Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study.

OBJECTIVES: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens. DESIGN: Multicenter retrospective observational study. SETTING: Tertiary care hospital and 15 community and academic centers of a large healthcare system. PATIENTS: Hospitalized patients with PE treated with systemic alteplase. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting. CONCLUSIONS: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

Change in serial liver stiffness measurement by magnetic resonance elastography and outcomes in NAFLD.

BACKGROUND AND AIMS: The impact of disease progression in NAFLD on liver outcomes remains poorly understood. We aimed to investigate NAFLD progression using longitudinal liver stiffness measurements (LSM) by serial magnetic resonance elastography (MRE) and the association with liver outcomes. APPROACH AND RESULTS: All adult patients with NAFLD who underwent at least two serial MREs for clinical evaluation at Mayo Clinic, Rochester, between 2007 and 2019 were identified from the institutional database. Progression and regression were defined based on LSM change of 19% above or below 19% of initial LSM, respectively, based on Quantitative Imaging Biomarker Alliance consensus. The association between change in LSM and liver-related outcomes occurring after the last MRE was examined using time-to-event analysis. A total of 128 participants underwent serial MREs (53% female, median age 59 years). The median time between paired MREs was 3.4 (range 1-10.7) years. NAFLD progression (LSM = +0.61 kPa/year) was identified in 17 patients (13.3%). NAFLD regression (-0.40 kPa/year) occurred in 35 patients (27.3%). Stable LSM was noted in 76 participants (59.4%). In NAFLD without cirrhosis at baseline ( n = 75), cirrhosis development occurred in 14% of LSM progressors and 2.9% of non-progressors ( p = 0.059) over a median 2.7 years of follow-up from the last MRE. Among those with compensated cirrhosis at baseline MRE ( n = 29), decompensation or death occurred in 100% of LSM progressors and 19% of non-progressors ( p < 0.001) over a median 2.5 years of follow-up after the last MRE. CONCLUSIONS: Noninvasive monitoring of LSM by conventional MRE is a promising method of longitudinal NAFLD monitoring and risk estimation of liver-related outcomes in NAFLD.

Impact of Continuous Infusion Ketamine Compared to Continuous Infusion Benzodiazepines on Delirium in the Intensive Care Unit.

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods: In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines.

Risk of arrhythmia in post-resuscitative shock after out-of-hospital cardiac arrest with epinephrine versus norepinephrine.

OBJECTIVE: To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. DESIGN: Retrospective cohort study. SETTING: A large multi-site health system with hospitals across the United States. PATIENTS: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71-2.20) or multivariable analysis (OR 1.34, 95% CI 0.68-2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37-16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74-12.18, p < 0.001). CONCLUSION: There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC.

Validation of a Simulation Model for Robotic Myomectomy.

STUDY OBJECTIVE: Several simulation models have been evaluated for gynecologic procedures such as hysterectomy, but there are limited published data for myomectomy. This study aimed to assess the validity of a low-cost robotic myomectomy model for surgical simulation training. DESIGN: Prospective cohort simulation study. SETTING: Surgical simulation laboratory. PARTICIPANTS: Twelve obstetrics and gynecology residents and 4 fellowship-trained minimally invasive gynecologic surgeons were recruited for a 3:1 novice-to-expert ratio. INTERVENTIONS: A robotic myomectomy simulation model was constructed using <$5 worth of materials: a foam cylinder, felt, a stress ball, bandage wrap, and multipurpose sealing wrap. Participants performed a simulation task involving 2 steps: fibroid enucleation and hysterotomy repair. Video-recorded performances were timed and scored by 2 blinded reviewers using the validated Global Evaluative Assessment of Robotic Skills (GEARS) scale (5-25 points) and a modified GEARS scale (5-40 points), which adds 3 novel domains specific to robotic myomectomy. Performance was also scored using predefined task errors. Participants completed a post-task questionnaire assessing the model's realism and utility. MEASUREMENTS AND MAIN RESULTS: Median task completion time was shorter for experts than novices (9.7 vs 24.6 min, p = .001). Experts scored higher than novices on both the GEARS scale (median 23 vs 12, p = .004) and modified GEARS scale (36 vs 20, p = .004). Experts made fewer task errors than novices (median 15.5 vs 37.5, p = .034). For interrater reliability of scoring, the intraclass correlation coefficient was calculated to be 0.91 for the GEARS assessment, 0.93 for the modified GEARS assessment, and 0.60 for task errors. Using the contrasting groups method, the passing mark for the simulation task was set to a minimum modified GEARS score of 28 and a maximum of 28 errors. Most participants agreed that the model was realistic (62.5%) and useful for training (93.8%). CONCLUSION: We have demonstrated evidence supporting the validity of a low-cost robotic myomectomy model. This simulation model and the performance assessments developed in this study provide further educational tools for robotic myomectomy training.

