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1.
Nat Biotechnol ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39313646

ABSTRACT

Tissue-level and organism-level biological processes often involve the coordinated action of multiple distinct cell types. The recent application of single-cell assays to many individuals should enable the study of how donor-level variation in one cell type is linked to that in other cell types. Here we introduce a computational approach called single-cell interpretable tensor decomposition (scITD) to identify common axes of interindividual variation by considering joint expression variation across multiple cell types. scITD combines expression matrices from each cell type into a higher-order matrix and factorizes the result using the Tucker tensor decomposition. Applying scITD to single-cell RNA-sequencing data on 115 persons with lupus and 83 persons with coronavirus disease 2019, we identify patterns of coordinated cellular activity linked to disease severity and specific phenotypes, such as lupus nephritis. scITD results also implicate specific signaling pathways likely mediating coordination between cell types. Overall, scITD offers a tool for understanding the covariation of cell states across individuals, which can yield insights into the complex processes that define and stratify disease.

2.
Transplant Proc ; 56(8): 1712-1720, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39198066

ABSTRACT

BACKGROUND: The mismatch between the number of patients awaiting kidney transplantation and the supply of donor organs has contributed to the increase in kidney transplantation from donors after circulatory death (DCD). Persistently long waiting times have led the transplant community to continue to explore the use of expanded- criteria DCD kidneys. In parallel, advances in organ preservation strategies have contributed to an overall increase in DCD organ transplantation and are altering the transplant landscape. Some of these techniques may improve kidney allograft outcomes and affect how DCD kidneys are used. We aimed to better understand practices in accepting DCD kidney offers in the modern era. METHODS: Directors of 196 US kidney transplant centers were emailed a link to an online survey over a 5-week period. RESULTS: Forty-eight out of the 364 directors (13%) responded, with all United Network for Organ Sharing regions represented. Definitions of warm ischemia time (WIT) used in DCD kidney evaluation varied widely among the respondents. The maximum total WIT limit varied, with 19 (39.6%) <60-minute responses, followed by 16 (33%) <90-minute responses, and 10 (20.8%) <120-minute responses. CONCLUSIONS: Despite increasing DCD kidney transplantation volumes in the United States, there are no standardized procurement biopsy practices, organ procurement organization preoperative protocols, or consensus definition or limits of WIT. Agreement on terminology may facilitate rapid clinical communication, efficiency of organ allocation and utilization, recording of data, research, and improvements in policy.


Subject(s)
Kidney Transplantation , Tissue Donors , Tissue and Organ Procurement , Humans , United States , Tissue and Organ Procurement/methods , Surveys and Questionnaires , Tissue Donors/supply & distribution , Organ Preservation/methods , Warm Ischemia
3.
J Neurosci ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39197942

ABSTRACT

The visual world is richly adorned with texture, which can serve to delineate important elements of natural scenes. In anes-thetized macaque monkeys, selectivity for the statistical features of natural texture is weak in V1, but substantial in V2, sug-gesting that neuronal activity in V2 might directly support texture perception. To test this, we investigated the relation between single cell activity in macaque V1 and V2 and simultaneously measured behavioral judgments of texture. We generated stim-uli along a continuum between naturalistic texture and phase-randomized noise and trained two macaque monkeys to judge whether a sample texture more closely resembled one or the other extreme. Analysis of responses revealed that individual V1 and V2 neurons carried much less information about texture naturalness than behavioral reports. However, the sensitivity of V2 neurons, especially those preferring naturalistic textures, was significantly closer to that of behavior compared with V1. The firing of both V1 and V2 neurons predicted perceptual choices in response to repeated presentations of the same ambiguous stimulus in one monkey, despite low individual neural sensitivity. However, neither population predicted choice in the second monkey. We conclude that neural responses supporting texture perception likely continue to develop downstream of V2. Fur-ther, combined with neural data recorded while the same two monkeys performed an orientation discrimination task, our results demonstrate that choice-correlated neural activity in early sensory cortex is unstable across observers and tasks, untethered from neuronal sensitivity, and thus unlikely to reflect a critical aspect of the formation of perceptual decisions.Significance statement As visual signals propagate along the cortical hierarchy, they encode increasingly complex aspects of the sensory environment and likely have a more direct relationship with perceptual experience. We replicate and extend previous results from anes-thetized monkeys differentiating the selectivity of neurons along the first step in cortical vision from area V1 to V2. However, our results further complicate efforts to establish neural signatures that reveal the relationship between perception and the neu-ronal activity of sensory populations. We find that choice-correlated activity in V1 and V2 is unstable across different observers and tasks, and also untethered from neuronal sensitivity and other features of nonsensory response modulation.

