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Objective To assess the effect of clinical pharmacists in daily audits, under the direction of an antimicrobial stewardship program, of antibiotic treatment durations for the common inpatient disease states of community-acquired pneumonia (CAP) and urinary tract infection (UTI). Patients and Methods This was a retrospective single-center cohort study that evaluated the difference in the duration of antibiotic therapy for CAP or non–catheter-associated UTI of hospitalized patients who received a daily audit by clinical pharmacists compared with patients who did not receive a daily audit. Retrospective chart review included randomly selected hospitalized patients diagnosed with CAP or UTI during preaudit and postaudit periods. Results The preaudit group had 64 patients; and the postaudit group, 51 patients. The therapy duration was 7 days in the preaudit group and 6 days in the postaudit group (P=.55). Fluoroquinolone use was reduced in the postaudit group and was significantly less than in the preaudit group (24 [37.5%] vs 7 [13.7%]; P=.007). Conclusion The daily audits of clinical pharmacists may be an effective method to reduce the duration of antibiotic therapy and are effective in the reduction of fluoroquinolone use. Additional studies must be done to further investigate the effects of clinical pharmacist antimicrobial stewardship efforts.

Rationale: The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contempora...

In clinical scenario surveys, inpatient providers were more likely to report continuing inappropriate (odds ratio, 2.02 [95% confidence interval, 1.35–3.03]; P

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; ≥1g/m(2)) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (≥1.0 μmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75–4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38–3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5–1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

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.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.Noninvasive monitoring of LSM by conventional MRE is a promising method of longitudinal NAFLD monitoring and risk estimation of liver-related outcomes in NAFLD.

Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) population. The objective of this cross-sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo-HSCT. An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow-up after allo-HSCT. Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses. In the entire cohort, 51% of subjects (n = 102) reported nonadherence to nonimmunosuppressant medications (95% confidence interval [CI], 44.07% to 57.93%) on the Morisky Medication Adherence Scale. Of the 153 patients taking oral immunosuppressant medications at the time of the survey, 58 (37.9%) reported nonadherence to immunosuppressant therapy (95% CI, 30.22% to 45.6%), as measured by the Immunosuppressant Therapy Adherence Scale. Younger age and distress were associated with medication nonadherence. Nonadherence to immunosuppressant therapy was associated with mild chronic graft-vs-host disease (cGVHD), and a similar trend was observed for moderate cGVHD. Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo-HSCT recipient, and further study to identify interventions to improve adherence in these patients is warranted.

Objective To determine the impact of a drug deactivation system to post-surgical patients on the rate of opioid prescription disposal. Patients and Methods Two hundred post-operative patients discharged after inpatient surgery at a large academic medical center. This study was conducted August 20, 2018, through November 30, 2018. Patients were provided with a drug deactivation system (DDS) and instruction sheet along with their opioid prescription. Three to 4 weeks after dismissal, patients were surveyed about quantity of opioids remaining, use of DDS or other disposal methods, and satisfaction with DDS if used. Results One hundred forty-nine of 200 (74.5%) patients were surveyed. One hundred six reported leftover opioids and 29 (27.3%) had disposed of these medications. By the time of survey, 23 (21.2%) participants with leftover opioids had used the DDS to destroy their remaining supply and an additional 33 (31.1%) participants reported plans to use the disposal bag on a future date. Of the 23 participants who used the DDS, 22 (96.0%) reported that they were very satisfied with the disposal process. Conclusion Participants are willing to use a DDS and are satisfied with the process; however, additional education is needed to ensure timely disposal.

Introduction: The incidence of augmented renal clearance (ARC) in the intensive care unit (ICU) is highly variable, and identification of these patients remains challenging. Objective: The objective of this study was to define the incidence of ARC in a cohort of critically ill adults, using serum Cr and cystatin C, and to identify factors associated with its development. Methods: This is a retrospective cohort study of critically ill patients without stage 2 or 3 acute kidney injury with both serum Cr and cystatin C available. The incidence of ARC was defined as a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)Cr-cystatin C-estimated glomerular filtration rate >130 mL/min. A multivariable logistic regression model using a penalized Lasso method was fit to identify independent predictors of ARC. Results: Among the 368 patients included in the study, indication for ICU admission was nonoperative in 55% of patients, and 9% of patients were admitted for major trauma. The overall incidence of ARC was low at 4.1%. In a multivariable logistic regression model, Charlson comorbidity index, major trauma, intracerebral hemorrhage, age, and Sequential Organ Failure Assessment score were found to predict ARC. Conclusion: The incidence of ARC in this study was low, but prediction models identified several factors for early identification of patients with risk factors for or who develop ARC, particularly in a cohort with a low baseline risk of ARC. These factors could be used to help identify patients who may develop ARC.

