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INTRODUCTION: The Allocation System for changes in Equity in Kidney Transplantation (ASCENT) study was a hybrid type 1 trial of a multicomponent intervention among 655 US dialysis facilities with low kidney transplant waitlisting to educate staff and patients about kidney allocation system (KAS) changes and increase access to and reduce racial disparities in waitlisting. Intervention components included a staff webinar, patient and staff educational videos, and facility-specific feedback reports. METHODS: Implementation outcomes were assessed using the Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework. Postimplementation surveys were administered among intervention group facilities (n = 334); interviews were conducted with facility staff (n = 6). High implementation was defined as using 3 to 4 intervention components, low implementation as using 1 to 2 components, and nonimplementation as using no components. RESULTS: A total of 331 (99%) facilities completed the survey; 57% were high implementers, 31% were low implementers, and 12% were nonimplementers. Waitlisting events were higher or similar among high versus low implementer facilities for incident and prevalent populations; for Black incident patients, the mean proportion waitlisted in low implementer facilities was 0.80% (95% confidence interval [CI]: 0.73-0.87) at baseline and 0.55% at 1-year (95% CI: 0.48-0.62) versus 0.83% (95% CI: 0.78-0.88) at baseline and 1.40% at 1-year (95% CI: 1.35-1.45) in high implementer facilities. Interviews revealed that the intervention helped facilities prioritize transplant education, but that intervention components were not uniformly shared. CONCLUSION: The findings provide important context to interpret ASCENT effectiveness results and identified key barriers and facilitators to consider for future modification and scale-up of multilevel, multicomponent interventions in dialysis settings.

OBJECTIVE: For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The studys objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD. METHODS: Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start. RESULTS: Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9 months (IQR:

Abstract Background Due to genetic depletion in nature, gene banks play a critical role in the long-term conservation of plant genetic resources and the provision of a wide range of plant genetic diversity for research and breeding programs. Genetic information on accessions facilitates gene bank management and can help to conserve limited resources and to identify taxonomic misclassifications or mislabelling. Here, we developed SNP markers for genotyping 4,187 mostly polyploid rose accessions from large rose collections, including the German Genebank for Roses. Results We filtered SNP marker information from the RhWag68k Axiom SNP array using call rates, uniformity of the four allelic dosage groups and chromosomal position to improve genotyping efficiency. After conversion to individual PACE® markers and further filtering, we selected markers with high discriminatory power. These markers were used to analyse 4,187 accessions with a mean call rate of 91.4%. By combining two evaluation methods, the mean call rate was increased to 95.2%. Additionally, the robustness against the genotypic groups used for calling was evaluated, resulting in a final set of 18 markers. Analyses of 94 pairs of assumed duplicate accessions included as controls revealed unexpected differences for eight pairs, which were confirmed using SSR markers. After removing the duplicates and filtering for accessions that were robustly called with all 18 markers, 141 out of the 1,957 accessions showed unexpected identical marker profiles with at least one other accession in our PACE® and SSR analysis. Given the attractiveness of NGS technologies, 13 SNPs from the marker set were also analysed using amplicon sequencing, with 76% agreement observed between PACE® and amplicon markers. Conclusions Although sampling error cannot be completely excluded, this is an indication that mislabelling occurs in rose collections and that molecular markers may be able to detect these cases. In future applications, our marker set could be used to develop a core reference set of representative accessions, and thus optimise the selection of gene bank accessions.

Abstract Aim was to evaluate the influence of different quantum iterative reconstruction (QIR) levels on the image quality of femoral photon-counting CT angiographies (PCD-CTA). Ultra-high resolution PCD-CTA were obtained from both extremities of five extracorporeally-perfused cadavers using constant tube voltage and maximum radiation dose (71.2 ± 11.0 mGy). Images were reconstructed with three kernels (Bv48, Bv60, Bv76) and the four available levels of QIR. Signal attenuation in the arterial lumen, muscle, and fat were measured. Contrast-to-noise ratios (CNR) and blurring scores were calculated for objective assessment. Six radiologists evaluated the subjective image quality using a pairwise comparison tool. Higher QIR level resulted in a decisive image noise reduction, especially with sharper convolution kernels (Bv60: Q1 11.5 ± 6.3 HU vs. Q4 8.4 ± 2.6 HU; p

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included. Allograft assessment included estimated glomerular filtration rate, urine protein-to-creatinine ratio, circulating antihuman leukocyte antigen donor-specific antibody, and kidney allograft histology. Individual predictions of allograft failure were calculated using the integrative box (iBox) system. Prediction performances were assessed using discrimination and calibration. The allograft evaluations were performed in 706 kidney transplant recipients at a median time of 9.1 (interquartile range, 3.3-19.2) months posttransplant; mean estimated glomerular filtration rate was 68.7 ± 28.1 mL/min/1.73 m2, and median urine protein-to-creatinine ratio was 0.1 (0.0-0.4) g/g, and 134 (19.0%) patients had antihuman leukocyte antigen donor-specific antibodies. The iBox exhibited accurate calibration and discrimination for predicting the outcomes up to 10 years after evaluation, with a C-index of 0.81 (95% confidence interval, 0.75-0.87). This study confirms the generalizability of the iBox to predict long-term kidney allograft failure in children, with performances similar to those reported in adults. These results support the use of the iBox to improve patient monitoring and facilitate clinical trials in children.

