Dierkhising, Ross

ObjectivesThe primary objective of this study was to determine whether pharmacist‐clinician collaborative (PCC) visits within 7 days after hospital discharge (early‐visit cohort) would reduce the risk of 30‐day hospital readmission compared with PCC visits eight or more days after hospital discharge (late‐visit cohort).MethodsThis retrospective study of adult primary care patients was conducted from July 26, 2013 to April 1, 2016. Patients who were included were receiving at least one medication that put them at high risk for emergent hospital admission and at least 10 total medications. A Cox proportional hazards model was used to assess 30‐day readmission risk between the two groups.ResultsThe early‐visit cohort included 393 patients; the late‐visit cohort included 109 patients. After adjusting for statistically different baseline characteristics and the LACE index score (which predicts the risk of death or unplanned readmission within 30 days after hospital discharge), 30‐day readmission risk was not significantly different between the late‐visit cohort and the early‐visit cohort (hazard ratio, 0.8; 95% confidence interval [CI], 0.34‐1.88; P = 0.61). Similarly, the difference was not significant 60 and 180 days after the PCC visit.ConclusionPatients in the early‐visit cohort had no greater risk of readmission 30 days after the visit than patients in the late‐visit cohort. Although previous research indicates that PCC visits may have significant benefits for decreasing readmission risk, delaying them may not increase the patient's risk. This finding may allow more flexibility in scheduling a pharmacist and a primary care clinician to meet with the patient.

Abstract Background Limited data exist to evaluate safety-related outcomes in Outpatient Parenteral Antimicrobial Therapy (OPAT) patients treated with antimicrobial agents for Gram-positive infections. Methods This retrospective, single-center study enrolled Mayo Clinic OPAT patients between 2013 and 2017. The primary objective of the study compared rates of therapy modification due to drug-related toxicity for staphylococcal infections treated with ceftriaxone, cefazolin, nafcillin, oxacillin, vancomycin, daptomycin, ceftaroline, linezolid, or ertapenem. Secondary objectives included determination of the frequency and type of adverse drug events (ADEs) attributed to OPAT and rate of readmission due to ADEs attributed to OPAT. Results One hundred seventy-two patients were identified (cefazolin n = 54, ceftriaxone n = 49, vancomycin n = 30, daptomycin n = 16, nafcillin n = 9, ertapenem n = 6, ceftaroline n = 4, oxacillin n = 3, linezolid n = 1). The overall treatment completion rates were high (153/172, 89.0%). Patients completed an average of 35.3 days (7 to 95) of therapy with their original antibiotic. Fourteen patients required change to a different antibiotic due to antimicrobial toxicity (ceftriaxone=5; vancomycin=2; cefazolin = 2; daptomycin = 2; ceftaroline = 1; nafcillin = 1; oxacillin = 1) and five patients experienced treatment failure required an additional agent (ceftriaxone = 2; nafcillin = 2; linezolid = 1). Adverse drug events (ADEs) were the most common reason for antimicrobial adjustment (14/19, 73.7%). The most common ADEs were hypokalemia (28/172, 16.3%) and diarrhea (25/172, 14.5%). There were only two cases of Clostridium difficile. Thirty-day readmissions due to antimicrobial therapy were low with 11 patients. Conclusion OPAT with Gram-positive agents used for staphylococcal infections is effective, but antimicrobial modifications still occur. Clinicians should be aware of the risk of ADEs and readmissions in OPAT patients. A multidisciplinary approach may enhance management of ADEs and possibly preventing readmissions Disclosures All authors: No reported disclosures.

Background: Antibiotic therapy with a macrolide and β-lactam or a fluoroquinolone for the empirical treatment of community-acquired pneumonia (CAP) in an inpatient non–intensive care setting is recommended per guidelines. Studies show that these treatments have similar outcomes, including death, adverse effects, and bacterial eradication. However, a comparison of 30-day readmission rates between these treatments is limited. Study Question: To determine whether 30-day readmissions for patients treated for CAP in a regional hospital differed between a fluoroquinolone monotherapy and a β-lactam plus macrolide combination therapy. Study Design: Retrospective cohort study of patients aged ≥18 years with a CAP diagnosis who were admitted to the same regional hospital from December 1, 2011, through December 1, 2016. Measures and Outcomes: Patients receiving a third-generation cephalosporin plus macrolide were compared with those receiving a respiratory fluoroquinolone. Exclusion criteria were concurrent or recent use of the study antibiotics; death, transfer, or transition to hospice; and diagnosis of hospital-acquired pneumonia or health care–associated pneumonia. The collected data were 30-day readmission rates, antibiotic regimens, demographic characteristics, and pneumonia severity index and comorbidity scores. Association between treatment group and readmissions was assessed with logistic regression. Association between readmissions and individual data points between the 2 treatment groups was calculated with multivariate regression and odds ratio (95% confidence interval). Results: Of 432 patients, 171 met inclusion criteria (fluoroquinolone group, n = 101; β-lactam plus macrolide group, n = 70). Thirty-day readmissions were not significantly different between the fluoroquinolone group and β-lactam plus macrolide group (P = 0.58). Increased 30-day readmissions were independently associated with male sex and hospital length of stay (P < 0.05). Length of stay was approximately 3 days and did not differ between treatment groups. Conclusions: No difference was seen in 30-day readmissions between CAP patients who received fluoroquinolone monotherapy and those who received β-lactam plus macrolide combination therapy.