4.
Clin Transplant ; 38(8): e15436, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39158959

ABSTRACT

BACKGROUND: Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable. METHODS: We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60 min), low fWIT (≤60 min), and kidneys transplanted from donors after brain death (DBD). RESULTS: Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI = 2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI = 1.4-3.1) have higher hazard ratios for 1-year graft failure. CONCLUSIONS: Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.


Subject(s)
Graft Survival , Kidney Transplantation , Tissue Donors , Tissue and Organ Procurement , Warm Ischemia , Humans , Male , Female , Retrospective Studies , Middle Aged , Follow-Up Studies , Tissue Donors/supply & distribution , Tissue and Organ Procurement/methods , Prognosis , Adult , Risk Factors , Survival Rate , Glomerular Filtration Rate , Kidney Function Tests , Graft Rejection/etiology , Kidney Failure, Chronic/surgery , Donor Selection
5.
Kidney Int ; 106(4): 712-722, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39074554

ABSTRACT

Current kidney perfusion protocols are not optimized for addressing the ex vivo physiological and metabolic needs of the kidney. Ex vivo normothermic perfusion may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. Here, we assessed the association of tissue metabolic changes with changes in a kidney injury biomarker and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12-hour ex vivo normothermic perfusion. The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean age of the deceased kidney donors was 43 years with an average cold ischemia time of 37 hours. Urine output and creatinine clearance progressively increased and peaked at six hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% confidence interval 1.5, 140) urinary neutrophil gelatinase-associated lipocalin at six hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branched chain amino acid metabolism and that their tissue levels negatively correlated with urine output among all kidneys at six hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Thus, we showed that six hours is needed for kidney function recovery during ex vivo normothermic perfusion and that branched chain amino acid metabolism may be a major determinant of organ function and resilience.


Subject(s)
Amino Acids, Branched-Chain , Biomarkers , Kidney Transplantation , Kidney , Lipocalin-2 , Organ Preservation , Perfusion , Tissue Donors , Humans , Perfusion/methods , Adult , Kidney Transplantation/methods , Male , Kidney/metabolism , Kidney/blood supply , Middle Aged , Female , Organ Preservation/methods , Amino Acids, Branched-Chain/metabolism , Biomarkers/urine , Biomarkers/metabolism , Lipocalin-2/urine , Lipocalin-2/metabolism , Time Factors , Cold Ischemia/adverse effects , Donor Selection/methods , Creatinine/blood , Creatinine/urine
6.
A A Pract ; 18(5): e01786, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38708942

ABSTRACT

We report a case of a 62-year-old woman with a decade-long history of atypical chest pain resulting in a largely negative cardiac workup, who developed significant angiographically demonstrated coronary vasospasm thought to be due to a small dose of intravenous ketamine. In patients with a history of atypical chest pain despite a reassuring cardiac evaluation, providers should carefully consider medications that may precipitate coronary vasospasm and be prepared to treat it accordingly.


Subject(s)
Coronary Vasospasm , Ketamine , Humans , Coronary Vasospasm/chemically induced , Ketamine/adverse effects , Ketamine/administration & dosage , Female , Middle Aged , Chest Pain/chemically induced , Coronary Angiography
8.
J Am Med Dir Assoc ; 25(6): 104956, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38431263