Abstract Background Determining whether a patient is eligible for kidney transplantation is complex. In this study, we estimate what proportion of patients with end-stage kidney disease (ESKD) might have been suitable candidates for kidney transplantation but were not referred. Methods We identified 43,952 people initiating dialysis for kidney failure between 2012 and 2017 in the states of Georgia, North Carolina, or South Carolina from the United States Renal Data System and linked to the Early-Steps to Transplant Access Registry to obtain data on referral and waitlisting up until December 2020. We identified ‘good transplant candidates’ as those who were waitlisted within 2-years of referral, among all patients referred within 1-year of dialysis initiation. Using propensity score cut-offs, logistic regression, and area under the curve (AUC), we then estimated the proportion of individuals who may have been good transplant candidates, but were not referred. Results Overall, 42.6% of incident dialysis patients were referred within one year and among them, 32.9% were waitlisted within 2 years of referral. Our model had reasonably good discrimination for identifying good transplant candidates with an AUC of 0.70 (95%CI 0.69–0.71), sensitivity of 0.68 and specificity of 0.61. Overall, 25% of individuals not referred for transplant may have been ‘good’ transplant candidates. Adding these patients to the existing 18,725 referred patients would increase the proportion of incident ESKD patients being referred within one year from 42.6% to 57.2% (a ~ 14.6% increase). Conclusions In this study, we show that a significant proportion of potentially good transplant candidates are not being referred for transplant. A ~ 14% increase in the proportion of patients being referred from dialysis facilities is both a meaningful and realistic goal and could lead to more qualified patients being referred and subsequently waitlisted for a lifesaving transplant.

Abstract: Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility– and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross– validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

BACKGROUND: The per diem financial structure of hospice care may lead agencies to consider patient-level factors when weighing admissions. OBJECTIVE: To investigate if treatment cost, disease complexity, and diagnosis are associated with hospice willingness to accept patients. DESIGN: In this 2019 online survey study, individuals involved in hospice admissions decisions were randomized to view one of six hypothetical patient vignettes: high-cost, high-complexity, low-cost, high-complexity, and low-cost, low-complexity within two diseases: heart failure and cystic fibrosis. Vignettes included demographics, prognoses, goals, and medications with costs. Respondents indicated their perceived likelihood of acceptance to their hospice; if likelihood was

In view of the rise of drug-resistant tuberculosis and difficult-to-treat related diseases caused by non-tuberculous mycobacteria, there is an urgent need for antimycobacterial drug discovery. Nα-aroyl-N-aryl-phenylalanine amides (AAPs) have been identified as antimycobacterial agents and are subject to lead optimization. The aim of the present study is to evaluate the impact of N-aryl ortho cyano substitution in a lead compound on the crystal and molecular structure and its in vitro activity against Mycobacterium abscessus. The title AAP can be conveniently synthesized from N-Boc-protected d-phenylalanine in two amide coupling steps using a previously established racemization-free method. Two polymorphic forms in the solid-state are described, as discovered by X-ray and electron diffraction. The introduction of a cyano group in the ortho position of the AAP N-aryl ring, however, leads to loss of in vitro activity against M. abscessus subsp. abscessus.

Abstract Purpose Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. Methods Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). Results Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3–3) was higher compared with conventional imaging at 120 kVp (2; 2–2), 100 kVp (1; 1–2), and 80 kVp (1; 1–1) (all p

Julie Barberio,1,2 Rohini K Hernandez,2 Ashley I Naimi,1 Rachel E Patzer,1,3 Christopher Kim,2 Timothy L Lash1 1Department of Epidemiology, Emory University, Atlanta, GA, USA; 2Center for Observational Research, Amgen, Inc, Thousand Oaks, CA, USA; 3Regenstrief Institute, Indianapolis, IN, USACorrespondence: Julie Barberio, Department of Epidemiology, Emory University, 1518 Clifton Road, Atlanta, GA, 30322, USA, Tel +1 404 727 3956, Email julie.barberio@emory.eduPurpose: Observational postapproval safety studies are needed to inform medication safety during pregnancy. Real-world databases can be valuable for supporting such research, but fitness for regulatory purpose must first be vetted. Here, we demonstrate a fit-for-purpose assessment of the Japan Medical Data Center (JMDC) claims database for pregnancy safety regulatory decision-making.Patients and Methods: The Duke-Margolis framework considers a database’s fitness for regulatory purpose based on relevancy (capacity to answer the research question based on variable availability and a sufficiently sized, representative population) and quality (ability to validly answer the research question based on data completeness and accuracy). To assess these considerations, we examined descriptive characteristics of infants and pregnancies among females ages 12– 55 years in the JMDC between January 2005 and March 2022.Results: For relevancy, we determined that critical data fields (maternal medications, infant major congenital malformations, covariates) are available. Family identification codes permitted linkage of 385,295 total mother–infant pairs, 57% of which were continuously enrolled during pregnancy. The prevalence of specific congenital malformation subcategories and maternal medical conditions were representative of the general population, but preterm births were below expectations (3.6% versus 5.6%) in this population. For quality, our methods are expected to accurately identify the complete set of mothers and infants with a shared health insurance plan. However, validity of gestational age information was limited given the high proportion (60%) of missing live birth delivery codes coupled with suppression of infant birth dates and inaccessibility of disease codes with gestational week information.Conclusion: The JMDC may be well suited for descriptive studies of pregnant people in Japan (eg, comorbidities, medication usage). More work is needed to identify a method to assign pregnancy onset and delivery dates so that in utero medication exposure windows can be defined more precisely as needed for many regulatory postapproval pregnancy safety studies.Keywords: routine health care data, international databases, database evaluation