Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS.

PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment. MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms. RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity (P = .004). Having chronic pain conditions (P < .001), prior severe stent pain (P = .021), and depressive symptoms at baseline (P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms. CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840.

Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.

AIMS: The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. METHODS AND RESULTS: A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 µmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. CONCLUSION: The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.

Role of autophagy in skin photoaging: A narrative review.

As the largest organ of the human body, the skin serves as the primary barrier against external damage. The continuous increase in human activities and environmental pollution has resulted in the ongoing depletion of the ozone layer. Excessive exposure to ultraviolet (UV) radiation enhances the impact of external factors on the skin, leading to photoaging. Photoaging causes physical and psychological damage to the human body. The prevention and management of photoaging have attracted increased attention in recent years. Despite significant progress in understanding and mitigating UV-induced photoaging, the precise mechanisms through which autophagy contributes to the prevention of photoaging remain unclear. Given the important role of autophagy in repairing UV-induced DNA damage and scavenging oxidized lipids, autophagy is considered a novel strategy for preventing the occurrence of photoaging and other UV light-induced skin diseases. This review aims to elucidate the biochemical and clinical features of photoaging, the relationship of skin photoaging and chronological aging, the mechanisms underlying skin photoaging and autophagy, and the role of autophagy in skin photoaging.

Mobile Application-Based Communication Facilitation Platform for Family Members of Critically Ill Patients: A Randomized Clinical Trial.

Importance: Unmet and racially disparate palliative care needs are common in intensive care unit (ICU) settings. Objective: To test the effect of a primary palliative care intervention vs usual care control both overall and by family member race. Design, Setting, and Participants: This cluster randomized clinical trial was conducted at 6 adult medical and surgical ICUs in 2 academic and community hospitals in North Carolina between April 2019 and May 2022 with physician-level randomization and sequential clusters of 2 Black patient-family member dyads and 2 White patient-family member dyads enrolled under each physician. Eligible participants included consecutive patients receiving mechanical ventilation, their family members, and their attending ICU physicians. Data analysis was conducted from June 2022 to May 2023. Intervention: A mobile application (ICUconnect) that displayed family-reported needs over time and provided ICU attending physicians with automated timeline-driven communication advice on how to address individual needs. Main Outcomes and Measures: The primary outcome was change in the family-reported Needs at the End-of-Life Screening Tool (NEST; range 0-130, with higher scores reflecting greater need) score between study days 1 and 3. Secondary outcomes included family-reported quality of communication and symptoms of depression, anxiety, and posttraumatic stress disorder at 3 months. Results: A total of 111 (51% of those approached) family members (mean [SD] age, 51 [15] years; 96 women [86%]; 15 men [14%]; 47 Black family members [42%]; 64 White family members [58%]) and 111 patients (mean [SD] age, 55 [16] years; 66 male patients [59%]; 45 Black patients [41%]; 65 White patients [59%]; 1 American Indian or Alaska Native patient [1%]) were enrolled under 37 physicians randomized to intervention (19 physicians and 55 patient-family member dyads) or control (18 physicians and 56 patient-family member dyads). Compared with control, there was greater improvement in NEST scores among intervention recipients between baseline and both day 3 (estimated mean difference, -6.6 points; 95% CI, -11.9 to -1.3 points; P = .01) and day 7 (estimated mean difference, -5.4 points; 95% CI, -10.7 to 0.0 points; P = .05). There were no treatment group differences at 3 months in psychological distress symptoms. White family members experienced a greater reduction in NEST scores compared with Black family members at day 3 (estimated mean difference, -12.5 points; 95% CI, -18.9 to -6.1 points; P < .001 vs estimated mean difference, -0.3 points; 95% CI, -9.3 to 8.8 points; P = .96) and day 7 (estimated mean difference, -9.5 points; 95% CI, -16.1 to -3.0 points; P = .005 vs estimated mean difference, -1.4 points; 95% CI, -10.7 to 7.8; P = .76). Conclusions and Relevance: In this study of ICU patients and family members, a primary palliative care intervention using a mobile application reduced unmet palliative care needs compared with usual care without an effect on psychological distress symptoms at 3 months; there was a greater intervention effect among White family members compared with Black family members. These findings suggest that a mobile application-based intervention is a promising primary palliative care intervention for ICU clinicians that directly addresses the limited supply of palliative care specialists. Trial Registration: ClinicalTrials.gov Identifier: NCT03506438.