Although magnetic resonance elastography (MRE) has been well-established for detecting and staging liver fibrosis, its prognostic role in determining outcomes of chronic liver disease (CLD) is mostly unknown.This retrospective study consisted of 1269 subjects who underwent MRE between 2007 and 2009 and followed up until death or last known clinical encounter or end of study period. Charts were reviewed for cirrhosis development, decompensation, and transplant or death. The cohort was split into baseline noncirrhosis (group 1), compensated cirrhosis (group 2), and decompensated cirrhosis (group 3). Cox-regression analysis with age, sex, splenomegaly, CLD etiology, Child-Pugh Score (CPS), Fibrosis-4 Index (FIB-4) score, and Model for End-Stage Liver Disease (MELD)-adjusted HR for every 1-kPa increase in liver stiffness measurement (LSM) were used to assess the predictive performance of MRE on outcomes. Group 1 (n = 821) had baseline median LSM of 2.8 kPa, and cirrhosis developed in 72 (8.8%) subjects with an overall rate of about 1% cirrhosis/year. Baseline LSM predicted the future cirrhosis with multivariable adjusted HR of 2.38 (p 0.0001) (concordance, 0.84). In group 2 (n = 277) with baseline median LSM of 5.7 kPa, 83 (30%) subjects developed decompensation. Baseline LSM predicted the future decompensation in cirrhosis with FIB-4 and MELD-adjusted HR of 1.22 (p 0.0001) (concordance, 0.75). In group 3 (n = 171) with median baseline LSM of 6.8 kPa (5.2, 8.4), 113 (66%) subjects had either death or transplant. Baseline LSM predicted the future transplant or death with HR of 1.11 (p = 0.013) (concordance 0.53) but not in CPS and MELD-adjusted models (p = 0.08).MRE-based LSM is independently predictive of development of future cirrhosis and decompensation, and has predictive value in future transplant/death in patients with CLD.

Background: Drug-related problems (DRPs) are common among patients seen in the emergency department (ED), but the true incidence is not clear. Objectives: The primary objective of this study was to determine the prevalence of DRPs among patients seen in a U.S. ED. The secondary objective was to categorize these DRPs by problem type and by medication class. Methods: This was a prospective observational cohort study of a random sample of ED patients between December 2011 and March 2013. ED pharmacists screened randomly selected patients for the presence of a DRP contributing to the ED visit. Four independent auditors evaluated the results to achieve consensus for the presence or absence of DRPs and categorization of the DRPs. Results: Among 1039 patients screened for DRPs, 308 (29.6%) were found to have at least 1 DRP contributing to the ED visit. Among a total of 443 DRPs, the most commonly identified categories were adverse drug reaction (n = 193 [43.6%]), ineffective medication (n = 69 [15.6%]), and subtherapeutic dosage (n = 68 [15.3%]). The most commonly implicated drug classes were cardiovascular medications (n = 113 [26.5%]), anti-infective medications (n = 52 [12.2%]), and analgesic medications (n = 58 [13.6%]). Conclusions: A substantial proportion of ED visits are associated in part or in total with DRPs. Adverse drug reactions and cardiovascular medications are the most common category and medication class implicated, respectively.

