Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design, Setting, and Participants: This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites. Interventions: Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis. Results: Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group). Conclusions and Relevance: In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Susceptibility Screening of HIV-1 Viruses to Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, in People with HIV-1 Suppressed by Antiretroviral Therapy.

BACKGROUND: HIV envelope (env) diversity may result in resistance to broadly neutralizing antibodies (bNAbs). Assessment of genotypic or phenotypic susceptibility to antiretroviral treatment is often performed in people with HIV-1 (PWH) and used for clinical trial screening for HIV-1 bNAb susceptibility. Optimal bNAb susceptibility screening methods are not yet clear. METHODS: Phenotypic and genotypic analyses were conducted on 124 screening samples from a Phase 1b study of bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS) administered with lenacapavir in virally suppressed PWH. Phenotypic analysis was conducted on integrated HIV-1 provirus and stimulated outgrowth virus, with susceptibility to bNAbs defined as 90% inhibitory concentration ≤2 µg/mL. The proviral DNA HIV env gene was genotyped using deep sequencing, and bNAb susceptibility predicted using published env amino acid signatures. RESULTS: Proviral phenotypic results were reported for 109 of 124 samples; 75% (82/109) were susceptible to teropavimab, 65% (71/109) to zinlirvimab, and 50% (55/109) to both bNAbs. Phenotypic susceptibility of outgrowth viruses was available for 39 samples; 56% (22/39) were susceptible to teropavimab, and 64% (25/39) to zinlirvimab. Phenotypic susceptibilities correlated between these methods: teropavimab r = 0.82 (P<0.0001); zinlirvimab r = 0.77 (P<0.0001). Sixty-seven samples had genotypic and phenotypic data. Proviral genotypic signatures predicted proviral phenotypic susceptibility with high positive predictive value (68-86% teropavimab; 63-90% zinlirvimab). CONCLUSIONS: bNAb susceptibility was correlated among all three in-vitro assays used to determine teropavimab and zinlirvimab susceptibility in virally suppressed PWH. These findings may help refine PWH selection criteria for eligibility for future studies.

Implementation of a transition of care pathway for low-risk patients presenting to the emergency department with venous thromboembolism.

Inpatient management of low-risk patients with venous thromboembolism (VTE) places a large resource burden on the healthcare system. Adult patients diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) in the emergency department (ED) have historically been hospitalized and treated with therapeutic anticoagulation. However, over the last two decades, outpatient treatment of patients with acute DVT and low risk PE has become increasingly accepted as an effective and safe option for patients given the low risk of short-term clinical deterioration. The purpose of this project was to establish a transition of care (TCM) program for patients with acute VTE presenting to the ED. The primary goals for the project included better quality patient follow-up in the Vascular Medicine Nurse Practitioner (NP) within one week and medication adherence. The second goal was increasing appropriate ED discharges for patients with low-risk VTE. Outcome metrics include the rate of early discharge of low-risk patients with VTE, follow-up in the Vascular Medicine NP clinic, and anticoagulant adherence.

Clinical and utilization outcomes with short stay units vs hospital admission for lower risk decompensated heart failure: a systematic review and meta-analysis.

