Research Spotlight

Greason, K. L., E. H. Blackstone, J. Rajeswaran, A. M. Lowry, L. G. Svensson, J. G. Webb, E. M. Tuzcu, C. R. Smith, R. R. Makkar, M. J. Mack, V. H. Thourani, S. K. Kodali, M. B. Leon and D. C. Miller (2020). “Inter- and intrasite variability of mortality and stroke for sites performing both surgical and transcatheter aortic valve replacement for aortic valve stenosis in intermediate-risk patients.” J Thorac Cardiovasc Surg 159(4): 1233-1244.e1234.

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OBJECTIVES: Multisite procedure-based randomized trials may be confounded by performance variability and variability among sites. Therefore, we studied variability in mortality and stroke after patients were randomized to surgical (SAVR) or transcatheter aortic valve replacement (TAVR) in the Placement of Aortic Transcatheter Valves-2A (PARTNER-2A) randomized trial. METHODS: Patients at intermediate risk for SAVR were randomized to SAVR (n = 1017) or TAVR (n = 1011) with a SAPIEN XT device (Edwards Lifesciences, Irvine, Calif) at 54 sites. Patients were followed to 2 years. A mixed-effect model quantified variability at intersite and intrasite levels. RESULTS: There were 336 deaths (SAVR 170, TAVR 166) and 176 strokes (SAVR 85, TAVR 91). Intersite variability for mortality was similar across sites for SAVR (hazard ratios ranging from 0.52-1.93 among sites) and TAVR (hazard ratios ranging from 0.49-2.03), but intersite variability for stroke was greater for SAVR (hazard ratios ranging from 0.44-2.26) than for TAVR (no detectable variability). Case mix and lower site trial volume accounted for 37% of mortality intersite variability for SAVR and 73% for TAVR, but only 14% for stroke for SAVR. Intrasite mortality hazard ratios demonstrated all but 1 site’s 95% confidence interval overlapped 1.0, indicating generally similar SAVR and TAVR mortalities within sites. CONCLUSIONS: Intersite variability was similar for mortality in SAVR and TAVR, but variability for stroke was greater for SAVR than for TAVR. Intrasite events were similar for both SAVR and TAVR. These findings suggest that in performance-based trials, site variability and its sources should be taken into account in analyzing and interpreting trial results.

Frazee, R., E. Garmon, C. Isbell, E. Bird and H. Papaconstantinou (2020). “Postoperative Opioid Prescription Reduction Strategy in a Regional Healthcare System.” J Am Coll Surg 230(4): 631-635.

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BACKGROUND: The CDC reported in 2017 that the largest increments in probability of continued use were observed after days 5 and 31 on opioid therapy. This study demonstrates the correlation between a system-wide pain management and opioid stewardship effort with reductions in discharge prescriptions for elective surgical patients. STUDY DESIGN: Discharge prescriptions were monitored through the electronic health record. Baseline prescribing patterns were established for the first quarter of 2018, preceding the first intervention in the multipronged opioid reduction initiative. Beginning in the second quarter of 2018, a series of pain management and opioid stewardship educational conferences were provided. Enhanced Recovery after Surgery protocols were simultaneously implemented system-wide. In the third quarter of 2018, a quality metric linked to compensation rewarded surgeons for limiting postoperative discharge prescriptions to 5 or fewer days. Opioid prescriptions were compared by quarter from January 2018 to March 2019 using chi-square and Kruskal-Wallis test with significance of p < 0.05. RESULTS: There were 31,814 patients who underwent elective surgical procedures during the study period. At baseline, the rate of postoperative opioid prescriptions of 5 or fewer days was 81%. This rate increased to 82%, 86%, 89%, and 92% in each successive quarter (p < 0.0001 for quarters 3 to 5). CONCLUSIONS: A system-wide, multipronged pain management and opioid reduction program significantly reduced opioid discharge prescriptions written for more than 5 days. This approach can serve as a model for other healthcare systems attempting to reduce opioid prescribing and combat the opioid crisis in the US.

Fleishman, A., K. Khwaja, J. D. Schold, C. D. Comer, P. Morrissey, J. Whiting, J. Vella, L. K. Kayler, D. Katz, J. Jones, B. Kaplan, M. Pavlakis, D. A. Mandelbrot and J. R. Rodrigue (2020). “Pain expectancy, prevalence, severity, and patterns following donor nephrectomy: Findings from the KDOC Study.” Am J Transplant 2020 Mar 17. [Epub ahead of print].

