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OBJECTIVE: We examined length of postpartum hospitalization for live births during the COVID-19 pandemic and explored how pandemic circumstances influenced postpartum hospital experiences. METHODS: We conducted a cross-provincial, convergent parallel mixed-methods study in Ontario (ON) and British Columbia (BC), Canada. We included birthing persons (BPs) with an in-hospital birth in ON from 1 January to 31 March 2019, 2021, and 2022 (quantitative), and BPs (≥18 years) in ON or BC from 1 May 2020 to 1 December 2021 (qualitative). We linked multiple health administrative datasets at ICES and developed multivariable linear regression models to examine length of hospital stay (quantitative). We conducted semi-structured interviews using qualitative descriptive to understand experiences of postpartum hospitalization (qualitative). Data integration occurred during design and interpretation. RESULTS: Relative to 2019, postpartum hospital stays decreased significantly by 3.29 hours (95% CI: -3.58 to -2.99; 9.2% reduction) in 2021 and 3.89 hours (95% CI: -4.17 to -3.60; 9.0% reduction) in 2022. After adjustment, factors associated with shortened stays included: giving birth during COVID-19, social deprivation (more ethnocultural diversity), midwifery care, multiparity, and lower newborn birth weight. Postpartum hospital experiences were impacted by risk perception of COVID-19 infection, clinical care and hospital services/amenities, visitor policies, and duration of stay. CONCLUSION: Length of postpartum hospital stays decreased during COVID-19, and qualitative findings described unmet needs for postpartum services. The integration of large administrative and interview data expanded our understanding of observed differences. Future research should investigate the impacts of shortened stays on health services outcomes and personal experiences. OBJECTIF: Nous avons examiné la durée d'hospitalisation post-partum pour les cas de naissance vivante pendant la pandémie de COVID-19 et exploré comment les circonstances de la pandémie ont influencé l'expérience post-partum à l'hôpital. MéTHODES: Nous avons mené une étude interprovinciale selon un modèle mixte parallèle et convergent en Ontario (Ont.) et en Colombie-Britannique (C.-B.), au Canada. Nous avons inclus les personnes ayant accouché à l'hôpital en Ont. entre le 1 janvier et le 31 mars 2019, 2021 et 2022 (quantitatif), et celles ayant accouché (≥ 18 ans) entre le 1 mai 2020 et le 1 décembre 2021 en Ont. ou en C.-B. (qualitatif). Nous avons relié plusieurs ensembles de données de santé administratives à l'ICES et développé des modèles de régression linéaire multivariable pour examiner la durée d'hospitalisation (quantitative). Nous avons mené des entretiens semi-structurés en utilisant une méthode qualitative descriptive pour comprendre les expériences d'hospitalisation post-partum (qualitative). L'intégration des données a eu lieu pendant la conception de l'étude et l'interprétation. RéSULTATS: Par rapport à 2019, la durée de l'hospitalisation post-partum a significativement diminué de 3,29 heures (IC à 95 % : -3,58 à -2,99; réduction de 9,2 %) en 2021 et de 3,89 heures (IC à 95 % : -4,17 à -3,60; réduction de 9,0 %) en 2022. Après ajustement, les facteurs associés à la réduction de la durée d'hospitalisation étaient les suivants : accouchement pendant la pandémie de COVID-19, manque de socialisation (plus grande diversité ethnoculturelle), prise en charge en pratique sage-femme, multiparité et poids plus faible du nouveau-né à la naissance. L'expérience d'hospitalisation post-partum était influencée par la perception du risque de contracter la COVID-19, les soins cliniques et les services et commodités à l'hôpital, les politiques relatives aux visiteurs et la durée de l'hospitalisation. CONCLUSION: La durée d'hospitalisation post-partum a diminué pendant la pandémie de COVID-19, et les résultats qualitatifs ont décrit des besoins non satisfaits en matière de services post-partum. L'intégration de grands ensembles de données administratives et d'entretiens a permis de mieux comprendre les différences observées. Les recherches futures devront se pencher sur l'impact de la réduction de la durée d'hospitalisation sur les résultats des services de santé et les expériences personnelles.