Population pharmacokinetic model of cefepime for critically ill adults: a comparative assessment of eGFR equations.

Cefepime exhibits highly variable pharmacokinetics in critically ill patients. The purpose of this study was to develop and qualify a population pharmacokinetic model for use in the critically ill and investigate the impact of various estimated glomerular filtration rate (eGFR) equations using creatinine, cystatin C, or both on model parameters. This was a prospective study of critically ill adults hospitalized at an academic medical center treated with intravenous cefepime. Individuals with acute kidney injury or on kidney replacement therapy or extracorporeal membrane oxygenation were excluded. A nonlinear mixed-effects population pharmacokinetic model was developed using data collected from 2018 to 2022. The 120 included individuals contributed 379 serum samples for analysis. A two-compartment pharmacokinetic model with first-order elimination best described the data. The population mean parameters (standard error) in the final model were 7.84 (0.24) L/h for CL1 and 15.6 (1.45) L for V1. Q was fixed at 7.09 L/h and V2 was fixed at 10.6 L, due to low observed interindividual variation in these parameters. The final model included weight as a covariate for volume of distribution and the eGFRcr-cysC (mL/min) as a predictor of drug clearance. In summary, a population pharmacokinetic model for cefepime was created for critically ill adults. The study demonstrated the importance of cystatin C to prediction of cefepime clearance. Cefepime dosing models which use an eGFR equation inclusive of cystatin C are likely to exhibit improved accuracy and precision compared to dosing models which incorporate an eGFR equation with only creatinine.

Association of adverse effects with high serum posaconazole concentrations.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered.

Drug level monitoring is commonly used to evaluate appropriate dosing and effectiveness of posaconazole, a medication used to treat fungal infections. Patients with high levels commonly had side effects. Posaconazole monitoring should be completed, and doses reduced when levels are high.

Why is the Implementation of Beta-Lactam Therapeutic Drug Monitoring for the Critically Ill Falling Short? A Multicenter Mixed-Methods Study.

BACKGROUND: Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%-20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM. METHODS: This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks. RESULTS: Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings. CONCLUSIONS: Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice.

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support.

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min (P = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Interactive video module and simulated model for uterine manipulation during laparoscopic hysterectomy.

BACKGROUND: Hysterectomy is one of the most common gynecologic surgeries, with an increasing proportion of hysterectomies performed by a laparoscopic approach. Uterine manipulation is critical for patient safety and surgical efficiency; however, the most junior member of the surgical team assumes the responsibility of uterine manipulation, commonly without preparation. The objective of our study was to determine whether kinesthetic learning using a low-cost simulated pelvic model while learning the uterine manipulation maneuvers of a laparoscopic hysterectomy improves learning efficacy and application efficiency compared to an interactive video module alone. METHODS: Our randomized control trial at an academic medical center included forty first-year and second-year medical students. Participants were randomized to the intervention group that used a low-cost simulated pelvic model for kinesthetic learning during the video module or the control group who only had the interactive video module to learn the uterine manipulation maneuvers of a laparoscopic hysterectomy. RESULTS: Participants in the intervention group were less likely to make unnecessary movements with demonstration of both pelvic side walls (right wall: control 78.9%, intervention 42.9%, p < 0.027; left wall: control 94.7%, intervention 66.7%, p < 0.046), and this was more pronounced in novice first-year participants (p < 0.009). Additionally, participants in the intervention group reported higher perceived preparedness (100% versus 71.4% in control group, p < 0.037). However, there was no difference in verbal or physical cues required, time per task, or force used between the groups. CONCLUSION: Kinesthetic practice may not be required for learning the uterine manipulation maneuvers of a laparoscopic hysterectomy, but it may be beneficial for more novice learners and to increase learners' perceived preparedness. Our novel interactive video module alone may be sufficient to prepare learners to perform uterine manipulation maneuvers prior to the operating room.

