Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Typologies of Sex Work Practice and Associations with the HIV Risk Environment and Risk Behaviors in Kazakhstan.

Women engaged in sex work (WESW) who use drugs are a key population in Kazakhstan's HIV epidemic. Global research suggests susceptibility to HIV varies by sex work environment. This study aims to identify evidence-based typologies of WESW and examine their associations with HIV risk. We surveyed 400 WESW who use drugs in two Kazakhstani cities, including questions on sociodemographic characteristics, social, physical, and economic risk environments, and sexual risk behaviors. Latent class analysis identified four distinct typologies of sex work practice: occasional sex work (n = 61, 15%), professional sex work for money (n = 187, 47%), sex work in exchange for drugs, goods, or other services (n = 117, 29%), and managed sex work under a boss/pimp/madam (n = 35, 9%). We then used logistic regression to examine associations between typologies and risk behaviors. Compared to professional sex work, occasional sex work was associated with lower odds of multiple sexual partners (aOR:0.46[95%CI:0.24,0.90]), of multiple paid clients (aOR:0.25[0.13,0.49]), and of > 1 instance of unprotected sex with a paying partner (aOR:0.33[0.17,0.63]). Compared to professional sex work, sex work for nonmonetary items was associated with higher odds of multiple sexual partners (aOR:1.85[0.96,3.67]) and of > 1 instance of unprotected sex with a paying partner (aOR:1.71[1.01,2.93]). Results suggest heterogeneity among WESW who use drugs in Kazakhstan, and that typologies of sex work are associated with varying HIV risk environment factors and risk behaviors. Effective HIV prevention efforts must be tailored to address these varying risk environments and the resulting variety of needs.

The αC-ß4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A.

Allosteric cooperativity between ATP and substrates is a prominent characteristic of the cAMP-dependent catalytic subunit of protein kinase A (PKA-C). This long-range synergistic action is involved in substrate recognition and fidelity, and it may also regulate PKA's association with regulatory subunits and other binding partners. To date, a complete understanding of this intramolecular mechanism is still lacking. Here, we integrated NMR(Nuclear Magnetic Resonance)-restrained molecular dynamics simulations and a Markov State Model to characterize the free energy landscape and conformational transitions of PKA-C. We found that the apoenzyme populates a broad free energy basin featuring a conformational ensemble of the active state of PKA-C (ground state) and other basins with lower populations (excited states). The first excited state corresponds to a previously characterized inactive state of PKA-C with the αC helix swinging outward. The second excited state displays a disrupted hydrophobic packing around the regulatory (R) spine, with a flipped configuration of the F100 and F102 residues at the αC-ß4 loop. We validated the second excited state by analyzing the F100A mutant of PKA-C, assessing its structural response to ATP and substrate binding. While PKA-CF100A preserves its catalytic efficiency with Kemptide, this mutation rearranges the αC-ß4 loop conformation, interrupting the coupling of the two lobes and abolishing the allosteric binding cooperativity. The highly conserved αC-ß4 loop emerges as a pivotal element to control the synergistic binding of nucleotide and substrate, explaining how mutations or insertions near or within this motif affect the function and drug sensitivity in homologous kinases.

The predictive value and reliability of ultrasound-guided synovial aspiration and biopsies for diagnosing periprosthetic shoulder infections.

INTRODUCTION: Preoperative diagnosis of periprosthetic shoulder infections (PSI) is difficult. Infections are mostly caused by low virulence bacteria and patients do not show typical signs of infection. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination with multiplex polymerase chain reaction (mPCR), serum markers, and/or synovial markers for the preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. MATERIALS AND METHODS: A prospective explorative diagnostic cohort study was performed including 55 patients undergoing revision shoulder replacement surgery. A shoulder puncture was performed preoperatively before incision to collect synovial fluid for mPCR analysis and for measurement of interleukin-6, calprotectin, white blood cell count (WBC), and polymorphonuclear cells. Also prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two for mPCR analysis. A blood sample was obtained to determine serum C-reactive protein, WBC, and erythrocyte sedimentation rate. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; the primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, blood and synovial markers, mPCR, and combinations thereof. RESULTS: Routine tissue cultures were positive for infection in 24 patients. Cultures from ultrasound-guided biopsies diagnosed infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively. The best diagnostic value was found for the combination of ultrasound-guided biopsies for culture, synovial WBC, and calprotectin with a sensitivity of 69.2%, specificity of 80.0%, PPV of 69.2%, and NPV of 80.0%. CONCLUSION: Ultrasound-guided biopsies for cultures alone and in combination with mPCR, and/or blood and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of PSI. LEVEL OF EVIDENCE: Diagnostic study level II.

