Impact of 2016 UNOS pediatric heart allocation policy changes on VAD utilization, waitlist, and post-transplant survival outcomes in children with CHD versus Non-CHD.

AIMS: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post-heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non-CHD patients before (Era-1) and after (Era-2) pediatric heart allocation policy implementation. METHODS: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era-1 and Era-2. RESULTS: 5551 patients were listed for HT, of whom 2447(44%) were in Era-1 and 3104(56%) were in Era-2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era-2, whereas the number of non-CHD patients listed as status 1A decreased, but status 1B increased. In Era-2 compared to Era-1, both temporary (1% to 4%, p < .001) and durable VAD (13.6% to 17.8%, p < .001) utilization increased, and the transplantation rate per 100-patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p = .06), whereas for non-CHD patients it decreased from 61 to 54 days (p < .001). Adjusted 90-day WL survival increased from 84% to 88%, p = .016 in CHD, but there was no significant change in non-CHD patients (p = .57). There was no significant difference in 1-year post-HT survival in CHD and non-CHD patients between Era-1 and Era-2. CONCLUSIONS: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non-CHD cohort, and 90-day WL survival probability improved in children with CHD without significant change in 1-year post-HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post-HT survival.

Do outcomes for heart transplantation differ based on donor and recipient race?

PURPOSE: There are limited data examining the impact of both donor and recipient race on outcomes following orthotopic heart transplant (OHT). The purpose of this study was to evaluate the relationship between donor and recipient race and OHT outcomes. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. A comparison was conducted based on donor and recipient race (White, Black, Hispanic, Other/Unknown). Races for which there were limited numbers were excluded from the analysis (Asian, n = 1292; American Indian, n = 132; Pacific Islander, n = 132, Multiple ethnicities, n = 225). The primary endpoint was survival at 30 days, 1 year survival, and post-transplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: A total of 41 841 OHT were included. Of the recipients, 29 894 (71%) were White, 8475 (20%) were Black, and 3472 (8%) were Hispanic. Of the donors 27 783 (66%) were White, 6277 (15%) were Black, 6576 (16%) were Hispanic, and 1205 (3%) were Unknown/Other race. In a comparison of recipient demographics, White recipients were older (54.09 ± 12.21 years) compared to Black (49.44 ± 12.83 years) and Hispanic (49.97 ± 13.27 years) recipients. All other differences between groups were not clinically significant. Black recipients were more likely to receive a heart with an "urgent" status (probability .80) compared to White (.73) and Hispanic (.75) recipients (p < .001). Hispanic recipients were more likely to receive a transplant when listed as "non-urgent" (Probability .47) compared to White (.37) and Black (.30) recipients (p < .001). In terms of outcomes, compared to White recipients, Hispanic patients experienced a decreased 30-day survival (OR 1.27; p = .011) and 1-year survival (OR 1.17; p = .016). In comparing Donor/Recipient combinations compared to a White Donor/White Recipient combination, overall survival was decreased in White donor/African American recipient (HR 1.36; p < .001), African American donor/African American recipient (HR 1.41; p < .001) and Hispanic donor/African American recipient (HR 1.30; p < .001) combinations (Table 1). CONCLUSIONS: African American and Hispanic recipients have decreased survival compared to White recipients after heart transplant. The African American donor does not decrease survival. Racial differences still exist in donor and recipient characteristics and recipient outcomes after OHT. Increasing the donor pool for all races and ethnicities would potentially benefit all recipients. Continued study is warranted in order to minimize these differences among recipients and identify factors that could be contributing to decreased survival, in order to optimize outcomes for African American and Hispanic recipients post-transplant and eliminate disparities.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

BACKGROUND: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. OBJECTIVE: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. DESIGN: Cross-sectional study. SETTING: Four U.S. community-based epidemiologic cohort studies with mGFR. PATIENTS: 3223 participants in 4 studies. MEASUREMENTS: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. RESULTS: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR - eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. LIMITATION: Single measurement of mGFR and serum markers without short-term replicates. CONCLUSION: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. PRIMARY FUNDING SOURCE: National Institutes of Health.