Transitioning patients from intravenous (IV) to oral antibiotic therapy has been shown to be a successful approach for several infections. However, minimal data exist evaluating outcomes following transition from to oral antibiotics for patients with bacteraemia secondary to a urinary tract infection (UTI). This study compared treatment failures between patients treated exclusively with IV antibiotics and those transitioned from IV to oral antibiotics for bacteraemia secondary to UTI.This single-centre, retrospective cohort study included hospitalised, non-critically ill adult patients treated with culture-susceptible antibiotic therapy for 7-21 days. Patients were divided into two cohorts based on the route of definitive antibiotic administration. Treatment failure was a composite outcome of death and recurrence of the index micro-organism within 21 days following negative blood cultures.Among the 346 patients enrolled, 82 (23.7%) were in the IV cohort and 264 (76.3%) were in the IV-to-oral cohort. A total of six treatment failures occurred; 2 (2.4%) in the IV cohort and 4 (1.5%) in the oral transition cohort (hazard ratio=0.62, 95% confidence interval 0.11-3.39; P=0.58). All failures were due to recurrence of the index organism. Secondary outcomes demonstrated a significantly higher rate of IV line-associated complications in the IV cohort (P=0.03) and a favourable hospital length of stay in the oral cohort (P0.001). Patients transitioned from IV to oral antibiotics based on culture-susceptibility data experienced similarly low rates of treatment failure as those who received exclusive IV therapy.

BACKGROUND Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P

Background: Post–cardiac surgery bleeding can have devastating consequences, and it is unknown if warfarin-induced rapid international normalized ratio (INR) rise during the immediate postoperative period increases bleed risk. Objective: To determine the impact of warfarin-induced rapid-rise INR on post–cardiac surgery bleeding. Methods: This was a single-center, retrospective chart review of post–cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester. Patients were grouped based on occurrence or absence of rapid-rise INR (increase ≥1.0 within 24 hours). The primary outcome compared bleed events between groups. Secondary outcomes assessed hospital length of stay (LOS) and identified risk factors associated with bleed events and rapid rise in INR. Results: During the study period, 2342 patients were included, and 56 bleed events were evaluated. Bleed events were similar between rapid-rise (n = 752) and non–rapid-rise (n = 1590) groups in both univariate (hazard ratio [HR] = 1.22; P = 0.594) and multivariable models (HR = 1.24; P = 0.561). Those with rapid-rise INR had longer LOS after warfarin administration (discharge HR = 0.84; P = 0.0002). The most common warfarin dose immediately prior to rapid rise was 5 mg. Risk factors for rapid-rise INR were low body mass index, female gender, and cross-clamp time. Conclusion and Relevance: This represents the first report to assess warfarin-related rapid-rise INR in post–cardiac surgery patients and found correlation to hospital LOS but not bleed events. Conservative warfarin dosing may be warranted until further research can be conducted.

Benefits of serial electrocardiographic (ECG) monitoring to detect QT prolongation in patients with hematological malignancies remain unclear. This retrospective, single-center, study evaluated 316 adult acute leukemia and high-risk MDS patients who received 11,775 patient-days of voriconazole prophylaxis during induction chemotherapy. Of these, 37 patients (16.2%) experienced QTc prolongation. Medications associated with QTc prolongation included furosemide, haloperidol, metronidazole, mirtazapine, prochlorperazine, and venlafaxine. Hypokalemia and hypomagnesemia were also significantly associated with QTc prolongation (HR 3.15

Summary Background & aims Adverse outcomes for hospitalized patients with sarcopenia are well documented, and identification of patients at risk remains challenging. The sarcopenia index (SI), previously defined as (serum creatinine/serum cystatin C) × 100, could be an inexpensive, readily accessible, objective tool to predict muscle mass and risk for adverse clinical outcomes. The aim of this study was to assess the validity of the SI as a predictor of muscle mass. Methods Retrospective study of critically ill adults admitted to Mayo Clinic from 2012 to 2015 with suspected sepsis and an available creatinine and serum cystatin C. Muscle surface area was quantified at the L3/4 vertebral level in patients with an abdominal CT scan (CTMSA). Multivariable regression modeling was used to assess the relationship between SI and CTMSA, as well as short-term clinical outcomes. Results The 171 included had a mean weight and body mass index (BMI) of 75.2 ± 16.4 kg and 26.0 ± 4.6 kg/m2 and abdominal CT scans were available for 81 (47%) patients. The SI correlated with CTMSA (r = 0.40). After adjustment for age, sex, severity of illness, and BMI, SI was independently associated with muscle mass (P = 0.001). A decrease in the SI (indicative of lower muscle mass) was also associated with frailty and worse short-term clinical outcomes. Conclusion The SI, a simple calculation from kidney function markers, is a significant predictor of muscle mass in this validation cohort of ICU patients. A low SI was associated with longer hospital length of stay and frailty. Future studies could explore whether the use of SI assists with identifying patients likely to benefit from pharmacotherapy-, nutrition-, or physical therapy-based interventions.

