Place of Death and Place of Care at the End of Life: Are They Correlated? A Retrospective Cohort Study of Ontario Decedents.

Background: Dying in nonpalliative acute care is generally considered inappropriate and avoidable. Place of death, a commonly reported big-dot indicator of end-of-life care quality, is often used as a proxy for place of care despite no empirical evidence for their correlations. Thus, we examined the correlations between place of death and place of care in the last month of life. We also investigated anecdotal claims that individuals cared in acute care often get discharged to die at home, and vice versa. Methods: We conducted a retrospective cohort study of Ontario decedents (18+) who died between January 1, 2015 and December 31, 2017. We identified individuals who died in nonpalliative acute care, palliative care unit, subacute care, long-term care (LTC), and the community. We calculated the number of days decedents spent in each setting in their last month of life, and used descriptive analyses to investigate their correlations. Results: Decedent's place of death generally correlated with their place of care in the last month of life-individuals who died in a particular setting spent more time in that setting than individuals who died elsewhere. Furthermore, 75.0% of individuals who spent more than two weeks of their last month in acute care died in acute care. Among individuals who died in the community and in LTC, 65.4% and 75.0%, respectively, spent zero days in acute care. Interpretation: We showed that place of death can be a useful high-level performance indicator, by itself and as a proxy for place of care, to gauge end-of-life quality and service provision/implementation.

Prevalence and patterns of multimorbidity among linguistic groups of patients receiving home care in Ontario: a retrospective cohort study.

BACKGROUND: Prior studies have demonstrated the negative impact of language barriers on access, quality, and safety of healthcare, which can lead to health disparities in linguistic minorities. As the population ages, those with multiple chronic diseases will require increasing levels of home care and long-term services. This study described the levels of multimorbidity among recipients of home care in Ontario, Canada by linguistic group. METHODS: Population-based retrospective cohort of 510,685 adults receiving home care between April 1, 2010, to March 31, 2018, in Ontario, Canada. We estimated and compared prevalence and characteristics of multimorbidity (2 or more chronic diseases) across linguistic groups (Francophones, Anglophones, Allophones). The most common combinations and clustering of chronic diseases were examined. Logistic regression models were used to explore the main predictors of 'severe' multimorbidity (defined as the presence of five or more chronic diseases). RESULTS: The proportion of home care recipients with multimorbidity and severe multimorbidity was 92% and 44%, respectively. The prevalence of multimorbidity was slightly higher among Allophones (93.6%) than among Anglophones (91.8%) and Francophones (92.4%). However, Francophones had higher rates of cardiovascular and respiratory disease (64.9%) when compared to Anglophones (60.2%) and Allophones (61.5%), while Anglophones had higher rates of cancer (34.2%) when compared to Francophones (25.2%) and Allophones (24.3%). Relative to Anglophones, Allophones were more likely to have severe multimorbidity (adjusted OR = 1.04, [95% CI: 1.02-1.06]). CONCLUSIONS: The prevalence of multimorbidity among Ontarians receiving home care services is high; especially for whose primary language is a language other than English or French (i.e., Allophones). Understanding differences in the prevalence and characteristics of multimorbidity across linguistic groups will help tailor healthcare services to the unique needs of patients living in minority linguistic situations.

A Health Survey-Based Prediction Equation for Incident CKD.

BACKGROUND: Prediction tools that incorporate self-reported health information could increase CKD awareness, identify modifiable lifestyle risk factors, and prevent disease. We developed and validated a survey-based prediction equation to identify individuals at risk for incident CKD (eGFR <60 ml/min per 1.73 m2), with and without a baseline eGFR. METHODS: A cohort of adults with an eGFR ≥70 ml/min per 1.73 m2 from Ontario, Canada, who completed a comprehensive general population health survey between 2000 and 2015 were included (n=22,200). Prediction equations included demographics (age, sex), comorbidities, lifestyle factors, diet, and mood. Models with and without baseline eGFR were derived and externally validated in the UK Biobank (n=15,522). New-onset CKD (eGFR <60 ml/min per 1.73 m2) with ≤8 years of follow-up was the primary outcome. RESULTS: Among Ontario individuals (mean age, 55 years; 58% women; baseline eGFR, 95 (SD 15) ml/min per 1.73 m2), new-onset CKD occurred in 1981 (9%) during a median follow-up time of 4.2 years. The final models included lifestyle factors (smoking, alcohol, physical activity) and comorbid illnesses (diabetes, hypertension, cancer). The model was discriminating in individuals with and without a baseline eGFR measure (5-year c-statistic with baseline eGFR: 83.5, 95% confidence interval [CI], 82.2 to 84.9; without: 81.0, 95% CI, 79.8 to 82.4) and well calibrated. In external validation, the 5-year c-statistic was 78.1 (95% CI, 74.2 to 82.0) and 66.0 (95% CI, 61.6 to 70.4), with and without baseline eGFR, respectively, and maintained calibration. CONCLUSIONS: Self-reported lifestyle and health behavior information from health surveys may aid in predicting incident CKD. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast.aspx?p=CJASN&e=2023_01_10_CJN05650522.mp3.