Pulmonary Surface Irregularity Score as a New Quantitative CT Marker for Idiopathic Pulmonary Fibrosis-a Pilot Study.

The purpose of this study is to evaluate the accuracy and inter-observer agreement of a quantitative pulmonary surface irregularity (PSI) score on high-resolution chest CT (HRCT) for predicting transplant-free survival in patients with IPF. For this IRB-approved HIPAA-compliant retrospective single-center study, adult patients with IPF and HRCT imaging (N = 50) and an age- and gender-matched negative control group with normal HRCT imaging (N = 50) were identified. Four independent readers measured the PSI score in the midlungs on HRCT images using dedicated software while blinded to clinical data. A t-test was used to compare the PSI scores between negative control and IPF cohorts. In the IPF cohort, multivariate cox regression analysis was used to associate PSI score and clinical parameters with transplant-free survival. Inter-observer agreement for the PSI score was assessed by intraclass correlation coefficient (ICC). The technical failure rate of the midlung PSI score was 0% (0/100). The mean PSI score of 5.38 in the IPF cohort was significantly higher than 3.14 in the negative control cohort (p < .001). In the IPF cohort, patients with a high PSI score (≥ median) were 8 times more likely to die than patients with a low PSI score (HR: 8.36; 95%CI: 2.91-24.03; p < .001). In a multivariate model including age, gender, FVC, DLCO, and PSI score, only the PSI score was associated with transplant-free survival (HR:2.11 per unit increase; 95%CI: 0.26-3.51; p = .004). Inter-observer agreement for the PSI score among 4 readers was good (ICC: 0.88; 95%CI: 0.84-0.91). The PSI score had high accuracy and good inter-observer agreement on HRCT for predicting transplant-free survival in patients with IPF.

Multiinstitutional Evaluation of the Liver Surface Nodularity Score on CT for Staging Liver Fibrosis and Predicting Liver-Related Events in Patients With Hepatitis C.

BACKGROUND. In single-institution multireader studies, the liver surface nodularity (LSN) score accurately detects advanced liver fibrosis and cirrhosis and predicts liver decompensation in patients with chronic liver disease (CLD) from hepatitis C virus (HCV). OBJECTIVE. The purpose of this study was to assess the diagnostic performance of the LSN score alone and in combination with the (FIB-4; fibrosis index based on four factors) to detect advanced fibrosis and cirrhosis and to predict future liver-related events in a multiinstitutional cohort of patients with CLD from HCV. METHODS. This retrospective study included 40 consecutive patients, from each of five academic medical centers, with CLD from HCV who underwent nontargeted liver biopsy within 6 months before or after abdominal CT. Clinical data were recorded in a secure web-based database. A single central reader measured LSN scores using software. Diagnostic performance for detecting liver fibrosis stage was determined. Multivariable models were constructed to predict baseline liver decompensation and future liver-related events. RESULTS. After exclusions, the study included 191 patients (67 women, 124 men; mean age, 54 years) with fibrosis stages of F0-F1 (n = 37), F2 (n = 44), F3 (n = 46), and F4 (n = 64). Mean LSN score increased with higher stages (F0-F1, 2.26 ± 0.44; F2, 2.35 ± 0.37; F3, 2.42 ± 0.38; F4, 3.19 ± 0.89; p < .001). The AUC of LSN score alone was 0.87 for detecting advanced fibrosis (≥ F3) and 0.89 for detecting cirrhosis (F4), increasing to 0.92 and 0.94, respectively, when combined with FIB-4 scores (both p = .005). Combined scores at optimal cutoff points yielded sensitivity of 75% and specificity of 82% for advanced fibrosis, and sensitivity of 84% and specificity of 85% for cirrhosis. In multivariable models, LSN score was the strongest predictor of baseline liver decompensation (odds ratio, 14.28 per 1-unit increase; p < .001) and future liver-related events (hazard ratio, 2.87 per 1-unit increase; p = .03). CONCLUSION. In a multiinstitutional cohort of patients with CLD from HCV, LSN score alone and in combination with FIB-4 score exhibited strong diagnostic performance in detecting advanced fibrosis and cirrhosis. LSN score also predicted future liver-related events. CLINICAL IMPACT. The LSN score warrants a role in clinical practice as a quantitative marker for detecting advanced liver fibrosis, compensated cirrhosis, and decompensated cirrhosis and for predicting future liver-related events in patients with CLD from HCV.