The Association of Adverse Childhood Experiences with Long-term Mood and Anxiety Disorders After Childhood Traumatic Brain Injury: A Population-based Case-Control Study.

OBJECTIVE: To assess the association between ACEs and the development of psychiatric disorders by age 25 among individuals who sustained TBI prior to age 10. DESIGN: Population-based case-control study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: 566 individuals (N=566) who sustained a TBI prior to age 10 were identified and classified using a validated TBI classification system. Among these individuals, cases with a subsequent mood or anxiety disorder prior to age 25 were identified through clinical diagnostic codes and manual record review. For each case, a 1:1 matched control was randomly selected from individuals with a pediatric TBI who did not have a mood/anxiety disorder prior to the matched case's mood/anxiety disorder. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Development of a mood/anxiety disorder. RESULTS: Among the 114 matched pairs of individuals with a TBI prior to age 10, a subsequent mood/anxiety diagnosis was significantly associated with a history of 10 of 14 ACE categories and with having an ACE score ≥1 (odds ratio 5.17; 95% confidence interval 2.78-9.59). CONCLUSIONS: This is the first population-based study to the authors' knowledge showing that among children who sustained a TBI prior to age 10, those who experienced ACEs are at increased risk of developing a mood or anxiety disorder.

The incidence of cardiovascular instability in patients receiving various vasopressor strategies for peri-intubation hypotension.

INTRODUCTION: Patients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. METHODS: This is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. RESULTS: Screening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). DISCUSSION: Cardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability.

Efficacy of analgesic and sub-dissociative dose ketamine for acute pain in the emergency department.

BACKGROUND: Acute pain accounts for over 70% of Emergency Department (ED) visits. Sub-dissociative dose ketamine (0.1-0.6 mg/kg) is safe and effective for the management of acute pain in the ED. However, the optimal dose of intravenous ketamine that provides effective analgesia and minimizes the risk of adverse effects has yet to be identified. The objective of this study was to describe an effective analgesia dose range of IV ketamine for acute pain in the ED. METHODS: This multi-center, retrospective cohort study evaluated adult patients who received analgesic and sub-dissociative dose ketamine for the management of acute pain between May 5, 2018, and August 30, 2021, in 21 emergency departments at academic, community, and critical access hospitals across four states. Patients were excluded if they received ketamine for an indication other than pain, such as procedural sedation or intubation, or for whom there was incomplete documentation for the primary outcome. Patients who received a ketamine dose <0.3 mg/kg were stratified into the low-dose group, and those who received a dose of 0.3 mg/kg or higher to the high-dose group. The primary outcome was change in pain scores within 60 min using a standard 11-point numeric rating scale (NRS). Secondary outcomes included incidence of adverse effects and use of rescue analgesics. Continuous variables were compared between dose groups using student t-test or Wilcoxon Rank-Sum test. Linear regression was used to assess the association between the change in NRS pain scores within 60 min and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid. RESULTS: From 3796 patient encounters screened for receipt of ketamine, 384 patients met inclusion criteria including 258 in the low-dose group, and 126 in the high-dose group. The primary reason for exclusion was incomplete documentation of pain scores, or ketamine used for sedation. Median baseline pain scores were 8.2 in the low-dose group and 7.8 in the high-dose group (difference 0.5; 95% CI 0 to 1, p = 0.04). Both groups demonstrated significant reductions in their mean NRS pain scores within 60 min following the first administration of IV ketamine. There were no differences in the change in pain scores between both groups (-2.2 vs -2.6, mean difference 0.4, 95% CI -0.4 to 1.1, p = 0.34). Use of rescue analgesics (40.7% vs 36.5%, p = 0.43) and adverse effects were similar between groups, including early discontinuation of the ketamine infusion (37.2% vs. 37.3%, p = 0.99). Overall, the most common adverse effects were agitation (7.3%) and nausea (7.0%). CONCLUSION: The analgesic efficacy and safety of high-dose sub-dissociative ketamine (≥0.3 mg/kg) was not superior to low-dose (< 0.3 mg/kg) for the management of acute pain in the ED. Low-dose ketamine <0.3 mg/kg is an effective and safe pain management strategy in this population.

Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Intraoperative Versus Postoperative Hydroxocobalamin for Vasoplegic Shock in Cardiothoracic Surgery.

OBJECTIVES: Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB. DESIGN: This was a historic cohort study. SETTING: The study was conducted at a quaternary academic cardiovascular surgery program. PARTICIPANTS: Adults undergoing cardiac surgery using CPB were participants in the study. INTERVENTIONS: Hydroxocobalamin (5 g) intravenously over 15 minutes. MEASUREMENTS AND MAIN RESULTS: The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p = 0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p = 0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (estimated difference 0.48 [95% CI -1.76-2.72], p = 0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups. CONCLUSIONS: A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock.

Pharmacist-provider collaborative visits after hospital discharge in a comprehensive acute kidney injury survivor model.

BACKGROUND: Postdischarge follow-up in primary care is an opportunity for pharmacists to re-evaluate medication use in acute kidney injury (AKI) survivors. Of the emerging AKI survivor care models described in literature, only one involved a pharmacist with limited detail about the direct impact. OBJECTIVE: This study aimed to describe pharmacist contributions to a comprehensive postdischarge AKI survivorship program in primary care (the AKI in Care Transitions [ACT] program). METHODS: The ACT program was piloted from May to December of 2021 at Mayo Clinic as a bundled care strategy for patients who survived an episode of AKI and were discharged home without the need for hemodialysis. Patients received education and care coordination from nurses before discharge and later completed postdischarge laboratory assessment and clinician follow-up in primary care. During the follow-up encounter, patients completed a 30-minute comprehensive medication management visit with a pharmacist focusing on AKI survivorship considerations. Medication therapy recommendations were communicated to a collaborating primary care provider (PCP) before a separate 30-minute visit with the patient. PCPs had access to clinical decision support with evidence-based post-AKI care recommendations. Medication-related issues were summarized descriptively. RESULTS: Pharmacists made 28 medication therapy recommendations (median 3 per patient, interquartile range 2-3) and identified 14 medication discrepancies for the 11 patients who completed the pilot program, and 86% of the medication therapy recommendations were acted on by the PCP within 7 days. Six recommendations were made to initiate renoprotective medications, and 5 were acted on (83%). CONCLUSION: During the pilot phase of a multifaceted transitional care program for AKI survivors, pharmacists' successfully identified and addressed multiple medication therapy problems, including for renally active drugs. These results demonstrate the potential for pharmacist-provider collaborative visits in primary care to improve safe and effective medication use in AKI survivors.

Pubic Symphysis to Sacrococcygeal Joint: A Poor Correlate to Other Spinopelvic Measurements.

BACKGROUND: The hip-spine relationship is increasingly recognized as critical for optimizing stability following total hip arthroplasty (THA). However, these measurements are not routinely obtained during THA workup. It has been suggested that insight can be gained from supine antero-posterior pelvis radiograph, measuring the distance from the superior border of the pubic symphysis to the sacro-coccygeal joint (PSCD). This study assessed the correlation between PSCD and lateral lumbar radiographic metrics in a cohort of preoperative THA patients. METHODS: We retrospectively evaluated 250 consecutive patients who underwent THA with preoperative supine antero-posterior pelvis and lateral lumbar radiographs. The mean age was 68 years (range, 42 to 89), 61% were women, and the mean body mass index was 30 kg/m2 (range, 19 to 52). Two reviewers measured PSCD, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), and lumbar lordosis (LL). Inter-observer reliability was calculated for all measurements, and correlation coefficients were calculated for PSCD with respect to PT, SS, PI, and LL. RESULTS: Correlations between PSCD and lumbar radiographic metrics were all statistically significant, except for PI in men but graded as "weak" or "very weak" for men and women, respectively, as follows: PT = -0.30 (P < .01) and -0.46 (P < .01); SS = 0.27 (P < .01) and 0.22 (P < .01); PI = -0.04 (P = .70) and -0.19 (P = .02); and LL = 0.45 (P < .01) and 0.30 (P < .01). Inter-observer reliability was graded as "strong" for every metric. CONCLUSION: The PSCD was weakly correlated with all evaluated lateral lumbar radiographic metrics in both sexes, despite strong inter-observer reliability. Therefore, PSCD cannot reliably serve as a proxy for evaluating the hip-spine relationship.

