A Joint Longitudinal-Survival Model with Possible Cure: An Analysis of Patient Outcomes on the Liver Transplant Waiting List

Data from transplant patients has many unique characteristics that can cause problems with statistical modeling. The patient\u27s underlying disease / health trajectory is known to affect both longitudinal biomarker values and the probability of both death and transplant. In liver transplant patients, biomarker values show a sharp exponential increase in the days preceding death or transplant. Patients who receive transplants show an immediate drop in biomarker values post-transplant, followed by an exponential decrease. Patients\u27 survival probabilities also change post-transplant, with dependencies on pre-transplant biomarker values. To properly incorporate these clinical features, we developed a joint longitudinal-survival model that links an exponential growth-decay longitudinal model to a modified cure survival model. This allows us to evaluate patient biomarker trajectories and survival times both pre- and post-transplant. The models are linked by patient-level shared random effects that appear in the biomarker trajectories and the frailties of the survival functions. Estimates are obtained via the EM algorithm, with random effects integrated out of the complete data likelihood function using adaptive quadrature techniques. Simulations show our model performs reasonably well under a variety of conditions. We demonstrate our methods using liver transplant data from the United Network of Organ Sharing (UNOS). We use total serum bilirubin as our longitudinal outcome, with age at waitlisting and gender as linear covariates. Gender is used as a covariate in the survival model both pre- and post-transplant

Ambulatory assisted living fallers at greatest risk for head injury

OBJECTIVES: To determine the relationship between head injuries sustained during each fall with various known high risk health and demographic factors predictive of falls. DESIGN: Prospective cohort study conducted over 1 year SETTING: Assisted living and skilled nursing units of a Continuing Care Retirement Community located in the northeastern United States. PARTICIPANTS: Sixty nine OAs who fell. MEASUREMENTS: Age, gender, diagnosis, high risk medication, functional, cognitive, ambulation/elimination status, mode of locomotion, fall related symptoms and the position of the fall, were analyzed using General Estimating Equations among elderly fallers with and without head injury. RESULTS: A total of 173 falls (average of 2.9 times) were observed for 62 patients who had complete injury data. Injuries were recorded in 40.5% of falls, with 41.4% being head injuries. Head injuries were more likely to be hematomas than lacerations (66.7% vs. 14.7%) and among assisted living residents (p=0.04). Head injured patients were more likely to be walking at the time of the fall (69% vs. 36.1%) and less likely to have bowel incontinence (3.5% vs. 28.5%; p=0.04). None of the high risk diagnosis or medications associated with falls risk increased risk for head injury. CONCLUSION: Those at greatest risk for head injury were ambulatory assisted living residents. None of the known clinical conditions predictive of risk to fall were predictive of head injury. For head injury prevention to be successful we need a closer examination of resident’s mobility, shoe-wear, health behavior with respect to ability to use assistive devices, and floor surface landing area. Future health policy implications include measures to ensure standard of care practices for head injured patients are in place.This is the peer reviewed version of the following article: Gray-Miceli, D. L., Ratcliffe, S. J. and Thomasson, A. (2013), Ambulatory Assisted Living Fallers at Greatest Risk for Head Injury. Journal of the American Geriatrics Society, 61: 1817–1819, which has been published in final form at https://dx.doi.org/10.1111/jgs.12467. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Peer reviewe

Waitlist Survival of Patients With Primary Sclerosing Cholangitis in the Model for End-Stage Liver Disease Era