Enhanced recovery after surgery multimodality pain regimen performs similar to PRN narcotics on outcomes and pain control after cardiac surgery: A quality improvement project.

BACKGROUND: While enhanced recovery after surgery (ERAS) pathways have been successfully applied for cardiac surgery, there has been limited research directly comparing ERAS protocols to ad hoc narcotic use after surgery. We hypothesized that a standardized ERAS protocol would provide similar pain management and psychoemotional outcomes while decreasing the use of opioids in the hospital and after discharge. METHODS: As part of a 7-month quality improvement project, cardiac surgery patients on a fast-tracked to extubate pathway were assigned pro re nata (PRN) narcotic pain management for 3 months (n = 49). After a 1-month ERAS protocol optimization period, a separate group of patients were given the ERAS protocol (n = 34). Clinical outcomes were gathered, and participants completed a quality of recovery survey that allowed for the assessment of pain and symptom control at four-time points after surgery. RESULTS: Among 83 participants, 66% were male and the mean age was 53 years. There were no differences in patient characteristics between PRN and ERAS groups (all p > .244). There were no differences between ERAS and PRN groups for surgery characteristics (all p > .060), inpatient outcomes (all p > .658), or after-discharge outcomes (all p > .397). Furthermore, across all time-point comparisons, there were no supported differences in patient-reported outcome and pain control between the ERAS and PRN narcotic groups (all p > .075). CONCLUSIONS: An ERAS protocol demonstrated similar patient outcomes and pain control to traditional opioid use for postoperative cardiac surgery patients. Further research is recommended to further confirm the results of this study.

Low-energy Gunshot-induced Tibia Fractures: What Proportion Develop Complications?

BACKGROUND: Gunshot injuries of the extremities are common in the United States, especially among people with nonfatal gunshot wounds. Controversy persists regarding the proper management for low-energy gunshot-induced fractures, likely stemming from varying reports on the likelihood of complications. There has yet to be published a study on a large cohort of patients with gunshot-induced tibia fractures on which to base our understanding of complications after this injury. QUESTIONS/PURPOSES: (1) What percentage of patients with low-energy gunshot-induced tibia fractures developed complications? (2) Was there an association between deep infection and fracture location, injury characteristics, debridement practices, or antibiotic use? METHODS: This was a multicenter retrospective study. Between January 2009 and December 2018, we saw 201 patients aged 16 years or older with a gunshot-induced fracture who underwent operative treatment; 2% (4 of 201) of those screened had inadequate clinical records, and 38% (76 of 201) of those screened had inadequate follow-up for inclusion. In all, 121 patients with more than 90 days of follow-up were included in the study. Nonunion was defined as a painful fracture with inadequate healing (fewer than three cortices of bridging bone) at 6 months after injury, resulting in revision surgery to achieve union. Deep infection was defined according to the confirmatory criteria of the Fracture-Related Infection Consensus Group. These results were assessed by a fellowship-trained orthopaedic trauma surgeon involved with the study. Complication proportions were tabulated. A Kaplan-Meier chart demonstrated presentations of deep infection by fracture location (proximal, shaft, or distal). Univariate statistics and multivariate Cox regression were used to examine the association between deep infection and fracture location, entry wound size, vascular injury, intravenous (IV) antibiotics in the emergency department (ED), deep and superficial debridement, the duration of postoperative IV antibiotics, and the use of topical antibiotics, while adjusting for age, race/ethnicity, smoking status, and BMI. A power analysis for the result of deep infection demonstrated that we would have had to observe a hazard ratio of 4.28 or greater for shaft versus proximal locations to detect statistically significant results at 80% power and alpha = 0.05. RESULTS: The overall complication proportion was 49% (59 of 121), with proportions of 14% (17 of 121) for infection, 27% (33 of 121) for wound complications, 20% (24 of 121) for nonunion, 9% (11 of 121) for hardware breakage, and 26% (31 of 121) for revision surgery. A positive association was present between deep infection and deep debridement (HR 5.51 [95% confidence interval 1.12 to 27.9]; p = 0.04). With the numbers available, we found no association between deep infection and fracture location, entry wound size, vascular injury, IV antibiotics in the ED, superficial debridement, the duration of postoperative IV antibiotics, and the use of topical antibiotics. CONCLUSION: In this multicenter study, we found a higher risk of complications in operative gunshot-induced tibia fractures than prior studies have reported. Infection, in particular, was much more common than expected based on prior studies. Consequently, surgeons might consider adopting the general management principles for nongunshot-induced open tibia fractures with gunshot-induced fractures, such as the use of IV antibiotics both initially and after surgery. Further research is needed to test and validate these approaches. LEVEL OF EVIDENCE: Level IV, therapeutic study.

