Research Spotlight

Posted October 15th 2019

Economic Analysis of Hospital Palliative Care: Investigating Heterogeneity by Noncancer Diagnoses.

Robert L. Fine M.D.

Robert L. Fine M.D.

May, P., C. Normand, E. Del Fabbro, R. L. Fine, R. S. Morrison, I. Ottewill, C. Robinson and J. B. Cassel (2019). “Economic Analysis of Hospital Palliative Care: Investigating Heterogeneity by Noncancer Diagnoses.” MDM Policy Pract Sep 10: eCollection 2019 Jul-Dec.

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Background. Single-disease-focused treatment and hospital-centric care are poorly suited to meet complex needs in an era of multimorbidity. Understanding variation in palliative care’s association with treatment choices is essential to optimizing interdisciplinary decision making in care of complex patients. Aim. To estimate the association between palliative care and hospital costs by primary diagnosis and multimorbidity for adults with one of six life-limiting conditions: heart failure, chronic obstructive pulmonary disease (COPD), liver failure, kidney failure, neurodegenerative conditions including dementia, and HIV/AIDS. Methods. Data from four studies (2002-2015) were pooled to provide an analytic dataset of 73,304 participants with mean costs $10,483, of whom 5,348 (7%) received palliative care. We estimated average effect of palliative care on direct hospital costs among the treated, using propensity scores to control for observed confounding. Results. Palliative care was associated with a statistically significant reduction in total direct costs for heart failure (estimated treatment effect: -$2666; 95% confidence interval [CI]: -$3440 to -$1892), neurodegenerative conditions (-$3523; -$4394 to -$2651), COPD (-$1613; -$2217 to -$1009), kidney failure (-$3589; -$5132 to -$2045), and liver failure (-$7574; -$9232 to -$5916). The association for liver failure patients was statistically significantly larger than for any other disease group. Cost-saving associations were also statistically larger for patients with multimorbidity than single disease for two of the six groups: neurodegenerative and liver failure. Conclusions. Heterogeneity in treatment effect estimates was observable in assessing association between palliative care and hospital costs for adults with serious life-limiting illnesses other than cancer. The results illustrate the importance of careful definition of palliative care populations in research and practice, and raise further questions about the role of interdisciplinary decision making in treatment of complex medical illness.


Posted October 15th 2019

Muc5b Variant Is Associated with Visually and Quantitatively Detected Preclinical Pulmonary Fibrosis.

Susan K. Mathai, M.D.

Susan K. Mathai, M.D.

Mathai, S. K., S. Humphries, J. A. Kropski, T. S. Blackwell, J. Powers, A. D. Walts, C. Markin, J. Woodward, J. H. Chung, K. K. Brown, M. P. Steele, J. E. Loyd, M. I. Schwarz, T. Fingerlin, I. V. Yang, D. A. Lynch and D. A. Schwartz (2019). “Muc5b Variant Is Associated with Visually and Quantitatively Detected Preclinical Pulmonary Fibrosis.” Thorax Sep 26. [Epub ahead of print].

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BACKGROUND: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. METHODS: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. FINDINGS: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. INTERPRETATION: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.


Posted October 15th 2019

Duets (Dallas Uterus Transplant Study): The Role of Imaging in Uterus Transplantation.

Gregory DePrisco, M.D.

Gregory DePrisco, M.D.

Mahmood, S., L. Johannesson, G. Testa and G. de Prisco (2019). “Duets (Dallas Uterus Transplant Study): The Role of Imaging in Uterus Transplantation.” SAGE Open Med Sep 9: eCollection 2019.

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Objective: Uterus transplantation is rapidly becoming a viable clinical option for women with uterine-factor infertility and a desire for parenthood. Radiological imaging plays a central role in selecting the optimal living donors for uterus transplantation and serves to exclude any pathology and evaluate the uterine vasculature. The latter is the most important variable in the ultimate technical success of the uterus transplant. In this first report of imaging in the setting of uterus transplantation, we report our experience with living-donor selection, and the evolution of the imaging techniques that ultimately allowed a significant improvement in donor selection and transplant outcome. We also suggest a framework for preoperative imaging in uterus transplantation. Methods: Between 2016 and 2018, 27 potential living donors were evaluated by imaging prior to uterine donation for uterus transplantation. Predonation imaging included a screening chest radiograph, dual-phase computed tomography (CT) angiograms of the abdomen and pelvis in the arterial and venous phases and pelvic sonography with Doppler. Seventeen potential donors additionally underwent multiphasic pelvic MR angiograms. The imaging performed was meant to display features of the vascular anatomy relevant for uterus transplantation. Results: Out of the 27 potential live donors who were evaluated by imaging, 9 eventually donated their uterus for transplantation. The most frequent reason for exclusion was suboptimal quality of the vessels (33%), including small uterine arteries, the presence of atherosclerosis or small size/poor quality of the uterine or utero-ovarian veins, or both. The next most common reason was voluntary patient withdrawal or failure to complete the evaluation process (28%). Three potential donors (16.6%) were rejected for uterine factors, fibroids, and/or adenomyosis. Other reasons for donor rejection included ABO incompatibility and unfavorable psychological evaluation. Conclusion: Diagnostic imaging plays a crucial role in selecting appropriate potential donors, screening prospective recipients, planning the graft procedure, and following up on any graft or nongraft-related complications in both the donor and recipient after the transplantation procedure is performed. Contrast-enhanced CT and MR angiographies have complementary roles, especially when evaluating the donor for adequacy of the arterial and venous supply to the uterine graft and the experience gained from our series indicates that the inclusion of both modalities contributed directly to successful uterus transplant graft survival by selecting patients with favorable arterial and venous vasculature.


