A multi-faceted approach to sex and gender equity in solid organ transplantation: The Women in Transplantation Initiative of The Transplantation Society.

The advancement of women's careers in transplantation continues to be challenging. Academic careers in both basic and clinical disciplines in transplantation, such as surgery and management of end organ failure in medical specialties, have been underrepresented by diverse genders and ethnicities. Over the last decade, the Women in Transplantation Initiative (WIT) has solidified to becoming an internationally recognized organization with activities focused on diversity and inclusion in terms of the sexes. The WIT organization is divided into 3 pillars that address career advancement and networking (Pillar 1), scientific investigation and presentations on sex and gender in transplantation (Pillar 2) and investigating and facilitating equitable access to transplantation for women throughout the world (Pillar 3). By taking this multipronged approach of collaborating across continents, leveraging virtual platforms for information dissemination and discussion, and providing financial support for research, WIT has become a highly visible grass roots organization that aims to improve the experience of women as transplant professionals as well as transplant donors and recipients.

An ex-ante cost-utility analysis of the deemed consent legislation compared to expressed consent for kidney transplantations in Nova Scotia.

BACKGROUND: This study was an ex-ante cost-utility analysis of deemed consent legislation for deceased organ donation in Nova Scotia, a province in Canada. The legislation became effective in January 2021. The study's objective was to assess the conditions necessary for the legislation change's cost-effectiveness compared to expressed consent, focusing on kidney transplantation (KT). METHOD: We performed a cost-utility analysis using a Markov model with a lifetime horizon. The study was from a Canadian payer perspective. The target population was patients with end-stage kidney disease (ESKD) in Atlantic Canada waitlisted for KT. The intervention was the deemed consent and accompanying health system transformations. Expressed consent (before the change) was the comparator. We simulated the minimum required increase in deceased donor KT per year for the cost-effectiveness of the deemed consent. We also evaluated how changes in dialysis and maintenance immunosuppressant drug costs and living donor KT per year impacted cost-effectiveness in sensitivity analyses. RESULTS: The expected lifetime cost of an ESKD patient ranged from $177,663 to $553,897. In the deemed consent environment, the expected lifetime cost per patient depended on the percentage increases in the proportion of ESKD patients on the waitlist getting a KT in a year. The incremental cost-utility ratio (ICUR) increased with deceased donor KT per year. Cost-effectiveness of deemed consent compared to expressed consent required a minimum of a 1% increase in deceased donor KT per year. A 1% increase was associated with an ICUR of $32,629 per QALY (95% CI: - $64,279, $232,488) with a 81% probability of being cost-effective if the willingness-to-pay (WTP) was $61,466. Increases in dialysis and post-KT maintenance immunosuppressant drug costs above a threshold impacted value for money. The threshold for immunosuppressant drug costs also depended on the percent increases in deceased donor KT probability and the WTP threshold. CONCLUSIONS: The deemed consent legislation in NS for deceased organ donation and the accompanying health system transformations are cost-effective to the extent that they are anticipated to contribute to more deceased donor KTs than before, and even a small increase in the proportion of waitlist patients receiving a deceased donor KT than before the change represents value for money.

What are the short-term annual cost savings associated with kidney transplantation?

BACKGROUND: Kidney transplantation (KT) is often reported in the literature as associated with cost savings. However, existing studies differ in their choice of comparator, follow-up period, and the study perspective. Also, there may be unobservable heterogeneity in health care costs in the patient population which may divide the population into groups with differences in cost distributions. This study estimates the cost savings associated with KT from a payer perspective and identifies and characterizes both high and low patient cost groups. METHOD: The current study was a population-based retrospective before-and-after study. The timespan involved at most three years before and after KT. The sample included end-stage kidney disease patients in Nova Scotia, a province in Canada, who had a single KT between January 1, 2011, and December 31, 2018. Each patient served as their control. The primary outcome measure was total annual health care costs. We estimated cost savings using unadjusted and adjusted models, stratifying the analyses by donor type. We quantified the uncertainty around the estimates using non-parametric and parametric bootstrapping. We also used finite mixture models to identify data-driven cost groups based on patients' pre-transplantation annual inpatient costs. RESULTS: The mean annual cost savings per patient associated with KT was $19,589 (95% CI: $14,013, $23,397). KT was associated with a 24-29% decrease in mean annual health care costs per patient compared with the annual costs before KT. We identified and characterized patients in three cost groups made of 2.9% in low-cost (LC), 51.8% in medium-cost (MC) and 45.3% in high-cost (HC). Cost group membership did not change after KT. Comparing costs in each group before and after KT, we found that KT was associated with 17% mean annual cost reductions for the LC group, 24% for the MC group and 26% for the HC group. The HC group included patients more likely to have a higher comorbidity burden (Charlson comorbidity index ≥ 3). CONCLUSIONS: KT was associated with reductions in annual health care costs in the short term, even after accounting for costs incurred during KT.

A Location-Based Objective Assessment of Physical Activity and Sedentary Behavior in Ambulatory Hemodialysis Patients.

BACKGROUND: Dialysis patients have reduced moderate to vigorous physical activity, and light physical activity. This has been shown in self-reported surveys and objective accelerometer studies. Less attention has been directed toward sedentary behavior, which is characterized by low energy expenditure (≤1.5 metabolic equivalents). Furthermore, locations where physical activity and sedentary behavior occur are largely unknown for dialysis patients. OBJECTIVES: The objectives of this study were (1) to determine the minutes per day of moderate to vigorous physical activity, light physical activity, and sedentary behavior for hemodialysis patients; (2) to describe differences in moderate to vigorous physical activity, light physical activity, and sedentary behavior comparing dialysis versus nondialysis days; and (3) to describe the locations where moderate to vigorous physical activity, light physical activity, and sedentary behavior occur using global positioning system (GPS) data. DESIGN: Cross-sectional study. SETTING: The study was performed at a tertiary care hospital in Nova Scotia, Canada. PATIENTS: A total of 50 adult in-center hemodialysis patients consented to the study. MEASUREMENTS: Physical activity and sedentary behavior were measured with an Actigraph-GT3X accelerometer. Location was determined using a Qstarz BT-Q1000X GPS receiver. METHODS: Minutes of daily activity were described as was percentage of wear time for each activity level across different locations during waking hours. Physical activity intensity, quantity, and location were also analyzed according to dialysis vs nondialysis days. RESULTS: Forty-three patients met requirements for accelerometer analysis, of whom 42 had GPS data. Median wear time was 836.5 min/day (interquartile range [IQR]: 788.3-918.3). Median minutes of daily wear time spent in sedentary behavior, light physical activity, and moderate to vigorous physical activity was 636 minutes (IQR: 594.1-730.1), 178 minutes (IQR: 144-222.1), and 1.6 minutes (IQR: 0.6-7.7), respectively. Proportion of daily wear time spent in sedentary behavior, light physical activity, and moderate to vigorous physical activity was 78.4% (IQR: 70.7-84.0), 21.5% (IQR: 16.0-26.9), and 0.2% (IQR: 0.1-1.1), respectively. Home was the dominant location for total linked accelerometer-GPS time (59.4%, IQR: 46.9-69.5) as well as for each prespecified level of activity. Significantly more sedentary behavior and less light physical activity occurred on dialysis days compared with nondialysis days (P ≤ .01, respectively). Moderate to vigorous physical activity did not differ significantly between dialysis and nondialysis days. LIMITATIONS: Small sample size from a single academic center may limit generalizability. Difficult to engage population as less than half of eligible dialysis patients provided consent. Physical activity may have been underestimated as devices were not worn for all waking hours or aquatic activities, and hip-based accelerometers may not capture stationary exercise. CONCLUSIONS: Ambulatory, in-center hemodialysis patients exhibit substantial sedentary behavior and minimal physical activity across a limited range of locations. Given the sedentary tendencies of this population, focus should be directed on increasing physical activity at any location frequented. Home-based exercise programs may serve as a potential adjunct to established intradialytic-based therapies given the amount of time spent in the home environment.