The effects of increased donor support time from organ donation referral to donor procurement on heart transplant recipient survival.

INTRODUCTION: Given the known deleterious cardiac effects of brain death (BD) physiology, we hypothesized that time from cardiac donation referral to procurement (donor support time [DST]), would negatively impact cardiac transplant recipient survival. METHODS: The United Network for Organ Sharing database was queried from 2007 to 2018, identifying 22,593 donor hearts for analysis. Multivariate logistic models for 30-day and 1-year survival, as well as Cox models for overall survival and posttransplant rejection, were used to assess adjusted outcomes. RESULTS: median DST was 3 days (interquartile range: 2-5 days). Ischemic time; distance between donor and recipient hospitals; and recipient age, creatinine, waitlist time, and length of stay were adjusted predictors of survival and rejection. DST was not associated with either outcome in aggregate; however, differential association by donor race was identified, with DST in any race recipient associated with 4% higher odds of 1-year mortality (p = .001; p value for interaction .005) but only a trend towards worse overall mortality (p = .064; p value for interaction .046). CONCLUSION: Thus, duration of exposure to BD physiology may have a differential impact on recipient outcomes based on donor race, suggesting that additional research is needed on donor immunologic, socioeconomic, and healthcare access factors that may impact cardiac transplant recipient outcomes.

Initial Institutional Experience with 18F-Fluciclovine PET-CT in Biochemical Recurrence of Prostate Cancer.

OBJECTIVES: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. METHODS: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. RESULTS: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. CONCLUSIONS: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

Third-trimester in utero fetal brain diffusion tensor imaging fiber tractography: a prospective longitudinal characterization of normal white matter tract development.

BACKGROUND: White matter is responsible for inter-neuronal connections throughout the brain that are a driving force in cognitive development. Diffusion tensor imaging (DTI) fiber tractography has been used to evaluate white matter development in the fetal brain; however, longitudinal studies of DTI fiber tractography to assess white matter development in the third trimester are lacking. OBJECTIVE: To characterize in utero longitudinal changes in the fetal brain DTI fiber tracts of normal third-trimester fetuses. MATERIALS AND METHODS: For this single-center prospective longitudinal observational pilot study, we recruited 28 pregnant females with normal third-trimester pregnancies who had routine prenatal ultrasound. MRI of the in utero fetal brain was performed with a Siemens 1.5-tesla (T) Espree scanner at 31 weeks, 33 weeks and 36 weeks of gestation, with 14 DTI tractography parameters quantified in 7 brain regions using DTI-studio version 2.4 (Johns Hopkins University, Baltimore, MD; n=98 measurements). We used multilevel mixed models to examine the relationship between longitudinal changes in DTI measurements and between 98 DTI measurements at 31 weeks and 4 routine fetal brain anatomical biometrics (n=392 assessments). RESULTS: We observed statistically significant decreases in radial diffusivity and apparent diffusion coefficient in 13 of 14 brain regions from 31 weeks to 36 weeks of gestation (P<0.001 for all regions except the genu of the corpus callosum). Significant decreases in radial diffusivity from weeks 33 to 36 and weeks 31 to 36 were seen in the corticospinal tracts, centrum semiovale, posterior limb of the internal capsule, and crus cerebri (P<0.001 for all). When considering all possible combinations of DTI fiber tract measurements and the routine morphological fetal brain biometrics, only 6% (24/392) had a significant association (P<0.05), indicating relative independence of the DTI fiber tract measurements from anatomical biometrics. CONCLUSION: In utero longitudinal changes in fetal brain DTI fiber tractography are quantifiable in normal third-trimester fetuses and are largely independent of morphological brain changes.

