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.

De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas After Liver Transplantation.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear. METHODS: In this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13-year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics. RESULTS: Of 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN-associated cancer and 5 cases of worrisome features) over an average follow-up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p > 0.05). Combined kidney and liver transplantation (p = 0.005) and pretransplant cholangiocarcinoma (p = 0.012) were associated with IPMN progression. CONCLUSION: IPMN progression is rare after liver transplantation even over an extended follow-up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

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.

Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1. METHODS: For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox). We compared values among 3 groups: homozygous G170R, heterozygous G170R, and non-G170R AGXT variants both before and after initiating pyridoxine (B6). RESULTS: Of 403 patients with PH1 in the registry, 83 met the inclusion criteria. Uox:cr decreased rapidly over the first 5 years of life. Both before and after B6 initiation, patients with non-G170R had the highest Uox:cr, 24-h Uox, and Pox. Patients with heterozygous G170R had similar Uox:cr to homozygous G170R prior to B6. Patients with homozygous G170R had the lowest 24-h Uox and Uox:cr after B6. Urinary oxalate excretion and Pox tend to decrease over time during childhood. eGFR over time was not different among groups. CONCLUSIONS: Children with PH1 under 5 years old have relatively higher urinary oxalate excretion which may put them at greater risk for nephrocalcinosis and kidney failure than older PH1 patients. Those with homozygous G170R variants may have milder disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Retrospective Evaluation of the Association of Oxacillin MIC on Acute Treatment Outcomes with Cefazolin and Antistaphylococcal Penicillins in Methicillin-Susceptible Staphylococcus aureus Bacteremia.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 µg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 µg/mL compared to strains with MIC of oxacillin < 1 µg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 µg/mL and 176 isolates with an MIC < 1 µg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 µg/mL and an MIC < 1 µg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 µg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Adverse childhood experiences and sexual dysfunction in midlife women: Is there a link?

BACKGROUND: One in 3 children has had at least 1 adverse childhood experience (ACE), and ACEs have been associated with multiple medical and psychiatric morbidities in women later in life, including greater menopause symptom burden. AIM: To evaluate the association between ACEs and female sexual dysfunction (FSD) in midlife women. METHODS: A cross-sectional analysis from DREAMS-the Data Registry on Experiences of Aging, Menopause, and Sexuality-was conducted with questionnaires completed by women aged 40 to 65 years who presented to a women's health clinic at Mayo Clinic in Rochester, Minnesota, from May 2015 to December 2016. History of ACEs was obtained with the validated ACE questionnaire. FSD was assessed by the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. OUTCOMES: The association between ACEs and FSD (defined as Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11) was evaluated via a multivariable logistic regression model, adjusting for age, menopause status, hormone therapy use, anxiety, depression, relationship satisfaction, hot flash severity, and history of abuse in the past year. RESULTS: Women (N = 1572) had a mean age of 53.2 years. Overall 59% reported having at least 1 ACE. When compared with no ACEs, a history of ≥4 ACEs significantly increased the odds of not being sexually active (odds ratio, 1.83; 95% CI, 1.30-2.57; P < .001). Among sexually active women, the proportion of women with FSD increased sequentially as the number of ACEs increased. In the univariate analysis, a history of ≥4 ACEs significantly increased the odds of FSD as compared with no ACEs (odds ratio, 2.12; 95% CI, 1.50-2.99; P < .001). The association remained statistically significant in the multivariable analysis after adjusting for confounders (odds ratio, 1.75; 95% CI, 1.15-2.68; P = .009). CLINICAL IMPLICATIONS: The findings highlight an opportunity for clinicians to screen for ACEs in women with sexual dysfunction and offer appropriate treatment and counseling as indicated. STRENGTHS AND LIMITATIONS: Strengths of the study include the large cohort, the use of validated tools for assessment of ACEs and FSD, and the adjustment for multiple potential confounding factors. Limitations include the cross-sectional study design, recall bias in reporting ACEs and recent abuse, and the low representation of racially and ethnically diverse women in the cohort. CONCLUSION: The study demonstrates an increased risk of sexual inactivity and sexual dysfunction in midlife women who experienced childhood adversity. The sexual dysfunction in women with ACEs seems to be independent of other factors that potentially affect female sexual function in midlife.