Design and pilot test of an implicit bias mitigation curriculum for clinicians.

Introduction: Clinician implicit racial bias (IB) may lead to lower quality care and adverse health outcomes for Black patients. Educational efforts to train clinicians to mitigate IB vary widely and have insufficient evidence of impact. We developed and pilot-tested an evidence-based clinician IB curriculum, "REACHing Equity." Methods: To assess acceptability and feasibility, we conducted an uncontrolled one-arm pilot trial with post-intervention assessments. REACHing Equity is designed for clinicians to: (1) acquire knowledge about IB and its impact on healthcare, (2) increase awareness of one's own capacity for IB, and (3) develop skills to mitigate IB in the clinical encounter. We delivered REACHing Equity virtually in three facilitated, interactive sessions over 7-9 weeks. Participants were health care providers who completed baseline and end-of-study evaluation surveys. Results: Of approximately 1,592 clinicians invited, 37 participated, of whom 29 self-identified as women and 24 as non-Hispanic White. Attendance averaged 90% per session; 78% attended all 3 sessions. Response rate for evaluation surveys was 67%. Most respondents agreed or strongly agreed that the curriculum objectives were met, and that REACHing Equity equipped them to mitigate the impact of implicit bias in clinical care. Participants consistently reported higher self-efficacy for mitigating IB after compared to before completing the curriculum. Conclusions: Despite apparent barriers to clinician participation, we demonstrated feasibility and acceptability of the REACHing Equity intervention. Further research is needed to develop objective measures of uptake and clinician skill, test the impact of REACHing Equity on clinically relevant outcomes, and refine the curriculum for uptake and dissemination.ClinicalTrials.gov ID: NCT03415308.

Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial.

BACKGROUND: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. METHODS: ARISTOTLE was a double-blind, randomised trial that enrolled 18,201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2·0-3·0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. FINDINGS: Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or ≥3, p for interaction=0·4457; or CHA(2)DS(2)VASc 1, 2, or ≥3, p for interaction=0·1210) or bleeding (HAS-BLED 0-1, 2, or ≥3, p for interaction=0·9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0·4018; CHA(2)DS(2)VASc, p for interaction=0·2059; HAS-BLED, p for interaction=0·7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0·22, 95% CI 0·10-0·48) than in those with HAS-BLED scores of 0-1 (HR 0·66, 0·39-1·12; p for interaction=0·0604). INTERPRETATION: Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events. FUNDING: Bristol-Myers Squibb and Pfizer.

Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.

BACKGROUND: Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. METHODS AND RESULTS: Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). CONCLUSION: The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.

Effect of a Coaching Intervention to Improve Cardiologist Communication: A Randomized Clinical Trial.