The association between recreational cannabis legalization, commercialization and cannabis-attributable emergency department visits in Ontario, Canada: an interrupted time-series analysis.

BACKGROUND AND AIMS: Recreational cannabis was legalized in Canada in October 2018. Initially, the Government of Ontario (Canada's largest province) placed strict limits on the number of cannabis retail stores before later removing these limits. This study measured changes in cannabis-attributable emergency department (ED) visits over time, corresponding to different regulatory periods. DESIGN: Interrupted time-series design using population-level data. Two policy periods were considered; recreational cannabis legalization with strict store restrictions (RCL, 17 months) and legalization with no store restrictions [recreational cannabis commercialization (RCC), 15 months] which coincided with the COVID-19 pandemic. Segmented Poisson regression models were used to examine immediate and gradual effects in each policy period. SETTING: Ontario, Canada. PARTICIPANTS: All individuals aged 15-105 years (n = 13.8 million) between January 2016 and May 2021. MEASUREMENTS: Monthly counts of cannabis-attributable ED visits per capita and per all-cause ED visits in individuals aged 15+ (adults) and 15-24 (young adults) years. FINDINGS: We observed a significant trend of increasing cannabis-attributable ED visits pre-legalization. RCL was associated with a significant immediate increase of 12% [incident rate ratio (IRR) = 1.12, 95% confidence interval (CI) = 1.02-1.23] in rates of cannabis-attributable ED visits followed by significant attenuation of the pre-legalization slope (monthly slope change IRR = 0.98, 95% CI = 0.97-0.99). RCC and COVID-19 were associated with immediate significant increases of 22% (IRR = 1.22, 95% CI = 1.09-1.37) and 17% (IRR = 1.17, 95% CI = 1.00-1.37) in rates of cannabis-attributable visits and the proportion of all-cause ED visits attributable to cannabis, respectively, with insignificant increases in monthly slopes. Similar patterns were observed in young adults. CONCLUSIONS: In Ontario, Canada, cannabis-attributable emergency department visits stopped increasing over time following recreational cannabis legalization with strict retail controls but then increased during a period coinciding with cannabis commercialization and the COVID-19 pandemic.

Children's Health Care Utilization and Cost in the Last Year of Life: A Cohort Comparison with and without Regional Specialist Pediatric Palliative Care.

Background: Research remains inconclusive regarding the impact of specialist pediatric palliative care (SPPC) on health care utilization and cost. Objective: To better understand and quantify the impact of regional SPPC services on children's health care utilization and cost near end of life. Design: A retrospective cohort study used administrative databases to compare outcomes for child decedents (age 31 days to 19 years) from two similar regions in Ontario, Canada between 2010 and 2014, wherein one region had SPPC services (SPPC+) and the other did not (SPPC-). Measurements: Administrative databases provided demographics, health care utilization (days), and costs Canadian dollars) across settings in the last year of life, and location of death. Multivariable analyses produced relative rates (RRs) of health care days (acute and home care), intensive care unit (ICU) days, and health care costs (inpatient, outpatient, home, and physician) as well as the odds ratio (OR) of in-hospital death. Counterfactual analysis quantified the differences in utilization and costs. Results: A total of 807 children were included. On multivariable analysis, residence in the SPPC+ region (n = 363) was associated with fewer mean health care days (RR = 0.73; 95% confidence interval [CI]: 0.59-0.90); fewer mean ICU days (RR = 0.64; 95% CI: 0.44-0.94); lower mean health care costs (RR = 0.71; 95% CI: 0.56-0.91); and lower likelihood of in-hospital death (OR = 0.67; 95% CI: 0.49-0.92). The counterfactual analysis estimated mean reductions of 16.2 days (95% CI: 14.4-18.0) and $24,940 (95% CI: $21,703-$28,177) per child in the SPPC+ region. Conclusions: Although not a causal study, these results support an association between regional SPPC services and decreased health care utilization, intensity, and cost for children near end of life.