CONTEXTE: Il a été démontré par des enquêtes d'auto-déclaration et des études objectives par accéléromètre que les patients en dialyse pratiquent peu d'activités modérées à vigoureuses et une activité physique légère. Les comportements sédentaires, caractérisés par une faible dépense énergétique (≤ 1,5 équivalent métabolique/MET), ont suscité moins d'intérêt. De plus, les endroits où l'activité physique et le comportement sédentaire sont pratiqués sont en grande partie inconnus des patients dialysés. OBJECTIFS: 1) Déterminer le nombre de minutes par jour d'activité physique modérée à vigoureuse, d'activité physique légère et de sédentarité chez les patients hémodialysés. 2) Décrire les différences d'activité physique modérée à vigoureuse, d'activité physique légère et de comportement sédentaire en comparant les journées de dialyse aux journées sans dialyse. 3) Recenser les endroits où les activités physiques modérées à vigoureuses, les activités physiques légères et les comportements sédentaires se produisent à l'aide des données du système de positionnement global (GPS). TYPE D'ÉTUDE: Étude transversale. CADRE: L'étude a été réalisée dans un hôpital de soins tertiaires en Nouvelle-Écosse (Canada).Sujets: Au total, 50 adultes hémodialysés en centre ont accepté de participer à l'étude. MESURES: Le niveau d'activité physique et les comportements sédentaires ont été mesurés à l'aide de l'accéléromètre Actigraph-GT3X. Les lieux ont été déterminés à l'aide d'un récepteur Qstarz BT-Q1000X GPS. MÉTHODOLOGIE: Le nombre de minutes d'activité quotidienne a été exprimé en pourcentage de temps de port de l'appareil pour chaque type d'activité, à différents endroits, pendant les heures d'éveil. L'intensité, la quantité et la localisation de l'activité physique ont également été analysées selon qu'il s'agissait ou non d'une journée de dialyse. RÉSULTATS: Quarante-trois patients remplissaient les conditions requises pour l'analyse par accéléromètre, dont 42 disposaient de données GPS. Le temps de port médian était de 836,5 minutes/jour (EIQ: 788,3-918,3). La médiane du nombre de minutes de port quotidien passées en période de sédentarité, d'activité physique légère ou d'activité modérée à vigoureuse était de 636 minutes (EIQ: 594,1-730,1), de 178 minutes (EIQ: 144-222,1) et de 1,6 minute (EIQ: 0,6-7,7), respectivement. La proportion du temps de port quotidien passé en comportement sédentaire, en activité physique légère et en activité physique modérée à vigoureuse était de 78,4 % (IQR 70,7-84,0), 21,5 % (IQR 16,0-26,9) et 0,2 % (IQR 0,1-1,1), respectivement. Le temps total pour le duo accéléromètre-GPS (59,4 %; IQR 46,9-69,5) et chacun des niveaux d'activité prédéfinis a été majoritairement enregistré au domicile. Les périodes de sédentarité et de faible activité physique ont été nettement plus observées les jours de dialyse en comparaison des jours sans dialyse (P ≤ ,01). L'activité physique modérée à vigoureuse n'a pas varié de façon significative, qu'il s'agisse ou non d'un jour de dialyse. LIMITES: La généralisation des résultats est limitée par la petite taille de l'échantillon et le fait que les sujets provenaient d'un seul centre. Aussi, le recrutement des sujets est difficile, moins de la moitié des patients admissibles a donné son consentement. Enfin, l'activité physique pourrait être sous-estimée puisque les appareils n'étaient pas portés pendant toutes les heures d'éveil ou lors des activités aquatiques, et qu'il est possible que l'accéléromètre, porté à la hanche, n'ait pas enregistré pas les exercices stationnaires. CONCLUSION: Les patients hémodialysés en centre sont très largement sédentaires et pratiquent une activité physique minimale dans un nombre limité d'endroits. Compte tenu de cette tendance, il convient de mettre l'accent sur l'augmentation de l'activité physique dans les lieux fréquentés par ces patients. Étant donné le temps passé à la maison, un programme d'exercices à domicile pourrait servir d'adjuvant potentiel aux traitements intradialytiques établis.

The Use of Donation After Circulatory Death Organs for Simultaneous Liver-kidney Transplant: To DCD or Not to DCD?

BACKGROUND: Because of the challenges with organ scarcity, many centers performing simultaneous liver-kidney transplant (SLKT) are opting to accept donation after circulatory death (DCD) organs as a means of facilitating earlier transplant and reducing death rates on the waitlist. It has been suggested, however, that DCD organs may have inferior graft and patient survival posttransplant compared with donation after neurologic death (DND) organs. METHODS: We created a Markov model to compare the overall outcomes of accepting a DCD SLKT now versus waiting for a DND SLKT in patients waitlisted for SLKT, stratified by base Model for End-Stage Liver Disease (MELD) score (≤20, 21-30, >30). RESULTS: Waiting for DND SLKT was the preferred treatment strategy for patients with a MELD score of 30 or less (incremental value of 0.54 and 0.36 quality-adjusted life years for MELD score of 20 or less and MELD score of 21 to 30 with DND versus DCD SLKT, respectively). The option to accept a DCD SLKT became the preferred choice for those with a MELD score greater than 30 (incremental value of 0.31 quality-adjusted life years for DCD versus DND SLKT). This finding was confirmed in a probabilistic sensitivity analysis and persisted when analyzing total life years obtained for accept DCD versus do not accept DCD. CONCLUSIONS: There is a benefit to accepting DCD SLKT for patients with MELD score greater than 30. Although not accepting DCD SLKT and waiting for DND SLKT is the preferred option for patients with MELD of 30 or less, the incremental value is small.