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PURPOSE: Immigrants are susceptible to marginalization due to social isolation, economic disadvantage and systemic bias. Our goal was to compare symptom burden between immigrant and long-term resident women undergoing breast cancer surgery in Ontario, Canada. METHODS: A population-level retrospective cohort-study using administrative databases was conducted. Women who underwent surgery for newly diagnosed breast cancer and were treated at regional cancer centers between 2010 and 2016 were included. The primary outcome was a moderate or severe (≥ 4) symptom score on the Edmonton Symptom Assessment System Scale (ESAS). RESULTS: There were 12,250 (87.2%) long-term Canadian residents and 1,806(12.8%) immigrants. Immigrants were younger (mean age 53 vs. 61 years); had a higher proportion residing in a lowest income quintile neighbourhood (22.2% vs 15.4%); were less often on a primary-care physician roster (83.7% vs. 90.4%); and were less often diagnosed with Stage I/II disease (80.9% vs. 84.6%) (all p < 0.01). The proportion of women with scores ≥ 4 was significantly higher amongst immigrant women for 7/9 symptom categories; with the largest differences for depression (24.9% vs. 20.2%, p < 0.01) and pain (28.0% vs. 22.4%, p < 0.01). On multivariable regression analysis, immigration status was associated with scores ≥ 4 for pain (OR 1.13, 95% CI 1.02-1.23). There was an association between moderate/severe pain and region of origin, but not length of stay in Canada or immigration class. CONCLUSIONS: This is the first study comparing symptom burden amongst immigrant and non-immigrant women with breast cancer at a population-level. Immigrant women with breast cancer undergoing surgery were found to have a higher burden of pain.
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Neoplasias de la Mama , Emigrantes e Inmigrantes , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico , Estudios Retrospectivos , Ontario/epidemiología , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: Preterm birth is an important outcome or exposure in epidemiologic research. When administrative data on measured gestational age is not available, parent-reported gestational age can be obtained from questionnaires, which is subject to potential bias. To our knowledge, few studies have assessed the validity of parent-reported gestational age categories, including commonly defined categories of preterm birth. METHODS: We used linked data from primarily healthy children <6 years of age in TARGet Kids! in Toronto, Canada, and ICES administrative healthcare data from April 2011 to March 2020. We assessed the criterion validity of questionnaire-based parent-reported gestational age by calculating sensitivity and specificity for term (≥37 weeks), late preterm (34-36 weeks), and moderately preterm (32-33 weeks) gestational age categories, using administrative healthcare records of gestational age as the criterion standard. We conducted subgroup analyses for various parent and socioeconomic factors that may influence recall. RESULTS: Of the 4684 participants, 97.3% correctly classified the gestational age category according to administrative healthcare data. Parent-reported gestational age sensitivity ranged from 83.7% to 98.5% and specificity ranged from 88.3% to 99.8%, depending on category. For each subgroup characteristic, sensitivity and specificity were all ≥70%. Lower educational attainment, lower family income, father reporting, ≥1 year since birth, ≥2 children, lower parent age, and reported gestational diabetes and/or hypertension were associated with slightly lower sensitivity and/or specificity. CONCLUSIONS: In this linked cohort, parent-reported gestational age categories had high accuracy. Criterion validity varied minimally among some parent and socioeconomic factors. Our findings can inform future quantitative bias analyses.