ABSTRACT

OBJECTIVES: The PoET (Prevention of Error-based Transfers) project seeks to align long-term care (LTC) home informed consent practices to existing legislation, thereby reducing consent-related error-based transfers to acute care. We sought to measure changes in resident-level palliative care provision after participating in the PoET Southwest Spread Project (PSSP), and to identify patient and LTC home characteristics associated with palliative care provision. DESIGN: Quasi-experimental matched (1:1 ratio) cohort study design using linked population-based health administrative data. SETTING: Sixty LTC homes (PSSP = 30; Control = 30) in Ontario, Canada, from November 2019 to December 2021. METHODS: We matched 30 PSSP to 30 control homes and described incidence rates for resident-level palliative care provision (ie, physician palliative care encounters and palliative medication prescriptions) during the 7-month postimplementation period. We used generalized linear mixed models to evaluate the association between PSSP implementation and palliative care provision during the postimplementation period. We adjusted for resident-level characteristics (ie, age, sex, comorbidity status) and home-level characteristics (ie, rurality status, profit model, COVID-19 impact). We identified a decedent subcohort to measure palliative care provision patterns during the last 2 months of life. RESULTS: We captured a matched cohort of 8894 residents (PSSP = 4103; Control = 4791). Incidence rates of palliative care encounters increased during the postimplementation period for PSSP (82.6 to 85.4 per 100 person-months) but not for control residents (68.8 to 65.3 per 100 person-months). After adjusting for key covariates, PSSP exposure was associated increased palliative care provision (incidence rate ratio 2.47, 95% CI 2.31-2.64) and palliative care medication prescription (1.16, 95% CI 1.12-1.20). Larger home size, certain health regions, and higher number of comorbidities were associated with increased physician palliative care encounters. CONCLUSIONS AND IMPLICATIONS: By promoting correct informed consent practices in LTC, PSSP participation increased palliative care provision for PSSP LTC residents across all settings.


Subject(s)
Palliative Care , Humans , Ontario , Female , Male , Aged , Aged, 80 and over , Cohort Studies , COVID-19/prevention & control , COVID-19/epidemiology , Long-Term Care , Nursing Homes , Patient Transfer/statistics & numerical data
9.
bioRxiv ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38464304

ABSTRACT

The visual world is richly adorned with texture, which can serve to delineate important elements of natural scenes. In anesthetized macaque monkeys, selectivity for the statistical features of natural texture is weak in V1, but substantial in V2, suggesting that neuronal activity in V2 might directly support texture perception. To test this, we investigated the relation between single cell activity in macaque V1 and V2 and simultaneously measured behavioral judgments of texture. We generated stimuli along a continuum between naturalistic texture and phase-randomized noise and trained two macaque monkeys to judge whether a sample texture more closely resembled one or the other extreme. Analysis of responses revealed that individual V1 and V2 neurons carried much less information about texture naturalness than behavioral reports. However, the sensitivity of V2 neurons, especially those preferring naturalistic textures, was significantly closer to that of behavior compared with V1. The firing of both V1 and V2 neurons predicted perceptual choices in response to repeated presentations of the same ambiguous stimulus in one monkey, despite low individual neural sensitivity. However, neither population predicted choice in the second monkey. We conclude that neural responses supporting texture perception likely continue to develop downstream of V2. Further, combined with neural data recorded while the same two monkeys performed an orientation discrimination task, our results demonstrate that choice-correlated neural activity in early sensory cortex is unstable across observers and tasks, untethered from neuronal sensitivity, and thus unlikely to reflect a critical aspect of the formation of perceptual decisions. Significance statement: As visual signals propagate along the cortical hierarchy, they encode increasingly complex aspects of the sensory environment and likely have a more direct relationship with perceptual experience. We replicate and extend previous results from anesthetized monkeys differentiating the selectivity of neurons along the first step in cortical vision from area V1 to V2. However, our results further complicate efforts to establish neural signatures that reveal the relationship between perception and the neuronal activity of sensory populations. We find that choice-correlated activity in V1 and V2 is unstable across different observers and tasks, and also untethered from neuronal sensitivity and other features of nonsensory response modulation.