A Randomized Controlled Trial of Kinematically and Mechanically Aligned Total Knee Arthroplasties: Long-Term Follow-Up.

BACKGROUND: The optimal alignment technique for total knee arthroplasty (TKA) remains controversial. We previously reported 6-month and 2-year results of a randomized controlled trial comparing kinematically versus mechanically aligned TKA. In the present study, we report the mean 13-year (range, 12.6-14.4) follow-up results from this trial. METHODS: The original cohort included 88 TKAs (44 kinematically aligned using patient-specific guides and 44 mechanically aligned using conventional instrumentation), performed from 2008 to 2009. After institutional review board approval, the health records of the original 88 patients were queried. Revisions, reoperations, and complications were recorded. There were 26 patients who died, leaving 62 patients for follow-up. Of these, 48 patients (77%) were successfully contacted via phone. Reoperations and complications were documented. Furthermore, a battery of patient-reported outcome measures (PROMs) (including Western Ontario and McMaster University Index, Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score Junior, Forgotten Joint Score, Modified-Single Assessment Numerical Evaluation, and patient satisfaction) were obtained. RESULTS: Of the original 88 patients in the study, 15 patients had at least one reoperation (17%) and 5 patients had undergone complete revision surgery (6%). There was no difference between the 2 alignment methods for major and minor reoperations (P = .66). The kinematically aligned total knees self-reported a nonstatistically significant (P = .16) improved satisfaction (96% versus 82%), but no difference in other PROMs compared to mechanically aligned TKAs. CONCLUSION: Kinematically aligned TKA demonstrates excellent mean 13-year results, comparable to mechanically aligned TKA with similar reoperations, complications, and PROMs.

Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.

BACKGROUND & AIMS: The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. METHODS: This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. RESULTS: A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. CONCLUSION: In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. LAY SUMMARY: For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.

Natural History of Nonalcoholic Fatty Liver Disease With Normal Body Mass Index: A Population-Based Study.

BACKGROUND & AIMS: The natural history of lean nonalcoholic fatty liver disease (NAFLD) is not well-understood. Consequently, patient counseling and disease management are limited. We aimed to compare the natural history of lean, overweight, and obese NAFLD in a U.S. population with long-term follow-up. METHODS: All adults diagnosed with NAFLD in Olmsted County, MN between 1996 and 2016 were identified, and all subsequent medical events were ascertained using a medical record linkage system. Subjects were divided on the basis of body mass index (BMI) at NAFLD diagnosis into 3 groups: normal, overweight, and obese. The probability to develop cirrhosis, decompensation, malignancies, cardiovascular events, or death among the 3 groups was estimated by using the Aalen-Johansen method, treating death as a competing risk. The impact of BMI categories on these outcomes was explored by using Cox proportional hazards regression analysis. RESULTS: A total of 4834 NAFLD individuals were identified: 414 normal BMI, 1189 overweight, and 3231 obese. Normal BMI NAFLD individuals were characterized by a higher proportion of women (66% vs 47%) and lower prevalence of metabolic comorbidities than the other 2 groups. In reference to obese, those with normal BMI NAFLD had a nonsignificant trend toward lower risk of cirrhosis (hazard ratio [HR], 0.33, 95% confidence interval [CI], 0.1-1.05). There were no significant differences in the risk of decompensation (HR, 0.79; 95% CI, 0.11-5.79), cardiovascular events (HR, 1.05; 95% CI, 0.73-1.51), or malignancy (HR, 0.87; 95% CI, 0.51-1.48). Compared with obese, normal BMI NAFLD had higher risk of all-cause mortality (HR, 1.96; 95% CI, 1.52-2.51). CONCLUSIONS: NAFLD with normal BMI is associated with a healthier metabolic profile and possibly a lower risk of liver disease progression but similar risk of cardiovascular disease and malignancy than obese NAFLD.