BACKGROUND Sarcopenia is associated with both increased wait-list mortality and mortality following liver transplantation. AIMS To determine the course of sarcopenia from transplant evaluation until 1 year post-transplant, and its implications on hospitalisation and mortality following liver transplantation. METHODS Two hundred and ninety-three transplant recipients from 2002 to 2006 had pre-transplant CT scans analysed at the third lumbar region for sarcopenia, myosteatosis and abdominal visceral fat content. Half the recipients had post-transplant CT scan for interpretation (161/293). RESULTS Sarcopenia was present in 146/293 (50%) of the patients pre-transplant. There was a significant decrease in muscle mass (loss 2.0 ± 4.9 cm2 /m2 ; P

Background. Acute kidney injury (AKI) is a common complication of treatment with liposomal amphotericin B (LAmB). The trajectory of renal recovery after LAmB-associated AKI has not been well described, nor has effect of LAmB dose on recovery of renal function been explored. Objective. Characterize the pattern of renal recovery after incident AKI during LAmB and determine potential influencing factors. Methods. This retrospective cohort study analyzed patients who developed a ≥50% increase in serum creatinine while on LAmB. Patients were followed up until complete renal recovery or death or for 30 days, whichever occurred first. The primary outcome was complete renal recovery, defined as serum creatinine convalescence to within 10% of the patient’s pretreatment baseline. Multivariable modeling was used to identify independent predictors of renal recovery. Results. Ninety-eight patients experienced nephrotoxicity during LAmB, 94% of which received doses Conclusion and Relevance. Our data suggests that LAmB dose did not impact the likelihood of renal recovery. Additional investigation is needed to confirm these findings when aggressive dosing strategies are employe. Additional research is also warranted to further characterize the course of recovery after LAmB-associated nephrotoxicity and comprehensive spectrum of renal outcomes.

BACKGROUND Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database. METHODS The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy. RESULTS Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS). CONCLUSIONS This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.

Sarcopenia and frailty are commonly encountered in patients with end-stage liver disease and are associated with adverse clinical outcomes, including decompensation and wait-list mortality. The impact of these entities in patients with differing disease etiologies has not been elucidated. We aim to ascertain the change in their prevalence over time on the wait list and determine their impact on hospitalization, delisting, and wait-list survival, specifically for patients with nonalcoholic steatohepatitis (NASH) and alcoholic liver disease (ALD). Adult patients who were evaluated for their first liver transplant from 2014 to 2016 with a primary diagnosis of NASH (n = 136) or ALD (n = 129) were included. Computed tomography scans were used to determine the presence of sarcopenia and myosteatosis. Frailty was diagnosed using the Rockwood frailty index. Patients with NASH had a significantly lower prevalence of sarcopenia (22% versus 47%; P < 0.001) but a significantly higher prevalence of frailty (49% versus 34%; P = 0.03) when compared with patients with ALD at the time of listing. In patients with NASH, sarcopenia was not associated with adverse events, but a higher frailty score was associated with an increased length of hospitalization (P = 0.05) and an increased risk of delisting (P = 0.02). In patients with ALD, univariate analysis showed the presence of sarcopenia was associated with an increased risk of delisting (P = 0.01). In conclusion, sarcopenia and frailty occur with differing prevalence with variable impact on outcomes in wait-listed patients with NASH and ALD.

BACKGROUND Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. METHODS A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. RESULTS Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). CONCLUSIONS Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.