Single-Institution Experience of Synovial Sarcoma.

OBJECTIVES: The purpose of this study was to investigate the patient population and outcomes of synovial sarcoma at a single institution. METHODS: A retrospective review of the medical records of 28 patients with synovial sarcoma diagnosed from 1992 to 2017 was performed. Demographics, staging, disease location, treatment, and response to treatment were reviewed. RESULTS: Individuals with larger tumors at the time of presentation had an increased risk of death. An additional factor associated with poor prognosis in synovial sarcoma was increasing patient age. The patient population had a higher rate of nonextremity disease and lower overall survival when compared with national averages. CONCLUSIONS: Nonextremity disease and large size of tumor at presentation may have contributed to the disparity in institutional outcomes from the national averages. The advanced presentation of synovial sarcoma remains a significant challenge in improving patient survival.

The Effect of Cardiac Preservation Solutions on Heart Transplant Survival.

BACKGROUND: Limited data exist that compare the predominant cardiac preservation solutions (CPSs). MATERIALS AND METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 1, 2004 to March 31, 2018, for donor hearts. Of 34,614 potential donors, 21,908 remained after applying the exclusion criteria. The CPS analyzed included saline, the University of Wisconsin (UW), cardioplegia, Celsior, and Custodiol. The primary endpoints were recipient survival and posttransplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: Saline was used as the CPS in 2549 patients (12%), UW in 10,549 (48%), cardioplegia in 1307 (6%), Celsior in 5081 (23%), and Custodiol in 2422 (11%). Donor age ranged from 15 to 68 y (mean = 32.0 y, median = 30.0 y), and 71% were male. Adjusted survival probabilities of recipients whose donor hearts were procured with saline was 96% 30 d, 90% 1 y, UW: 97% 30 d, 92% 1 y, cardioplegia: 95% 30 d, 87% 1 y, Celsior: 96% 30 d, 90% 1 y, and Custodiol: 97% 30 d, 92% 1 y. When these comparisons were adjusted for donor age, sex, ethnicity, ischemic time, recipient age, sex, ethnicity, creatinine, ventricular assist device (VAD), length of stay, region and days on waiting list, cardioplegia solution was demonstrated to have a higher risk of death (30 d, 1 y, overall) and posttransplant rejection versus UW (odds ratio 1.70, P = 0.001; odds ratio 1.63, P < 0.001; hazard ratio 1.22, P < 0.001; hazard ratio 1.21, P < 0.001, respectively). CONCLUSIONS: Cardioplegia solutions for cardiac preservation are associated with a higher mortality in heart transplant recipients.

Pharmacist linkage in care transitions: From academic medical center to community.