With over 1 million primary heart failure (HF) hospitalizations annually, nearly 80% of patients who present to the emergency department with decompensated HF (DHF) are hospitalized. Short stay units (SSU) present an alternative to hospitalization, yet the effectiveness of the SSU strategy of care is not well known. This study is to determine the effectiveness of a SSU strategy compared with hospitalization in lower-risk patients with DHF. Our primary outcome was a composite of 30-day mortality and re-hospitalization. Key secondary outcomes included 90-day mortality and re-hospitalization, costs, and 30-day days-alive-and-out-of-hospital (DAOOH). This is a systematic review and meta-analysis, following PRISMA guidelines. MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, and Web of Science were searched from inception through February 2024. Either randomized trials or comparative observational studies were included if they compared outcomes between low-risk ED DHF patients admitted to an SSU (defined as an observation unit with expected stay ≤ 48 h) vs. admitted to the hospital. Two authors independently screened all titles and abstracts and then identified full texts for inclusion. Data extraction and risk of bias assessments were performed by two authors in parallel. The primary outcome was a composite of death or readmission within 30 days, reported as relative risk (RR), where a RR < 1 favored the SSU strategy. Secondary outcomes included 90-day mortality and re-hospitalization, costs, and 1-month days-alive-and-out-of-hospital (DAOOH). Of the 467 articles identified by our search strategy, only 3 full text articles were included. In meta-analysis for the primary outcome of 30-day death or readmission, the RR was 0.95 (95% CI = 0.56 to 1.63; I2 = 0%) for patients randomized to SSU vs hospitalization (2 studies, 241 patients). There were only 2 total deaths at 30 days in the 2 studies (total N = 258) which reported 30-day mortality, both in hospitalized patients. Only one study reported 90-day outcomes, showing no significant differences. Costs were lower in the SSU arm from one study, and 30-day DAOOH also favored SSU based on a single randomized trial. Based on very limited evidence, SSU provides similar efficacy for 30-day and 90-day mortality and readmission compared to hospitalization. An SSU strategy appears safe and may be cost effective.

The Relationship of Pain Intensity, Perceived Injustice, and Pain Catastrophizing to Heart Rate Variability In Naturally Occurring Acute Pain.

OBJECTIVES: Chronic pain disorders are among the most common and affect approximately 20% of the US population, leading to disproportionately high medical expenditures and negative economic impact. Behavioral factors of pain catastrophizing and perceived injustice are associated with pain intensity in chronic pain. Diminished heart rate variability (HRV) is also strongly associated with chronic pain. These factors have been less explored earlier in the pain experience and it is unclear whether they play a role in the transition from acute to chronic pain. The aim of this study was to determine the relationship between pain catastrophizing, perceived injustice, pain intensity and HRV in naturally occurring acute pain. METHODS: Ninety-seven subjects were recruited from local outpatient physical therapy clinics. Seated HRV was captured on ninety-four subjects via Polar chest strap while subjects were taking a survey via iPad. In addition to sociodemographic data, the survey included the Pain Catastrophizing Scale (PCS), Injustice Experience Questionnaire (IEQ), and Numeric Pain Rating Scale (NPRS). The natural log of high frequency power (lnHFP) HRV was used in the statistical analysis. RESULTS: Multiple regression modeling revealed that lower pain catastrophizing, higher perceived injustice, and lower pain intensity were associated with lower HRV, and accounted for 11.4% of the variance in HRV. DISCUSSION: While greater chronic pain intensity is associated with lower HRV, the relationship is reversed in the setting of acute pain. These findings highlight the need to better understand the unique factors that contribute to lower HRV in the acute phase.

Inpatient Use of Guideline-Directed Medical Therapy During Heart Failure Hospitalizations Among Community-Based Health Systems.

BACKGROUND: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains underused. Acute heart failure (HF) hospitalization represents a critical opportunity for rapid initiation of evidence-based medications. However, data on GDMT use at discharge are mostly derived from national quality improvement registries. OBJECTIVES: This study aimed to describe contemporary GDMT use patterns across HF hospitalizations at community-based health systems. METHODS: The authors identified HF hospitalizations from 2016 to 2022 in a U.S. database aggregating deidentified electronic health record data from more than 30 health systems. In-hospital and discharge rates of GDMT use were reported for eligible HFrEF patients. Factors associated with inpatient GDMT use and predischarge discontinuation were evaluated with the use of multivariable models. RESULTS: A total of 20,387 HF hospitalizations among 13,729 HFrEF patients were identified. Renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were administered during 70%, 86%, and 37% of eligible hospitalizations, respectively. Angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors were used in 17% and 8% of eligible hospitalizations, respectively. Discharge GDMT rates were low. Triple/quadruple therapy was administered in 26% of hospitalizations, falling to 14% on discharge. Predischarge GDMT discontinuations were associated with inpatient hypotension, hyperkalemia, and worsening renal function, but 43%-57% had no medical contraindications. In adjusted analyses, use of 3 or more GDMT classes was associated with fewer 90-day all-cause deaths and HF readmissions compared with less comprehensive GDMT. CONCLUSIONS: Inpatient GDMT use in a national analysis of HF hospitalizations was lower than reported in quality improvement registries. High discontinuation rates emphasize an unmet need for inpatient and postdischarge strategies to optimize GDMT use.