Posted October 15th 2019

Discovery and Validation of a Biomarker Model (Preserve) Predictive of Renal Outcomes after Liver Transplantation.

Göran Klintmalm M.D.

Göran Klintmalm M.D.

Levitsky, J., S. K. Asrani, G. Klintmalm, T. Schiano, A. Moss, K. Chavin, C. Miller, K. Guo, L. Zhao, L. W. Jennings, M. Brown, B. Armstrong and M. Abecassis (2019). “Discovery and Validation of a Biomarker Model (Preserve) Predictive of Renal Outcomes after Liver Transplantation.” Hepatology Sep 11. [Epub ahead of print].

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A high proportion of patients develop chronic kidney disease after liver transplantation. We aimed to develop clinical/protein models to predict future GFR deterioration in this population. In independent multicenter discovery (CTOT14) and single center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma samples at month 3 after liver transplant in recipients with preserved GFR who demonstrated subsequent GFR deterioration vs. preservation by year 1, and year 5 in the BUMC cohort. In CTOT14, we also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n=60). Levels of beta2-microglobulin and CD40 antigen and presence of HCV infection predicted early (year 1) GFR deterioration (AUC 0.814). We observed excellent validation of this model (AUC 0.801) in the BUMC cohort (n=50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75) and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including beta2-microglobulin and CD40, correlated with GFR changes over the first year. Conclusion: We have validated a clinical/protein model (PRESERVE) that early after liver transplantation can predict future renal deterioration vs. preservation with high accuracy. This model may help select recipients at higher risk for subsequent chronic kidney disease for early, proactive renal sparing strategies.


Posted October 15th 2019

Tildrakizumab Efficacy and Safety Are Not Altered by Metabolic Syndrome Status in Patients with Psoriasis: Post Hoc Analysis of 2 Phase 3 Randomized Controlled Studies (Resurface 1 and Resurface 2).

Alan M. Menter M.D.

Alan M. Menter M.D.

Lebwohl, M. G., C. L. Leonardi, N. N. Mehta, A. B. Gottlieb, A. M. Mendelsohn, J. Parno, S. J. Rozzo and A. Menter (2019). “Tildrakizumab Efficacy and Safety Are Not Altered by Metabolic Syndrome Status in Patients with Psoriasis: Post Hoc Analysis of 2 Phase 3 Randomized Controlled Studies (Resurface 1 and Resurface 2).” J Am Acad Dermatol Sep 26. [Epub ahead of print].

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This post hoc analysis evaluated tildrakizumab efficacy, durability of response, and safety in patients with moderate to severe chronic psoriasis with vs without metabolic syndrome (MetS) using pooled data from 2 phase 3, double-blind, randomized, placebo-controlled studies (reSURFACE 1 [NCT01722331] and 2 [NCT01729754]). Patients with vs without MetS had higher prevalence of pre-existing cardiovascular disease and diabetes and higher median baseline weight and body mass index (BMI). Six (4.1%) patients with MetS (n=5 tildrakizumab 100 mg; n=1 tildrakizumab 200 mg) and 25 (4.5%) patients without MetS (n=12 tildrakizumab 100 mg; n=13 tildrakizumab 200 mg) did not complete the study. Percentages of patients with ≥75% improvement on the Psorasis Area and Severity Index (PASI 75 responders) at weeks 12 and 52 were comparable between patients with and without MetS for both tildrakizumab doses. Percentages of PASI 90 and PASI 100 responders through week 52 were similar regardless of MetS status for both tildrakizumab doses. Tildrakizumab efficacy through week 52 was maintained comparably in patients with and without MetS. Reductions in mean PASI from baseline were similar regardless of MetS status for both tildrakizumab doses. Percentages of patients with ≥1 serious adverse event (AE) and those with ≥1 serious infection were similar in patients with and without MetS. The most common serious AEs for patients with vs without MetS were gastrointestinal and cardiac disorders following tildrakizumab 100 mg and injury / procedural complications and nervous system disorders following tildrakizumab 200 mg. Fatal AEs occurred in 2 patients with MetS (both tildrakizumab 100 mg) and 2 patients without MetS (1 per tildrakizumab dose). Infection was the most commonly reported treatment-emergent AE (TEAE). Incidence was similar in patients with and without MetS receiving tildrakizumab 100 mg and numerically higher in patients with vs without MetS receiving tildrakizumab 200 mg. Incidence of cardiovascular events did not vary by MetS status, and there were no reports of diabetes worsening after treatment. Weight increases through week 28 were limited (~1 kg on average) in patients with and without MetS across both tildrakizumab doses. Exposure-adjusted rates of tier 1 TEAEs were comparable across doses regardless of MetS status. These post hoc analyses were not powered for statistical analyses based on MetS status, and populations were not matched for smoking history and other potential co-factors. Although abdominal obesity is more highly correlated with MetS risk factors relative to BMI, the latter was used as abdominal obesity data were not collected. Sample sizes for patients with MetS were relatively small; further evaluation of the effect of weight only on treatment efficacy and safety was not feasible because only 25 patients with BMI <30 kg/m2 met ≥3 criteria for MetS. Despite limitations, these results suggest efficacy, safety, and drug survival of tildrakizumab are comparable in patients with psoriasis regardless of MetS status. (Excerpt from text of this article-in-press.)