Background and Aims Strong evidence supports the use of radiofrequency ablation (RFA) in the management of dysplastic/neoplastic Barrett’s esophagus (BE). Recently, the efficacy of the cryoballoon ablation (CBA) system was demonstrated in multicenter cohort studies. We aimed to assess the comparative effectiveness and safety of these 2 ablation modalities for endoscopic eradication therapy (EET) in a cohort study. Methods Data were abstracted on patients with dysplastic BE or intramucosal carcinoma undergoing EET using RFA or CBA as the primary ablation modality at 2 referral centers. The primary outcome was the rate of complete remission intestinal metaplasia (CRIM). Secondary outcomes were rates of complete remission of dysplasia (CRD) and adverse events. Cox proportional hazards models and propensity scored–matched analyses were conducted to compare outcomes. Results Three hundred eleven patients (CBA, 85 patients; RFA, 226 patients) with a median follow-up of 1.5 years (interquartile range, .8, 2.5) in the RFA group and 2.0 years (interquartile range, 1.3, 2.5) in the CBA group were studied. On multivariable analyses, the chances of reaching CRD and CRIM were not influenced by ablation modality. Propensity score–matched analysis revealed a comparable chance of achieving CRIM (CBA vs RFA: hazard ratio, 1.24; 95% confidence interval, .79-1.96; P = .35) and CRD (CBA vs RFA: hazard ratio, 1.19; 95% confidence interval, .82-1.73; P = .36). The CBA group had a higher stricture rate compared with the RFA group (10.4% vs 4.4%, P = .04). Conclusions Histologic outcomes of EET using CBA and RFA for dysplastic BE appear to be comparable. A randomized trial is needed to definitively compare outcomes between these 2 modalities.

The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow-up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1-year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1-year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1-point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5-0.79) in the validation set. Independent predictors of death or transplant during follow-up included higher MRS at the time of ERCP (P < 0.0001; hazard ratio [HR], 2.33 for every 1-point increase), lower total serum bilirubin before ERCP (P = 0.031; HR, 0.91 for every 1 mg/dL increase), and persistence of jaundice after endoscopic therapy (P = 0.003; HR, 2.30). Conclusion: Resolution of jaundice after endoscopic treatment of biliary strictures is associated with longer transplant-free survival of patients with PSC. The likelihood of resolution is affected by demographic, hepatic, and biliary variables and can be predicted using noninvasive data. These findings may refine the use of ERCP in patients with jaundice with PSC.

Purpose: As the prevalence of provider burnout continues to increase, it is critical to identify interventions that may impact provider satisfaction, such as an integrated clinical pharmacist. This study aimed to assess the perceived effect of pharmacist integration on primary care provider satisfaction and drivers of provider burnout in the primary care setting. Methods: A cross-sectional survey with 11 questions across 4 domains was distributed to primary care providers in a large integrated health system. Results: Of 295 providers invited to take the survey, 119 responded (40% response rate). Most providers had worked with a pharmacist for at least 2 years and utilized them weekly or daily. At least 87% of provider respondents strongly agreed or somewhat agreed that the integrated clinical pharmacist reduced their workload by working directly with patients and non-provider staff, improved overall medication use, helped patients meet health goals and quality measures, and overall helped them to effectively manage their panel of patients. Providers found greater meaning in work through the presence of the clinical pharmacist, which allowed them more time to focus on professionally fulfilling aspects of their work and helped them feel less emotional exhaustion. Overall, 91% of providers were extremely satisfied with the clinical pharmacy service. Conclusions: These findings may be used to justify the expansion of clinical pharmacy services in primary care to practice areas experiencing problems with 4 specific drivers of provider burnout: workload and job demands, efficiency and resources, meaning in work, and social support and community at work.