Patient Preferences for Attributes of Androgen Deprivation Therapies in Prostate Cancer: A Discrete Choice Experiment with Latent Class Analysis.

INTRODUCTION: Medical androgen deprivation therapy (ADT) options have expanded for patients with advanced prostate cancer (PC). Historically, ADT was primarily available in long-acting injectable formulations. In 2020, the first oral formulation was US Food and Drug Administration-approved for adults with advanced PC. This study's aim was to assess patient preferences for attributes of medical ADT, including mode of administration, side effects, impact on sexual interest, and out-of-pocket (OOP) costs, and to segment respondents into distinct groups based on their treatment choice patterns. METHODS: A cross-sectional survey was conducted among US residents aged > 40 years with PC, employing a discrete choice experiment to assess preferences for ADT attributes. For each choice task, respondents were asked to select the hypothetical treatment profile that they preferred out of two presented. Latent class analysis (LCA) was conducted to estimate attribute-level preference weights and calculate attribute relative importance for groups of respondents with similar treatment preferences. RESULTS: A total of 304 respondents completed the survey (mean age 64.4 years). LCA identified four preference groups, named according to the attribute each group considered most important: Sexual interest, Cost-sensitive, Favors daily pill, and Favors injection. Most respondents in the Sexual interest group were < 65 years, while the Cost-sensitive group was mostly ≥ 65 years. Favors daily pill had the highest proportion of ADT-naïve individuals. On average, respondents in these groups preferred an oral medication. Favors injection, which had the highest proportion of ADT-experienced individuals, preferred infrequent intramuscular injections, lower chance of post-ADT testosterone recovery, and lower OOP cost. CONCLUSION: Respondents differed in their preferences regarding ADT attributes, highlighting the need for patient involvement in their treatment decisions. Effective communication between healthcare providers and patients about the benefits and risks of available therapies should be encouraged to ensure that patients receive the PC treatment that best meets their needs.

Prostate cancers often depend on the male sex hormone, testosterone, to grow. Androgen deprivation therapy (ADT) is used to lower testosterone levels in patients with advanced prostate cancer. ADT options available to patients have different characteristics, including how they are taken (injection or pill), side effects, impact on sexual interest, and costs. Researchers wanted to understand which ADT characteristics were most important to groups of patients with similar preferences. To do this, they gave 304 patients a series of two hypothetical (meaning not real) examples of ADT options with different characteristics and asked them to choose the option that they preferred most. Researchers found that patients could be separated into four different groups based on their preferences for ADT characteristics. One group preferred an ADT that had the least impact on their interest in sex. These patients were mainly younger than 65 years old. A second group preferred a lower cost ADT. These patients were mainly 65 years or older. A third group preferred a pill that could be taken once a day by mouth. Most of these patients did not take ADT in the past. A fourth group preferred an ADT that was given in a physician's office as an injection every 6 months. These patients mainly had taken ADT in the past. This study shows that patients have different preferences for ADT treatment characteristics. It is important for doctors to discuss the different ADT options with patients to find the treatment that best meets their needs.

The utility of urine sodium-guided diuresis during acute decompensated heart failure.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry-guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium-guided strategies.

Derivation and external validation of a portable method to identify patients with pulmonary embolism from radiology reports: The READ-PE algorithm.

