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Non-T cell-inflamed immunologically “cold” tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB), and can be sculpted by tumor cell genomics. Here we evaluated how Retinoblastoma (Rb) tumor suppressor loss of function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy. We performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we utilized isogenic murine models of Rb-deficient prostate cancer (PC) for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy. Rb loss was enriched in non-T cell-inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I interferon (IFN) signaling within tumor cells, resulting in differential macrophage and T cell-mediated tumor growth inhibition and sensitization of Rb-deficient PC to ICB. BETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient PC to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient PC.

Background Two Labrador retriever littermates were identified based on incidentally noted marked microcytosis and inappropriate metarubricytosis. Muscle atrophy was noted and associated with distinctive pathological findings in biopsy samples from 1 dog studied. The disorder represents a rare clinical entity of suspected congenital dyserythropoiesis and polymyopathy. Clinicopathologic changes were similar to a previously reported syndrome of congenital dyserythropoiesis, congenital polymyopathy, and cardiac disease in 3 related English Springer Spaniel (ESS) dogs, but the dogs reported here did not have apparent cardiac disease. Interventions Bone marrow aspiration, electromyography, muscle biopsies, and an echocardiogram were performed on dog 1. Results supported dyserythropoiesis and congenital polymyopathy similar to reports in ESS dogs, but did not identify obvious cardiac disease. Conclusion The clinicopathologic changes of dyserythropoiesis and polymyopathy provide an easily recognizable phenotype for what appears to be a low morbidity syndrome. Early recognition may decrease unnecessary testing or euthanasia.

In this report, we describe a novel genetic basis for congenital dyserythropoietic anemia and polymyopathy in Labrador Retriever littermates characterized by incidental detection of marked microcytosis, inappropriate metarubricytosis, pelvic limb weakness and muscle atrophy. A similar syndrome has been described in English Springer Spaniel littermates with an early onset of anemia, megaesophagus, generalized muscle atrophy and cardiomyopathy. Muscle histopathology in both breeds showed distinctive pathological changes consistent with congenital polymyopathy. Using whole genome sequencing and mapping to the CanFam4 (Canis lupus familiaris reference assembly 4), a nonsense variant in the EHBP1L1 gene was identified in a homozygous form in the Labrador Retriever littermates. The mutation produces a premature stop codon that deletes approximately 90% of the protein. This variant was not present in the English Springer Spaniels. Currently, EHPB1L1 is described as critical to actin cytoskeletal organization and apical-directed transport in polarized epithelial cells, and through connections with Rab8 and a BIN1-dynamin complex generates membrane vesicles in the endocytic recycling compartment. Furthermore, EHBP1L1 knockout mice die early and develop severe anemia. The connection of EHBP1L1 to BIN1 and DMN2 functions is particularly interesting due to BIN1 and DMN2 mutations being causative in forms of centronuclear myopathy. This report, along with an independent study conducted by another group, are the first reports of an association of EHBP1L1 mutations with congenital dyserythropoietic anemia and polymyopathy.

Compared with fresh blood, stored equine donor blood results in spurious tube crossmatch incompatibilities. Interpretation of blood crossmatch results is considered subjective.We aimed to determine if the duration of canine donor blood storage impacts compatibility testing using a standard gel column crossmatch and evaluate interobserver variation in the interpretation of crossmatch results.Observational study. Whole blood segments were obtained from 23 canine packed red blood cell (RBC) units for use in crossmatches after storage for 0, 7, 14, 21, 28, and 35 days. Major and minor crossmatches were performed using serum and RBCs, respectively, from two to three healthy "recipient" dogs per unit. All crossmatch results were interpreted by four observers, of whom three were blinded.All major crossmatches (n = 61) were compatible on day 0 and remained compatible through day 35 of storage. All minor crossmatches (n = 69) were compatible at all time points, except for five donor pairs with 1 to 3+ agglutination. Repeat testing of these five donor pairs confirmed crossmatch incompatibilities on days 0 through 35, with no change in the degree of incompatibility over time. There was substantial agreement among four observers in determining compatibility (κ = 0.94) and scoring incompatibility (κ = 0.76).The current practice of performing canine crossmatches with whole blood segments stored for up to 35 days is acceptable, with no spurious changes in compatibility expected over time. The substantial interobserver agreement suggests that the gel column is suitable for performing canine crossmatches in a laboratory setting with multiple personnel.

In this report, we describe a novel genetic basis for congenital dyserythropoietic anemia and polymyopathy in Labrador Retriever littermates characterized by incidental detection of marked microcytosis, inappropriate metarubricytosis, pelvic limb weakness and muscle atrophy. A similar syndrome has been described in English Springer Spaniel littermates with an early onset of anemia, megaesophagus, generalized muscle atrophy and cardiomyopathy. Muscle histopathology in both breeds showed distinctive pathological changes consistent with congenital polymyopathy. Using whole genome sequencing and mapping to the CanFam4 (

