Perspectives of US Medical Residency and Fellowship Applicants on No-Stakes Campus Visits.

Background Virtual interviews may limit an applicant's ability to ascertain the culture of a training program. No-stakes campus visits (NSCVs) have been offered but their value is unknown. Objective The purpose of our study was to determine factors that influence applicants' rank lists and determine barriers to and perceptions of NSCVs and their impact on applicants' final rank lists. Methods All interviewed applicants of graduate medical education (GME) programs who agreed to participate in the study were emailed a survey after the 2023 National Resident Matching Program Match. The survey contained sections on demographics, perspectives on factors affecting ranking decisions, and perceptions of NSCVs. Results Of 796 applicants, 183 (22.9%) who interviewed at 16 different Mayo Clinic GME programs responded to the survey. Of 131 respondents who answered whether they accepted an NSCV offer, 39 (29.8%) accepted. Of 35 respondents who answered whether they thought attending NSCVs impacted their rank, 19 (54.3%) were either uncertain or said yes. Of 34 respondents who answered whether the NSCV influenced their ranking of the program, 16 (47.1%) said their rank did not change, 12 (35.3%) said they ranked the program higher, and 5 (14.7%) said they ranked the program lower. For respondents who did not attend NSCVs, financial burden and lack of time were primary reasons. Conclusions NSCVs are perceived positively by most respondents. Many either believed they influenced their position on the program's rank list or were unsure. Most respondents said NSCVs either improved or did not change their ranking of the program.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Noninfectious Ascites Neutrophilia in a Patient With Polycythemia Vera.

A 59-year-old woman with polycythemia vera-related portal hypertension requiring frequent paracentesis was admitted for asymptomatic recurrent spontaneous bacterial peritonitis, which was diagnosed based on elevated polymorphonuclear (PMN) count. She had multiple similar admissions during which she was treated with antibiotics. The patient had chronic baseline leukocytosis due to polycythemia vera. Repeat paracentesis after intravenous antibiotics demonstrated persistent elevation of PMN count without clinical symptoms. A multidisciplinary team concluded that the increased PMN count was secondary to polycythemia. The patient was diagnosed with omental extramedullary hematopoiesis, a rare condition causing elevated PMN count in the absence of bacterial contamination.

A Flipped Classroom Pilot in Neonatal Mechanical Ventilation.

Background: Pediatric residents frequently manage critically ill neonates but have limited systematic training in mechanical ventilation (MV). Competing demands, varying learner levels, and topic complexity contribute to inconsistent education. A blended learning approach may be ideally suited to achieve meaningful learning but has not been described for this topic and learner. Objective: To design, implement, and evaluate a flipped classroom for pediatric residents in neonatal MV. Methods: We used Kern's six-step framework for curricular development to create a flipped classroom curriculum in neonatal MV. Individual prework included interaction with six prerecorded animated whiteboard videos, while in-person learning occurred in small groups at the bedside of a ventilated infant. A mixed-methods evaluation included surveys, quantitative knowledge test scores (before, immediately after, and six months after course completion), and qualitative analysis of participant focus groups. Results: Twenty-six learners participated in the curriculum. Mean knowledge test scores rose and were sustained after course completion (51% baseline, 82% immediate posttest, 90% retention; P < 0.001). Learners identified various design elements, technology affordances, and instructor factors as meaningful, and they identified unexpected impacts of the curriculum beyond knowledge acquisition, including effects on professional identities, interdisciplinary communication skills, and contribution to the culture of safety. Conclusion: This curriculum aligned with resident roles, was meaningful to learners, and led to long-term increases in knowledge scores and access to quality education; flipped classroom design using meaningful learning theory and leveraging animated whiteboard technology may be a useful strategy for other highly complex topics in graduate medical education.

Impact of an Online Program of Bubble Continuous Positive Airway Pressure Education in a Resource-Constrained Setting.