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BACKGROUND: Functional decline is common following acute hospitalization and is associated with hospital readmission, institutionalization, and mortality. People with functional decline may have difficulty accessing post-discharge medical care, even though early physician follow-up has the potential to prevent poor outcomes and is integral to high-quality transitional care. We sought to determine whether recent functional decline was associated with lower rates of post-discharge physician follow-up, and whether this association changed during the COVID-19 pandemic, given that both functional decline and COVID-19 may affect access to post-discharge care. METHOD: We conducted a retrospective cohort study using health administrative data from Ontario, Canada. We included patients over 65 who were discharged from an acute care facility during March 1st, 2019 - January 31st, 2020 (pre-COVID-19 period), and March 1st, 2020 - January 31st, 2021 (COVID-19 period), and who were assessed for home care while in hospital. Patients with and without functional decline were compared. Our primary outcome was any physician follow-up visit within 7 days of discharge. We used propensity score weighting to compare outcomes between those with and without functional decline. RESULTS: Our study included 21,771 (pre-COVID) and 17,248 (COVID) hospitalized patients, of whom 15,637 (71.8%) and 12,965 (75.2%) had recent functional decline. Pre-COVID, there was no difference in physician follow-up within 7 days of discharge (Functional decline 45.0% vs. No functional decline 44.0%; RR = 1.02, 95% CI 0.98-1.06). These results did not change in the COVID-19 period (Functional decline 51.1% vs. No functional decline 49.4%; RR = 1.03, 95% CI 0.99-1.08, Z-test for interaction p = 0.72). In the COVID-19 cohort, functional decline was associated with having a 7-day physician virtual visit (RR 1.15; 95% CI 1.08-1.24) and a 7-day physician home visit (RR 1.64; 95% CI 1.10-2.43). CONCLUSIONS: Functional decline was not associated with reduced 7-day post-discharge physician follow-up in either the pre-COVID-19 or COVID-19 periods. In the COVID-19 period, functional decline was positively associated with 7-day virtual and home-visit follow-up.
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COVID-19 , Pacientes Ambulatorios , Humanos , Alta del Paciente , Cuidados Posteriores , Estudios de Cohortes , Estudios de Seguimiento , Pandemias , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/terapia , Hospitales , Ontario/epidemiologíaRESUMEN
BACKGROUND: Evidence suggests that accelerated postnatal growth in children is detrimental for adult cardiovascular health. It is unclear whether children born late preterm (34-36 weeks) compared to full term (≥ 39 weeks), have different growth trajectories. Our objective was to evaluate the association between gestational age groups and growth trajectories of children born between 2006-2014 and followed to 2021 in Ontario, Canada. METHODS: We conducted a retrospective cohort study of children from singleton births in TARGet Kids! primary care network with repeated measures of weight and height/length from birth to 14 years, who were linked to health administrative databases. Piecewise linear mixed models were used to model weight (kg/month) and height (cm/month) trajectories with knots at 3, 12, and 84 months. Analyses were conducted based on chronological age. RESULTS: There were 4423 children included with a mean of 11 weight and height measures per child. The mean age at the last visit was 5.9 years (Standard Deviation: 3.1). Generally, the more preterm, the lower the mean value of weight and height until early adolescence. Differences in mean weight and height for very/moderate preterm and late preterm compared to full term were evident until 12 months of age. Weight trajectories were similar between children born late preterm and full term with small differences from 84-168 months (mean difference (MD) -0.04 kg/month, 95% CI -0.06, -0.03). Children born late preterm had faster height gain from 0-3 months (MD 0.70 cm/month, 95% CI 0.42, 0.97) and 3-12 months (MD 0.17 cm/month, 95% CI 0.11, 0.22). CONCLUSIONS: Compared to full term, children born late preterm had lower average weight and height from birth to 14 years, had a slightly slower rate of weight gain after 84 months and a faster rate of height gain from 0-12 months. Follow-up is needed to determine if growth differences are associated with long-term disease risk.