Although the Scholarship of Teaching and Learning (SoTL) claims to focus on student learning, some have argued that SoTL studies often adopt a narrow view of learning and focus more on teaching than on learning. In this paper, we explore whether teaching is the primary focus of recent articles published from 2013-2017 in three international, self-identified SoTL journals: Teaching and Learning Inquiry: The ISSOTL Journal (TLI), The International Journal for the Scholarship of Teaching and Learning (ijSOTL), and The Journal of the Scholarship of Teaching and Learning (JoSoTL). Based on our analysis of the 299 empirical articles, we argue that they portray SoTL as a field focused primarily on teacher activity rather than student learning, despite efforts to broaden its scope.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most malignant neoplasm of the pancreas, and is refractory to most therapeutic strategies, including immunotherapy. We have previously demonstrated that loss of CDKN2A in PDAC tumor cells promotes an immunologically-cold tumor microenvironment, which can be counteracted through the use of bromodomain and extraterminal domain inhibitors (BETi). The immunosuppressive PDAC tumor microenvironment is also characterized by a dense desmoplastic stroma, rich in cancer associated fibroblasts (CAFs). These CAFs are a highly plastic population of cells, comprised of myofibroblastic, inflammatory, and antigen-presenting CAFs (myCAFs, iCAFs, and apCAFs, respectively). Previously research has suggested BETi can alter the function of CAFs, suggesting this therapeutic strategy may be effective at targeting both the tumor and stromal compartments of PDAC. Here we hypothesize that BETi enhances anti-tumor immunity in CDKN2A-deficient PDAC by modulating the phenotype and function of PDAC CAFs. METHODS: Isogenic wild-type and CDKN2A-deficient KPCluc pancreatic cancer cell lines were used in conjunction with KPCluc-derived murine CAF cells. CAF spheroids were used to evaluate the effects of BETi on CAF phenotype (as measured by flow cytometry) and function (as measured by NanoString analysis, checkpoint ligand expression by flow cytometry, and T cell migration assays). Additionally, the impact of BETi-induced modulation of CAF phenotype and function on wild-type and CDKN2A-deficient tumor cell spheroids was measured by flow cytometry. RESULTS: Treatment of pancreatic CAFs with BETi induced expression of genes associated with DNA damage responses and type I IFN expression. Additionally, while CAF supernatants suppressed T cell migration in vitro, treatment with BETi restored T cell migration across a transwell. This was due in part to DNA damage/STING/NF-κB signaling induced in PDAC CAF following BETi. Supernatants from BETi-treated PDAC CAFs were found to modulate PD-L1 expression on PDAC tumor cells. Direct treatment of CAFs with BETi induced a dramatic dose- and time-dependent polarization of CAF spheroids towards a myCAF phenotype. However, while BETi induced DNA damage/STING/NF-κB signaling in CAF cells, this signaling did not contribute towards this myCAF polarization, as treatment of CAF spheroids with BETi and STING or NF-κB inhibitors did not impact myCAF polarization. Additional mechanisms of polarization are currently being evaluated and will be updated at presentation. CONCLUSIONS: BET inhibition modulates CAF cell phenotype and function to promote anti-tumor immune responses. Taken together with the impact of BET inhibition on CDKN2A-deficient PDAC tumor cells, these data suggest BETi is a rational treatment approach to promote anti-tumor immunity in this genetically defined immunotherapy resistant patient population. Citation Format: Trisha Minocha, Alison Thomas, Brian M. Olson. BET inhibition reprograms pancreatic cancer associated fibroblasts to promote anti-tumor immunity. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5173.

PurposeNon-T cell-inflamed immunologically “cold” tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB), and can be sculpted by tumor cell genomics. Here we evaluated how Retinoblastoma (Rb) tumor suppressor loss of function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy.Experimental DesignWe performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we utilized isogenic murine models of Rb-deficient prostate cancer (PC) for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy.ResultsRb loss was enriched in non-T cell-inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I interferon (IFN) signaling within tumor cells, resulting in differential macrophage and T cell-mediated tumor growth inhibition and sensitization of Rb-deficient PC to ICB.ConclusionsBETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient PC to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient PC.STATEMENT OF TRANSLATIONAL RELEVANCERb LOF is one of the most common genomic alterations in human cancer, occurring in approximately 1/3 of advanced malignancies, Furthermore, loss of Rb correlates with enhanced aggressiveness and poor therapeutic outcomes. In this study, we demonstrate that loss of Rb is also associated with an immunosuppressive tumor microenvironment and lack of responsiveness to immune checkpoint blockade (ICB). As a strategy to overcome Rb LOF induced immunosuppression, we have demonstrated that BETi treatment drives STING/NF-κB signaling and type I interferon production within tumor cells, resulting in immune-mediated tumor control in Rb-deficient PC, which is accentuated by the combination with ICB and ADT. These findings provide a roadmap for maximizing the clinical translation of BET inhibitors into the clinic to treat aggressive-variant Rb-deficient PC.

Rationale & Objective Surveillance blood work is routinely performed in maintenance hemodialysis (HD) recipients. Although more frequent blood testing may confer better outcomes, there is little evidence to support any particular monitoring interval. Study Design Retrospective population-based cohort study. Setting & Participants All prevalent HD recipients in Ontario, Canada, as of April 1, 2011, and a cohort of incident patients commencing maintenance HD in Ontario, Canada, between April 1, 2011, and March 31, 2016. Exposure Frequency of surveillance blood work, monthly versus every 6 weeks. Outcomes The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia. Analytical Approach Cox proportional hazards with adjustment for demographic and clinical characteristics was used to evaluate the association between blood testing frequency and all-cause mortality. Secondary outcomes were evaluated using the Andersen-Gill extension of the Cox model to allow for potential recurrent events. Results 7,454 prevalent patients received care at 17 HD programs with monthly blood sampling protocols (n=5,335 patients) and at 8 programs with blood sampling every 6 weeks (n=2,119 patients). More frequent monitoring was not associated with a lower risk for all-cause mortality compared to blood sampling every 6 weeks (adjusted HR, 1.16; 95% CI, 0.99-1.38). Monthly monitoring was not associated with a lower risk for any of the secondary outcomes. Results were consistent among incident HD recipients. Limitations Unmeasured confounding; limited data for center practices unrelated to blood sampling frequency; no information on frequency of unscheduled blood work performed outside the prescribed sampling interval. Conclusions Monthly routine blood testing in HD recipients was not associated with a lower risk for death, cardiovascular events, or hospitalizations as compared with testing every 6 weeks. Given the health resource implications, the frequency of routine blood sampling in HD recipients deserves careful reassessment.

