Hypothermia or Machine Perfusion in Kidney Donors.

BACKGROUND: Therapeutic hypothermia in brain-dead organ donors has been shown to reduce delayed graft function in kidney recipients after transplantation. Data are needed on the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation. METHODS: At six organ-procurement facilities in the United States, we randomly assigned brain-dead kidney donors to undergo therapeutic hypothermia (hypothermia group), ex situ kidney hypothermic machine perfusion (machine-perfusion group), or both (combination-therapy group). The primary outcome was delayed graft function in the kidney transplant recipients (defined as the initiation of dialysis during the first 7 days after transplantation). We also evaluated whether hypothermia alone was noninferior to machine perfusion alone and whether the combination of both methods was superior to each of the individual therapies. Secondary outcomes included graft survival at 1 year after transplantation. RESULTS: From 725 enrolled donors, 1349 kidneys were transplanted: 359 kidneys in the hypothermia group, 511 in the machine-perfusion group, and 479 in the combined-therapy group. Delayed graft function occurred in 109 patients (30%) in the hypothermia group, in 99 patients (19%) in the machine-perfusion group, and in 103 patients (22%) in the combination-therapy group. Adjusted risk ratios for delayed graft function were 1.72 (95% confidence interval [CI], 1.35 to 2.17) for hypothermia as compared with machine perfusion, 1.57 (95% CI, 1.26 to 1.96) for hypothermia as compared with combination therapy, and 1.09 (95% CI, 0.85 to 1.40) for combination therapy as compared with machine perfusion. At 1 year, the frequency of graft survival was similar in the three groups. A total of 10 adverse events were reported, including cardiovascular instability in 9 donors and organ loss in 1 donor owing to perfusion malfunction. CONCLUSIONS: Among brain-dead organ donors, therapeutic hypothermia was inferior to machine perfusion of the kidney in reducing delayed graft function after transplantation. The combination of hypothermia and machine perfusion did not provide additional protection. (Funded by Arnold Ventures; ClinicalTrials.gov number, NCT02525510.).

Rheumatology Clinicians' Perceptions of Telerheumatology Within the Veterans Health Administration: A National Survey Study.

INTRODUCTION: The Department of Veterans Affairs Veterans Health Administration (VA) Strategic Plan (Fiscal Year 2018-2024) identified four priorities for care including easy access, timely and integrated care, accountability, and modernization, all of which can be directly or indirectly impacted by telemedicine technologies. These strategic goals, coupled with an anticipated rheumatology workforce shortage, has created a need for additional care delivery methods such as clinical video telehealth application to rheumatology (ie, telerheumatology). Rheumatology clinician perceptions of clinical usefulness telerheumatology have received limited attention in the past. The present study aimed to evaluate rheumatologists' perceptions of and experiences with telemedicine, generally, and telerheumatology, specifically, within the VA. MATERIALS AND METHODS: A 38-item survey based on an existing telehealth providers' satisfaction survey was developed by two VA rheumatologists with experience in telemedicine as well as a social scientist experienced in survey development and user experience through an iterative process. Questions probed VA rheumatology clinician satisfaction with training and information technology (IT) supports, as well as barriers to using telemedicine. Additionally, clinician perceptions of the impact and usefulness of and appropriate clinical contexts for telerheumatology were evaluated. The survey was disseminated online via VA REDCap to members of the VA Rheumatology Consortium (VARC) through a LISTSERV. The study protocol was approved by the host institution IRB through expedited review. Survey responses were analyzed using descriptive statistics. RESULTS: Forty-five anonymous responses (20% response rate) were collected. Of those who responded, 47% were female, 98% were between 35 and 64 years old, 71% reported working at an academic center, and the majority was physician-level practitioners (98%). Respondents generally considered themselves to be tech savvy (58%). Thirty-six percent of the sample reported past experience with telemedicine, and, of those, 29% reported experience with telerheumatology specifically. Clinicians identified the greatest barrier to effective telerheumatology as the inability to perform a physical exam (71%) but agreed that telerheumatology is vital to increasing access to care (59%) and quality of care (40%) in the VA. Overall, regardless of experience with telemedicine, respondents reported that telerheumatology was more helpful for management of rheumatologic conditions rather than initial diagnosis. CONCLUSIONS: While the majority of rheumatology clinicians did not report past experience with telerheumatology, they agreed that it has potential to further the VA mission of improved access and quality of care. Rheumatology clinicians felt the suitability of telerheumatology is dependent on the phase of care. As remote care technologies continue to be rapidly adopted into clinic, clinician perceptions of and experiences with telemedicine will need to be addressed in order to maintain high-quality and clinician- and patient-centric care within VA rheumatology.