Background: Respiratory distress is a leading cause of preterm infant mortality in sub-Saharan Africa. Bubble continuous positive airway pressure (CPAP) is emerging as a potentially safe, cost-effective way of delivering noninvasive respiratory support in low-income and middle-income countries. However, without healthcare providers who are knowledgeable and skilled in the use of this technology, suboptimal neonatal care and related health disparities are likely to persist. Objective: We hypothesized that an Internet-based, blended curriculum on bubble CPAP for bedside providers in low-resource mother-baby units (MBUs) could be developed and implemented and lead to improvements in clinical knowledge, reasoning, and learner confidence in bubble CPAP. Methods: Clinical educators from Israel, Ghana, and the United States used the analysis, design, development, implementation, and evaluation (ADDIE) design framework to create an online curriculum for two MBUs in Kumasi, in the Ashanti Region of Ghana. Participants completed pre and post curriculum knowledge tests and completed surveys on their perspectives. Results: Fifty-four interdisciplinary health professionals from the MBUs participated in the curriculum. Median knowledge test scores improved from 64% (interquartile range [IQR] = 50-72%) to 81% (IQR = 71-89%) after participation in the curriculum (P < 0.001). Learners reported high levels of confidence with bubble CPAP after participating in the curriculum and evaluated the curricular components highly. Conclusion: An online curriculum was successfully implemented and led to changes in healthcare worker knowledge in bubble CPAP. This may be an effective way to deliver education to healthcare professionals in resource-constrained countries and warrants further study.

Poor Neonatal Adaptation After Antidepressant Exposure During the Third Trimester in a Geographically Defined Cohort.

Objective: To examine the associations between antidepressant exposure during the third trimester of pregnancy, including individual drugs, drug doses, and antidepressant combinations, and the risk of poor neonatal adaptation (PNA). Patients and Methods: The Rochester Epidemiology Project medical records-linkage system was used to study infants exposed to selective serotonin reuptake inhibitors (SSRIs; n=1014), bupropion, (n=118), serotonin-norepinephrine reuptake inhibitors (n=80), antidepressant combinations (n=20), or other antidepressants (n=22) during the third trimester (April 11, 2000-December 31, 2013). Poor neonatal adaptation was defined based on a review of medical records. Poisson regression was used to examine the risk of PNA with serotonergic antidepressant and drug combinations compared with that with bupropion monotherapy as well as with high- vs standard-dose antidepressants. When possible, analyses were performed using propensity score (PS) weighting. Results: Forty-four infants were confirmed cases of PNA. Serotonin-norepinephrine reuptake inhibitor monotherapy, antidepressant combinations, and paroxetine monotherapy were associated with a significantly higher risk of PNA than bupropion monotherapy in unweighted analyses. High-dose SSRI exposure was associated with a significantly increased risk of PNA in unadjusted (relative risk, 2.61; 95% confidence interval, 1.35-5.04) and PS-weighted models (relative risk, 2.29; 95% confidence interval, 1.17-4.48) compared with standard-dose SSRI exposure. The risk of PNA was significantly higher with high-dose paroxetine and sertraline than with standard doses in the PS-weighted analyses. The other risk factors for PNA included maternal anxiety disorders. Conclusion: Although the frequency of PNA in this cohort was low (3%-4%), the risk of PNA was increased in infants exposed to serotonergic antidepressants, particularly with SSRIs at higher doses, during the third trimester of pregnancy compared with that in infants exposed to standard doses. Potential risk factors for PNA also included third-trimester use of paroxetine (especially at higher doses) and maternal anxiety.

Evaluation of the Impact of Ritlecitinib on Organic Cation Transporters Using Sumatriptan and Biomarkers as Probes.