Objective To assess the effect of a pharmacist-driven, polymerase chain reaction (PCR)−based nasal screening protocol for methicillin-resistant Staphylococcus aureus (MRSA) on vancomycin therapy duration and on rates of adverse drug events and 30-day hospital readmission. Patients and Methods From July 8, 2017, through January 31, 2019, we performed a retrospective, multicenter, preimplementation-postimplementation study. Patients with a vancomycin order to treat lower respiratory tract infection (LRTI) underwent MRSA PCR screening; tests were ordered by health care providers, including physicians, physician assistants, and advanced practice registered nurses. During the preimplementation period (July 8, 2017, through September 30, 2018), pharmacists could order MRSA PCR screening only after receiving a verbal order from a health care provider. During the postimplementation period (October 1, 2018, through January 31, 2019), a collaborative practice agreement allowed pharmacists to order MRSA PCR screening tests. Results The preimplementation group included 241 patients, and the postimplementation group included 74 patients. Of these patients, 124 in the preimplementation group and 62 in the postimplementation group received MRSA PCR screening. Twenty patients (16.1%) in the preimplementation group and 9 (14.5%) in the postimplementation group had a positive MRSA PCR screening test result (between-group difference, 1.6%; P=.80). Duration of therapy was significantly shorter in the postimplementation group (median [interquartile range], 14.3 [5.0-28.6] hours vs 24.0 [12.4-47.0] hours; P Conclusion Vancomycin therapy carries a risk of adverse events and may increase health care costs. A pharmacist-driven protocol for MRSA nasal swab PCR screening effectively reduces the duration of vancomycin therapy for patients with lower respiratory tract infection.

The US government affirmed the opioid epidemic as a public health emergency in late 2017. Prior to that, as part of the Heroin, Opiate, Prevention, and Education (HOPE) Agenda, the state of Wisconsin enacted 2015 Wisconsin Act 266. This law, which went into effect April 1, 2017, requires prescribers to review data from the state's enhanced Prescription Drug Monitoring Program (ePDMP) before issuing an opioid prescription, in order to reduce inappropriate prescriptions and, ultimately, decrease opioid overuse.To evaluate the effect of 2015 Wisconsin Act 266 on opioid prescriptions for acute pain in Mayo Clinic Health System sites in northwest Wisconsin.This retrospective review included all eligible patients who were discharged from emergency or urgent care departments in the Mayo Clinic Health System at northwest Wisconsin sites during the study period. The quantity of opioids prescribed (measured in morphine milligram equivalents per patient encounter) and the total number of opioid prescriptions were compared for the periods May and June 2016 (prior to implementation of Act 266) versus May and June 2017 (post-implementation of Act 266).A 33% reduction occurred in the median opioid quantity prescribed per patient encounter in the post-implementation period vs the pre-implementation period (The HOPE Agenda, specifically 2015 Wisconsin Act 266, appears to have had a positive effect on decreased opioid prescriptions for acute pain at Mayo Clinic Health System sites in northwest Wisconsin.

Background and Aims Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett’s esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort. Methods Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). Results Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM. Conclusions These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett’s esophagus.

Background Benzodiazepines are the conventional mainstay to manage alcohol withdrawal; however, patients are subsequently at increased risk for poor sleep, cravings, and return to drinking. Research on alternative pharmacologic agents to facilitate safe alcohol withdrawal is scant. Gabapentin is one medication shown in small studies to reduce the need for benzodiazepines in the setting of alcohol withdrawal. The continuation of gabapentin after alcohol withdrawal appears to be safe during early sobriety and may aid in reducing alcohol-related cravings or returning to alcohol consumption. Use of a gabapentin-based, benzodiazepine-sparing protool began in early 2015 by the Mayo Clinic, Rochester, Consultation-Liaison Psychiatry Service. Objective A retrospective chart review was conducted to detect any safety concerns with use of a gabapentin protocol for alcohol withdrawal syndrome. Methods Secondary outcomes were derived by comparing a matched cohort of patients who received benzodiazepines for alcohol withdrawal syndrome. Results Seventy-seven patients had their alcohol withdrawal managed via a gabapentin protocol during the study period. No patients required transfer to a higher level of care or had a documented withdrawal seizure. Length of stay between the gabapentin protocol group and benzodiazepine group were similar. Conclusion This preliminary data has supported the frequent use of this protocol in the general internal medicine practice and formalization of an institutional order set of this protocol for mild to moderate alcohol withdrawal syndrome. Prospective studies are required to validate findings.