Outcomes, Satisfaction, and Costs of a Rheumatology Telemedicine Program: A Longitudinal Evaluation.

OBJECTIVES: Rural veterans with inflammatory arthritis (IA) lack medical access because of geographic barriers. Telemedicine (TM) holds great promise in relieving these disparities. We have prospectively measured patient-centered data surrounding a TM care program at a federal health system and compared these with usual care (UC). METHODS: Veterans with previously established IA were enrolled in TM follow-up. Data collected longitudinally before and after entering the program included Routine Assessment of Patient Index Data 3 (RAPID-3), out-of-pocket visit costs and distances traveled, and patient satisfaction instruments. Demographics were recorded. Similar data were collected on a convenience sample of concurrent IA patients receiving UC. RESULTS: Eighty-five patients were observed, including 25 receiving TM care and 60 receiving UC. No differences in demographics, satisfaction scores, or RAPID-3 were noted at baseline between groups. Univariate linear regression of cross-sectional baseline data suggests satisfaction instrument scores were predicted by RAPID-3 (ß = -0.64/10 points, p = 0.01), as well as distance (ß = -0.19/100 miles, p = 0.02) and cost (ß = -0.37/$100, p = 0.05). A multivariate model indicates both distance (ß = -0.17/100 miles, p = 0.02) and RAPID-3 (ß = -0.47/10 points, p < 0.03) were predictors for visit satisfaction. In longitudinal follow-up via TM, satisfaction (Δ = 0.03, p = 0.94) and RAPID-3 (Δ = 0.27, p = 0.89) remained similar to baseline among TM patients, whereas distance traveled (Δ = -384.8 miles/visit, p < 0.01) and visit costs (Δ = -$113.8/visit, p < 0.01) were reduced. CONCLUSIONS: Patient-reported outcomes for care delivered via TM were similar to UC, with significant cost and distance savings. Patient-centered factors such as distance to care should be considered in design care delivery models, as they appear to drive patient satisfaction in conjunction with disease control.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis.

AIM: To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS: Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs (DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics. RESULTS: Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events (-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events (+5.85 mg/dL, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events (-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (ß = -0.58, P = 0.01) and hydroxychloroquine (ß = -5.78, P = 0.01) use as predictors of lower post-medication-initiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure (ß = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events. CONCLUSION: No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

Drug-Induced Gastrointestinal and Hepatic Disease Associated with Biologics and Nonbiologic Disease-Modifying Antirheumatic Drugs.

A variety of gastrointestinal adverse drug reactions are seen in nearly all conventional antirheumatic medications, ranging from nausea to life-threatening drug-induced liver injury. Rheumatologists should be particularly familiar with hepatotoxicity associated with long-term methotrexate use, and the range of unique hepatic, biliary, and pancreatic manifestations associated with azathioprine. Hepatitis B virus reactivation is the most serious gastrointestinal disease risk associated with many biological therapies, particularly rituximab. Gastrointestinal perforation may be a specific concern for agents directed at interleukin-6 pathways, and some reports have raised the question of whether interleukin-17 inhibition may elevate inflammatory bowel disease risk.

Myosin-Vb functions as a dynamic tether for peripheral endocytic compartments during transferrin trafficking.

BACKGROUND: Myosin-Vb has been shown to be involved in the recycling of diverse proteins in multiple cell types. Studies on transferrin trafficking in HeLa cells using a dominant-negative myosin-Vb tail fragment suggested that myosin-Vb was required for recycling from perinuclear compartments to the plasma membrane. However, chemical-genetic, dominant-negative experiments, in which myosin-Vb was specifically induced to bind to actin, suggested that the initial hypothesis was incorrect both in its site and mode of myosin-Vb action. Instead, the chemical-genetic data suggested that myosin-Vb functions in the actin-rich periphery as a dynamic tether on peripheral endosomes, retarding transferrin transport to perinuclear compartments. RESULTS: In this study, we employed both approaches, with the addition of overexpression of full-length wild-type myosin-Vb and switching the order of myosin-Vb inhibition and transferrin loading, to distinguish between these hypotheses. Overexpression of full-length myosin-Vb produced large peripheral endosomes. Chemical-genetic inhibition of myosin-Vb after loading with transferrin did not prevent movement of transferrin from perinuclear compartments; however, virtually all myosin-Vb-decorated particles, including those moving on microtubules, were halted by the inhibition. Overexpression of the myosin-Vb tail caused a less-peripheral distribution of early endosome antigen-1 (EEA1). CONCLUSION: All results favored the peripheral dynamic tethering hypothesis.