Ritlecitinib, an inhibitor of Janus kinase 3 and hepatocellular carcinoma family kinases, is in development as potential treatment for several inflammatory diseases. In vitro studies presented ritlecitinib as an inhibitor of hepatic organic cation transporter (OCT) 1, renal transporters OCT2 and multidrug and toxin extrusion (MATE) proteins 1/2K using multiple substrates, and ritlecitinib's major inactive metabolite M2, as an inhibitor of OCT1. A clinical interaction study with an OCT1 drug probe (sumatriptan) and relevant probe biomarkers for OCT/MATE was conducted to assess the effect of ritlecitinib on these transporters in healthy adult participants. The selectivity of sumatriptan for OCT1 was confirmed through a series of in vitro uptake assays. A simple static model was used to help contextualize the observed changes in sumatriptan area under the plasma concentration-time curve (AUC). Coadministration of a single 400-mg dose of ritlecitinib increased sumatriptan AUC from time 0 to infinity (AUCinf ) by ≈30% relative to a single 25-mg sumatriptan administration alone. When administered 8 hours after a ritlecitinib dose, sumatriptan AUCinf increased by ≈50% relative to sumatriptan given alone. Consistent with OCT1 inhibition, the AUC from time 0 to 24 hours of isobutyryl-L-carnitine decreased by ≈15% after ritlecitinib. Based on the evaluation of the renal clearance of N1 -methylnicotinamide, ritlecitinib does not exert clinically meaningful inhibition on renal OCT2 or MATE1/2K. This study confirmed that ritlecitinib and M2 are inhibitors of OCT1 but not OCT2 or MATE1/2K in healthy adults.

Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Natural History Study.

OBJECTIVE: We characterize the most recent natural history of necrotizing enterocolitis (NEC), as this is an essential first step in guiding the prevention and treatment of this disease in the present day. STUDY DESIGN: We performed a retrospective cohort study of neonates who were born at 23 to 29 weeks' gestation and birth weight <1,500 g who received care from the Pediatrix Medical Group between 2004 and 2019. We assessed the incidence of medical and surgical NEC and the patterns of initial antibiotic treatment to develop a contemporary cohort for further analysis. Among patients discharged between 2015 and 2019, we characterized the stage-specific risk factors for patients diagnosed with medical or surgical NEC, as well as patterns of disease onset, progression, biomarkers, and outcomes. We used the same approach to characterize patients diagnosed with suspected NEC. RESULTS: Among 34,032 patients in the contemporary cohort, 1,150 (3.4%) were diagnosed with medical NEC and 543 (1.6%) were diagnosed with surgical NEC. The temporal pattern of disease onset was different for medical and surgical NEC, with gestational age- and birth weight-specific risk disparities emerging earlier in surgical NEC. Thirty-day mortality was much greater among surgical NEC patients (medical NEC 16.4% vs. surgical NEC 43.0%), as were rates of various in-hospital and long-term outcomes. Suspected NEC was diagnosed in 1,256 (3.7%) patients, among whom risk factors and disease onset, progression, and outcomes closely resembled those of medical NEC. CONCLUSION: Analyzing data from a contemporary cohort enabled us to characterize the current, stage-specific natural history of NEC, including novel insights into suspected NEC. Future studies could leverage this cohort to characterize how specific patient characteristics, care processes, or biomarkers may influence or predict disease outcomes. KEY POINTS: · The incidence of NEC has reached a stable baseline in recent years.. · Risk factors for NEC vary in a stage-specific manner.. · The stage-specific onset and progression of NEC differ by gestational age and birth weight..

Automated Microfluidic System with Active Mixing Enables Rapid Analysis of Biomarkers in 5 µL of Whole Blood.

We developed a microfluidic device for the rapid analysis of biomarkers in small volumes of whole blood. This device includes an onboard plasma separation module connected to a downstream bioanalysis module in which plasma mixes with reagents and the results of a colorimetric assay are recorded. Actuation of onboard microvalves within a bioanalysis module creates active mixing conditions that allowed us to achieve solution homogeneity within 5 min. To demonstrate utility, we carried out glucose detection in our device. With 5 µL of whole blood as an input, our microfluidic device enabled a time-to-answer of 10 min with a limit of detection of 0.21 ± 0.04 mM for glucose. This device has immediate applications for rapid and sensitive monitoring of hypoglycemia at the point of care (POC). Furthermore, our automated microfluidic device represents a platform technology that may be used to detect other biomarkers in whole blood.