Background Evidence supporting adjunctive corticosteroids during the treatment of Pneumocystis jirovecii pneumonia (PcP) in adults without HIV is minimal and controversial. Methods This retrospective cohort study included P jirovecii pneumonia-positive, hospitalized patients without HIV admitted to the Mayo Clinic from 2006 to 2016. Change from baseline in the respiratory component of the Sequential Organ Failure Assessment score (SOFAresp) at day 5 was compared between early (within 48 h) steroid recipients and nonrecipients by using multivariable logistic regression and in a propensity-matched analysis. Results Among the 323 included patients (early steroids, n = 258; no steroids, n = 65), the median (interquartile range) age was 65 (53, 73) years, 63% were male, and 92% were white. Severity-adjusted regression and propensity-matched analyses found that early administration of steroids was associated with less improvement in SOFAresp at day 5 compared with no steroids (P = .001 and P = .017, respectively). No differences were observed in the odds of having at least a one-point improvement in SOFAresp at day 5 compared with baseline between groups (adjusted OR, 0.76 [95% CI, 0.24-2.28]; P = .61). Overall 30-day mortality was 22.9% (95% CI, 18.2-27.4). No differences in mortality, length of stay, admission to the ICU, or need for mechanical ventilation were found between early steroid recipients and nonrecipients. Conclusions The addition of early corticosteroids to anti-Pneumocystis therapy in patients without HIV was not associated with improved respiratory outcomes.

Objective To determine whether a pharmacist visit after hospital dismissal for patients taking at least 1 medication that places patients at high risk for emergent hospital admissions (termed high-risk medication) would decrease the risk of hospital readmission at 30 days compared with usual care. Patients and Methods This was a retrospective study at a tertiary care center conducted from July 26, 2013, through April 1, 2016. We reviewed outcomes among patients who did or did not have a post–hospital dismissal pharmacist visit immediately before a clinician visit. We included patients who were at least 18 years old and were taking at least 10 total medications at hospital dismissal, 1 or more of which were high-risk medications. A Cox proportional hazards model was used to compare the risk of 30-day readmission between the groups. Results The study cohort included 502 patients in each group (pharmacist + clinician group and clinician-only group). After adjusting for differences in background demographic characteristics, patients in the pharmacist + clinician group were significantly less likely to be readmitted to the hospital within 30 days postdismissal compared with the clinician-only group (hazard ratio, 0.49; 95% CI, 0.35-0.69; P Conclusion Patients seen by a pharmacist immediately before a clinician visit after hospital dismissal had a lower risk of readmission than patients who had a clinician-only visit. Patients taking high-risk medications for hospital admissions are ideal candidates for pharmacist involvement.

Purpose Results of a study of prescribers’ responses to a pharmacogenomics-based clinical decision support (CDS) alert designed to prompt thiopurine S -methyltransferase (TPMT) status testing are reported. Methods A single-center, retrospective, chart review–based study was conducted to evaluate prescriber compliance with a pretest CDS alert that warned of potential thiopurine drug toxicity resulting from deficient TPMT activity due to TPMT gene polymorphism. The CDS alert was triggered when prescribers ordered thiopurine drugs for patients whose records did not indicate TPMT status or when historical thiopurine use was documented in the electronic health record. The alert pop-up also provided a link to online educational resources to guide thiopurine dosing calculations. Results During the 9-month study period, 500 CDS alerts were generated: in 101 cases (20%), TPMT phenotyping or TPMT genotyping was ordered; in 399 cases (80%), testing was not ordered. Multivariable regression analysis indicated that documentation of historical thiopurine use was the only independent predictor of test ordering. Among the 99 patients tested subsequent to CDS alerts, 70 (71%) had normal TPMT activity, 29 (29%) had intermediate activity, and none had deficient activity. The online resources provided thiopurine dosing recommendations applicable to 24 patients, but only 3 were prescribed guideline-supported doses after CDS alerts. Conclusion The pretest CDS rule resulted in a large proportion of neglected alerts due to poor alerting accuracy and consequent alert fatigue. Prescriber usage of online thiopurine dosing resources was low.

Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients. This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries. A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions. This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.

