Trajectories of health-related quality of life among renal transplant patients associated with graft failure and symptom distress: Analysis of the BENEFIT and BENEFIT-EXT trials.

Understanding the correlation between transplant symptoms, health-related quality of life (HRQoL), and graft outcomes is needed to support patient-focused drug development and posttransplant management. A post-hoc analysis of patient-reported outcomes from the Phase III belatacept trials was conducted in order to investigate the interrelationship between trajectories of HRQoL, symptom experience, and allograft outcomes. HRQoL and symptom experience were evaluated using Short-Form 36 Survey (SF-36) and Modified Transplant Symptom Occurrence and Distress Scale (MTSOSD-59R), respectively. HRQoL was captured in 831 eligible renal transplant patients at baseline, 12, 24, and 36 months posttransplant. Following transplantation, patients reported improvements in all SF-36 subscales compared to baseline. Latent class analysis revealed four trajectories in perceived general health, which were associated with graft failure after adjustment. Compared to patients with good perceived health, patients with fair and poor perceived health had 4.7 (95% confidence interval [CI] 1.5-14.8, P < .01) and 19.8 (95% CI 5.9-66.0, P < .01) times the risk of graft failure, respectively. Using multinomial logistic regression, different sets of symptoms were associated with perceived general health at baseline and 12 months posttransplant. The study supports monitoring HRQoL and symptom experience to capture each patient's health perspective, improve drug development, and optimize posttransplant management.

Twitter Communication During an Outbreak of Hepatitis A in San Diego, 2016-2018.

Objectives. To examine how and what information is communicated via social media during an infectious disease outbreak.Methods. In the context of the 2016 through 2018 hepatitis A outbreak in San Diego County, California, we used a grounded theory-based thematic analysis that employed qualitative and quantitative approaches to uncover themes in a sample of public tweets (n = 744) from Twitter, a primary platform used by key stakeholders to communicate to the public during the outbreak.Results. Tweets contained both general and hepatitis A-specific information related to the outbreak, restatements of policy and comments critical of government responses to the outbreak, information with the potential to shape risk perceptions, and expressions of concern regarding individuals experiencing homelessness and their role in spreading hepatitis A. We also identified misinformation and common channels of content driving themes that emerged in our sample.Conclusions. Public health professionals may identify real-time public risk perceptions and concerns via social media during an outbreak and target responses that fulfill the informational needs of those who seek direction and reassurance during times of uncertainty.

Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab.

PURPOSE: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K. METHODS: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms. RESULTS: Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24. CONCLUSION: EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.

The Knowledge Assessment of Renal Transplantation (KART) 2.0: Development and Validation of CKD and Transplant Knowledge Scales.

BACKGROUND AND OBJECTIVES: Many individuals with kidney disease, particularly those belonging to racial and ethnic minority groups and whose primary language is not English, lack knowledge related to kidney disease symptoms, physiologic functions of the kidney, and benefits and risks of kidney transplantation. Valid instruments to assess patients' knowledge of CKD and kidney transplantation are needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a sample of 977 patients with stages 3-5 CKD in the Kaiser Permanente health system, we developed the Knowledge Assessment of Renal Transplantation (KART) 2.0 instrument. We conducted cognitive interviews followed by item response theory (IRT) to reduce 48 candidate items. Construct validity was tested by examining differences in scores between patients who spent <1 and ≥1 hour receiving CKD and transplant education. RESULTS: Cognitive interviews modified four items and omitted 11. IRT analyses resulted in two scales: the KART 2.0-Transplant Knowledge Scale (16 items; Cronbach's α=0.8) and the KART 2.0-CKD Knowledge Scale (nine items; Cronbach's α=0.79). Differential item functioning showed that the scales were unbiased to capture knowledge across self-identified race, primary language, CKD stage, and sex. Both scales distinguished patients who had spent <1 and ≥1 hour speaking with health professionals (effect size [ES]=0.33 [transplant], 0.54 [CKD]; P<0.001 for both), reading about kidney disease (ES=0.45 [transplant], 0.62 [CKD]; P<0.001), reading about kidney transplantation (ES=0.67 [transplant], 0.69 [CKD]; P<0.001), and reading about living donor kidney transplant (ES=0.76 [transplant], 0.62 [CKD]; P<0.001). CONCLUSIONS: The KART 2.0 is a valid tool to assess patients' knowledge of CKD and kidney transplantation.

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing.

Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving bone marrow ablation followed by hematopoietic stem cell transplantation in multiple myeloma and acute myeloid leukemia patients indicate that cf-mRNA levels reflect the transcriptional activity of bone marrow-resident hematopoietic lineages during bone marrow reconstitution. Mechanistically, stimulation of specific bone marrow cell populations in vivo using growth factor pharmacotherapy show that cf-mRNA reflects dynamic functional changes over time associated with cellular activity. Our results shed light on the biology of the circulating transcriptome and highlight the potential utility of cf-mRNA to non-invasively monitor bone marrow involved pathologies.

Antibody response to Achromobacter xylosoxidans during HIV infection is associated with lower CD4 levels and increased lymphocyte activation.

Inflammation during HIV infection is associated with worse disease outcomes and progression. Many mechanisms have been indicted, including HIV itself, coinfections, and gut microbial translocation. Concerning microbial translocation, we hypothesized that adaptive immune responses to a specific bacterial species known to be present in gut-associated lymphoid tissue are higher among HIV-infected individuals than among HIV-uninfected controls and are associated with T cell activation and lower CD4 T cell counts. By characterizing the IgG response to Achromobacter xylosoxidans, we found that HIV-infected participants who were immunoresponsive (n = 48) had significantly lower CD4 percentages (P = 0.01), greater CD4 activation (percentages of RA(-) CD38(+)) (P = 0.03), and higher soluble CD14 (P = 0.01). HIV-positive individuals had higher anti-A. xylosoxidans IgG titers than HIV-uninfected individuals (P = 0.04). The results suggest an abnormal adaptive immune activation to gut microflora during HIV infection.