Importance: Communication between cardiologists and patients can significantly affect patient comprehension, adherence, and satisfaction. To our knowledge, a coaching intervention to improve cardiologist communication has not been tested. Objective: To evaluate the effect of a communication coaching intervention to teach evidence-based communication skills to cardiologists. Design, Setting, and Participants: This 2-arm randomized clinical trial was performed at outpatient cardiology clinics at an academic medical center and affiliated community clinics, and from February 2019 through March 2020 recruited 40 cardiologists and audio recorded 161 patients in the preintervention phase and 240 in the postintervention phase. Data analysis was performed from March 2022 to January 2023. Interventions: Half of the cardiologists were randomized to receive a coaching intervention that involved three 1:1 sessions, 2 of which included feedback on their audio-recorded encounters. Communication coaches taught 5 skills derived from motivational interviewing: (1) sitting down and making eye contact with all in the room, (2) open-ended questions, (3) reflective statements, (4) empathic statements, and (5) "What questions do you have?" Main Outcomes and Measures: Coders unaware of study arm coded these behaviors in the preintervention and postintervention audio-recorded encounters (objective communication). Patients completed a survey after the visit to report perceptions of communication quality (subjective communication). Results: Analysis included 40 cardiologists (mean [SD] age, 47 [9] years; 7 female and 33 male) and 240 patients in the postintervention phase (mean [SD] age, 58 [15] years; 122 female, 118 male). When controlling for preintervention behaviors, cardiologists in the intervention vs control arm were more likely to make empathic statements (intervention: 52 of 117 [44%] vs control: 31 of 113 [27%]; P = .05); to ask, "What questions do you have?" (26 of 117 [22%] vs 6 of 113 [5%]; P = .002); and to respond with empathy when patients expressed negative emotions (mean ratio of empathic responses to empathic opportunities, 0.50 vs 0.20; P = .004). These effects did not vary based on patient or cardiologist race or sex. We found no arm differences for open-ended questions or reflective statements and were unable to assess differences in patient ratings due to ceiling effects. Conclusions and Relevance: In this randomized clinical trial, a communication coaching intervention improved 2 key communication behaviors: expressing empathy and eliciting questions. Empathic communication is a harder-level skill that may improve the patient experience and information comprehension. Future work should explore how best to assess the effect of communication coaching on patient perceptions of care and clinical outcomes and determine its effectiveness in larger, more diverse samples of cardiologists. Trial Registration: ClinicalTrials.gov Identifier: NCT03464110.

Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study.

BACKGROUND: Growing evidence indicates that anhedonia is a multifaceted construct. This study examined the possibility of identifying subgroups of people with anhedonia using multiple reward-related measures to provide greater understanding the Research Domain Criteria's Positive Valence Systems Domain and pathways for developing treatments. METHODS: Latent profile analysis of baseline data from a study that examined the effects of a novel kappa opioid receptor (KOR) antagonist drug on measures and biomarkers associated with anhedonia was used to identify subgroups. Measures included ventral striatal activation during the Monetary Incentive Delay task, response bias in the Probabilistic Reward Task, reward valuation scores from the Effort-Expenditure for Rewards Task, and scores from reward-related self-report measures. RESULTS: Two subgroups were identified, which differed on self-report measures of reward. Participants in the subgroup reporting more anhedonia also reported more depression and had greater illness severity and functional impairments. Graphs of change with treatment showed a trend for the less severe subgroup to demonstrate higher response to KOR antagonist treatment on the neuroimaging measure, probabilistic reward task, and ratings of functioning; the subgroup with greater severity showed a trend for higher treatment response on reward-related self-report measures. LIMITATIONS: The main limitations include the small sample size and exploratory nature of analyses. CONCLUSIONS: Evidence of possible dissociation between self-reported measures of anhedonia and other measures with respect to treatment response emerged. These results highlight the importance for future research to consider severity of self-reported reward-related deficits and how the relationship across measurement methods may vary with severity.

SOX9 in Keratinocytes Regulates Claudin 2 Transcription during Skin Aging.

In order to prove that SOX9 in keratinocytes regulates claudin 2 transcription during skin aging, the skin of 8-week-old and 24-month-old mice is sequenced to obtain a differentially expressed gene SOX9. The gene is mainly expressed in keratinocytes, and it increases first and then decreases from newborn to aging. Six core sequences of SOX9 and claudin 2 are predicted from Jaspar. The double Luciferase Report shows that overexpression of SOX9 induces the full-length promoter of claudin 2 significantly and has no effect on the mutation and cleavage plasmid without SOX9 response. Claudin 2 is consistent with SOX9 in the skin of mice of different ages, and SOX9 is strongly positively correlated with claudin 2. Finally, overexpression of SOX9 and claudin 2 will delay PM2.5-induced keratinocyte senescence. The silencing of claudin 2 leads to the loss of SOX9 function. It is clearly evident that SOX9 can affect the transcription of claudin 2, which increases first and then decreases in the process of mice from newborn to aging. SOX9 inhibits proinflammatory mediators, increases antioxidant capacity, and restores keratin differentiation. It can effectively prevent melanin deposition and delay aging.