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Nacimiento Prematuro , Recién Nacido , Adolescente , Adulto , Niño , Femenino , Humanos , Estudios Retrospectivos , Bases de Datos Factuales , Edad Gestacional , Ontario/epidemiologíaRESUMEN
OBJECTIVES: The PoET (Prevention of Error-based Transfers) project seeks to align long-term care (LTC) home informed consent practices to existing legislation, thereby reducing consent-related error-based transfers to acute care. We sought to measure changes in resident-level palliative care provision after participating in the PoET Southwest Spread Project (PSSP), and to identify patient and LTC home characteristics associated with palliative care provision. DESIGN: Quasi-experimental matched (1:1 ratio) cohort study design using linked population-based health administrative data. SETTING: Sixty LTC homes (PSSP = 30; Control = 30) in Ontario, Canada, from November 2019 to December 2021. METHODS: We matched 30 PSSP to 30 control homes and described incidence rates for resident-level palliative care provision (ie, physician palliative care encounters and palliative medication prescriptions) during the 7-month postimplementation period. We used generalized linear mixed models to evaluate the association between PSSP implementation and palliative care provision during the postimplementation period. We adjusted for resident-level characteristics (ie, age, sex, comorbidity status) and home-level characteristics (ie, rurality status, profit model, COVID-19 impact). We identified a decedent subcohort to measure palliative care provision patterns during the last 2 months of life. RESULTS: We captured a matched cohort of 8894 residents (PSSP = 4103; Control = 4791). Incidence rates of palliative care encounters increased during the postimplementation period for PSSP (82.6 to 85.4 per 100 person-months) but not for control residents (68.8 to 65.3 per 100 person-months). After adjusting for key covariates, PSSP exposure was associated increased palliative care provision (incidence rate ratio 2.47, 95% CI 2.31-2.64) and palliative care medication prescription (1.16, 95% CI 1.12-1.20). Larger home size, certain health regions, and higher number of comorbidities were associated with increased physician palliative care encounters. CONCLUSIONS AND IMPLICATIONS: By promoting correct informed consent practices in LTC, PSSP participation increased palliative care provision for PSSP LTC residents across all settings.
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Cuidados Paliativos , Humanos , Ontario , Femenino , Masculino , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , COVID-19/prevención & control , COVID-19/epidemiología , Cuidados a Largo Plazo , Casas de Salud , Transferencia de Pacientes/estadística & datos numéricosRESUMEN
BACKGROUND: Pomalidomide-based regimens are the cornerstone of treatment for relapsed/refractory MM (RRMM). Despite the high incidence of chronic kidney disease (CKD) in RRMM, individuals with advanced CKD have been excluded from phase II/III RCTs, creating a gap in our understanding of the effects of pomalidomide use in patients with RRMM complicated with advanced CKD. We undertook a cohort to study to understand the efficacy safety of pomalidomide-based regimens among patients with CKD using real-world data. METHODS: Population-based, cohort study of patients ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. Primary outcome was all-cause mortality. Secondary outcomes were time-to-major adverse kidney events (MAKE), time-to-next treatment, kidney response and safety. RESULTS: Total 748 patients with RRMM utilizing pomalidomide were included; 440 had preserved kidney function, 210 had moderate CKD (eGFR 30-59 mL/min/1.73m2), and 98 had advanced CKD (eGFR < 30 mL/min/1.73m2). Mean age was 70.2 years, 43.3% were women. Patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group (aHR 1.37, 95% CI 1.06, 1.78). MAKE was higher in advanced CKD (aHR 1.70, 95% CI 1.03, 2.35). Kidney response was similar between moderate and severe CKD groups (aOR 1.04, 95%, CI 0.56-1.90). Safety outcomes were similar between groups. CONCLUSIONS: Patients with advanced CKD and RRMM on pomalidomide-based regimens exhibited reduced survival and a higher risk for MAKE. However, the probability of experiencing some degree of kidney recovery is 50% in both moderate and severe CKD, with comparable safety outcomes.
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OBJECTIVES: Population-based chronic disease surveillance systems were likely disrupted by the COVID-19 pandemic. The objective of this study was to examine the immediate and ongoing impact of the COVID-19 pandemic on the claims-based incidence of dementia. METHODS: We conducted a population-based time series analysis from January 2015 to December 2021 in Ontario, Canada. We calculated the monthly claims-based incidence of dementia using a validated case ascertainment algorithm drawing from routinely collected health administrative data. We used autoregressive linear models to compare the claims-based incidence of dementia during the COVID-19 period (2020-2021) to the expected incidence had the pandemic not occurred, controlling for seasonality and secular trends. We examined incidence by source of ascertainment and across strata of sex, age, community size and number of health conditions. RESULTS: The monthly claims-based incidence of dementia dropped from a 2019 average of 11.9 per 10 000 to 8.5 per 10 000 in April 2020 (32.6% lower than expected). The incidence returned to expected levels by late 2020. Across the COVID-19 period there were a cumulative 2990 (95% CI 2109 to 3704) fewer cases of dementia observed than expected, equivalent to 1.05 months of new cases. Despite the overall recovery, ascertainment rates continued to be lower than expected among individuals aged 65-74 years and in large urban areas. Ascertainment rates were higher than expected in hospital and among individuals with 11 or more health conditions. CONCLUSIONS: The claims-based incidence of dementia recovered to expected levels by late 2020, suggesting minimal long-term changes to population-based dementia surveillance. Continued monitoring of claims-based incidence is necessary to determine whether the lower than expected incidence among individuals aged 65-74 and in large urban areas, and higher than expected incidence among individuals with 11 or more health conditions, is transitory.