Exploring planet geology through force-feedback telemanipulation from orbit.

Current space exploration roadmaps envision exploring the surface geology of celestial bodies with robots for both scientific research and in situ resource utilization. In such unstructured, poorly lit, complex, and remote environments, automation is not always possible, and some tasks, such as geological sampling, require direct teleoperation aided by force-feedback (FF). The operator would be on an orbiting spacecraft, and poor bandwidth, high latency, and packet loss from orbit to ground mean that safe, stable, and transparent interaction is a substantial technical challenge. For this scenario, a control method was developed that ensures stability at high delay without reduction in speed or loss of positioning accuracy. At the same time, a new level of safety is achieved not only through FF itself but also through an intrinsic property of the approach preventing hard impacts. On the basis of this method, a tele-exploration scenario was simulated in the Analog-1 experiment with an astronaut on the International Space Station (ISS) using a 6-degree-of-freedom (DoF) FF capable haptic input device to control a mobile robot with manipulator on Earth to collect rock samples. The 6-DoF FF telemanipulation from space was performed at a round-trip communication delay constantly between 770 and 850 milliseconds and an average packet loss of 1.27%. This experiment showcases the feasibility of a complete space exploration scenario via haptic telemanipulation under spaceflight conditions. The results underline the benefits of this control method for safe and accurate interactions and of haptic feedback in general.

Impact of Cirrhotic Cardiomyopathy Diagnosed According to Different Criteria on Patients with Cirrhosis Awaiting Liver Transplantation: A Retrospective Cohort Study.

BACKGROUND: Recently, the Cirrhotic Cardiomyopathy Consortium (Consortium) proposed criteria to replace the World Congress of Gastroenterology (WGO) criteria for cirrhotic cardiomyopathy (CCM) using contemporary echocardiography parameters. We assessed the impact of substituting WGO by Consortium criteria on the frequency of diagnosis and clinical outcomes in patients with cirrhosis awaiting liver transplantation (LT). METHODS: Consecutive adults with cirrhosis approved for LT with echocardiography evaluation from January 2014 to December 2016 were screened. Patients with structural heart diseases were excluded. Two primary outcomes were: (1) frequency of CCM; (2) association of CCM with pre-transplant mortality. The secondary outcomes were pre-LT complications of acute kidney injury (AKI) and/or hepatic encephalopathy (HE), and post-LT mortality. RESULTS: Of 386 patients screened, 278 were included. 238 (85.6%) and 208 (74.8%) patients met Consortium and WGO criteria, respectively; 180 (64.7%) patients fulfilled both the criteria, while 12 (4.3%) patients had no evidence of CCM by either criterion. Pre-LT mortality rates in Consortium-CCM group were similar to the other groups (19.3% vs 20.2% vs 25.0%). The patients with advanced diastolic dysfunction (DD) per Consortium-CCM criteria had higher mortality than the other groups. The rates of pre-LT AKI/HE rates and post-LT mortality were similar in Consortium-CCM and WGO-CCM groups. CONCLUSION: The Consortium criteria do not impact the prevalence of CCM compared to WGO criteria and have similar predictive accuracy. Presence of advanced DD per the Consortium criteria increases the risk of pre-LT mortality and complications of AKI/HE. The patients with advanced DD could benefit from further monitoring and treatment.

Mortality Risk Factors among Infants Receiving Dialysis in the Neonatal Intensive Care Unit.