Socio-ecological impacts of extreme weather events in two informal settlements in Nairobi, Kenya.

Climate change is expected to profoundly impact health and coping and widen social and environmental inequalities. People living in informal settlements are especially vulnerable to climate change as they are often located in ecologically sensitive areas more susceptible to extreme weather events (EWEs), such as floods, droughts, and heat waves. Women residing in informal settlements are especially vulnerable to climate change and related EWEs because they are more likely to experience worse health-related impacts than men but are less likely to have access to health-related services. Despite this inequality, there is a dearth of research that focuses on the impacts of EWEs on women in informal settlements. This study aims to explore the multidimensional impacts of EWEs on the daily lives of women in informal settlements through the lens of socio-ecological theory. Study data is from six monthly surveys (1 September 2022-28 February 2023) collected from a probability sample of 800 women living in two of the largest informal settlements in Nairobi, Kenya. This data is part of an ongoing longitudinal study that uses community participatory methods to investigate the effects of climate change on health and wellbeing in informal settlements by a team of 16 community health volunteers who lead data collection and provide expertise in ongoing analysis. Findings show profound impacts on women's health and wellbeing across individual, micro-, meso-, exo-, and macrosystems. These include physical and mental health, financial disruptions, property issues, social impacts, and impacts on their surrounding physical environment, such as disrupted food or water access, poor air quality, drainage issues, and safety concerns. In addition, findings highlight the critical importance of the chrono- and biosphere systems in research focused on the impacts of climate change and related EWEs among climate-vulnerable communities and marginalized populations within them.

Crossroads of Choice: A qualitative study of the factors influencing decisions to transition from sex work among women engaged in sex work in Southern Uganda.

Background: Women Engaged in commercial Sex Work (WESW) are exposed to behavioral, biological, and structural factors that exacerbate their risk to HIV infection and other sexually transmitted infections. While commercial sex work may appear voluntary, WESW are more likely to be constrained to selling sex due to limited viable alternatives. To effectively support this vulnerable group of women, it is critical to understand factors that facilitate and impede their decisions to transition from sex work into other careers or jobs. The current study explored women's decision to transition from sex work into other careers or jobs. Methods: Semi-structured in-depth interviews were conducted with 53 WESW aged 20-47 enrolled within a larger study-Kyaterekera study, a randomized clinical trial (N = 542) implemented in 19 HIV hotspots in the Southern region of Uganda. Participants were selected based on their intervention attendance (high/medium/low attendance). The interviews were conducted in Luganda the widely spoken language in the study area to explore the factors influencing women's decisions to from transition from sex work to other jobs or careers. The main interview question used for this study was, "What are some of the factors that may influence whether you would transition from sex work to other jobs or vocations?". All interviews were audio-recorded, transcribed verbatim and translated into English. Thematic analysis in Dedoose software was used to analyze the data. Results: Participants reported three primary types of decisions, including considering leaving sex work, deciding to leave, and continuing sex work. The emerging themes from the interviews were categorized into individual and structural level facilitators and barriers to leave sex work. Individual level factors included issues of stigma, discrimination, and aging as factors that facilitated women's decision to leave sex work. At the structural level, factors which include interpersonal stigma and discrimination (from immediate family and community members), physical and sexual violence and income related factors were identified as facilitators and barriers to leaving sex work. Conclusion: Our study highlights the complex decision-making processes among WESW as they navigate transitions to alternative jobs or careers. By advocating for multifaceted interventions and policies tailored to the diverse challenges faced by WESW, our study contributes to a more informed approach to supporting their transition out of sex work.

Innovative ideas, strategies, and resources to attract students to the pharmacy profession: Report of the 2023-2024 AACP Student Affairs Committee.