BACKGROUND: Identification of pulmonary embolism (PE) across a cohort currently requires burdensome manual review. Previous approaches to automate capture of PE diagnosis have either been too complex for widespread use or have lacked external validation. We sought to develop and validate the Regular Expression Aided Determination of PE (READ-PE) algorithm, which uses a portable text-matching approach to identify PE in reports from computed tomography with angiography (CTA). METHODS: We identified derivation and validation cohorts of final radiology reports for CTAs obtained on adults (≥ 18 years) at two independent, quaternary academic emergency departments (EDs) in the United States. All reports were in the English language. We manually reviewed CTA reports for PE as a reference standard. In the derivation cohort, we developed the READ-PE algorithm by iteratively combining regular expressions to identify PE. We validated the READ-PE algorithm in an independent cohort, and compared performance against three prior algorithms with sensitivity, specificity, positive-predictive-value (PPV), negative-predictive-value (NPV), and the F1 score. RESULTS: Among 2948 CTAs in the derivation cohort 10.8 % had PE and the READ-PE algorithm reached 93 % sensitivity, 99 % specificity, 94 % PPV, 99 % NPV, and 0.93 F1 score, compared to F1 scores ranging from 0.50 to 0.85 for three prior algorithms. Among 1206 CTAs in the validation cohort 9.2 % had PE and the algorithm had 98 % sensitivity, 98 % specificity, 85 % PPV, 100 % NPV, and 0.91 F1 score. CONCLUSIONS: The externally validated READ-PE algorithm identifies PE in English-language reports from CTAs obtained in the ED with high accuracy. This algorithm may be used in the electronic health record to accurately identify PE for research or surveillance. If implemented at other EDs, it should first undergo local validation and may require maintenance over time.

The impact of neoadjuvant relugolix on multi-dimensional patient-reported fatigue.

Introduction: Androgen deprivation therapy has been shown to improve cancer control when combined with radiotherapy. Relugolix is an oral GnRH receptor antagonist that achieves rapid profound testosterone suppression, which may increase the perception and/or impact of fatigue. This study sought to evaluate neoadjuvant relugolix-induced fatigue in prostate cancer patients prior to the start of stereotactic body radiation therapy (SBRT). Methods: Relugolix was initiated at least two months before SBRT. The 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was collected at baseline and one hour prior to SBRT initiation. A five-point scale was used to score individual items. Overall scores range from 0-52 and individual item scores were converted to 0-100, with higher scores reflecting less fatigue. Five "experience" items explored self-perceptions of fatigue, and eight "impact" items sought to evaluate the effect of fatigue on daily activities. Items were evaluated for statistical significance (paired t-test, p < 0.05) and clinical significance (minimally important difference (MID); 0.5 standard deviation from baseline). Results: Between March 2021 to December 2023, 89 men were treated at Georgetown with neoadjuvant relugolix and SBRT. Mean age was 71 years (range: 49-87). Median initiation of relugolix was 4.5 months prior to SBRT (range: 2-14.2 months). 93% patients achieved castration (testosterone levels ≤ 50 ng/dL) and 85% patients achieved profound castration (testosterone levels ≤ 20 ng/dL). 87 patients completed the FACIT-F questionnaire, with an average overall score of 45.6 at baseline and 41.0 at SBRT initiation. This difference was statistically and clinically significant (p < 0.01, MID = 3.55). Patients experienced an increase in fatigue for 12 of 13 items, with statistically significant changes for 11 items. Three of five experience items showed a clinically significant increase in fatigue. Only two of eight impact items were clinically significant. Discussion: Our study shows that relugolix significantly increases fatigue, affecting multiple areas of life. While the fatigue does not appear to generally impact a patient's ability to carry out normal activities, patients demonstrate frustration with being too tired for these activities. It is essential for clinicians to counsel prostate cancer patients on the impact of neoadjuvant relugolix on quality-of-life issues like fatigue.

Distinguishing Physiological Ureter Uptake From an Involved Lymph Node in Staging Prostate-Specific Membrane Antigen (PSMA) Scans: Implications for Radiation Planning.