OBJECTIVES: To identify risk factors associated with mortality for infants receiving dialysis in the neonatal intensive care unit (NICU). STUDY DESIGN: In this retrospective cohort study, we extracted data from the Pediatrix Clinical Data Warehouse on all infants who received dialysis in the NICU from 1999 to 2018. Using a Cox proportional hazards model with robust SEs we estimated the mortality hazard ratios associated with demographics, birth details, medical complications, and treatment exposures. RESULTS: We identified 273 infants who received dialysis. Median gestational age at birth was 35 weeks (interquartile values 33-37), median birth weight was 2570 g (2000-3084), 8% were small for gestational age, 41% white, and 72% male. Over one-half of the infants (59%) had a kidney anomaly; 71 (26%) infants died before NICU hospital discharge. Factors associated with increased risk of dying after dialysis initiation included lack of kidney anomalies, Black race, gestational age of <32 weeks, necrotizing enterocolitis, dialysis within 7 days of life, and receipt of paralytics or vasopressors (all P < .05). CONCLUSION: In this cohort of infants who received dialysis in the NICU over 2 decades, more than 70% of infants survived. The probability of death was greater among infants without a history of a kidney anomaly and those with risk factors consistent with greater severity of illness at dialysis initiation.

Predictors of survival in portopulmonary hypertension: a 20-year experience.

BACKGROUND AND OBJECTIVES: Portopulmonary hypertension (PoPH) is a rare complication of portal hypertension associated with poor survival. Scarce data is available on predictors of survival in PoPH with conflicting results. We sought to characterize the outcomes and variables associated with survival in a large cohort of patients with PoPH in an American population of patients. STUDY DESIGN AND METHODS: We identified PoPH patients from the Cleveland Clinic Pulmonary Hypertension Registry between 1998 and 2019. We collected prespecified data, particularly focusing on hepatic and cardiopulmonary assessments and tested their effect on long-term survival. RESULTS: Eighty patients with PoPH with a mean ± SD age of 54 ± 10 years, (54% females) were included in the analysis. The median Model for End-Stage Liver Disease with sodium (MELD-Na) score was 13.0 (10.0-18.0) at PoPH diagnosis. World Health Association functional class III-IV was noted in 57%. Mean pulmonary arterial pressure was 47 ± 10 mmHg and pulmonary vascular resistance 6.0 ± 2.8 Woods units. A total of 63 (78.5%) patients were started on pulmonary arterial hypertension (PAH)-specific treatment during the first 6 months of diagnosis. Survival rates at 1-, 3- and 5-year were 77, 52 and 34%, respectively. Cardiopulmonary hemodynamics as well as PAH-specific treatment did not affect survival. In the multivariable model, MELD-Na, resting heart rate and the presence of hepatic encephalopathy were independent predictors of survival. CONCLUSION: PoPH patients have poor 5-year survival which is strongly associated to the severity of underlying liver disease and not to the hemodynamic severity of PoPH; therefore efforts should be focused in facilitating liver transplantation for these patients.

Training fellows in neonatal tele-resuscitation using a simulation-based mastery learning model.

BACKGROUND: Neonatal tele-resuscitation uses real-time, audio-video telemedicine to connect neonatologists with community hospital care teams during advanced neonatal resuscitations. While telemedicine continues to expand, best practices for training fellows in tele-resuscitation are not known. OBJECTIVE: We aimed to develop a neonatal tele-resuscitation curriculum using a simulation-based mastery learning model that provides neonatal-perinatal medicine (NPM) fellows with the knowledge, skills, and behaviors needed to lead tele-resuscitations. METHODS: Using technology-enhanced simulation education and a mastery learning model, we developed a longitudinal pilot tele-resuscitation curriculum. From 07/2018 to 03/2021, NPM fellows participated in the curriculum, which included individualized telemedicine learning, observing and leading simulated tele-resuscitations, and finally, performing clinical (non-simulated) tele-resuscitations. A performance assessment tool was developed to assess competency through eight questions mapped to the Accreditation Council for Graduate Medical Education (ACGME) core competencies, with responses on a 1 to 5 scale (1 = critical deficiencies; 5 = competence of an expert). RESULTS: Four NPM fellows participated in the curriculum, progressing through the curriculum at an individualized pace. Median scores on the three learning modules were 96-100%. Fellows participated in variable number of simulated tele-resuscitations based on when mastery was achieved (2-3 supervised simulations per fellow, 1-4 unsupervised simulations per fellow). In total, eighteen simulated tele-resuscitations (eight unsupervised, 10 supervised) and one clinical tele-resuscitation were conducted. Twenty-five performance assessments were completed. Assessment scores across the ACGME competencies were consistently high, with mean scores ranging from 4.2-4.6, with 4 equating to 'ready for unsupervised practice' and 5 equating to 'competence of an expert'. CONCLUSIONS: As telemedicine use continues to expand, curricula that improve learners' comfort with and proficiency in tele-resuscitation are essential. A simulation-based mastery learning model may be one approach that affords learners gradual exposure to and mastery of complex tele-resuscitation skills and behaviors.