10.
Transplant Direct ; 10(3): e1581, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38380346

ABSTRACT

Background: Few studies have evaluated the efficacy of transverse abdominis plane (TAP) block in patients undergoing hand-assisted laparoscopic live-donor nephrectomy (HALN). We aimed to evaluate the analgesic effectiveness of TAP block as part of a multimodal pain management regimen in patients undergoing HALN. Methods: We retrospectively reviewed the medical records of living kidney donors at our center between June 2016 and February 2020. HALNs were performed via a transperitoneal approach through a suprapubic incision. Additional laparoscopic ports were used in the upper midabdomen. In consenting donors, TAP block was performed postoperatively under ultrasound guidance with either a single-shot or continuous infusion of long-acting local anesthetic (0.2%-0.5% ropivacaine). All the patients received postoperative around-the-clock ketorolac and acetaminophen. Results: Overall, 72 donors received the block (block group, 38 single-shot, 34 continuous), whereas 86 donors did not receive the block (control group). Baseline characteristics were comparable between the groups except for body weight (control: 71.8 ±â€…13.3 versus block: 77.8 ±â€…17.3 kg; P = 0.01) and intraoperative opioid dose (32.1 ±â€…9.6 versus 26.6 ±â€…10.7 morphine milligram equivalents; P < 0.001). After adjusting for baseline differences, postoperative opioid requirements were similar between the groups. When the baseline pain scale was adjusted for, there was no difference in the overall pain scale scores between the groups (P = 0.242). Subgroup analyses comparing single-shot or continuous TAP versus control did not show any differences. Conclusions: With the caveat of the retrospective nature of the study, the adjunctive effect of TAP block after transabdominal HALN was limited when other multimodal analgesia was used.

11.
Genome Biol ; 25(1): 28, 2024 01 22.
Article in English | MEDLINE | ID: mdl-38254214

ABSTRACT

Genetic regulation of gene expression is a complex process, with genetic effects known to vary across cellular contexts such as cell types and environmental conditions. We developed SURGE, a method for unsupervised discovery of context-specific expression quantitative trait loci (eQTLs) from single-cell transcriptomic data. This allows discovery of the contexts or cell types modulating genetic regulation without prior knowledge. Applied to peripheral blood single-cell eQTL data, SURGE contexts capture continuous representations of distinct cell types and groupings of biologically related cell types. We demonstrate the disease-relevance of SURGE context-specific eQTLs using colocalization analysis and stratified LD-score regression.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation , Quantitative Trait Loci , Transcriptome , Sequence Analysis, RNA
12.
JAMA Surg ; 159(1): 60-68, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37910090

ABSTRACT

Importance: Despite the unmet need, many deceased-donor kidneys are discarded or not recovered. Inefficient allocation and prolonged ischemia time are contributing factors, and early detection of high-risk donors may reduce organ loss. Objective: To evaluate the feasibility of machine learning (ML) and natural language processing (NLP) classification of donors with kidneys that are used vs not used for organ transplant. Design, Setting, and Participants: This retrospective cohort study used donor information (structured donor characteristics and unstructured donor narratives) from the United Network for Organ Sharing (UNOS). All donor offers to a single transplant center between January 2015 and December 2020 were used to train and validate ML models to predict donors who had at least 1 kidney transplanted (at our center or another center). The donor data from 2021 were used to test each model. Exposures: Donor information was provided by UNOS to the transplant centers with potential transplant candidates. Each center evaluated the donor and decided within an allotted time whether to accept the kidney for organ transplant. Main Outcomes and Measures: Outcome metrics of the test cohort included area under the receiver operating characteristic curve (AUROC), F1 score, accuracy, precision, and recall of each ML classifier. Feature importance and Shapley additive explanation (SHAP) summaries were assessed for model explainability. Results: The training/validation cohort included 9555 donors (median [IQR] age, 50 [36-58] years; 5571 male [58.3%]), and the test cohort included 2481 donors (median [IQR] age, 52 [40-59] years; 1496 male [60.3%]). Only 20% to 30% of potential donors had at least 1 kidney transplanted. The ML model with a single variable (Kidney Donor Profile Index) showed an AUROC of 0.69, F1 score of 0.42, and accuracy of 0.64. Multivariable ML models based on basic a priori structured donor data showed similar metrics (logistic regression: AUROC = 0.70; F1 score = 0.42; accuracy = 0.62; random forest classifier: AUROC = 0.69; F1 score = 0.42; accuracy = 0.64). The classic NLP model (bag-of-words model) showed its best metrics (AUROC = 0.60; F1 score = 0.35; accuracy = 0.59) by the logistic regression classifier. The advanced Bidirectional Encoder Representations From Transformers model showed comparable metrics (AUROC = 0.62; F1 score = 0.39; accuracy = 0.69) only after appending basic donor information. Feature importance and SHAP detected the variables (and words) that affected the models most. Conclusions and Relevance: Results of this cohort study suggest that models using ML can be applied to predict donors with high-risk kidneys not used for organ transplant, but the models still need further elaboration. The use of unstructured data is likely to expand the possibilities; further exploration of new approaches will be necessary to develop models with better predictive metrics.