Prostate-specific membrane antigen (PSMA) imaging has become a mainstay diagnostic tool in staging unfavorable primary prostate cancer (PC) and identifying sites of recurrence in previously treated PC. One of the biggest pitfalls of PSMA imaging is rapid radionucleotide excretion in the urine via the​ kidneys, ureters, and bladder.​ The positron-emission tomography (PET) images obtained show increased radiotracer activity in these structures, which can occlude or even mimic true malignant disease. We describe the diagnostic challenges encountered in differentiating benign versus malignant disease with PSMA scans. A 78-year-old male presented ​to our outpatient radiation oncology office ​with high-risk prostate cancer. His medical history was significant for ulcerative colitis (UC). Magnetic resonance imaging (MRI) revealed an enlarged prostate and a Prostate Imaging Reporting and Data System (PI-RADS) class 4 lesion. A subsequent transperineal biopsy confirmed unilateral Gleason 8 adenocarcinoma. A PSMA PET scan was read as increased uptake in the right prostate and a left external iliac node. The patient, having been initially informed of a positive lymph node metastasis, sought a second opinion,​resulting in​​ ​a CT urogram that revealed physiologic ureteral uptake. We were thus able to avoid lymph node radiation and morbidity to the surrounding bowel, already chronically inflamed with ulcerative colitis. This study ​demonstrates the ​potential for misinterpretation of PSMA uptake in the ureter as lymph node metastases. We discuss how peri-uretic activity can hinder accurate visualization of pelvic lymph node metastases. This study highlights the need for careful image interpretation of PSMA uptake patterns in order to avoid diagnostic errors and unnecessary radiation to ​at-risk​​ ​organs in prostate cancer management.

Time from admission to randomization and the effect of empagliflozin in acute heart failure: A post-hoc analysis from EMPULSE.

AIMS: Patients hospitalized for acute heart failure (HF) could be enrolled in EMPULSE (NCT04157751) upon haemodynamic stabilization and between 24 h and 5 days after hospital admission. The timing of treatment initiation may influence the efficacy and safety of drugs such as empagliflozin. The aim of this study was to evaluate patient characteristics, clinical events, and treatment effects according to time from admission to randomization. METHODS AND RESULTS: The EMPULSE population was dichotomized by median time from hospital admission to randomization (1-2 days vs. 3-5 days). The primary outcome was a hierarchical composite endpoint of time to all-cause death, number of HF events, time to first HF event, and a ≥5-point difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline after 90 days, analysed using the win ratio (WR) method. Patients randomized later (3-5 days, average time 3.9 days; n = 312) had a higher risk of experiencing clinical events than patients randomized earlier (1-2 days, average time 1.7 days; n = 215). The treatment effect favoured empagliflozin versus placebo in patients randomized later (3-5 days: WR 1.69, 95% confidence interval [CI] 1.26-2.25) but was attenuated in patients randomized earlier (1-2 days: WR 1.04, 95% CI 0.74-1.44) (interaction p = 0.029). A similar pattern was observed for the composite of HF hospitalization or cardiovascular death and all-cause hospitalizations (interaction p < 0.1 for both). The reduction of N-terminal pro-B-type natriuretic peptide levels was more pronounced with empagliflozin among patients randomized later than in patients randomized earlier (interaction p = 0.004). CONCLUSIONS: Among patients hospitalized for acute HF enrolled in EMPULSE, those randomized later after hospital admission (3-5 days) experienced greater clinical benefit with empagliflozin than those randomized earlier (1-2 days). These findings should be confirmed in future studies before clinical application.

Frontloading Home Physical Therapy Visits for Patients With Heart Failure: A Multi-center Randomized Controlled Trial.