Regulatory Approved Monoclonal Antibodies Contain Framework Mutations Predicted From Human Antibody Repertoires.

Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences in silico could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using baseline human antibody repertoire sequences. Our analysis shows that human antibody repertoire-based PSSMs are consistent across individuals and demonstrate high correlations between related germlines. We show that mutations in existing therapeutic antibodies can be accurately predicted solely from baseline human antibody sequence data. We find that mAbs developed using humanized mice had more human-like FR mutations than mAbs originally developed by hybridoma technology. A quantitative assessment of entire framework regions of therapeutic antibodies revealed that there may be potential for improving the properties of existing therapeutic antibodies by incorporating additional mutations of high frequency in baseline human antibody repertoires. In addition, high frequency mutations in baseline human antibody repertoires were predicted in silico to reduce immunogenicity in therapeutic mAbs due to the removal of T cell epitopes. Several therapeutic mAbs were identified to have common, universally high-scoring framework mutations, and molecular dynamics simulations revealed the mechanistic basis for the evolutionary selection of these mutations. Our results suggest that baseline human antibody repertoires may be useful as predictive tools to guide mAb development in the future.

Prediction of Progression in Polycystic Kidney Disease Using the Kidney Failure Risk Equation and Ultrasound Parameters.

BACKGROUND: The kidney failure risk equation (KFRE) is a validated risk algorithm for predicting the risk of kidney failure in chronic kidney disease (CKD) patients regardless of etiology. Patients with autosomal dominant polycystic kidney disease (AD-PCKD) experience long disease trajectories and as such identifying individuals at risk of kidney failure would aid in intervention. OBJECTIVE: To examine the utility of the KFRE in predicting adverse kidney outcomes compared with existing risk factors in a cohort of patients with AD-PCKD. METHODS: Retrospective cohort study of AD-PCKD patients referred to a tertiary care center with a baseline kidney ultrasound and a KFRE calculation. Cox proportional hazards were used to examine the association of the KFRE and composite of an eGFR decline of >30% or the need for dialysis/transplantation. Discrimination and calibration of a parsimonious fully adjusted model and a model containing only total kidney volume (TKV) with and without the addition of the KFRE was determined. RESULTS: Of 340 patients with AD-PCKD eligible, 221 (65%) met inclusion criteria. Older age, cardiac disease, cancer, higher systolic blood pressure, albuminuria, lower eGFR and a higher initial TKV were more common in patients with a higher KFRE. A total of 120 events occurred over a median patient follow-up time of 3.2 years. KFRE was independently associated with the composite kidney outcome. Addition of the KFRE significantly improved discrimination and calibration in a TKV only model and a fully adjusted model. CONCLUSIONS: In a diverse, referral population with AD-PCKD, the KFRE was associated with adverse kidney outcomes and improved risk prediction.