Subject(s)
Kidney Transplantation , Humans , Male , Middle Aged , Cohort Studies , Retrospective Studies , Kidney , Tissue Donors
13.
J Am Heart Assoc ; 13(1): e031498, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38156519

ABSTRACT

BACKGROUND: We aim to examine the association between primary care physicians' billing of Q050A, a pay-for-performance heart failure (HF) management incentive fee code, and the composite outcome of mortality, hospitalization, and emergency department visits. METHODS AND RESULTS: This population-based cohort study linked administrative health databases in Ontario, Canada, for patients with HF aged >66 years between January 1, 2008, and March 31, 2020. Cases were patients with HF who had a Q050A fee code billed. Cases and controls were matched 1:1 on age, sex, patient status on being rostered to a primary care physician, cardiologist, or internist visit in the 6 months before study enrollment, Johns Hopkins Adjusted Clinical Group resource use bands, days between HF diagnosis and study enrollment (±2 years), and the logit of the propensity score. A Cox proportional hazards model assessed the association of Q050A with the outcome. A total of 59 664 cases had a Q050A billed, whereas 244 883 patients did not. Before matching, patients who had a Q050A billed were more likely to be men (52% versus 49%), were rostered to a primary care physician (100% versus 96%), had a higher Charlson Comorbidity Index, and had higher health care costs. The mean follow-up was 481 days for cases and 530 days for controls. The composite outcome (hazard ratio, 1.11 [95% CI, 1.09-1.12]) was significantly higher for cases than controls. CONCLUSIONS: The Q050A incentive improved financial compensation for primary care physicians managing patients with HF but was not associated with improvements in the outcome. Research on promoting evidence-based HF management is warranted.


Subject(s)
Heart Failure , Motivation , Male , Humans , Infant, Newborn , Female , Cohort Studies , Retrospective Studies , Reimbursement, Incentive , Heart Failure/diagnosis , Heart Failure/therapy , Hospitalization , Primary Health Care , Ontario/epidemiology
14.
iScience ; 26(10): 107813, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37810211

ABSTRACT

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

15.
J Am Med Dir Assoc ; 24(12): 1888-1897, 2023 12.
Article in English | MEDLINE | ID: mdl-37777186

ABSTRACT

OBJECTIVES: To measure changes in resident-level acute care transfer rates after the PoET Southwest Spread Project (PSSP), and to identify patient and long-term care (LTC) home characteristics associated with acute care transfers after program launch. DESIGN: Quasi-experimental matched (1:1 ratio) cohort study design using linked population-based health administrative data. SETTING: Sixty publicly funded LTC homes (PSSP = 30; control = 30) in Ontario, Canada, from November 2019 to December 2021. METHODS: We matched 30 PSSP homes to 30 control homes with similar characteristics and described incidence rates for resident-level acute care transfers during the 7-month post-implementation period. We used generalized linear mixed models to evaluate the association between PSSP implementation and acute care transfers during the post-implementation period. We adjusted resident-level characteristics (ie, age, sex, comorbidity status) and home-level characteristics (ie, rurality status, profit model, COVID-19 impact). We identified a decedent sub-cohort to measure transfer patterns during the last 2 months of life. RESULTS: A matched cohort of 8894 residents (PSSP = 4103; control = 4791) was captured. Incidence rates of transfers increased during the post-implementation period for both PSSP (78.8 to 80.9 transfers per 1000 person-months) and control residents (66.9 to 67.9 transfers per 1000 person-months). After adjusting for covariates of interest, PSSP exposure was associated with a reduction in acute care transfers during the post-implementation period after adjusting for covariates (incidence rate ratio, 0.73; 95% CI, 0.62-0.87; P = .0002). Older age and select health regions were associated with reduced transfers, whereas higher comorbidity status and higher COVID-19 outbreak days were associated with increases. Similar patterns persisted for transfers during the last 2 months of life. CONCLUSIONS AND IMPLICATIONS: This study systematically evaluated the impact of an ethics-based health care intervention in LTC using health care utilization databases. PoET implementation is associated with reduced acute care transfer rates, especially in the last 2 months of life in LTC.