The ability of the Model for End-Stage Liver Disease (MELD) score to capture the urgency of transplantation may not be generalizable to patients with primary sclerosing cholangitis (PSC) because these patients face unique risks of death or removal from the liver transplant waitlist due to disease-specific complications (eg, repeated bouts of bacterial cholangitis and cholangiocarcinoma). We constructed Cox regression models to determine whether disease-based differences exist in waitlist mortality before liver transplantation. We compared the times to death or withdrawal from the waitlist due to clinical deterioration among patients with or without PSC in the United States after the implementation of the MELD allocation score. Over an 8-year period, 14,073 non-PSC patients (20.5%) and 432 PSC patients (13.6%) died or were removed (P < 0.0001). The adjusted hazard ratio (HR) for PSC was 0.72 [95% confidence interval (CI) 0.66-0.79], which indicated that these patients had a lower time-dependent risk of death or removal from the waitlist in comparison with patients without PSC. This difference was explained in part by the groups' different probabilities of portal hypertension complications at listing because adjustments for these intermediate endpoints moved the HR closer to the null (0.84, 95% CI = 0.74-0.97). In comparison with patients with other forms of end-stage liver disease, patients with PSC are less likely to die or be removed from the waitlist because of clinical deterioration; therefore, the prevailing practice in some centers and regions of preemptively referring PSC patients for living donor transplantation or exception points should be reconsidered. Liver Transpl 17:1355-1363, 2011. (C) 2011 AASLD

Current Trends in Living Donor Liver Transplantation for Primary Sclerosing Cholangitis

Background. Use of the Model for End-Stage Liver Disease (MELD) score has improved the efficiency of allocating deceased donor organs for liver transplant. However, its use may reduce access to deceased donor livers for patients with primary sclerosing cholangitis (PSC) due to the weighting of the MELD score variables. To overcome such barriers in the post-MELD era, clinicians might refer patients with PSC, relative to patients without PSC, for living donor transplants more frequently. Methods. To test this hypothesis, we examined patients in the United Network for Organ Sharing database from December 1, 1994, to May 31, 2009. Results. In multivariable models conditioned on transplant center, patients with PSC were significantly more likely to receive a living donor transplant in both the pre-MELD (odds ratio [OR] = 2.75; 95% confidence interval [CI], 2.20-3.44) and post-MELD eras (OR = 4.08; 95% CI, 3.45-4.82). There was a significant interaction between PSC and post-MELD era of transplantation (OR = 1.48; 95% CI, 1.11-1.97), indicating that patients with PSC were more likely to receive living donor transplants at baseline relative to patients without PSC, and that this effect was magnified following the introduction of the MELD score. Conclusions. These findings raise the possibility that allocating livers on the basis of MELD score may have yielded the unintended consequence of increasing rates for living donor transplants for patients with PSC relative to patients with other forms of end-stage liver disease. Future research is needed to determine whether the practice of selectively transplanting patients with PSC with living donor transplants is associated with differences in clinical outcomes

Race, Rehabilitation, and 30-Day Readmission After Elective Total Knee Arthroplasty

Introduction: To examine racial variations in access to postacute care (PAC) and rehabilitation (Rehab) services following elective total knee arthroplasty and whether where patients go after surgery for PAC/Rehab is associated with 30-day readmission to acute care facility. Materials and Methods: Sample consisted of 129 522 patients discharged from 169 hospitals in the State of Pennsylvania between fiscal years 2008 and 2012. We used multinomial regression models to assess the relationship between patient race and discharge destination after surgery, for patients aged 18 to 64 years and for those aged 65 and older. We used multivariable (MV) regression and propensity score (PS) approaches to examine the relationship between patient discharge destination after surgery for PAC/Rehab and 30-day readmission, controlling for key individual- and facility-level factors. Results: Lower proportions of younger patients compared to those older than 65 were discharged to inpatient rehabilitation facilities (IRFs; 5.8% vs 12.6%, respectively) and skilled nursing facilities (SNFs; 15.2% vs 32.7%, respectively) compared to home-based Rehab (self-care; 23.3% vs 14.2%, respectively). Compared to whites, African American patients had significantly higher odds of discharge to IRF (age < 65, odds ratio = 2.04; age ≥ 65, odds ratio = 1.64) and to SNF (age < 65, odds ratio = 2.86; age ≥ 65, odds ratio = 2.19) and discharge to home care in patients younger than 65 years (odds ratio = 1.31). The odds of 30-day readmission among patients discharged to an IRF (MV odds ratio = 7.76; PS odds ratio = 8.34) and SNF (MV odds ratio = 2.01; PS odds ratio = 1.83) were significantly higher in comparison to patients discharged home with self-care. Conclusion: African American patients with knee replacement are more likely to be discharged to inpatient Rehab settings following surgery. Inpatient Rehab is significantly associated with 30-day readmission to acute care facility