Background There is demonstrated benefit with fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing resistance necessitate investigation of alternative therapies. Objectives To compare the incidence of febrile neutropenia in high-risk patients with haematological malignancy receiving a fluoroquinolone with those receiving an oral third-generation cephalosporin (OTGC) as antibacterial prophylaxis during chemotherapy-induced neutropenia. Methods A retrospective, matched, single-centre study comparing clinical and microbiological outcomes in acute leukaemia patients receiving fluoroquinolones versus OTGCs as antibacterial prophylaxis after chemotherapy. Results A total of 120 patients (levofloxacin n = 80, OTGC n = 40) were included and matched. The 30 day incidence of febrile neutropenia was 89.7% (95% CI = 82.4-93.9). The rates of febrile neutropenia were similar between antimicrobials (OTGC versus levofloxacin HR = 0.90, 95% CI = 0.54-1.52, P = 0.70). The most frequent site of infection was the bloodstream (line related) (n = 24, 62%) and the majority (n = 28, 72%) of infections were caused by Gram-positive organisms. Groups were similar in terms of site of infection (P = 0.91) and morphology of recovered microorganisms (P = 0.74). There were significantly more cultures positive for Enterobacter spp. in the OTGC group (P = 0.043). Three patients died during follow-up (from first dose up to 30 days after the last dose) (30 day survival = 99.2%, 95% CI = 97.5-100), with only two of the reported deaths attributable to infection. Conclusions These findings demonstrate comparable rates of febrile neutropenia and culture positivity with an increase in cultures positive for Enterobacter spp. when OTGCs are compared with levofloxacin for antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted.

Background Due to the malabsorptive nature of the Roux-en-Y gastric bypass (RYGB), there is a potential for impaired absorption of oral medications. Clinical outcomes of patients who receive oral antibiotics after RYGB have not been adequately described in the literature. Objectives The primary objective was composite therapeutic failure. Secondary objectives included comparing failure rates between antibiotic classes and at various time points since RYGB. Setting University hospital, United States. Methods Patients with a history of RYGB and controls who received an eligible oral antibiotic for urinary tract infection, skin and soft tissue infection, or community acquired pneumonia between April 1, 2008, and September 30, 2015, were included via retrospective chart review. Therapeutic failure rates between groups were compared and adjusted for body mass index and infection type. Failure rates among antibiotic classes and various time points since RYGB (0–1 yr, 1–1.9 yr, and≥2 yr) were also compared. Results A total of 58 RYGB and 128 controls met inclusion and exclusion criteria. Composite therapeutic failure occurred in the RYGB and control group in 14 (24.1%) and 20 patients (15.6%), respectively (P = .18; odds ratio, 1.8; 95% confidence interval .8–4.4). RYGB patients who received fluoroquinolones or sulfonamides had a significantly increased risk of therapeutic failure. Conclusions RYGB was not associated with a statistically significant increased risk of composite therapeutic failure of oral antibiotics in the treatment of urinary tract infection, skin and soft tissue infection, or community acquired pneumonia compared with patients with no history of gastrointestinal resection. Further research is warranted to understand clinical outcomes of RYGB patients who receive oral antibiotics.

Low-grade dysplasia (LGD) is a risk factor for progression in Barrett's esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess predictors of progression in a multicenter BE-LGD cohort.All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression.244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5-139.4) in a propensity score stratified model.In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.

Rationale The relationship between depressive symptoms and adverse outcomes for patients with cardiac problems has been well established for several decades. However, less is known about other factors that may influence psychosocial outcomes for cardiac patients. Objective To evaluate the association between baseline happiness and depressed mood on later psychosocial functioning among cardiac patients. Method Participants ( N = 250) were patients who had received medical treatment at an academic medical center for a cardiac event. Participants completed questionnaires at two time points: Approximately 2 weeks after they had been discharged from the hospital (baseline) and again 12 weeks later. Participants completed validated measures of depressed mood, happiness, health distress, expectations about health, and quality of life. Results Baseline depressed mood and happiness both significantly predicted health-related distress and depressive symptoms at follow up. Happiness ratings were associated with lower distress and depressed mood, whereas scores for depressive symptoms showed the opposite pattern. Happiness, but not depressed mood, was a significant predictor of more positive quality of life ratings. Conversely, only depressed mood was a significant predictor of less positive expectations about health. Conclusion The results of this study suggest that investigating positive baseline affect in addition to depressed mood provides additional useful information that may help explain why some patients have more negative outcomes following cardiac events.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m2), obese (30–39.9 kg/m2), and morbidly obese (⩾ 40 kg/m2). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82–1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62–1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.