Frontloading home care visits has been found to be effective in the nursing profession but has not been investigated in physical therapy (PT) practice. This study aimed to examine the impact of frontloading home PT visits on function in persons with heart failure (HF). This was a prospective multi-center randomized controlled trial with blinded raters. A total of 82 ambulatory patients with a primary diagnosis of HF discharged from an acute care facility to home care participated in the study. Subjects were randomly allocated to an experimental frontloaded group (FLG) or control group (CG) for 4 weeks. FLG visit frequencies were five sessions per week for 2 weeks, and three sessions per week for 2 weeks. The CG received two sessions per week for 4 weeks. Functional measures including the 2-minute step test (2MST), 2-minute walk test (2MWT), gait speed (GS), Timed Up and Go (TUG), and 30-second chair rise test (30-CRT) were collected at the onset of care, at the end of 2 weeks and 4 weeks. The groups were statistically similar at baseline for all measures. All subjects significantly improved scores in all functional measures over time, within-subject main effect (p < .01). Significant between-subject effects were noted for 30-CRT (p = .04). Interaction effects were noted for GS (p = .03) and TUG test (p = .02). This is the first study to report meaningful improvements in function in individuals with HF. Significant treatment effect differences between the FLG and CG were found for GS, TUG, and 30-CRT. Future studies should examine the use of a standardized intervention to validate the effectiveness of frontloading home visits on quality of life and readmission rates.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. METHODS: 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC). The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal). During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. RESULTS: The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy. The rates of late > Grade 3 GU toxicity and > Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities. Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral. Three underwent salvage cryotherapy and three received salvage ADT. CONCLUSIONS:  In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT. However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hope that recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

The Effects of a Core Stabilization Training Program on the Performance of Functional Tasks in Firefighters.

The purpose of this study was to observe if core stabilization training plays a significant role in firefighter time-to-completion during a functional performance test. A within subjects study design was used in which subjects (n = 13, 84.6% male, 33.7 ± 7.4 years of age, 91.06 ± 13.29 kg, 25.79 ± 6.55 percent body fat, 8.96 ± 7.51 years of firefighting experience) completed two performance tests (pre and post core training), comprised of 7 firefighter-specific exercises performed while wearing a 22.68 kg weight vest to mimic typical firefighter equipment. Between testing sessions, subjects were prescribed specific core stabilization exercises to perform at least three days a week for a total of 4 weeks. Time-to-completion was significantly quicker between the first (300.89 ± 42.11s) and second (256.92 ± 34.31s) performance testing, on average by 43.8 seconds (p < 0.001). Body mass index (p = 0.065) and rating of perceived exertion during testing (p = 0.084) did not significantly decrease across the course of the study. Adequate fitness is essential to firefighters' job task performance. Data from this study suggests that regular core stabilization training may assist in optimizing the effectiveness, and potentially safety, of firefighters' performance in high intensity functional skills.

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design Setting and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Interventions: Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov ( NCT04885530 ).

Hidden Impurities Generate False Positives in Single Atom Catalyst Imaging.

Single-atom catalysts (SACs) are an emerging class of materials, leveraging maximum atom utilization and distinctive structural and electronic properties to bridge heterogeneous and homogeneous catalysis. Direct imaging methods, such as aberration-corrected high-angle annular dark-field scanning transmission electron microscopy, are commonly applied to confirm the atomic dispersion of active sites. However, interpretations of data from these techniques can be challenging due to simultaneous contributions to intensity from impurities introduced during synthesis processes, as well as any variation in position relative to the focal plane of the electron beam. To address this matter, this paper presents a comprehensive study on two representative SACs containing isolated nickel or copper atoms. Spectroscopic techniques, including X-ray absorption spectroscopy, were employed to prove the high metal dispersion of the catalytic atoms. Employing scanning transmission electron microscopy imaging combined with single-atom-sensitive electron energy loss spectroscopy, we scrutinized thin specimens of the catalysts to provide an unambiguous chemical identification of the observed single-atom species and thereby distinguish impurities from active sites at the single-atom level. Overall, the study underscores the complexity of SACs characterization and establishes the importance of the use of spectroscopy in tandem with imaging at atomic resolution to fully and reliably characterize single-atom catalysts.

Effects of Nontraditional Division III Lacrosse Participation on Movement Pattern Quality and Dynamic Postural Control.