Over the past 2 decades, the Academy has witnessed an increase in new colleges and schools of pharmacy and, simultaneously, a decrease in student applications, resulting in a decline in enrollment across most institutions. Although the number of students pursuing a Doctor of Pharmacy degree has been dropping, the Academy is responsible for bolstering recruitment to effectively prepare a robust pharmacy workforce to care for our ever-growing and complex patient populations. The 2023-2024 Student Affairs Committee (SAC) was convened to explore new ideas, develop innovative strategies, and gather supportive resources that can be utilized by colleges and schools of pharmacy to attract students to the pharmacy profession. The SAC was charged with developing a framework for a video mini-series that utilizes the art of storytelling to promote the pharmacy profession to prospective students. Secondarily, the SAC was charged with developing a plan to engage with students who apply but do not ultimately get accepted into nonpharmacy health professions programs and consider recommendations for targeting pharmacy technicians to pursue a PharmD degree. To accomplish this work, we created videos and proposed other innovative tools and flexible pathways to assist in recruiting students into the pharmacy profession. We also conducted a literature and website review, engaged in professional networking across the Academy, and proposed best practices to enhance student recruitment. In addition, we offered 8 recommendations to the American Association of Colleges of Pharmacy and 7 suggestions to colleges and schools of pharmacy to attract students to the pharmacy profession.

Distinct Serum Glial Fibrillary Acidic Protein and Neurofilament Light Time-Courses After Rapid Head Rotations.

Traumatic brain injury (TBI) causes significant neurophysiological deficits and is typically associated with rapid head accelerations common in sports-related incidents and automobile accidents. There are over 1.5 million TBIs in the United States each year, with children aged 0-4 being particularly vulnerable. TBI diagnosis is currently achieved through interpretation of clinical signs and symptoms and neuroimaging; however, there is increasing interest in minimally invasive fluid biomarkers to detect TBI objectively across all ages. Pre-clinical porcine models offer controlled conditions to evaluate TBI with known biomechanical conditions and without comorbidities. The objective of the current study was to establish pediatric porcine healthy reference ranges (RRs) of common human serum TBI biomarkers and to report their acute time-course after nonimpact rotational head injury. A retrospective analysis was completed to quantify biomarker concentrations in porcine serum samples collected from 4-week-old female (n = 215) and uncastrated male (n = 6) Yorkshire piglets. Subjects were assigned to one of three experimental groups (sham, sagittal-single, sagittal-multiple) or to a baseline only group. A rapid nonimpact rotational head injury model was used to produce mild-to-moderate TBI in piglets following a single rotation and moderate-to-severe TBI following multiple rotations. The Quanterix Simoa Human Neurology 4-Plex A assay was used to quantify glial fibrillary acidic protein (GFAP), neurofilament light (Nf-L), tau, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1). The 95% healthy RRs for females were calculated and validated for GFAP (6.3-69.4 pg/mL), Nf-L (9.5-67.2 pg/mL), and UCH-L1 (3.8-533.7 pg/mL). Rising early, GFAP increased significantly above the healthy RRs for sagittal-single (to 164 and 243 pg/mL) and increased significantly higher in sagittal-multiple (to 494 and 413 pg/mL) groups at 30 min and 1 h postinjury, respectively, returning to healthy RRs by 1-week postinjury. Rising later, Nf-L increased significantly above the healthy RRs by 1 day in sagittal-single (to 69 pg/mL) and sagittal-multiple groups (to 140 pg/mL) and rising further at 1 week (single = 231 pg/mL, multiple = 481 pg/mL). Sagittal-single and sagittal-multiple UCH-L1 serum samples did not differ from shams or the healthy RRs. Sex differences were observed but inconsistent. Serum GFAP and Nf-L levels had distinct time-courses following head rotations in piglets, and both corresponded to load exposure. We conclude that serum GFAP and Nf-L offer promise for early TBI diagnosis and intervention decisions for TBI and other neurological trauma.

Fibrinogen binding to histones in circulation protects against adverse cellular and clinical outcomes.