Association of outborn versus inborn birth status on the in-hospital outcomes of neonates treated with therapeutic hypothermia: A propensity score-weighted cohort study.

OBJECTIVE: To compare the risk of in-hospital mortality and morbidity between outborn and inborn neonates treated with whole body hypothermia. METHODS: The association of outborn birth status with in-hospital mortality and morbidity, prior to NICU discharge or transfer, was assessed in a large historical cohort of neonates who had therapeutic hypothermia initiated on the day of birth. The cohort was restricted to neonates born at ≥35 weeks gestational age from 2007 to 2018. Since the sample was non-random, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalance in baseline maternal and neonatal characteristics between outborn and inborn neonates. Cox proportional hazards regression was used to assess the association between outborn status and in-hospital mortality. RESULTS: There were 4447 neonates included in the study (2463 outborn). Outborn status was not significantly associated with an increased risk of in-hospital mortality in the unadjusted cohort (HR = 1.17, 95% CI 0.97-1.42, p = 0.10) or IPW cohort (HR = 1.09, 95% CI 0.95-1.26, p = 0.22). However, in the IPW cohort, outborn neonates were significantly more likely to have seizures (28% vs 24%, p = 0.006), anticonvulsant exposure (46% vs 41%, p = 0.002), and gastrostomy tube placement (5.8% vs 3.8%, p = 0.009) during their newborn hospitalization. CONCLUSION: Outborn status was not significantly associated with increased in-hospital mortality among neonates treated with whole body hypothermia. However, outborn neonates were more likely to have seizures, receive anticonvulsant treatment, and undergo gastrostomy tube placement. Further study is needed to better understand the etiologies of these outcome disparities and potential implications for long-term neurodevelopmental outcomes.

Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis.

INTRODUCTION: To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage. METHODS: We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016. Patients were followed from the date of diagnosis to the time of last abdominal imaging, liver transplantation, or HCC diagnosis. Multivariable Cox regression analysis was performed to evaluate the risk factors associated with HCC development, stratified by fibrosis stage. RESULTS: A total of 1,072 patients were included: 122 patients with F3 fibrosis and 950 patients with cirrhosis. No HCC was observed during 602 person-year follow-up among F3 patients. Among patients with cirrhosis, HCC developed in 82 patients with the annual incidence rate of 1.90 per 100 person-years (95% confidence interval [CI], 1.53-2.35). Multivariable analysis in patients with cirrhosis demonstrated that HCC development was associated with male sex (hazard ratio [HR] 4.06, 95% CI, 2.54-6.51, P < 0.001), older age (HR, 1.05, 95% CI, 1.03-1.08, P < 0.001), and CTP score (HR, 1.38, 95% CI, 1.18-1.60, P < 0.001). Statin use was associated with a lower risk of developing HCC (HR, 0.40, 95% CI, 0.24-0.67, P = 0.001). Each 365 increment in cumulative defined daily dose of statin use reduced HCC risk by 23.6%. DISCUSSION: Our findings suggest that patients with NASH and bridging fibrosis have a low risk of HCC. Dose-dependent statin use reduced HCC risk significantly in patients with NASH cirrhosis.