Background/Purpose: No studies have observed the effects of a collegiate lacrosse season on movement pattern quality, dynamic postural control, or the accuracy of athletes' perceived movement pattern quality. The purpose was to examine the effects of a nontraditional fall season on movement pattern quality, perceived movement pattern quality, and dynamic postural control in collegiate lacrosse athletes. Design: Cross-sectional laboratory study. Methods: Fifty men's (age=19.38±1.24 years, height=182.63±6.16 cm, mass=82.37±8.46 kg) and 22 women's (age=19.68±1.17 years, height=165.10±6.88 cm, mass=64.09±8.72 kg) lacrosse players were recruited. Outcome measures included individual Functional Movement Screen™ (FMS™) scores, self-reported perceived movement pattern quality scores, lower and upper extremity Y-Balance Test (YBT) measurements, and active dorsiflexion range of motion (ROM) before the start and again at the end of the fall lacrosse season. Pre- and post-season measurements were assessed using paired t-tests and chi-squared analyses. Results: FMS™ composite scores did not significantly change from preseason to postseason for males (p=0.74) or females (p=0.07). Male perceived movement pattern quality was significantly higher than measured for 10 of 12 movements (p<0.05). Female perceived movement pattern quality was significantly higher than measured for four of 12 movements (p<0.05). Asymmetry frequency significantly increased in males in the hurdle step from two individuals to nine (χ21=25.52, p<0.01), inline lunge from 10 to 20 (χ21=12.50, p<0.01), and shoulder mobility from 4 to 21 (χ21=78.53, p<0.01). Asymmetries in male athletes significantly decreased in the active straight leg raise from 26 to 8 (χ21=25.96, p<0.01). YBT composite scores increased in males for the right leg (p=0.001) and left leg (p<0.03). Right dorsiflexion ROM (p<0.001) and left dorsiflexion ROM (p<0.001) significantly decreased in males from preseason to postseason. YBT scores for the right leg significantly increased in females from preseason to postseason (p=0.01). YBT scores for females for the right arm significantly increased from preseason to postseason (p=0.045). Conclusions: A 5-week season may not change overall movement pattern quality of men's or women's lacrosse players, but some individual movement scores diminished. Athletes may overestimate self-reported movement pattern quality and are therefore unlikely to individually address movement deficits. Male dynamic postural control may change throughout a season, resulting in a potential increased risk of injury later in the season due to compensatory patterns or changes in mobility, proprioception, or balance. Level of Evidence: 3b.

Treatment effects of empagliflozin in hospitalized heart failure patients across the range of left ventricular ejection fraction - Results from the EMPULSE trial.

AIM: The EMPULSE (EMPagliflozin in patients hospitalised with acUte heart faiLure who have been StabilizEd) trial showed that, compared to placebo, the sodium-glucose cotransporter 2 inhibitor empagliflozin (10 mg/day) improved clinical outcomes of patients hospitalized for acute heart failure (HF). We investigated whether efficacy and safety of empagliflozin were consistent across the spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: A total of 530 patients hospitalized for acute de novo or decompensated HF were included irrespective of LVEF. For the present analysis, patients were classified as HF with reduced (HFrEF, LVEF ≤40%), mildly reduced (HFmrEF, LVEF 41-49%) or preserved (HFpEF, LVEF ≥50%) ejection fraction at baseline. The primary endpoint was a hierarchical outcome of death, worsening HF events (HFE) and quality of life over 90 days, assessed by the win ratio. Secondary endpoints included individual components of the primary endpoint and safety. Out of 523 patients with baseline data, 354 (67.7%) had HFrEF, 54 (10.3%) had HFmrEF and 115 (22.0%) had HFpEF. The clinical benefit (hierarchical composite of all-cause death, HFE and Kansas City Cardiomyopathy Questionnaire total symptom score) of empagliflozin at 90 days compared to placebo was consistent across LVEF categories (≤40%: win ratio 1.35 [95% confidence interval 1.04, 1.75]; 41-49%: win ratio 1.25 [0.66, 2.37)] and ≥50%: win ratio 1.40 [0.87, 2.23], pinteraction = 0.96) with a favourable safety profile. Results were consistent across individual components of the hierarchical primary endpoint. CONCLUSION: The clinical benefit of empagliflozin proved consistent across LVEF categories in the EMPULSE trial. These results support early in-hospital initiation of empagliflozin regardless of LVEF.