in the absence of illness, to also incorporate population health through health policy, advocacy, and community engagement to account for structural and social determinants of health. Currently, the US guidelines for UME lack structured training in health policy or advocacy, leaving trainees ill-equipped to assume their role as physician-advocates or to engage with communities. There is an undeniable need to educate future physicians on legislative advocacy toward improving the social determinants of health through the creation of evidence-based health policy, in addition to training in effective techniques to engage in partnership with the communities in which physicians serve. The authors of this article also present curricular case studies around two programs at their institution that could be used to implement similar programs at other US medical schools.

P030Interest in rh testing and rho(d) immune globulin received among patients obtaining first-trimester medication abortion through virtual clinics

<h3>Objectives</h3> Despite an absence of evidence that Rho(D) immune globulin is necessary before first-trimester abortion, current US guidelines are mixed regarding whether routine Rh testing and Rho(D) immune globulin are required. We sought to assess knowledge of blood type, interest in Rh testing, and Rho(D) immune globulin received if Rh-negative among patients receiving direct-to-patient telehealth for medication abortion care and who would not otherwise need to travel to a clinic for care. <h3>Methods</h3> We analyzed survey data from patients obtaining medication abortion through telehealth in 21 states and Washington, DC as part of the California Home Abortion by Telehealth Study between October 2020 and January 2021. The survey included questions about patients' blood type, interest in receiving Rh testing, and whether Rh-negative patients have received Rho(D) immune globulin. Clinics counseled patients about low risks of Rh sensitization early in pregnancy. <h3>Results</h3> Among all 1,378 respondents who answered survey questions on Rh, 713 (51.7%) patients knew their blood type and among these, 172 (24.1%) reported they were Rh-negative. One clinic asked all patients with unknown blood types (n=202) about their interest in Rh testing, among whom 201 (99.5%) were not interested in Rh testing. Among Rh-negative patients, 2.91% did obtain Rho(D) immune globulin. <h3>Conclusions</h3> Most patients who choose telehealth services for medication abortion are not interested in Rh testing or have not received Rho(D) immune globulin. Guidelines that continue to mandate Rh testing and Rho(D) immune globulin for first-trimester abortions should be reconsidered based on low patient interest and lack of demonstrated clinical necessity in the existing literature.

Dofetilide use is not associated with increased mortality in patients with left ventricular hypertrophy and atrial fibrillation.

Left ventricular hypertrophy (LVH) is common in patients with atrial fibrillation (AF), however, many antiarrhythmic drugs (AADs) are contraindicated. US guidelines recommend avoiding pure class III antiarrhythmics such as dofetilide in patients with significant LVH due to concern for an increased risk of death, however, clinical data is lacking. We sought to determine if dofetilide use was associated with increased mortality in patients with LVH. Patients ≥18 years of age with AF and LVH ≥ 1.4 cm were included. A group of patients treated with dofetilide and a control group of patients without a history of AAD use were propensity matched. The primary outcome was all-cause mortality at 3 years and secondary outcomes were total number of all-cause hospitalizations and hospitalizations related to AF. There were 359 patients in each of the groups. Baseline variables were well-matched. The primary outcome of all-cause mortality occurred in 7% of patients in the dofetilide group and 12% of patients in the control group (hazard ratio: 0.90, 95% confidence interval: 0.53-1.53). Total all-cause hospitalizations were higher in the control group but hospitalizations for AF were no different. In a propensity-matched cohort of 718 patients with AF and LVH, dofetilide was not associated with increased mortality at 3 years. Our study adds to prior data demonstrating the safety of dofetilide in this population despite guideline recommendations against its use. Given the limited options for AF management in LVH patients, dofetilide may be reasonable for symptomatic AF management.

Safety Procedures to Work with West Nile Virus in Biosafety Level 3 Facilities.

West Nile virus (WNV) can cause severe and sometimes fatal disease, but we do not have treatments or therapeutics to manage these outcomes. Since its introduction to the USA in 1999, WNV has been handled in a biosafety level 3 laboratory to decrease risk to researchers, requiring strict safety protocols and important considerations with planning experiments. Recent changes in US guidelines suggest that WNV can be handled at a lower biosafety level due to its endemicity in the USA and generally minor symptoms, but some research still requires the use of the agent at biosafety level 3. This chapter will briefly discuss the considerations of biosafety when working with WNV.