OBJECTIVES: To improve the care of patients discharged from the University of Mississippi Medical Center (UMMC) after treatment for acute myocardial infarction, heart failure, pneumonia, and chronic obstructive pulmonary disease; reduce preventable hospital readmissions; and inform future care transition collaborations between hospital teams and community pharmacies. SETTING: Study was conducted at UMMC, UMMC outpatient pharmacies, and targeted community pharmacies. PRACTICE DESCRIPTION: UMMC is the state's only academic health science center, providing all levels of care. Participants were at UMMC's 722-bed hospital in Jackson, MS. Participating pharmacies included 2 UMMC outpatient pharmacies and community pharmacy research partner sites within 60 miles of UMMC. PRACTICE INNOVATION: A pharmacist transitions coordinator (PTC) worked with inpatient and community-based pharmacists to provide predischarge medication reconciliation and 30 days of medications on discharge. The PTC with access to inpatient and outpatient records facilitated communication among settings/providers. Community pharmacists provided telephonic and face-to-face medication therapy management (MTM). EVALUATION: The project was structured as a prospective, randomized controlled trial of pharmacist-led care coordination during transition from inpatient to community setting, with follow-up MTM by community pharmacists. In this intention-to-treat analysis, readmission rates were assessed with propensity adjustment. Drug therapy problems (DTPs) identified/resolved were assessed and reported through descriptive statistics. RESULTS: Ninety-six patients were enrolled. Positive outcomes in overall reduced readmission rates were observed in the intervention group at 30, 60, 90, and 180 days, although statistical significance was not achieved because of limited enrollment. Approximately 60% participated in MTM postdischarge, with 453 interventions and 169 DTPs identified and addressed (98% > 1 DTP; 20% > 5 DTPs). Implementation experience includes PTC successes, new partnerships, and connectivity among all providers, as well as enrollment challenges, follow-up, and service delivery timeframe. CONCLUSION: With access to patient records, pharmacists have the potential to positively affect patient outcomes through medication management during care transitions.

Liver Surface Nodularity Score Allows Prediction of Cirrhosis Decompensation and Death.

Purpose To determine whether use of the liver surface nodularity (LSN) score, a quantitative biomarker derived from routine computed tomographic (CT) images, allows prediction of cirrhosis decompensation and death. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with cirrhosis and Model for End-Stage Liver Disease (MELD) score within 3 months of initial liver CT imaging between January 3, 2006, and May 30, 2012, were identified from electronic medical records (n = 830). The LSN score was measured by using CT images and quantitative software. Competing risk regression was used to determine the association of the LSN score with hepatic decompensation and overall survival. A risk model combining LSN scores (<3 or ≥3) and MELD scores (<10 or ≥10) was created for predicting liver-related events. Results In patients with compensated cirrhosis, 40% (129 of 326) experienced decompensation during a median follow-up period of 4.22 years. After adjustment for competing risks including MELD score, LSN score (hazard ratio, 1.38; 95% confidence interval: 1.06, 1.79) was found to be independently predictive of hepatic decompensation. Median times to decompensation of patients at high (1.76 years, n = 48), intermediate (3.79 years, n = 126), and low (6.14 years, n = 152) risk of hepatic decompensation were significantly different (P < .001). Among the full cohort with compensated or decompensated cirrhosis, 61% (504 of 830) died during the median follow-up period of 2.26 years. After adjustment for competing risks, LSN score (hazard ratio, 1.22; 95% confidence interval: 1.11, 1.33) and MELD score (hazard ratio, 1.08; 95% confidence interval: 1.06, 1.11) were found to be independent predictors of death. Median times to death of patients at high (0.94 years, n = 315), intermediate (2.79 years, n = 312), and low (4.69 years, n = 203) risk were significantly different (P < .001). Conclusion The LSN score derived from routine CT images allows prediction of cirrhosis decompensation and death. ©RSNA, 2016 Online supplemental material is available for this article.

Quantifying predictive accuracy in survival models.

For time-to-event outcomes in medical research, survival models are the most appropriate to use. Unlike logistic regression models, quantifying the predictive accuracy of these models is not a trivial task. We present the classes of concordance (C) statistics and R 2 statistics often used to assess the predictive ability of these models. The discussion focuses on Harrell's C, Kent and O'Quigley's R 2, and Royston and Sauerbrei's R 2. We present similarities and differences between the statistics, discuss the software options from the most widely used statistical analysis packages, and give a practical example using the Worcester Heart Attack Study dataset.

Vascular imaging abnormalities and cognition: mediation by cortical volume in nondemented individuals: atherosclerosis risk in communities-neurocognitive study.