This study aimed to assess the impact of a National Reporting Indicator (NRI) on rates of reporting of suspected adverse drug reactions using the Yellow Card scheme following the introduction of the NRI in Wales (UK) in April 2014.Yellow Card reporting data for general practitioners and other reporting groups in Wales and England for the financial years 2014-15 (study period 1) and 2015-16 (study period 2) were obtained from the Medicines and Healthcare Products Regulatory Agency and compared with those for 2013-14 (pre-NRI control period).The numbers of Yellow Cards submitted by general practitioners in Wales were 271, 665 and 870 in the control period, study period 1 and study period 2, respectively. This is equivalent to an increase of 145% in study period 1 and 221% in study period 2 compared with the 12-month control period (2013-14). Corresponding increases in England were 17% and 37%, respectively (P .001 chi-squared test). The numbers of Yellow Cards submitted by other groups in Wales were 906, 795 and 947 in each of the study periods.Introduction of the NRI corresponded with a significant increase in the number of Yellow Cards submitted by general practitioners in Wales. General practitioner reporting rates continued to increase year on year through to 2018-19 with the NRI still in place. No concomitant change was found in reporting rates by other groups in the health boards in Wales.

INTRODUCTION The cause of constipation is multifactorial and common problem for patients on hemodialysis. A lack of strong evidence on suitable treatment strategies means there is an unorganized approach to selecting therapies, which can exacerbate constipation or worsen symptoms. Clinicians and patients would benefit from a content and face validated treatment algorithm for treating constipation. In this study, our objective was to develop and content and face validate a constipation treatment toolkit for patients on hemodialysis, consisting of treatment algorithm, and patient information tools (pamphlet and video). METHODS Literature searches were performed to develop an initial toolkit using Lynn's method for developing content-valid clinical tools. Content and face validity were evaluated as per Lynn's method for determining content validity; the algorithm was evaluated by Canadian nephrology clinicians, while patient information tools were evaluated by clinicians and patients. Components were rated on a Likert scale for content relevance and on a 5-point scale for face validity. After each round, the content validity index (CVI) score was calculated and revisions were made based on feedback. FINDINGS A total of 23 clinicians and 15 patients were interviewed across three validation rounds. After three rounds, the treatment algorithm achieved content (overall CVI = 0.93) and face (91% agreement) validity. Our patient information tools achieved content and face validity (pamphlet overall CVI = 0.99, 85.5% agreement; video overall CVI = 0.99, 90.5% agreement). DISCUSSION A treatment algorithm and patient information toolkit for the treatment of constipation in patients on hemodialysis were content and face validated via expert review. Further research will be needed to ascertain the effectiveness and implementation of this toolkit.

The present study aimed to evaluate the impact of a filmed research-based drama—Fit for Dialysis—and an exercise program on patients’ physical activity and fitness outcomes. Nineteen (10 at the intervention site, 9 at the control site) older patients with a medical diagnosis of hemodialysis-dependent end-stage renal disease were recruited from two acute care hospitals in urban central Canada where they were receiving out-patient hemodialysis care. Participants at the intervention site viewed Fit for Dialysis prior to participating in a 16-week exercise program. Participants at the control site participated only in the 16-week exercise program. Physical activity, measured by total intradialytic exercise time (TIDE), and physical fitness, measured by the Two-Minute Walk Test (2MWT). Secondary measures included: Timed Up and Go (TUG), Grip Strength, Duke Activity Status Index (DASI), Godin Leisure-Time Exerciser Questionnaire (GLTEQ), and pedometer step count. TIDE, TUG, and GLTEQ were better at the intervention site compared to the control site at all time points measured. However, the change over time was not different between the sites. The 2MWT improved over time at the intervention site for those who exercised consistently. No significant differences between sites, or over time were found for any of the other measures. Further research is needed to determine the effectiveness of this intervention to facilitate the incorporation of exercise into the care and treatment of HD patients.

Quality metrics or indicators help guide quality improvement work by reporting on measurable aspects of health care upon which improvement efforts can focus. For recipients of in-center hemodialysis (ICHD) in Canada, it is unclear what ICHD quality indicators exist and whether they adequately cover different domains of health care quality.To identify and evaluate current Canadian ICHD quality metrics to document a starting point for future collaborations and standardization of quality improvement in Canada.Environmental scan of quality metrics in ICHD, and subsequent indicator evaluation using a modified Delphi approach.Canadian ICHD units.Sixteen-member pan-Canadian working group with expertise in ICHD and quality improvement.We classified the existing indicators based on the Institute of Medicine (IOM) and Donabedian frameworks.Each metric was rated by a 5-person subcommittee using a modified Delphi approach based on the American College of Physicians/Agency for Healthcare Research and Quality criteria. We shared these consensus ratings with the entire 16-member panel for additional comments.We identified 27 metrics that are tracked across 8 provinces, with only 9 (33%) tracked by multiple provinces (ie, more than 1 province). We rated 9 metrics (33%) as "necessary" to distinguish high-quality from low-quality care, of which only 2 were tracked by multiple provinces (proportion of patients by primary access and rate of vascular access-related bloodstream infections). Most (16/27, 59%) indicators assessed the IOM domains of safe or effective care, and none of the "necessary" indicators measured the IOM domains of timely, patient-centered, or equitable care.The environmental scan is a nonexhaustive list of quality indicators in Canada. The panel also lacked representation from patients, administrators, and allied health professionals, with more representation from academic sites.Quality indicators in Canada mainly focus on safe and effective care, with little provincial overlap. These results highlight current gaps in quality of care measurement for ICHD, and this initial work should provide programs with a starting point to combine highly rated indicators with newly developed indicators into a concise balanced scorecard that supports quality improvement initiatives across all aspects of ICHD care.not applicable.Les mesures ou indicateurs de la qualité contribuent à guider les travaux d’amélioration de la qualité des soins de santé en indiquant les aspects mesurables sur lesquels les efforts peuvent se concentrer. On connait peu les indicateurs de la qualité existant au Canada pour les bénéficiaires de l’hémodialyse en centre (HDC). On ignore également si ces indicateurs couvrent adéquatement les différents domaines de la qualité des soins de santé.Définir et évaluer les mesures actuelles de la qualité des soins d’HDC au Canada. Ces travaux serviront à documenter le point de départ de futures collaborations et la normalisation de l’amélioration de la qualité au Canada.Analyse contextuelle des mesures de la qualité en HDC, suivie de leur évaluation par une méthode Delphi modifiée.Des unités d’HDC au Canada.Un groupe de travail pancanadien constitué de 16 membres ayant une expertise en HDC et en amélioration de la qualité.Les indicateurs existants ont été évalués à l’aide des modèles de l’IOM (Chaque indicateur a été évalué par un sous-comité de cinq personnes à l’aide d’une méthode Delphi modifiée basée sur les critères de l’Nous avons répertorié 27 indicateurs suivis dans 8 provinces, dont 9 (33 %) sont suivis dans plus d’une province. Neuf indicateurs (33 %) ont été classés comme « nécessaires » pour départager les soins de haute qualité des soins de faible qualité, dont seulement deux (la proportion de patients selon l’accès primaire et le taux de bactériémies liées à l’accès vasculaire) sont suivis par plusieurs provinces. La majorité des indicateurs (16/27; 59 %) a évalué les domaines de l’IOM relatifs aux soins sûrs ou efficaces; aucun des indicateurs « nécessaires » n’a mesuré les domaines de l’IOM relatifs aux soins opportuns, centrés sur le patient ou équitables.Au Canada, l’analyse contextuelle consiste en une liste non exhaustive d’indicateurs de la qualité. Le groupe de travail manquait de représentants des patients, des administrateurs et des professionnels paramédicaux, les sites universitaires étant mieux représentés.Au Canada, les indicateurs de la qualité se concentrent principalement sur la prestation de soins sûrs et efficaces, et les chevauchements entre les provinces sont rares. Ces résultats mettent en évidence les lacunes actuelles dans l’évaluation de la qualité des soins d’HDC. Ces travaux préliminaires devraient fournir aux programmes un point de départ pour combiner des indicateurs bien cotés à d’autres nouvellement développés dans une fiche d’évaluation concise destinée à soutenir les initiatives d’amélioration de la qualité dans tous les aspects des soins entourant l’HDC.Sans objet.

The present study aimed to evaluate the impact of a filmed research-based drama-Fit for Dialysis-and an exercise program on patients' physical activity and fitness outcomes.Nineteen (10 at the intervention site, 9 at the control site) older patients with a medical diagnosis of hemodialysis-dependent end-stage renal disease were recruited from two acute care hospitals in urban central Canada where they were receiving out-patient hemodialysis care. Participants at the intervention site viewed Fit for Dialysis prior to participating in a 16-week exercise program. Participants at the control site participated only in the 16-week exercise program. Physical activity, measured by total intradialytic exercise time (TIDE), and physical fitness, measured by the Two-Minute Walk Test (2MWT). Secondary measures included: Timed Up and Go (TUG), Grip Strength, Duke Activity Status Index (DASI), Godin Leisure-Time Exerciser Questionnaire (GLTEQ), and pedometer step count.TIDE, TUG, and GLTEQ were better at the intervention site compared to the control site at all time points measured. However, the change over time was not different between the sites. The 2MWT improved over time at the intervention site for those who exercised consistently. No significant differences between sites, or over time were found for any of the other measures.Further research is needed to determine the effectiveness of this intervention to facilitate the incorporation of exercise into the care and treatment of HD patients.

Research in big data, informatics, and bioinformatics has grown dramatically (Andreu-Perez J, et al., 2015, IEEE Journal of Biomedical and Health Informatics 19, 1193–1208). Advances in gene sequencing technologies, surveillance systems, and electronic medical records have increased the amount of health data available. Unconventional data sources such as social media, wearable sensors, and internet search engine activity have also contributed to the influx of health data. The purpose of this study was to describe how ‘big data’, ‘informatics’, and ‘bioinformatics’ have been used in the animal health and veterinary medical literature and to map and chart publications using these terms through time. A scoping review methodology was used. A literature search of the terms ‘big data’, ‘informatics’, and ‘bioinformatics’ was conducted in the context of animal health and veterinary medicine. Relevance screening on abstract and full-text was conducted sequentially. In order for articles to be relevant, they must have used the words ‘big data’, ‘informatics’, or ‘bioinformatics’ in the title or abstract and full-text and have dealt with one of the major animal species encountered in veterinary medicine. Data items collected for all relevant articles included species, geographic region, first author affiliation, and journal of publication. The study level, study type, and data sources were collected for primary studies. After relevance screening, 1093 were classified. While there was a steady increase in ‘bioinformatics’ articles between 1995 and the end of the study period, ‘informatics’ articles reached their peak in 2012, then declined. The first ‘big data’ publication in animal health and veterinary medicine was in 2012. While few articles used the term ‘big data’ (n = 14), recent growth in ‘big data’ articles was observed. All geographic regions produced publications in ‘informatics’ and ‘bioinformatics’ while only North America, Europe, Asia, and Australia/Oceania produced publications about ‘big data’. ‘Bioinformatics’ primary studies tended to use genetic data and tended to be conducted at the genetic level. In contrast, ‘informatics’ primary studies tended to use non-genetic data sources and conducted at an organismal level. The rapidly evolving definition of ‘big data’ may lead to avoidance of the term.

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials.L’hémodialyse constitue un traitement essentiel au maintien de la vie pour les personnes atteintes d’insuffisance rénale. Les patients hémodialysés voient cependant leur qualité et leur espérance de vie réduites. Des données de recherches probantes, provenant de vastes essais cliniques contrôlés à répartition aléatoire, sont nécessaires pour améliorer l’expérience, les résultats et les soins des patients hémodialysés. Grâce au soutien des Instituts de recherche en santé du Canada (IRSC) et de leur Stratégie de recherche axée sur le patient (SRAP), l’initiative sur les essais cliniques novateurs (ECN) en centres d’hémodialyse a réuni divers intervenants en santé rénale (chercheurs, patients, fournisseurs de soins et administrateurs), du Canada et de partout dans le monde, lors d’un colloque qui s’est tenu à Toronto les 2 et 3 juin 2018. Ce colloque a permis d’accroître la sensibilisation et les connaissances sur la conduite d’essais cliniques novateurs, répartis en grappes, pragmatiques et intégrés aux soins d’hémodialyse de routine. Cette rencontre a également fourni une occasion de discuter de nouvelles idées d’essais cliniques et de susciter les appuis nécessaires à leur réalisation. Le colloque s’est déroulé sous forme de présentations structurées, de discussions animées en groupe et de rétroaction de la part d’un comité d’experts. Les idées de recherche prometteuses et les partenariats issus de ce colloque continueront d’être développés pour soutenir la réalisation d’essais cliniques futurs de grande envergure.

OBJECTIVE To describe the outcome of young adults treated for hypoxemic respiratory failure with extracorporeal membrane oxygenation as neonates. DESIGN The study was designed as a multisite, cross sectional survey. SETTING The survey was completed electronically or on paper by subjects and stored in a secure data base. SUBJECTS Subjects were surviving neonatal extracorporeal membrane oxygenation patients from eight institutions who were18 years old or older. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A questionnaire modified from the 2011 Behavioral Risk Factor Surveillance System and the 2011 National Health Interview Survey with additional unique questions was completed by subjects. Results were compared to age-matched national Behavioral Risk Factor Surveillance System and National Health Interview Survey data. One hundred and forty-six subjects participated (8.9% of eligible candidates). The age at questionnaire submission was 23.7 ± 2.89 years. Subjects differed statistically from national cohorts by being more satisfied with life (93% vs 84.2%); more educated (some college or degree; 80.1% vs 57.7%); more insured for healthcare (89.7% vs 72.3%); less frequent users of healthcare in the last 12 months (47.3% vs 58.2%); more limited because of physical, mental, and developmental problems (19.9% vs 10.9%); and having more medical complications. Furthermore, learning problems occurred in 29.5% of the study cohort. The congenital diaphragmatic hernia group was generally less healthy and less well educated, but equally satisfied with life. Perinatal variables contributed little to outcome prediction. CONCLUSIONS Most young adult survivors in this study cohort treated with extracorporeal membrane oxygenation as neonates are satisfied with their lives, working and/or in college, in good health and having families. These successes are occurring despite obstacles involving health issues such as asthma, attention deficit disorder, learning difficulties, and vision and hearing problems; this is especially evident in the congenital diaphragmatic hernia cohort. Selection bias inherent in such a long-term study may limit generalizability, and it is imperative to note that our sample may not be representative of the whole.

Background Acute liver failure resulting from drug-induced liver injury can lead to the development of neurological complications called hepatic encephalopathy (HE). Hepatic transforming growth factor beta 1 (TGFβ1) is upregulated due to liver failure in mice and inhibiting circulating TGFβ reduced HE progression. However, the specific contributions of TGFβ1 on brain cell populations and neuroinflammation during HE are not known. Therefore, the aim of this study was to characterize hepatic and brain TGFβ1 signaling during acute liver failure and its contribution to HE progression using a combination of pharmacological and genetic approaches. Methods C57Bl/6 or neuron-specific transforming growth factor beta receptor 2 (TGFβR2) null mice (TGFβR2ΔNeu) were treated with azoxymethane (AOM) to induce acute liver failure and HE. The activity of circulating TGFβ1 was inhibited in C57Bl/6 mice via injection of a neutralizing antibody against TGFβ1 (anti-TGFβ1) prior to AOM injection. In all mouse treatment groups, liver damage, neuroinflammation, and neurological deficits were assessed. Inflammatory signaling between neurons and microglia were investigated in in vitro studies through the use of pharmacological inhibitors of TGFβ1 signaling in HT-22 and EOC-20 cells. Results TGFβ1 was expressed and upregulated in the liver following AOM injection. Pharmacological inhibition of TGFβ1 after AOM injection attenuated neurological decline, microglia activation, and neuroinflammation with no significant changes in liver damage. TGFβR2ΔNeu mice administered AOM showed no effect on liver pathology but significantly reduced neurological decline compared to control mice. Microglia activation and neuroinflammation were attenuated in mice with pharmacological inhibition of TGFβ1 or in TGFβR2ΔNeu mice. TGFβ1 increased chemokine ligand 2 (CCL2) and decreased C-X3-C motif ligand 1 (CX3CL1) expression in HT-22 cells and reduced interleukin-1 beta (IL-1ß) expression, tumor necrosis factor alpha (TNFα) expression, and phagocytosis activity in EOC-20 cells. Conclusion Increased circulating TGFβ1 following acute liver failure results in activation of neuronal TGFβR2 signaling, driving neuroinflammation and neurological decline during AOM-induced HE. Electronic supplementary material The online version of this article (10.1186/s12974-019-1455-y) contains supplementary material, which is available to authorized users.

A 22 year old woman was admitted to hospital with confusion, pyrexia, and two episodes of loss of consciousness while at work that day. She described having felt tired in the preceding week. She had no medical history of note and did not smoke or drink alcohol. She did not take any regular medications and did not use recreational drugs. The patient was born in the UK. Her parents were from Nigeria. She had no recent foreign travel or contact with anyone who was unwell. Her heart rate was 115 beats/min, blood pressure 100/80 mm Hg, temperature 38.5°C, respiratory rate 20 breaths/min, and oxygen saturations 100% on room air. Blood results are shown in table 1 and blood film in fig 1. View this table: Table 1 Blood test results Fig. 1 Blood film ×40 magnification 1. What is the most likely diagnosis? 2. What other initial tests are important? 3. How is this condition treated? ### 1. What is the most likely diagnosis? The following factors make thrombotic thrombocytopenic purpura (TTP) the most likely diagnosis: Fig. 2 Blood film ×40 magnification showing schistocytes and thrombocytopenia TTP requires immediate haematologist assessment. TTP is a thrombotic microangiopathy. Haemolytic uraemic syndrome, another thrombotic microangiopathy, is a differential. Thrombotic microangiopathy (TMA) is indicated by thrombocytopenia in the full blood count and microangiopathic haemolytic anaemia on the blood film.1 ADAMTS13 enzyme activity …

Background Patients with end-stage renal disease are at high risk for medical errors given their comorbidities, polypharmacy and coordination of care with other hospital departments. We previously developed a hemodialysis safety checklist (Hemo Pause) to be jointly completed by nurses and patients. Our objective was to determine the feasibility of using this checklist during every hemodialysis session for 3 months. Methods We conducted a single-center, prospective time series study. A convenience sample of 14 nurses and 22 prevalent in-center hemodialysis patients volunteered to participate. All participants were trained in the administration of the Hemo Pause checklist. The primary outcome was completion of the Hemo Pause checklist, which was assessed at weekly intervals. We also measured the acceptability of the Hemo Pause checklist using a local patient safety survey. Results There were 799 hemodialysis treatments pre-intervention (13 January–5 April 2014) and 757 post-intervention (5 May–26 July 2014). The checklist was completed for 556 of the 757 (73%) treatments. Among the hemodialysis nurses, 93% (13/14) agreed that the checklist was easy to use and 79% (11/14) agreed it should be expanded to other patients. Among the hemodialysis patients, 73% (16/22) agreed that the checklist made them feel safer and should be expanded to other patients. Conclusions The Hemo Pause safety checklist was acceptable to both nurses and patients over 3 months. Our next step is to spread this checklist locally and conduct a mixed methods study to determine mechanisms by which its use may improve safety culture and reduce adverse events.

This article will demonstrate how to conduct a quality improvement project using the change idea generated in “How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem” by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan–Do–Study–Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.

To change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.

Quality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.

Rationale & Objective Hemodialysis patients are at increased risk for COVID-19 transmission due, in part, to difficulty maintaining physical distancing. Our hemodialysis unit experienced a COVID-19 outbreak despite following symptom-based screening guidelines. We describe the course of the COVID-19 outbreak and the infection control measures taken for mitigation. Study Design Retrospective cohort study Setting & Participants 237 maintenance hemodialysis patients and 93 hemodialysis staff at a single hemodialysis centre in Toronto, Canada. Exposure Universal screening of patients and staff with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Outcomes The primary outcome was detection of SARS-CoV-2 in nasopharyngeal samples from patients and staff using reverse transcriptase-polymerase chain reaction (RT-PCR) . Analytical Approach Descriptive statistics were used for clinical characteristics and the primary outcome. Results Eleven (4.6%) of 237 hemodialysis patients and 11 of 93 (12%) staff members had a positive RT-PCR test for SARS-CoV-2. Among individuals testing positive, 12 of 22 (55%) were asymptomatic at time of testing, and 7 of 22 (32%) were asymptomatic for the duration of follow-up. One patient was hospitalized at the time of SARS-CoV-2 infection and four additional patients with positive tests were subsequently hospitalized. Two patients (18%) required admission to the intensive care unit. After 30 days follow-up no patients had died or required mechanical ventilation. No hemodialysis staff required hospitalization. Universal droplet and contact precautions were implemented during the outbreak. Hemodialysis staff with SARS-CoV-2 infection were placed on home quarantine regardless of symptom status. Patients with SARS-CoV-2 infection including asymptomatic individuals were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR testing. Analysis of the outbreak identified two index cases with subsequent nosocomial transmission within the dialysis unit and in shared shuttle buses to the hemodialysis unit. Limitations Single centre study. Conclusions Universal SARS-CoV-2 testing and universal droplet and contact precautions in the setting of an outbreak appeared to be effective in preventing further transmission., Graphical abstract, Plain Language Summary: The COVID-19 pandemic has presented unique challenges to patients on hemodialysis. Despite having risk factors for severe infection, dialysis patients must visit healthcare facilities thrice weekly, where physical distancing is challenging. Despite protocols in place to identify and isolate symptomatic individuals, we report a COVID-19 outbreak in a hemodialysis unit in Toronto, Ontario, which prompted the screening of all hemodialysis patients and most staff for SARS-CoV-2 infection detected in nasopharyngeal swabs specimens, regardless of symptoms. Eleven of 237 (4.6%) hemodialysis patients and 11 of 93 (12%) of staff tested positive for COVID-19. Notably 55% of those testing positive were asymptomatic at the time of testing. This study demonstrates the importance of universal testing in stopping the spread of COVID-19 during an outbreak.

Pathogenic variants in the X-chromosome Aristaless-related homeobox (ARX) gene contribute to intellectual disability, epilepsy, and associated comorbidities in affected males. Here, we report a novel splice variant in ARX in a family with three affected individuals. The proband had early onset developmental and epileptic encephalopathy, his brother and mother had severe and mild intellectual disability, respectively. Massively parallel sequencing identified a novel c.1449-1G>C in intron 4 of the ARX gene, predicted to abolish the splice acceptor site, retaining intron 4 and leading to a premature termination codon immediately after exon 4. As exon 5 is the last exon of the ARX gene, the premature termination codon at position p.L484* would be predicted to escape nonsense-mediated mRNA decay, potentially producing at least some C-terminally truncated protein. Analysis of cDNA from patient lymphoblastoid cells confirmed retention of intron 4 and loss of detectable expression of ARX mRNA across exon 4 to exon 5. We review published cases of variants that lead to altered or early termination of the ARX protein, but not complete loss of function, and are associated with phenotypes of intellectual disability and infantile onset developmental and epileptic encephalopathies, including Ohtahara and West syndromes. Taken together, this novel splice variant retaining intron 4 is likely to be the cause of the early onset developmental and epileptic encephalopathy in the proband.

Background Exercise improves functional outcomes and quality of life of older patients with end-stage renal disease undergoing hemodialysis. Yet exercise is not promoted as part of routine care. Health care providers and family carers rarely provide encouragement for patients to exercise, and the majority of older patients remain largely inactive. There is thus the need for a shift in the culture of hemodialysis care towards the promotion of exercise for wellness, including expectations of exercise participation by older patients, and encouragement by health care providers and family carers. Film-based educational initiatives hold promise to effect cultures of best practice, but have yet to be utilized in this population. Methods We developed a research-based film, Fit for Dialysis, to promote exercise for wellness in hemodialysis care. Using a qualitative approach, we evaluated the effects that resulted from engagement with this film (e.g. knowledge/attitudes regarding the importance of exercise-based principles of wellness) as well as the generative mechanisms of these effects (e.g. realism, aesthetics). We also explored the factors related to patients, family carers, and health care providers that influenced engagement with the film, and the successful uptake of the key messages of Fit for Dialysis. We conducted qualitative interviews with 10 patients, 10 health care providers, and 10 family carers. Data were analyzed using thematic analysis. Results The film was perceived to be effective in increasing patients’, family carers’ and health care providers’ understanding of the importance of exercise and its benefits, motivating patients to exercise, and in increasing encouragement by family carers and health care providers of patient exercise. Realism (e.g. character identification) and aesthetic qualities of the film (e.g. dialogue) were identified as central generative mechanisms. Conclusions Fit for Dialysis is well-positioned to optimize the health and wellbeing of older adults undergoing hemodialysis. Trial registration NCT02754271 (ClinicalTrials.gov), retroactively registered on April 21, 2016.

The mental health of patients living with end-stage kidney disease (ESKD) is an important aspect of their care. According to national survey data, depressive disorders affect about 9% of the North American population (Kessler, Chiu, Demler, Merikangas,Walters, 2005). A review of psychological distress and depression across the spectrum of chronic kidney disease indicates that the prevalence of depression in ESKD is reported to be about four times that of the general population and it is associated with adverse outcomes including low quality-of-life ratings, graft failure, and death after renal transplantation (Zalai, Szeifert,Novak, 2012). At St. Michael’s Hospital (SMH), patients on hemodialysis (HD) requiring psychiatry consultation had traditionally been referred to a dedicated outpatient psychiatrist. This presented challenges around access to psychiatry assessment and follow-up, as patients were reluctant to attend appointments outside of HD visits. The team recognized these challenges and addressed them through the introduction of the Medical Psychiatry NP (MP NP) role, as the point-of-care consultant in HD.

A major decision for patients with stage 5 chronic kidney disease (CKD) relates to vascular access (VA) for treatment. Patients who receive pre-dialysis care often defer making a decision, which results in initiation of hemodialysis (HD) with a central venous catheter (CVC) in an urgent or emergent situation. Little is known about how individuals make decisions around VA. In this context, a mixed-methods study was undertaken to explore uncertainty related to changing their VA from an existing CVC to a graft or fistula. Quantitative assessment was measured using the SURE tool and interviews with patients and nurses were conducted. Results revealed that none of the 16 patient participants reported uncertainty. Qualitative findings revealed that patient decisions about access were impacted by observations, experiences, and dialogue in the hemodialysis unit. Study findings have important implications including the challenge of reconciling epidemiologic population-based risk measurement to the individual patient’s situation. Moreover, the SURE tool was viewed as a mechanism to open a dialogue to confirm patients’ decisions and provide further education and/or support following HD initiation.

Purpose To assess cancer nurses’ perceptions of responsibility, confidence levels, and practice in relation to survivorship care for people with a haematological malignancy on completion of treatment. Methods A prospective cross-sectional survey was conducted. An online survey was distributed to members of two Australian professional bodies. Results A total of 310 cancer nurses participated in the study, representing a response rate of 28%. The participants generally agreed that all survivorship care items were part of their role. Of the 17 survivorship care items, the three items receiving the lowest confidence scores were discussing fertility issues, discussing employment and financial issues and discussing how to identify signs of cancer recurrence. The least performed survivorship care items were discussing fertility issues, communicating survivorship care with primary health care team (i.e. General Practitioners) and discussing sexuality issues. Older age, more years of experience, having a post-graduate qualification, working in non-metropolitan area were associated with higher levels of perception of responsibilities and confidence (p

Evidence suggests that exercise training for hemodialysis patients positively improves morbidity and mortality outcomes, yet exercise programs remain rare and are not systematically incorporated into care. We developed a research-based film, Fit for Dialysis, designed to introduce, motivate, and sustain exercise for wellness amongst older hemodialysis patients, and exercise counseling and support by nephrologists, nurses, and family caregivers. The objective of this clinical trial is to determine whether and in what ways Fit for Dialysis improves outcomes and influences knowledge/attitudes regarding the importance of exercise for wellness in the context of end-stage renal disease. This 2-site parallel intervention trial will recruit 60 older hemodialysis patients from two urban hospitals. The trial will compare the film + a 16-week exercise program in one hospital, with a 16-week exercise-only program in another hospital. Physical fitness and activity measures will be performed at baseline, 8 and 16 weeks, and 12 weeks after the end of the program. These include the 2-min Walk Test, Grip Strength, Duke Activity Status Index, and the Timed Up-and-Go Test, as well as wearing a pedometer for one week. Throughout the 16-week exercise program, and at 12 weeks after, we will record patients’ exercise using the Godin Leisure-time Exercise Questionnaire. Patients will also keep a diary of the exercise that they do at home on non-dialysis days. Qualitative interviews, conducted at baseline, 8, and 16 weeks, will explore the impact of Fit for Dialysis on the knowledge/attitudes of patients, family caregivers, and nephrology staff regarding exercise for wellness, and in what ways the film is effective in educating, motivating, or sustaining patient exercise during dialysis, at home, and in the community. This research will determine for whom Fit for Dialysis is effective, why, and under what conditions. If Fit for Dialysis is proven beneficial to patients, nephrology staff and family caregivers, research-based film as a model to support exercise promotion and adherence could be used to support the National Kidney Foundation’s guideline recommendation (NKF-KDOQI) that exercise be incorporated into the care and treatment of dialysis patients. NCT02754271 (ClinicalTrials.gov), retroactively registered on April 21, 2016.

Summary Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, caused by deficiency of the enzyme glucocerebrosidase, required for the degradation of glycosphingolipids. Clinical manifestations include hepatosplenomegaly, thrombocytopenia, bone disease and a bleeding diathesis, frequently resulting in presentation to haematologists. Historically managed by splenectomy, transfusions and orthopaedic surgery, the development of specific therapy in the form of intravenous enzyme replacement therapy in the 1990s has resulted in dramatic improvements in haematological and visceral disease. Recognition of complications, including multiple myeloma and Parkinson disease, has challenged the traditional macrophage-centric view of the pathophysiology of this disorder. The pathways by which enzyme deficiency results in the clinical manifestations of this disorder are poorly understood; altered inflammatory cytokine profiles, bioactive sphingolipid derivatives and alterations in the bone marrow microenvironment have been implicated. Further elucidating these pathways will serve to advance our understanding not only of GD, but of associated disorders.

Malaria elimination in Europe has been the focus of significant national and international effort, and in 2015 the WHO declared for the first time that there were no indigenous cases of malaria in the WHO European region.1 However, since that time there have been several localised outbreaks of malaria in countries throughout Europe. We report two cases of vivax malaria in individuals returning from Northern Cyprus, which was declared malaria free in 1967. One further case of vivax malaria, also in an individual returning from the Cyprian resort of Esentepe in August 2017, has been highlighted by the Centers for Disease Control and Prevention.2 Our patients were siblings aged 10 and …

Gaucher disease (GD) is an inherited enzyme deficiency characterised by progressive cytopenias, hepatosplenomegaly and destructive bone disease. It is diagnosed by demonstration of beta glucosidase deficiency but may be suspected in presence of abnormal storage cells on tissue biopsy. Specific treatment is available in the form of enzyme replacement (ERT) and is effective in reversing many disease features. Delayed treatment has been associated with increased disease complications. This retrospective review of a single centre cohort of 86 patients was undertaken to ascertain if the diagnostic journey had improved since the introduction of ERT and commissioning of services. Fifty-six percent of patients presented primarily with features related to thrombocytopenia or splenomegaly with a median time from symptom onset to diagnosis of 2 years (range 0.5–26 years), 19% experiencing delays of 5 or more years. Seventy-five percent of patients were diagnosed by haematologists, 68% following an abnormal bone marrow biopsy. Raised serum ACE levels, low HDL cholesterol and raised ferritin were identified as prevalent laboratory abnormalities at the time of diagnosis. These features, coupled with the relative preservation of haemoglobin and white cell counts compared to the platelet count, help identify patients presenting to haematologists with a possible diagnosis of GD earlier in the diagnostic pathway.

To achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).

You are a charge nurse in a large hemodialysis unit in Ontario.One of the clerical staff has approached you today to assist withan update to her statistics on new and existing patients in yourunit. You are asked to clarify the cause of death for one patientand to clarify the date of transfer to the home dialysis programfor peritoneal dialysis on another patient. Finally, you are asked toremind the nurse practitioner (NP) to complete a registration formfor another patient who has just started chronic hemodialysis inyour unit. While you know the collection of data is important, thereare lots of patients to look after and you feel frustrated by havingto take time away from planning urgent hemodialysis requests--which are your priority--to source out information to complete aform. You reflect on this need for statistical data and wonder wherethe information on this form ends up and how it helps your patientswho are living with end stage kidney disease (ESKD).