Licorice zinc suppresses melanogenesis via inhibiting the activation of P38MAPK and JNK signaling pathway in C57BL/6J mice skin.

PURPOSE: The active melanocytes in the skin were affected by hormones and ultraviolet (UV) irradiation. Licorice zinc has a whitening effect, which may have a prominent potential in the treatment of pigmented skin disease. METHODS: Modeling chloasma C57BL/6J mice by daily progesterone injection (15 mg/kg) and ultraviolet B (UVB) irradiation (λ = 312 nm, 2 h/day) for 30 days. Then, mice were given 0.65, 1.3, and 2.6 (g/kg) of licorice zinc and tranexamic acid 250 mg daily by oral administration for 14 days, respectively. Hematoxylin and eosin and Fontana-Masson staining, and Western blotting (WB) were performed to test the inhibitory of melanogenesis and activation of c-Jun-N-terminal (JNK)/p38 mitogen-activated protein kinases (MAPK) for licorice zinc. Melanogenesis was induced by α-melanocyte-stimulating hormone in vitro. Cell counting kit-8, melanin content determination, and WB were performed to verify the inhibitory effect of licorice zinc on melanogenesis. RESULTS: The present study showed that licorice zinc decreased melanin formation, cutaneous tissue injury, and the phosphorylation of JNK and P38MAPK, which was caused by UVB irradiation in vivo. In vitro, licorice zinc showed opposite effects from JNK/p38 activator. Meanwhile, tyrosinase-related protein-1, tyrosinase, and microphthalmia-associated transcription factor were decreased too. CONCLUSIONS: Licorice zinc induced a decrease in melanin synthesis by inhibiting the JNK and the P38MAPK signaling pathway, suggesting licorice zinc is a potential agent of anti-chloasma.

Insight into the ecology of vaginal bacteria through integrative analyses of metagenomic and metatranscriptomic data.

BACKGROUND: Vaginal bacterial communities dominated by Lactobacillus species are associated with a reduced risk of various adverse health outcomes. However, somewhat unexpectedly, many healthy women have microbiota that are not dominated by lactobacilli. To determine the factors that drive vaginal community composition we characterized the genetic composition and transcriptional activities of vaginal microbiota in healthy women. RESULTS: We demonstrate that the abundance of a species is not always indicative of its transcriptional activity and that impending changes in community composition can be predicted from metatranscriptomic data. Functional comparisons highlight differences in the metabolic activities of these communities, notably in their degradation of host produced mucin but not glycogen. Degradation of mucin by communities not dominated by Lactobacillus may play a role in their association with adverse health outcomes. Finally, we show that the transcriptional activities of L. crispatus, L. iners, and Gardnerella vaginalis vary with the taxonomic composition of the communities in which they reside. Notably, L. iners and G. vaginalis both demonstrate lower expression of their cholesterol-dependent cytolysins when co-resident with Lactobacillus spp. and higher expression when co-resident with other facultative and obligate anaerobes. The pathogenic potential of these species may depend on the communities in which they reside and thus could be modulated by interventional strategies. CONCLUSIONS: Our results provide insight to the functional ecology of the vaginal microbiota, demonstrate the diagnostic potential of metatranscriptomic data, and reveal strategies for the management of these ecosystems.

Examining the relationship between clinician communication and patient participatory behaviors in cardiology encounters.