Subject(s)
COVID-19 , Long-Term Care , Humans , Nursing Homes , Cohort Studies , Routinely Collected Health Data , COVID-19/epidemiology , Ontario/epidemiology
16.
Am J Transplant ; 23(3): 316-325, 2023 03.
Article in English | MEDLINE | ID: mdl-36906294

ABSTRACT

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.


Subject(s)
Frailty , Organ Transplantation , Tissue and Organ Procurement , Female , Humans , Healthcare Disparities , Kidney , Tissue Donors , United States , Waiting Lists
18.
JAMA Surg ; 158(3): 319-321, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36542367

ABSTRACT

This cohort study compares graft survival of kidneys from small and very small pediatric donors in women vs men with end-stage kidney disease.


Subject(s)
Kidney Failure, Chronic , Tissue Donors , Male , Humans , Child , Female , Kidney Failure, Chronic/surgery , Graft Survival , Kidney
19.
Article in English | MEDLINE | ID: mdl-36121587

ABSTRACT

OBJECTIVE: In this retrospective cohort study of consecutive patients with atrial fibrillation and surgical or transcatheter bioprosthetic valve, we compared the efficacy and safety of direct oral anticoagulants with warfarin. METHODS: Using linked health administrative databases housed at the Institute for Clinical Evaluative Sciences, we identified consecutive patients in Ontario (Canada) 65 years of age or older with AF who underwent bioprosthetic valve replacement between 1 April 2012 and 31 March 2017. We created a time-varying Cox model to examine the relationship between the type of anticoagulant and time to thrombotic or bleeding events after adjustment for baseline risk of thrombosis using the CHA2DS2-VASc score and risk of bleeding using the HAS-BLED scores. We conducted prespecified subgroup analyses according to whether valve implantation was surgical or transcatheter. RESULTS: We identified 2245 eligible patients. The mean age was 79 years, 41% were female, and 39% had transcatheter aortic valve replacement. Risk of death or thrombosis was not different between direct oral anticoagulants and warfarin after adjustment for CHA2DS2-VASc score (hazard ratio [HR] 1.02, 95% confidence interval [CI], 0.83-1.25). Risk of death or bleeding was not different between direct oral anticoagulants and warfarin after adjustment for HAS-BLED score (HR 0.89, 95% CI 0.75-1.07). Subgroup analyses of surgical or transcatheter valves were consistent with overall results. CONCLUSIONS: In a real-world population of patients with atrial fibrillation and bioprosthetic valve replacement, we found no difference between direct oral anticoagulants and warfarin with regard to the risk of thrombosis or bleeding.

20.
CMAJ ; 194(21): E730-E738, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35636759

ABSTRACT

BACKGROUND: Because there are no standardized reporting systems specific to residents of retirement homes in North America, little is known about the health of this distinct population of older adults. We evaluated rates of health services use by residents of retirement homes relative to those of residents of long-term care homes and other populations of older adults. METHODS: We conducted a retrospective cohort study using population health administrative data from 2018 on adults 65 years or older in Ontario. We matched the postal codes of individuals to those of licensed retirement homes to identify residents of retirement homes. Outcomes included rates of hospital-based care and physician visits. RESULTS: We identified 54 733 residents of 757 retirement homes (mean age 86.7 years, 69.0% female) and 2 354 385 residents of other settings. Compared to residents of long-term care homes, residents of retirement homes had significantly higher rates per 1000 person months of emergency department visits (10.62 v. 4.48, adjusted relative rate [RR] 2.61, 95% confidence interval [CI] 2.55 to 2.67), hospital admissions (5.42 v. 2.08, adjusted RR 2.77, 95% CI 2.71 to 2.82), alternate level of care (ALC) days (6.01 v. 2.96, adjusted RR 1.51, 95% CI 1.48 to 1.54), and specialist physician visits (6.27 v. 3.21, adjusted RR 1.64, 95% CI 1.61 to 1.68), but a significantly lower rate of primary care visits (16.71 v. 108.47, adjusted RR 0.13, 95% CI 0.13 to 0.14). INTERPRETATION: Residents of retirement homes are a distinct population with higher rates of hospital-based care. Our findings can help to inform policy debates about the need for more coordinated primary and supportive health care in privately operated congregate care homes.


Subject(s)
Nursing Homes , Retirement , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Long-Term Care , Male , Ontario , Retrospective Studies
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