BACKGROUND: Circulating histones are released by extensive tissue injury or cell death and play important pathogenic roles in critical illnesses. Their interaction with circulating plasma components and the potential roles in the clinical setting are not fully understood. OBJECTIVES: We aimed to characterize the interaction of histones with fibrinogen and explore its roles in vitro, in vivo, and in patient samples. METHODS: Histone-fibrinogen binding was assessed by electrophoresis and enzyme-linked immunosorbent assay-based affinity assay. Functional significance was explored using washed platelets and endothelial cells in vitro and histone-infusion mouse models in vivo. To determine clinical translatability, a retrospective single-center cohort study was conducted on patients requiring intensive care admission (n = 199) and validated in a cohort of hospitalized patients with COVID-19 (n = 69). RESULTS: Fibrinogen binds histones through its D-domain with high affinity (calf thymus histones, KD = 18.0 ± 5.6 nM; histone 3, KD = 2.7 ± 0.8 nM; and histone 4, KD = 2.0 ± 0.7 nM) and significantly reduces histone-induced endothelial damage and platelet aggregation in vitro and in vivo in a histone-infusion mouse model. Physiologic concentrations of fibrinogen can neutralize low levels of circulating histones and increase the cytotoxicity threshold of histones to 50 µg/mL. In a cohort of patients requiring intensive care, a histone:fibrinogen ratio of ≥6 on admission was associated with moderate-severe thrombocytopenia and independently predicted mortality. This finding was validated in a cohort of hospitalized patients with COVID-19. CONCLUSION: Fibrinogen buffers the cytotoxic properties of circulating histones. Detection and monitoring of circulating histones and histone:fibrinogen ratios will help identify critically ill patients at highest risk of adverse outcomes who might benefit from antihistone therapy.

A Trial of Automated Outbreak Detection to Reduce Hospital Pathogen Spread.

BACKGROUND: Detection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown. METHODS: We conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods. RESULTS: Real-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92). CONCLUSIONS: Automated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

Nonfatal Emergency Department Visits Associated with Fall-Related Fractured Skulls of Infants Aged 0-4 Months.

BACKGROUND: Children aged 0-4 years have the highest rate of emergency department (ED) visits for traumatic brain injury (TBI); falls are the leading cause. Infants younger than 2 years are more likely to sustain a fractured skull after a fall. OBJECTIVE: This study examined caregiver actions and products associated with ED visits for fall-related fractured skulls in infants aged 0-4 months. METHODS: Data were analyzed from the 2001-2017 National Electronic Injury Surveillance System-All Injury Program. Case narratives of infants aged 0-4 months who visited an ED for a fall-related skull fracture were examined to code caregiver actions preceding the fall. Product codes determined fall location and product type involved (e.g., flooring, bed, or stairs). All national estimates were weighted. RESULTS: There were more than 27,000 ED visits (weighted estimate) of infants aged 0-4 months for a nonfatal fall-related fractured skull between 2001 and 2017. Most were younger than 2 months (46.7%) and male (54.4%). Falls occurred primarily in the home (69.9%) and required hospitalization (76.4%). Primary caregiver actions coded involved placing (58.6%), dropping (22.7%), and carrying an infant (16.6%). Floor surfaces were the most common product (mentioned in 24.0% of the cases). CONCLUSIONS: Fall-related fractured skulls are a health and developmental concern for infants, highlighting the importance of a comprehensive assessment at the time of the injury to better understand adult actions. Findings indicated the need to develop prevention messages that include safe carrying and placement of infants.

Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.

BACKGROUND: The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. METHODS: A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. RESULTS: A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2 ms vs. 8.9 ± 32.6 ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2 ms vs. 24.0 ± 25.1 ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (- 7.5 ± 8.7 bpm vs. - 8.5 ± 13.9 bpm vs. - 8.3 ± 13.2 bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36 days vs. 4.2 ± 1.0 days, p < 0.0001). CONCLUSION: IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias.

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

RATIONALE: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. OBJECTIVES: We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH). METHODS: We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. MEASUREMENTS AND MAIN RESULTS: Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups. CONCLUSIONS: Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03229499.

Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.

Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020). Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. Trial Registration: ClinicalTrials.gov Identifier: NCT03697096.

Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial.

Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020. Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. Trial Registration: ClinicalTrials.gov Identifier: NCT03697070.

Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.

Examining the Intrapersonal, Interpersonal and Community Level Correlates of Access to Medical Care Among Women Employed by Sex Work in Southern Uganda: A cross-sectional Analysis of the Kyaterekera Study.