BACKGROUND AND PURPOSE: The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that the cerebral cortical volume mediated these relationships. METHODS: Total of 1906 nondemented participants (59% women; 25% African-American; mean age, 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MRI for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined the associations of cognitive domain outcomes with cerebral volumes (hippocampus and separate groups of posterior and frontal cortical regions of interest) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated the associations between cerebrovascular imaging features and cognition. RESULTS: In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function. In mediation analyses, WMH and infarct associations on psychomotor speed/executive function were significantly attenuated, but not abolished, by the inclusion of the posterior cortical regions of interest volume in the models, and the infarcts on psychomotor speed/executive function association were attenuated, but not abolished, by inclusion of the frontal cortical regions of interest volume. CONCLUSIONS: Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are 1 candidate for such a clinically covert process.

Urinary CYP eicosanoid excretion correlates with glomerular filtration in African-Americans with chronic kidney disease.

Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), i.e., 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), play an important role in the regulation of renal tubular and vascular function. The present study for the first time profiled HETEs and epoxygenase derived dihydroxyeicosatetraenoic acid diHETEs levels in spot urines and plasma in 262 African American patients from the University of Mississippi Chronic Kidney Disease Clinic and 31 African American controls. Significant correlations in eGFR and urinary 20-HETE/creatinine and 19-HETE/creatinine levels were observed. The eGFR increased by 17.47 [p=0.001] and 60.68 [(p=0.005]ml/min/for each ng/mg increase in 20-HETE and 19-HETE levels, respectively. Similar significant positive associations were found between the other urinary eicosanoids and eGFR and also with 19-HETE/urine creatinine concentration and proteinuria. We found that approximately 80% of plasma HETEs and 30% diHETEs were glucuronidated and the fractional excretion of 20-HETE was less than 1%. These results suggest that there is a significant hepatic source of urinary 20-HETE glucuronide and EETs with extensive renal biotransformation to metabolites which may play a role in the pathogenesis of CKD.

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection.

Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

A regionally tailored epidemiological forecast and monitoring program to guide a healthcare system in the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods. METHODS: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance. RESULTS: A consolidated forecast and monitoring report was produced weekly and proved to be an effective, vital source of information and guidance as the healthcare system navigated the inherent uncertainty of the pandemic. Forecasts provided accurate and precise information that informed critical decisions on resource planning, bed capacity and staffing management, and infection prevention strategies. CONCLUSIONS: In this paper, we have presented the framework used in our epidemiological forecast and monitoring program at Atrium Health, as well as provided recommendations for implementation by other healthcare systems and institutions to facilitate use in future pandemics.

Retrospective analysis of SGLT2 inhibitors in heart failure with preserved ejection fraction.

AIMS: Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality. HF with preserved ejection fraction (HFpEF), or diastolic failure, accounts for half of all HF cases and differs from HF with reduced ejection fraction (HFrEF). Patients with HFpEF are typically older, female, and commonly seen with chronic kidney disease (CKD), one of the leading independent risk factors for mortality in these patients. Unfortunately, drugs that had shown significant improvements in mortality in HFrEF have not shown similar benefits in HFpEF. Recently, sodium glucose transporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular morbidity and mortality in HFrEF patients and slow down CKD progression. This study aimed to elucidate the impact of this drug class on mortality and risk of end stage renal disease in patients with HFpEF, which is currently unclear. METHODS AND RESULTS: We retrospectively analysed the Research Data Warehouse containing electronic health records from de-identified patients (n = 1 266 290) from the University of Mississippi Medical Center from 2013 to 2022. HFpEF patients had an average follow-up of 4 ± 2 years. Factors associated with increased all-cause mortality during HFpEF included age, male sex, and CKD. Interestingly, the only treatments associated with significant improvements in survival were angiotensin converting enzyme inhibitors/angiotensin receptor blockers and SGLT2i, regardless of CKD or diabetes status. Additionally, SGLT2i use was also associated with significant decrease in the risk of end stage renal disease. CONCLUSIONS: Our results support the use of SGLT2i in an HFpEF population with relatively high rates of hypertension, CKD, and black race and suggests that improvements in mortality may be through preserving kidney function.