Subcutaneous tanezumab for osteoarthritis: Is the early improvement in pain and function meaningful and sustained?

BACKGROUND: To evaluate if early improvements in pain and function with subcutaneous tanezumab are meaningful and sustained over 24 weeks. METHODS: Patients with moderate-to-severe osteoarthritis (hip or knee) in Europe and Japan were randomized to placebo, tanezumab 2.5 mg or tanezumab 5 mg (baseline, Week 8 and Week 16). Outcomes included: average daily index joint pain score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales, rescue medication use, WOMAC responders (within-patient ≥30% reduction in WOMAC Pain or Physical Function), Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders (within-patient) and Patient-reported Treatment Impact Assessment-Modified questionnaire. RESULTS: Patients received placebo (n = 282), tanezumab 2.5 mg (n = 283) or tanezumab 5 mg (n = 284). Changes from baseline in average daily index joint pain (within the first week) and WOMAC subscales (Week 2 through Week 24) were greater for each tanezumab group versus placebo (least squares [LS] mean, unadjusted p ≤ .05). Rescue medication use (days/week) was lower for each tanezumab group versus placebo from Week 2 through Week 12 (LS mean, unadjusted p ≤ .05) but not at Week 16 or 24. A higher proportion of each tanezumab group than placebo achieved ≥30% reduction from baseline in WOMAC Pain or Physical Function, or OMERACT-OARSI response (Week 2 through Week 24, unadjusted p ≤ .05), or were satisfied with treatment at Week 24 (unadjusted p ≤ .05). CONCLUSIONS: Subcutaneous tanezumab, compared with placebo, reduced pain within the first week, and pain and function were improved throughout 24 weeks. The proportions of responders and patients satisfied were higher with tanezumab than placebo. ClinicalTrials.gov:NCT02709486. SIGNIFICANCE: This exploratory analysis of data from a placebo-controlled, Phase 3 study of patients with moderate-to-severe osteoarthritis of the hip or knee for whom standard analgesics were not effective or could not be taken, found that onset of efficacy of subcutaneous tanezumab was within the first week, and efficacy was maintained through the 24-week treatment period. Tanezumab was effective in those patients with the most radiologically severe osteoarthritis.

Survival of Ventilated Extremely Premature Neonates With Severe Intraventricular Hemorrhage.

BACKGROUND: Severe intraventricular hemorrhage (IVH) is a leading mortality risk factor among extremely premature neonates. Because other life-threatening conditions also occur in this population, it is unclear whether severe IVH is independently associated with death. The existence and potential implications of regional variation in severe IVH-associated mortality are unknown. METHODS: We performed a retrospective cohort study of mechanically ventilated neonates born at 22 to 29 weeks' gestation who received care in 242 American NICUs between 2000 and 2014. After building groups composed of propensity score-matched and center-matched pairs, we used the Cox proportional hazards analysis to test our hypothesis that severe IVH would be associated with greater all-cause in-hospital mortality, defined as death before transfer or discharge. We also performed propensity score-matched subgroup analyses, comparing severe IVH-associated mortality among 4 geographic regions of the United States. RESULTS: In our analysis cohort, we identified 4679 patients with severe IVH. Among 2848 matched pairs, those with severe IVH were more likely to die compared with those without severe IVH (hazard ratio 2.79; 95% confidence interval 2.49-3.11). Among 1527 matched pairs still hospitalized at 30 days, severe IVH was associated with greater risk of death (hazard ratio 2.03; 95% confidence interval 1.47-2.80). Mortality associated with severe IVH varied substantially between geographic regions. CONCLUSIONS: The early diagnosis of severe IVH is independently associated with all-cause in-hospital mortality in extremely premature neonates. Regional variation in severe IVH-associated mortality suggests that shared decision-making between parents and neonatologists is strongly influenced by ultrasound-based IVH assessment and classification.