Women employed by sex work (WESW) experience significant gaps in accessing necessary healthcare services, leading to unmet health needs. Yet, there is a dearth of literature on the barriers to medical care access among WESW in Uganda. We used data from the Kyaterekera baseline to examine the correlates of access to medical care among WESW, defined as the ability of individuals to obtain the necessary healthcare services they require in a timely, affordable, and equitable manner. The Kyaterekera study recruited 542 WESW aged 18-58 years from Southern Uganda. We conducted a multilevel linear regression model to determine the intrapersonal (age, education level, marital status, HIV knowledge, and asset ownership), interpersonal (family cohesion and domestic violence attitudes), and community (community satisfaction, sex work stigma and distance to health facility) level correlates of access to medical care among WESW. Intrapersonal and interpersonal factors were associated with access to medical care among WESW. There was no significant association between community level factors and access to medical care. WESW with secondary education (ß = 0.928, 95% CI = 0.007, 1.849) were associated with increased access to medical care. WESW with high asset ownership (ß = -1.154, 95% CI= -1.903, -0.405), high family cohesion (ß = -0.069, 95% CI= -0.106, -0.031), and high domestic violence attitudes (ß = -0.253, 95% CI= -0.438, -0.068) were associated with decreased access to medical care. The findings emphasize the critical need for targeted family strengthening interventions to enhance family support for WESW and address domestic violence.

Parents Report Positive Changes in Parental Feeding Practices 12 Months After Intervention.

OBJECTIVE: Determine self-reported parental feeding behavior changes and perspectives on parental feeding intervention at 12-month follow-up. METHODS: Telephone focus groups using a 2 × 2 design (English/Spanish × in-class or online) with Expanded Food and Nutrition Education Program participants (n = 37) with children 2-8 years and high exposure to the Food, Feeding, and Your Family intervention (7 lessons). Researchers (n = 3) independently identified themes. RESULTS: Parental behavior changes that (1) positively influenced children's diets, (2) involved children in food-related activities, (3) eased stressful situations around food, (4) led to healthier food choices, and (5) saved money when food shopping. Commonly implemented practices included establishing structured mealtime routines, introducing new foods multiple times, and encouraging children's eating competence. Online participants noted materials were easily accessible via text messages. CONCLUSIONS AND IMPLICATIONS: Incorporating parental feeding content (in-class or online) into nutrition education interventions, such as the Expanded Food and Nutrition Education Program, supports developing positive parental feeding behaviors in families with low income.

The impact of an economic empowerment intervention on intimate partner violence among women engaged in sex work in southern Uganda: A cluster randomized control trial.

Women engaged in sex work (WESW) are at heightened risk of experiencing intimate partner violence (IPV) compared to women in the general population. This study examines the impact of an economic empowerment intervention on IPV among WESW in Southern Uganda. We used data from 542 WESW in Southern Uganda recruited from 19 HIV hotspots between June 2019 and March 2020. Eligible participants were 18+ years old, engaged in sex work-defined as vaginal or anal sexual intercourse in exchange for money, alcohol, or other goods, reported at least one episode of unprotected sexual intercourse in the past 30 days with a paying, casual, or regular sexual partner (spouse, main partner). We analyzed data collected at baseline, 6, and 12months of follow up. To examine the impact of the intervention on IPV, separate mixed-effects logistic regression models were run for each type of IPV (physical, emotional, and sexual) as experienced by participants in the last 90 days. Results show that the intervention was efficacious in reducing emotional and physical IPV as evidenced by a statistically significant intervention main effect for emotional IPV, χ2(1) = 5.96, p = 0.015, and a significant intervention-by-time interaction effect for physical IPV, χ2(2) = 13.19, p < 0.001. To qualify the intervention impact on physical IPV, pairwise comparisons showed that participants who received the intervention had significantly lower levels of physical IPV compared to those in the control group at six months (contrasts = -0.12 (95% CI: -0.22, -0.02), p = 0.011). The intervention, time, and intervention-by-time main effects for sexual IPV were not statistically significant. Our findings suggest economic empowerment interventions as viable strategies for reducing emotional IPV among WESW. However, it is also essential to understand the role of interventions in addressing other forms of IPV especially for key populations at high risk of violence, HIV, and STI. The study was registered at ClinicalTrials.gov, ID: NCT03583541.