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Postoperative pain is an outcome of importance to potential living kidney donors (LKDs). We prospectively characterized the prevalence, severity, and patterns of acute or chronic postoperative pain in 193 LKDs at six transplant programs. Three pain measurements were obtained from donors on postoperative Day (POD) 1, 3, 7, 14, 21, 28, 35, 41, 49, and 56. The median pain rating total was highest on POD1 and declined from each assessment to the next until reaching a median pain-free score of 0 on POD49. In generalized linear mixed-model analysis, the mean pain score decreased at each pain assessment compared to the POD3 assessment. Pre-donation history of mood disorder (adjusted ratio of means [95% confidence interval (CI)]: 1.40 [0.99, 1.98]), reporting “severe” on any POD1 pain descriptors (adjusted ratio of means [95% CI]: 1.47 [1.12, 1.93]) and open nephrectomy (adjusted ratio of means [95% CI]: 2.61 [1.03, 6.62]) were associated with higher pain scores across time. Of the 179 LKDs who completed the final pain assessment, 74 (41%) met criteria for chronic postsurgical pain (CPSP), that is, any donation-related pain on POD56. Study findings have potential implications for LKD education, surgical consent, postdonation care, and outcome measurements.

Filardo, G., G. Ailawadi, B. D. Pollock, B. da Graca, T. K. Phan, V. Thourani and R. J. Damiano, Jr. (2020). “Postoperative atrial fibrillation: Sex-specific characteristics and effect on survival.” J Thorac Cardiovasc Surg 159(4): 1419-1425.e1411.

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BACKGROUND: We sought to fill important gaps in the existing evidence regarding new-onset atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG) by comparing the incidence, characteristics, and effect on long-term survival between men and women. METHODS: Nine thousand two hundred three consecutive patients without preoperative AF underwent isolated CABG from 2002 to 2010 at 3 US academic medical centers and 1 high-volume specialty cardiac hospital. Detailed data on CABG AF events detected via continuous in-hospital electrocardiogram/telemetry monitoring were supplemented with Society of Thoracic Surgeons data, and survival data, censored at October 31, 2011, using a copy of the Social Security Death Master File archived before state-owned data were removed (November 1, 2011). RESULTS: Propensity-adjusted (Society of Thoracic Surgeons-recognized risk factors) incidence of post-CABG AF was 31.5% overall, 32.8% in men, and 27.4% in women. Over the 9-year study period, women had a significantly lower risk of post-CABG AF (absolute difference, -5.3% [95% confidence interval (CI), -10.5% to -0.6%]), and significantly shorter first (-2.9 hours; 95% CI, -5.8 to 0.0), and longest (-4.3 hours; 95% CI, -8.3 to -0.3) AF duration. Post-CABG AF was associated with significantly increased risk of long-term mortality (overall hazard ratio [HR], 1.56; 95% CI, 1.45-1.67; men HR, 1.57; 95% CI, 1.49-1.65; women HR, 1.54; 95% CI, 1.14-2.07). CONCLUSIONS: In our study, women had lower adjusted risk of post-CABG AF and experienced shorter episodes. The adjusted risk of long-term mortality was 56% greater among patients who developed post-CABG AF compared with those who did not. The effect of post-CABG AF on long-term survival did not differ between the sexes.

DiNorcia, J., S. S. Florman, B. Haydel, P. Tabrizian, R. M. Ruiz, G. B. Klintmalm, S. Senguttuvan, D. D. Lee, C. B. Taner, E. C. Verna, K. J. Halazun, M. Hoteit, M. H. Levine, W. C. Chapman, N. Vachharajani, F. Aucejo, M. H. Nguyen, M. L. Melcher, A. D. Tevar, A. Humar, C. Mobley, M. Ghobrial, T. L. Nydam, B. Amundsen, J. F. Markmann, J. Berumen, A. W. Hemming, A. N. Langnas, C. A. Carney, D. L. Sudan, J. C. Hong, J. Kim, M. A. Zimmerman, A. Rana, M. L. Kueht, C. M. Jones, T. M. Fishbein, D. Markovic, R. W. Busuttil and V. G. Agopian (2020). “Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma: Analysis From the US Multicenter HCC Transplant Consortium.” Ann Surg 271(4): 616-624.

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OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes