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Abstract Despite an increasing desire to use historical cohorts as “synthetic” controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012–2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

To comprehensively support national and international initiatives for sustainable development, land cover products need to be reliably and routinely generated within operational frameworks. Coupled with consistent semantics and taxonomies, ensuring confidence in mapping land cover for multiple time periods, facilitates informed decision-making at scales appropriate to multiple policy domains. The United Nations Food and Agriculture Organisation (FAO) Land Cover Classification System (LCCS) provides a taxonomy that comparable at different scales, level of detail and geographic location. The Open Data Cube (ODC) initiative offers a framework for operational continental-scale land cover mapping using analysis-ready Earth Observation data. This study utilised the FAO LCCS framework and the Landsat sensor data through Digital Earth Australia (DEA; Australia’s ODC instance) to generate consistent and continent-wide land cover mapping (DEA Land Cover) of the Australian continent. DEA Land Cover provides annual maps from 1988 to 2020 at 25 m resolution. Output maps were validated with ∼12,000 independent validation points, giving an overall map accuracy of 80%. DEA Land Cover provides Australia with a nationally consistent picture of land cover, with an open-source software package using readily available global coverage data and demonstrates a pathway of adoption for national implementations across the world.

MYH9-related disorders (MYH9-RDs) caused by mutation of the MYH9 gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP). This may result in inappropriate treatment with corticosteroids, immunosupressants and in some cases, splenectomy. We explored the efficacy of next generation sequencing (NGS) with a candidate gene panel to establish the aetiology of thrombocytopenia for individuals who had been referred to our center from hematologists in the Australasian region in whom the cause of thrombocytopenia was suspected to be secondary to an inherited condition but which remained uncharacterized despite phenotypic investigations. Pathogenic MYH9 variants were detected in 15 (15/121, 12.4%) individuals and the pathogenecity of a novel variant of uncertain significance was confirmed in a further two related individuals following immunofluorescence (IF) staining performed in our laboratory. Concerningly, only one (1/17) individual diagnosed with MYH9-RD had been referred with this as a presumptive diagnosis, in all other cases (16/17, 94.1%), a diagnosis was not suspected by referring clinicians, indicating a lack of awareness or a failing of our diagnostic approach to these conditions. We examined the mean platelet diameter (MPD) measurements as a means to better identify and quantify platelet size. MPDs in cases with MYH9-RDs were significantly larger than controls (p < 0.001) and in 91% were greater than a previously suggested threshold for platelets in cases of ITP. In addition, we undertook IF staining in a proportion of cases and confirm that this test and/or NGS are satisfactory diagnostic tests. We propose that fewer cases of MYH9-RDs would be missed if diagnostic algorithms prioritized IF and/or NGS in cases of thrombocytopenia associated with giant platelets, even if döhle-like bodies are not appreciated on the peripheral blood film. Finally, our report describes the long-term use of a thrombopoietin agonist in a case of MYH9-RD that had previously been diagnosed as ITP, and demonstrates that treatment with these agents may be possible, and is well tolerated, in this group of patients.

This article explores the current debate around family-school partnerships. Traditional family-school partnership theories do not account for the intended voices of Cambodian families. This article draws from existing research on Southeast Asian families more generally in order to develop a research-based, data-driven family-school partnership conceptual framework for Cambodian American families. It is believed that a pro-ethnic, voice-centric family-school partnership fosters an inclusive, supportive learning environment for Cambodian children. The logic undergirding that belief assumes that this partnership is likelyto increase cultural awareness between critical home-school partners. At the very least, the proposed concept model serves as a theoretical building block upon which an empirical research study can be built. That study is encouraged to explore the implications of establishing a family-school partnership that reflects the sense and sensibilities of Cambodian families, particularly those stemming from lower income backgrounds. Implicit in the review is the premium placed on challenging Eurocentric, middle-class partnership paradigms to account for the authentic voices of ethnic minorities, and the utility of disaggregating data for Southeast Asians, given the array of cultural and linguistic differences spanningthe Asian American community.

Abstract Background Language and cultural discordance refer to when a physician and patient do not share the same language or culture. This can create barriers to providing high-quality care at the end-of-life (EoL). This study explores the intersections of language, culture, geography, and care model in EoL care from the perspectives of palliative care physicians. Methods In this exploratory-descriptive qualitative study, semi-structured interviews (1-h) were conducted virtually between July and November 2023. We interviewed 16 family physicians with experience providing linguistic and/or culturally discordant palliative/EoL care in various urban, suburban, and rural regions of Ontario, who practiced at community and hospital outpatient clinics, home-based care, or long-term care homes. We used reflexive thematic analysis to identify themes across the interviews guided by the intersectionality theoretical framework. Results We identified three themes 1) Visible barriers to care access due to the inability to communicate accurate information and insufficient time spent during appointments with patients; 2) Invisible barriers to care access, shaped by the Eurocentric approach to palliative care and physicians’ lack of awareness on cultural discordance; 3) Workplace supports that currently exist and interventions that physicians would like to see. Community physicians following fee-for-service models were less likely to have access to professional interpreter services. Physicians in long-term care emphasized resource limitations to providing culturally-appropriate care environments. Conclusion Cultural discordance required awareness of personal biases, while language discordance hindered basic communication. These findings will be useful in informing clinical practice guidelines and mobilizing policy-level change to improve palliative/EoL care for patients from linguistic and cultural minority groups.

Abstract Background Appropriate use of medication is a key indicator of the quality of care provided in long-term care (LTC). The objective of this study was to determine whether resident-facility language concordance/discordance is associated with the odds of potentially inappropriate prescribing of antipsychotics (PIP-AP) in LTC. Methods We conducted a population-based, retrospective cohort study of LTC residents in Ontario, Canada from 2010 to 2019. We obtained resident language from standardized resident assessments, and derived facility language by determining the proportion of residents belonging to each linguistic group within individual LTC homes. Using linked administrative databases, we identified all instances of PIP-AP during a 1-year follow-up period. PIP-AP was defined using the STOPP-START criteria, which have previously been shown to predict adverse clinical events such as emergency department (ED) visits and hospitalizations. The association between linguistic factors and PIP-AP was assessed using adjusted multivariable logistic regression analysis. Results We identified 198,729 LTC residents consisting of 162,814 Anglophones (81.9%), 6,230 Francophones (3.1%), and 29,685 Allophones (14.9%). The odds of PIP-AP of were higher for both Francophones (aOR 1.15, 95% CI 1.08–1.23) and Allophones (aOR 1.11, 95% CI 1.08–1.15) when compared to Anglophones. When compared to English LTC homes, French LTC homes had greater odds of PIP-AP (aOR 1.12, 95% CI 1.05–1.20), while Allophone homes had lower odds of PIP-AP (aOR 0.82, 95% CI 0.77–0.86). Residents living in language-discordant LTC homes had higher odds of PIP-AP when compared to LTC residents living in language-concordant LTC homes (aOR 1.07, 95% CI 1.04–1.10). Conclusion This study identified linguistic factors related to the odds of PIP-AP in LTC, suggesting that the linguistic environment may have an impact on the quality of care provided to residents.

Cell-death-inducing DNA fragmentation factor-alpha (DFFA)-like effector b (CIDEB) was first identified as an apoptosis-inducing protein. Further research revealed a pivotal role in lipid metabolism, regulating very-low-density lipoprotein (VLDL), lipid droplets (LD), sterol response element-binding protein (SREBP), and chylomicrons. Recent studies have uncovered that rare germline variants in CIDEB protect against liver diseases, including MAFLD, cirrhosis, and viral hepatitis. Furthermore, CIDEB influences steps of the hepatitis C virus (HCV) replication cycle. This review summarizes the current knowledge about CIDEB’s roles in apoptosis, lipid metabolism, and viral hepatitis, and highlights its critical role in liver diseases.

Abstract Background Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. Methods 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. Results Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p

Objectives: This study aimed to assess the acceptability, value, and perceived barriers of using electronic risk calculators for predicting and communicating the risk of death in community-dwelling older adults. Methods: One focus group and eight interviews were conducted with 16 participants with experience caring for patients or family members at end of life. A prototype mortality risk tool was used to anchor discussions. Data were analysed using a qualitative content analysis approach. Results: Five themes emerged: acceptability, communication, barriers to use, broadening the circle of care, and tool limitations. Participants found the tool helpful for preparation, planning, and providing care, but disagreed on its community availability. Personalized risk estimates were valued for facilitating early goals of care conversations and normalizing discussions about death. However, concerns were raised about the tool's interpretation for individuals with different language, cultural, or educational backgrounds. Conclusions: While electronic risk calculators were found to be acceptable, balancing autonomy with varying preferences for receiving the information and potential need for support is crucial. Innovation: Providing patient-oriented life-expectancy estimates can enhance decisional capacity and facilitate shared decision-making between patients, their families, and healthcare professionals. Further research is needed to explore effective communication of personalized risk tools and additional benefits, harms, and barriers to implementation.

Background: Distal radius fractures are a common presentation in the orthopedic practice. There is extensive literature on the appropriate management of these injuries based on age, displacement, and other factors. Attritional tendon ruptures are a rare but described complication in both surgically and closed managed fractures. We report a case of delayed extensor indicis and extensor digitorum tendon rupture after conservatively managed distal radius fracture. Case report: A 68 year old female presents with a right wrist injury after a mechanical fall. She was found to have an isolated right distal radius fracture with minimal displacement. She was immobilized in a splint for 5 weeks and progressed to full weightbearing activity at 8 weeks. 14 weeks after injury, she suffered attritional rupture of the EIP and EDC tendons to the index finger. Intraoperatively impending rupture of the EPL tendon was also noted. She successfully underwent tendon reconstruction but had persistent index extensor lag at final follow-up. Literature review: There are 643,000 distal radius fractures annually, with an extensor tendon rupture incidence of up to 5% in those treated without surgery. This most commonly involves the EPL tendon. Tendon reconstruction and tendon transfer are the mainstays of operative management of these complications. Clinical relevance: Distal radius fractures with attritional tendon ruptures present a relatively rare but challenging problem. This case reports one of the only examples of isolated index extensor rupture in an adult and highlights the importance of clinical vigilance and patient counseling on the possible complications.

Introduction A clinical prediction tool to estimate life expectancy in community-dwelling individuals living with dementia could inform healthcare decision-making and prompt future planning. An existing Ontario-based tool for community-dwelling elderly individuals does not perform well in people living with dementia specifically. This study seeks to develop and validate a clinical prediction tool to estimate survival in community-dwelling individuals living with dementia receiving home care in Ontario, Canada.Methods and analysis This will be a population-level retrospective cohort study that will use data in linked healthcare administrative databases at ICES. Specifically, data that are routinely collected from regularly administered assessments for home care will be used. Community-dwelling individuals living with dementia receiving home care at any point between April 2010 and March 2020 will be included (N≈200 000). The model will be developed in the derivation cohort (N≈140 000), which includes individuals with a randomly selected home care assessment between 2010 and 2017. The outcome variable will be survival time from index assessment. The selection of predictor variables will be fully prespecified and literature/expert-informed. The model will be estimated using a Cox proportional hazards model. The model’s performance will be assessed in a temporally distinct validation cohort (N≈60 000), which includes individuals with an assessment between 2018 and 2020. Overall performance will be assessed using Nagelkerke’s R2, discrimination using the concordance statistic and calibration using the calibration curve. Overfitting will be assessed visually and statistically. Model performance will be assessed in the validation cohort and in prespecified subgroups.Ethics and dissemination The study received research ethics board approval from the Sunnybrook Health Sciences Centre (SUN-6138). Abstracts of the project will be submitted to academic conferences, and a manuscript thereof will be submitted to a peer-reviewed journal for publication. The model will be disseminated on a publicly accessible website (www.projectbiglife.com).Trial registration number NCT06266325 (clinicaltrials.gov).

BackgroundOnline democratic deliberation (ODD) may foster public engagement in new health strategies by providing opportunities for knowledge exchange between experts, policy makers, and the public. It can favor decision-making by generating new points of view and solutions to existing problems. Deliberation experts recommend gathering feedback from participants to optimize future implementation. However, this online modality has not been frequently evaluated. ObjectiveThis study aims to (1) assess the quality of an ODD held in Quebec and Ontario, Canada, on the topic of COVID-19 triage protocols for access to critical care in an extreme pandemic context and (2) determine its transformative aspect according to the perceptions of participants. MethodsWe conducted a simultaneous ODD in Quebec and Ontario on May 28 and June 4, 2022, with a diversified target audience not working in the health care system. We used a thematic analysis for the transcripts of the deliberation and the written comments of the participants related to the quality of the process. Participants responded to a postdeliberation questionnaire to assess the quality of the ODD and identify changes in their perspectives on COVID-19 pandemic triage protocols after the deliberation exercise. Descriptive statistics were used. An index was calculated to determine equality of participation. ResultsThe ODD involved 47 diverse participants from the public (n=20, 43% from Quebec and n=27, 57% from Ontario). Five themes emerged: (1) process appreciation, (2) learning experience, (3) reflecting on the common good, (4) technological aspects, and (5) transformative aspects. A total of 46 participants responded to the questionnaire. Participants considered the quality of the ODD satisfactory in terms of process, information shared, reasoning, and videoconferencing. A total of 4 (80%) of 5 participants reported at least 1 change of perspective on some of the criteria and values discussed. Most participants reported that the online modality was accessible and user-friendly. We found low polarization when calculating equal participation. Improvements identified were measures to replace participants when unable to connect and optimization of time during discussions. ConclusionsOverall, the participants perceived the quality of ODD as satisfactory. Some participants self-reported a change of opinion after deliberation. The online modality may be an acceptable alternative for democratic deliberation but with some organizational adaptations.

Metabolic dysfunction-associated fatty liver disease (MAFLD), the leading cause of end-stage liver disease in developed countries, is expected to increase over the next decade. Characterized by hepatic steatosis, MAFLD is commonly studied in animal models. Here, we generated a human induced pluripotent stem cell (iPSC) line from a patient homozygous of the protective MTARC1 gene variant rs2642438:A. This line displays a normal karyotype and typical pluripotent stem cell morphology and can differentiate into all three germ layers in vitro.

Abstract Background Language barriers can impact health care and outcomes. Valid and reliable language data is central to studying health inequalities in linguistic minorities. In Canada, language variables are available in administrative health databases; however, the validity of these variables has not been studied. This study assessed concordance between language variables from administrative health databases and language variables from the Canadian Community Health Survey (CCHS) to identify Francophones in Ontario. Methods An Ontario combined sample of CCHS cycles from 2000 to 2012 (from participants who consented to link their data) was individually linked to three administrative databases (home care, long-term care [LTC], and mental health admissions). In total, 27,111 respondents had at least one encounter in one of the three databases. Language spoken at home (LOSH) and first official language spoken (FOLS) from CCHS were used as reference standards to assess their concordance with the language variables in administrative health databases, using the Cohen kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV). Results Language variables from home care and LTC databases had the highest agreement with LOSH (kappa = 0.76 [95%CI, 0.735–0.793] and 0.75 [95%CI, 0.70–0.80], respectively) and FOLS (kappa = 0.66 for both). Sensitivity was higher with LOSH as the reference standard (75.5% [95%CI, 71.6–79.0] and 74.2% [95%CI, 67.3–80.1] for home care and LTC, respectively). With FOLS as the reference standard, the language variables in both data sources had modest sensitivity (53.1% [95%CI, 49.8–56.4] and 54.1% [95%CI, 48.3–59.7] in home care and LTC, respectively) but very high specificity (99.8% [95%CI, 99.7–99.9] and 99.6% [95%CI, 99.4–99.8]) and predictive values. The language variable from mental health admissions had poor agreement with all language variables in the CCHS. Conclusions Language variables in home care and LTC health databases were most consistent with the language often spoken at home. Studies using language variables from administrative data can use the sensitivity and specificity reported from this study to gauge the level of mis-ascertainment error and the resulting bias.