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.

AbstractBackgroundTacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.MethodsTo assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.ResultsThe median percent tacrolimus dose change was an increase of 66.7% (IQR28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR−52.3%, −30.9%). Five cases of allograft rejection were observed.ConclusionIn conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.

Study Objective Serum creatinine ( S c r ) concentration is used to calculate estimated glomerular filtration rate (e GFR ) for medication dosing. Serum cystatin C (CysC) concentration has been proposed as an adjunct or alternative to S cr . This study sought to evaluate the possible impact of using CysC in eGFR equations on drug dose recommendations in hospitalized patients with infections. Design Retrospective analysis of prospectively collected data. Setting Large academic tertiary care medical center. Patients A total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015. Measurements and Main Results Standardized S c r and CysC measured at the time of antibiotic dosing were used to estimate GFR from the three Chronic Kidney Disease Epidemiology Collaborative ( CKD ‐ EPI ) equations using S c r (eGFR Cr ), CysC( eGFR CysC ), or a combination of S c r and CysC (eGFR Cr‐CysC ), and these values were compared with estimated creatinine clearance (eCl cr ) from the Cockcroft‐Gault equation (standard of care for drug dosage adjustments). The eGFR s were categorized into five common dosage adjustment strata (lower than 20, 20–49, 50–79, 80–130, and higher than 130 ml/min), and agreement between equations was tested with the weighted κ statistic. Recommended drug doses varied considerably between the eC l cr and the CKD ‐ EPI equations (weighted κ [95% confidence interval]: eGFR Cr 0.73 [0.68–0.79], eGFR CysC 0.42 [0.35–0.5], eGFR Cr‐CysC 0.65 [0.6–0.71]). If eGFR Cr, eGFR CysC , or eGFR Cr‐CysC were used instead of eC l cr to dose drugs, 11%, 12%, and 8% of doses, respectively, would be higher, and 12%, 38%, and 24% of doses, respectively, would be lower. Conclusion Significant discordance in drug doses was observed when the CKD ‐ EPI equations were used in place of eCl cr . When CysC was included in eGFR equations, recommended doses were often lower. Further study is needed to develop and test drug‐specific dosing guidelines that incorporate alternate renal biomarkers and/or more contemporary eGFR equations.

AbstractBackgroundThe mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements.MethodsTwenty‐four‐hour pH impedance studies performed off medications in Caucasian men with a normal endoscopic examination were assessed for level of acid exposure and MNBI. Four patient groups were studied: Group 1, Not obese and normal acid exposure; Group 2, Obese and normal acid exposure; Group 3, Not obese and increased acid exposure; and Group 4, Obese with increased acid exposure.ResultsOne hundred patients were studied (25 in each group). Mean esophageal mucosal impedance (MI) was substantially lower in obese patients without reflux (Group 2) and non‐obese patients with reflux (Group 3) compared to normal controls (non‐obese, no reflux, Group 1). MI was progressively lower in the distal (vs the proximal) esophagus in GER patients, compared to those without GER. This difference persisted in the presence or absence of obesity. In contrast, in obese patients, the mean MI was significantly lower throughout the esophagus when compared to the non‐obese patients and also persisted in the presence and absence of accompanying reflux. Obesity and reflux were both independently negatively correlated with MI.ConclusionObesity is associated with abnormal esophageal MNBI. In contrast to gastro‐esophageal reflux, this decrease is pan‐esophageal. These data may support a systemic mechanism by which obesity alters the esophageal barrier function.

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.

Left ventricular assist device (LVAD) pump thrombosis occurs in up to 8.4% of patients within 3-months postimplantation. Thromboelastography (TEG) could be used to signal hypercoagulability at LVAD implantation to predict patients at high risk for thrombosis. We sought to evaluate whether TEG maximum amplitude (MA) hypercoagulability (MA ≥69 mm) at the time of LVAD implantation predicts pump thrombosis. A single center, retrospective, nested case–control study was conducted using patients from January 1, 2005, to March 31, 2015. Each pump thrombosis case was matched to two control subjects based on age ± 5 years, sex, and duration of follow-up. A multivariable logistic regression analysis was performed on the matched sets; the odds ratio with 95% confidence interval (CI) was calculated to estimate the relative risk. Thirty-seven age- and sex-matched case–control sets were included for a total of 111 study participants. TEG-MA hypercoagulability occurred in 10.8% of the case group versus 6.8% of controls. There was no association between TEG-MA hypercoagulability and device thrombosis (odds ratio 1.71, 95% confidence interval 0.42–7.05, p = 0.46). Utilization of baseline TEG-MA hypercoagulability to detect individuals at risk for LVAD thrombosis is a novel concept. This study found no significant association between TEG-MA and LVAD thrombosis.