CONTEXTE: L'équation KFRE (kidney failure risk equation) est un algorithme validé pour prédire le risque de défaillance rénale chez les patients atteints d'IRC, quelle que soit l'étiologie. Les patients souffrant de polykystose rénale autosomique dominante (ADPKD) connaissent une longue trajectoire de maladie et, à ce titre, le dépistage des individus présentant un risque élevé d'insuffisance rénale pourrait faciliter les interventions. OBJECTIF: Examiner l'efficacité de la KFRE à prédire le risque d'issues rénales défavorables dans une cohorte de patients atteints d'ADPKD comparativement aux facteurs de risque existants. MÉTHODOLOGIE: Cette étude de cohorte rétrospective porte sur des patients atteints d'ADPKD aiguillés vers un centre de soins tertiaires avec une échographie rénale de référence et un calcul de KFRE. Un modèle de risques proportionnels de Cox a été employé pour analyser la relation entre la KFRE et un déclin composite du DFGe supérieur à 30% ou le besoin de dialyse ou de transplantation. La discrimination et la calibration d'un modèle parcimonieux entièrement corrigé et d'un modèle ne tenant compte que du volume rénal total (VRT), avec ou sans l'ajout de la KFRE, ont été déterminées. RÉSULTATS: Des 340 patients atteints d'ADPKD et admissibles à l'étude, 221 (65%) satisfaisaient les critères d'inclusion. Les patients présentant un résultat élevé à la KFRE étaient souvent plus âgés et étaient plus fréquemment atteints des troubles suivants: maladies cardiovasculaires, cancer, pression systolique élevée, albuminurie, faible DFGe et VRT initial plus élevé. Un total de 120 événements sont survenus au cours de la période de suivi médiane (3,2 ans). La KFRE a été associée de façon indépendante à l'issue rénale composite. L'ajout de la valeur de KFRE a considérablement amélioré la discrimination et la calibration des deux modèles employés (VRT seulement et modèle entièrement corrigé). CONCLUSION: L'utilisation de la KFRE a été associée à des issues rénales défavorables et à une meilleure prédiction du risque d'insuffisance rénale dans une population de référence diversifiée composée de patients atteints d'ADPKD.

Severe autoimmune hemolytic anemia with renal neoplasm.

Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

ET743: Chemical analysis of the sea squirt Ecteinascidia turbinata ecosystem.

The sea squirt Ecteinascidia turbinata produces the powerful drug ET743. In this study Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS) are systematically used to measure elemental and molecular species in a Florida Keys mangrove ecosystem that contains the sea squirt. ICP-AES is used to measure the concentration of 27 elements down to the parts per billion level in 16 organisms and 3 sediment samples that reside in the mangrove ecosystem including turtle grass, blue crabs, fire sponge, and lettuce slugs. MALDI-MS is used to search for ET743 in these same organisms and sediment samples. A mass spectral feature corresponding to ET743 is identified in the extract of the sea squirt, red mangrove root (Rhizophera mangle), the schoolmaster snapper (Lutjanus griseus), and a sediment sample taken from the ecosystem. We use MALDI-MS to study the impact that various environmental conditions, such as UV light, I(2), cation binding (Fe(+3), Zn(+2), Pb(+2), Cu(+2)), metal oxide nanoparticles (FeO, CuO, TiO(2), ZnO, Al(2)O(3)), a common mineral (CaCO(3)), and extremes in acidity (0.1 M HCl, 0.1 M NaOH) have on the ET743 structure. The data provide potential structures (degradation products, metal-ligand complexes, etc.) that might be present in organism or sedimentary extracts that are similar to ET743. We are studying the marine geochemistry of this ecosystem so a broth can be developed and tested for producing this marine natural product.

Identifying bryostatins and potential precursors from the bryozoan Bugula neritina.

The bryozoan species Bugula neritina contains the anticancer agent bryostatin. Bryostatin has been extracted from these sessile marine invertebrates since the late 1960s from the Gulf of California, Gulf of Mexico, as well as various locations on the eastern and western rims of the Pacific Ocean. In this work we are focusing on animals harvested in the Gulf of Mexico near Alligator Point (Florida). Using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) we measure the concentration of 70 elements in B. neritina, a sea squirt, and the sediment from the point of harvesting. This data has helped us generate an extraction process for marine natural products. Combining UV/VIS absorbance measurements with Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometer (MALDI-TOF-MS), we demonstrated that the specific form of bryostatin extracted is a function of the solvent. A 9.4T Fourier Transform-Ion Cyclotron Resonance (FT-ICR) mass spectrometer, whose sensitivity, mass accuracy, and resolving power allowed the exact empirical formulas of potential precursors of bryostatin to be identified, was employed. Finally we examine extracts of 14 marine species of the Gulf of Mexico, from the sand trout (Cynoscion arenarius) to chicken liver sponge (Chrondrilla nucula), all recently collected, which had shown some medicinal activity thirty years ago in a National Cancer Institute study. By the MALDI-TOF-MS, we were able to identify mass spectral features that correspond to different variations of the basic bryostatin structure, which raises the question if the bryozoans are the original source of bryostatin.