OBJECTIVES: Examine the association of coder ratings of cardiologist behaviors and global scores of cardiologist communication style with patient participation in clinic encounters. METHODS: We coded transcripts of clinic encounters for patient participatory behaviors: asking questions, assertive statements, and expressing negative emotions; clinician behavior counts: reflective statements, open-ended questions, empathic statements, and eliciting questions. We used general linear regression models to examine associations of mean number of patient participatory behaviors with clinician behaviors. RESULTS: Our sample included 161 patients of 40 cardiologists. Patient female gender was associated with on average 2.1 (CI: 0.06, 4.1; p = 0.04) more patient participatory behaviors. In an adjusted model, clinician reflective statements were associated with on average 0.3 (CI: 0.04, 0.4; p = 0.02) more patient participatory behaviors. A clinician making at least one empathic statement was associated with on average 3.7 (CI: 0.2, 7.1; p = 0.04) more patient participatory behaviors. CONCLUSIONS: These results demonstrate that some individual clinician behaviors are associated with higher patient participation in cardiology encounters. PRACTICE IMPLICATIONS: Clinician reflective and empathic statements may be important targets in communication training to increase patient participation. SECTION: Communication Studies.

Characteristics Associated with Burnout among Cardiologists in an Academic Medical Setting: Baseline Survey Results from a Communication Coaching RCT.

OBJECTIVES: Clinician burnout poses risks not just to clinicians but also to patients and the health system. Cardiologists might be especially prone to burnout due to performing high-risk procedures, having to discuss serious news, and treating diseases that incur significant morbidity and mortality. Few have attempted to examine which cardiologists might be at higher risk of burnout. Knowing at-risk cardiologists can help frame resilience interventions. METHODS: We enrolled 41 cardiologists across five ambulatory cardiology clinics into a randomized controlled trial where we assessed the Maslach Burnout Inventory at baseline. We used bivariate analyses to assess associations between cardiologist demographics and burnout. RESULTS: Cardiologists reported low burnout for depersonalization and personal accomplishment and moderate levels for emotional exhaustion. Female cardiologists reported emotional exhaustion scores in the "low" range (M = 12.3; SD = 10.06), compared to male cardiologists whose score was in the "moderate" range 19.6 (SD = 9.59; p = 0.113). Cardiologists who had greater than 15 years in practice reported higher mean scores of emotional exhaustion, indicating moderate burnout (M = 20.0, SD = 10.63), compared to those with less than 15 years in practice (M = 16.6, SD = 9.10; p = 0.271). CONCLUSIONS: In this sample, unlike prior studies, male cardiologists reported more burnout. Consistent with prior work, mid-level cardiologists might be at highest risk of emotional exhaustion.

Highly Specialized Carbohydrate Metabolism Capability in Bifidobacterium Strains Associated with Intestinal Barrier Maturation in Early Preterm Infants.

"Leaky gut," or high intestinal barrier permeability, is common in preterm newborns. The role of the microbiota in this process remains largely uncharacterized. We employed both short- and long-read sequencing of the 16S rRNA gene and metagenomes to characterize the intestinal microbiome of a longitudinal cohort of 113 preterm infants born between 240/7 and 326/7 weeks of gestation. Enabled by enhanced taxonomic resolution, we found that a significantly increased abundance of Bifidobacterium breve and a diet rich in mother's breastmilk were associated with intestinal barrier maturation during the first week of life. We combined these factors using genome-resolved metagenomics and identified a highly specialized genetic capability of the Bifidobacterium strains to assimilate human milk oligosaccharides and host-derived glycoproteins. Our study proposes mechanistic roles of breastmilk feeding and intestinal microbial colonization in postnatal intestinal barrier maturation; these observations are critical toward advancing therapeutics to prevent and treat hyperpermeable gut-associated conditions, including necrotizing enterocolitis (NEC). IMPORTANCE Despite improvements in neonatal intensive care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality. "Leaky gut," or intestinal barrier immaturity with elevated intestinal permeability, is the proximate cause of susceptibility to NEC. Early detection and intervention to prevent leaky gut in "at-risk" preterm neonates are critical for decreasing the risk of potentially life-threatening complications like NEC. However, the complex interactions between the developing gut microbial community, nutrition, and intestinal barrier function remain largely uncharacterized. In this study, we reveal the critical role of a sufficient breastmilk feeding volume and the specialized carbohydrate metabolism capability of Bifidobacterium in the coordinated postnatal improvement of the intestinal barrier. Determining the clinical and microbial biomarkers that drive the intestinal developmental disparity will inform early detection and novel therapeutic strategies to promote appropriate intestinal barrier maturation and prevent NEC and other adverse health conditions in preterm infants.

Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor.

An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. Anti-Xa activity, determined by either anti-Xa-LMWH (r = 0.9671; P < 0.0001) or anti-Xa-apixaban (r = 0.9669; P < 0.0001) correlated strongly and in a linear fashion with apixaban plasma concentrations. The correlations for each method were equally strong at low (<100 ng/ml) (r = 0.86, P < 0.0001; r = 0.85, P < 0.0001), intermediate(100-200 ng/ml) (r = 0.73, P < 0.0001; r = 0.69, P < 0.0001) and high (>200 ng/ml) (r = 0.91, P < 0.0001; r = 0.91, P < 0.0001) plasma concentrations of apixaban, respectively. Our pharmacokinetic and pharmacodynamic substudy suggests that an apixaban-mediated anticoagulant effect can be detected even at very low plasma concentrations using a standard laboratory chromogenic anti-Xa assay with either LMWH or apixaban calibrators. While establishing parameters for safety and efficacy will require further investigation, an ability to discern the presence of a drug effect may provide clinically useful information.

Heparin-associated anti-Xa activity and platelet-derived prothrombotic and proinflammatory biomarkers in moderate to high-risk patients with acute coronary syndrome.

Heparin compounds, to include fractionated and unfractionated preparations, exert both antithrombotic and antiinflammatory effects through combined inhibition of factor Xa and thrombin. The contribution of modulated platelet activity in vivo is less clearly defined. The SYNERGY library was a prospectively designed repository for candidate clinical, hemostatic, platelet, and molecular biomarkers from patients participating in SYNERGY--a large-scale, randomized clinical trial evaluating the comparative benefits of unfractionated heparin (UFH) and enoxaparin in high-risk patients with acute coronary syndrome (ACS). Samples were collected from 201 patients enrolled at 26 experienced, participating sites and shipped to established core laboratories for analysis of platelet, endothelium-derived, inflammatory and coagulation activity biomarkers. Tissue factor pathway inhibitor (TFPI)--a vascular endothelial cell-derived factor Xa regulatory protein-correlated directly with plasma anti-Xa activity (unadjusted: r = 0.23, P < 0.0001; adjusted: ß = 0.10; P = 0.001), as did TFPI-fXa complexes (unadjusted: r = 0.34, P < 0.0001; adjusted: ß = 0.38; P = < 0.0001). In contrast, there was a direct and inverse relationship between anti-Xa activity and two platelet-derived biomarkers-plasminogen activator inhibitor-1 (unadjusted: r = -0.18, P = 0.0012; adjusted: ß = -0.10; P = 0.021) and soluble CD40 ligand (unadjusted: r = -0.11, P = 0.05; adjusted: ß = -0.13; P = 0.049). All measured analyte relationships persisted after adjustment for age, creatinine clearance, weight, sex, and duration of treatment. Differences in biomarkers between patients receiving UFH and those randomized to enoxaparin were not observed. The ability of heparin compounds to affect the prothrombotic and proinflammatory states which characterize ACS may involve factor Xa-related modulation of platelet activation and expression. Whether this potentially beneficial effect is direct or indirect and achieved, at least in part, through the release of endothelial cell-derived coagulation regulatory proteins will require further investigation.