Burden of Emergency Medical Services Usage by Dialysis Patients.

BACKGROUND: Patients receiving chronic dialysis often require emergent and inpatient care; however, only a minimal amount is known about their out-of-hospital/inter-hospital use of Emergency Medical Services (EMS). The purpose of this study was to describe the utilization of EMS in a cohort of dialysis patients. METHODS: We analyzed a cohort of adult (≥18 years) chronic dialysis patients within the Nova Scotia Health Authority Central Zone Renal Program who initiated chronic dialysis between January 1, 2009 and June 30, 2013 (last follow up July 1, 2015). Dialysis patient data was linked to regional EMS data. Requests for EMS, including encounter type, day of the week, and patient characteristics were described. RESULTS: The cohort consisted of 468 patients of whom 79% (N = 361) had an EMS encounter. There were a total of 8,774 EMS encounters for the entire cohort. Patients who had an EMS encounter tended to be older (64 ± 14 years), compared to those without an encounter (55 ± 16 years, P < 0.001) and also had a higher burden of comorbidity. Transfers (including those between facilities) accounted for 89% of all encounters (N = 7,826), followed by emergency department (ED) transports (N = 749, 9%). Overall, 79% of all non-transfers underwent transport to the ED. For patients receiving thrice weekly in-center hemodialysis, the highest EMS utilization for ED transport occurred on the first hemodialysis day after the long dialysis break (22%, P < 0.01). The lowest proportion of ED transports occurred on the day after hemodialysis day 3. CONCLUSION: Utilization of EMS services by dialysis patients is considerable, particularly for transfers. This highlights a potential area to be targeted for reducing resource utilization. Calls requiring transport to the ED occurred most often on Mondays and Tuesdays, the day after the long-dialysis break, and may represent a time of heightened risk for in-center hemodialysis patients.

Whole-genome characterization in pedigreed non-human primates using genotyping-by-sequencing (GBS) and imputation.

BACKGROUND: Rhesus macaques are widely used in biomedical research, but the application of genomic information in this species to better understand human disease is still in its infancy. Whole-genome sequence (WGS) data in large pedigreed macaque colonies could provide substantial experimental power for genetic discovery, but the collection of WGS data in large cohorts remains a formidable expense. Here, we describe a cost-effective approach that selects the most informative macaques in a pedigree for 30X WGS, followed by low-cost genotyping-by-sequencing (GBS) at 30X on the remaining macaques in order to generate sparse genotype data at high accuracy. Dense variants from the selected macaques with WGS data are then imputed into macaques having only sparse GBS data, resulting in dense genome-wide genotypes throughout the pedigree. RESULTS: We developed GBS for the macaque genome using a digestion with PstI, followed by sequencing of size-selected fragments at 30X coverage. From GBS sequence data collected on all individuals in a 16-member pedigree, we characterized high-confidence genotypes at 22,455 single nucleotide variant (SNV) sites that were suitable for guiding imputation of dense sequence data from WGS. To characterize dense markers for imputation, we performed WGS at 30X coverage on nine of the 16 individuals, yielding 10,193,425 high-confidence SNVs. To validate the use of GBS data for facilitating imputation, we initially focused on chromosome 19 as a test case, using an optimized panel of 833 sparse, evenly-spaced markers from GBS and 5,010 dense markers from WGS. Using the method of "Genotype Imputation Given Inheritance" (GIGI), we evaluated the effects on imputation accuracy of 3 different strategies for selecting individuals for WGS, including 1) using "GIGI-Pick" to select the most informative individuals, 2) using the most recent generation, or 3) using founders only.  We also evaluated the effects on imputation accuracy of using a range of from 1 to 9 WGS individuals for imputation. We found that the GIGI-Pick algorithm for selection of WGS individuals outperformed common heuristic approaches, and that genotype numbers and accuracy improved very little when using >5 WGS individuals for imputation. Informed by our findings, we used 4 macaques with WGS data to impute variants at up to 7,655,491 sites spanning all 20 autosomes in the 12 remaining macaques, based on their GBS genotypes at only 17,158 loci. Using a strict confidence threshold, we imputed an average of 3,680,238 variants per individual at >99 % accuracy, or an average 4,458,883 variants per individual at a more relaxed threshold, yielding >97 % accuracy. CONCLUSIONS: We conclude that an optimal tradeoff between genotype accuracy, number of imputed genotypes, and overall cost exists at the ratio of one individual selected for WGS using the GIGI-Pick algorithm, per 3-5 relatives selected for GBS. This approach makes feasible the collection of accurate, dense genome-wide sequence data in large pedigreed macaque cohorts without the need for more expensive WGS data on all individuals.