History of infertility and sexual dysfunction in midlife women: Is there a link?

BACKGROUND: Infertility has been linked with an increased risk of sexual dysfunction in reproductive-aged women, with longer periods of infertility associated with a greater risk. AIM: The study's aim was to examine whether a history of infertility treatment in women is linked to sexual dysfunction during midlife. METHODS: The cross-sectional study was conducted among sexually active women, between the ages of 45 and 65 years, who sought consultation at the women's health clinics at a US tertiary care center. History of infertility treatment was assessed with a single question that asked participants if they were treated for infertility in the past. The association between a history of infertility treatment and sexual dysfunction-which was diagnosed by a combination of Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale-Revised score ≥11-was assessed in a multivariable logistic regression model that adjusted for multiple confounders. OUTCOMES: The primary outcome was sexual dysfunction in midlife women. RESULTS: The analysis included 5912 women, with a mean age of 54.1 years. Nearly 16% of women reported receiving treatment for infertility. More than half the women (55%) had sexual dysfunction: 56.3% of those with previous fertility treatments and 54.4% of those without any fertility treatment (P = .3). Receiving treatment for infertility in the younger years did not significantly increase the odds of sexual dysfunction in midlife in univariate (odds ratio, 1.08; 95% CI, 0.94-1.24; P = .3) and multivariable analyses (odds ratio, 1.11; 95% CI, 0.96-1.29; P = .17). CLINICAL IMPLICATIONS: While infertility is known to be predictive of sexual dysfunction in women during their reproductive years, there was no association between a history of infertility treatment and sexual dysfunction in midlife women in the current study. STRENGTHS AND LIMITATIONS: The study used validated questionnaires accounting for sexual complaints and distress and adjusted for multiple confounding factors. Limitations include the selection bias introduced by the study of women presenting for evaluation of sexual dysfunction, which may have been a result of factors stronger than the influence of infertility. Other limitations include the study's cross-sectional nature with suboptimal racial and ethnic representation. CONCLUSION: Although infertility is commonly associated with female sexual dysfunction in women of reproductive age, the association was not present in midlife women in the current study.

Progression of fibrosis in liver transplant recipients with hepatitis C before and after sustained virologic response.

BACKGROUND: Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV. AIMS: We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR). METHODS: We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non-invasive imaging. RESULTS: Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR = .11, p < .001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p < .001) whereas Group B showed minimal change on protocol annual biopsy (-.02, p = .80). After SVR, most patients were followed non-invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (-.19, p < .001). CONCLUSION: HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR.

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.

Assessment of bleeding risk in low-weight patients receiving prophylactic subcutaneous unfractionated heparin.

BACKGROUND: Underweight patients may be at an increased risk of bleeding while receiving venous thromboembolism (VTE) prophylaxis. Additional evidence is needed to identify patient-specific factors associated with bleeding. The objective of the study was to describe the incidence and identify risk factors associated with bleeding in low-weight (⩽ 60 kg) adult patients receiving subcutaneous unfractionated heparin (SQH) for VTE prophylaxis. METHODS: This was a single-center, retrospective, nested case-control study of low-weight patients receiving SQH for VTE prophylaxis for ⩾ 48 hours. Cases, patients with clinically relevant bleeding while receiving SQH, and controls, patients without a bleeding event, were matched in a 1:3 ratio for age, sex, primary service (surgical or medical), and time at risk of bleeding on SQH to determine factors associated with bleeding. RESULTS: A total of 3761 patients met the inclusion criteria, of which 38 cases of clinically relevant bleeding were identified. The bleeding incidence was 1% at hospital day 6 and 2.8% at hospital day 14. Most patients in this study (69%) received SQH 5000 units three times daily. ICU admission at SQH start was associated with bleeding, OR 2.97 (95% CI 1.21-7.29). CONCLUSION: Bleeding in low-weight patients on prophylactic SQH was uncommon. Patients admitted to the ICU at time of SQH start may be at a higher risk of bleeding. Further studies are needed to detect additional risk factors associated with bleeding and investigate the effects of reduced dosing in this population.

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.