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COVID-19 , Demencia , Humanos , Ontario/epidemiología , COVID-19/epidemiología , Pandemias , Factores de Tiempo , Demencia/epidemiologíaRESUMEN
OBJECTIVES: To measure changes in resident-level acute care transfer rates after the PoET Southwest Spread Project (PSSP), and to identify patient and long-term care (LTC) home characteristics associated with acute care transfers after program launch. DESIGN: Quasi-experimental matched (1:1 ratio) cohort study design using linked population-based health administrative data. SETTING: Sixty publicly funded LTC homes (PSSP = 30; control = 30) in Ontario, Canada, from November 2019 to December 2021. METHODS: We matched 30 PSSP homes to 30 control homes with similar characteristics and described incidence rates for resident-level acute care transfers during the 7-month post-implementation period. We used generalized linear mixed models to evaluate the association between PSSP implementation and acute care transfers during the post-implementation period. We adjusted resident-level characteristics (ie, age, sex, comorbidity status) and home-level characteristics (ie, rurality status, profit model, COVID-19 impact). We identified a decedent sub-cohort to measure transfer patterns during the last 2 months of life. RESULTS: A matched cohort of 8894 residents (PSSP = 4103; control = 4791) was captured. Incidence rates of transfers increased during the post-implementation period for both PSSP (78.8 to 80.9 transfers per 1000 person-months) and control residents (66.9 to 67.9 transfers per 1000 person-months). After adjusting for covariates of interest, PSSP exposure was associated with a reduction in acute care transfers during the post-implementation period after adjusting for covariates (incidence rate ratio, 0.73; 95% CI, 0.62-0.87; P = .0002). Older age and select health regions were associated with reduced transfers, whereas higher comorbidity status and higher COVID-19 outbreak days were associated with increases. Similar patterns persisted for transfers during the last 2 months of life. CONCLUSIONS AND IMPLICATIONS: This study systematically evaluated the impact of an ethics-based health care intervention in LTC using health care utilization databases. PoET implementation is associated with reduced acute care transfer rates, especially in the last 2 months of life in LTC.
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COVID-19 , Cuidados a Largo Plazo , Humanos , Casas de Salud , Estudios de Cohortes , Datos de Salud Recolectados Rutinariamente , COVID-19/epidemiología , Ontario/epidemiologíaRESUMEN
OBJECTIVE: We examine annual rates of emergency department (ED) visits, hospital admissions, and alternate levels of care (ALC) days (ie, the number of days that an older adult remained in hospital when they could not be safely discharged to an appropriate setting in their community) among older adults. DESIGN: Repeated cross-sectional study. SETTING AND PARTICIPANTS: Linked, individual-level health system administrative data on community-dwelling persons, home care recipients, residents of assisted living facilities, and residents of nursing homes aged 65 years and older in Ontario, Canada, from January 1, 2013, to December 31, 2019. METHODS: We calculated rates of ED visits, hospital admissions, and ALC days per 1000 individuals per older adult population per year. We used a generalized linear model with a gaussian distribution, log link, and year fixed effects to obtain rate ratios. RESULTS: There were 1,655,656 older adults in the community, 237,574 home care recipients, 42,600 older adults in assisted living facilities, and 94,055 older adults in nursing homes in 2013; there were 2,129,690 older adults in the community, 281,028 home care recipients, 56,975 older adults in assisted living facilities, and 95,925 older adults in nursing homes in 2019. Residents of assisted living facilities had the highest rates of ED visits (1260.692019 vs 1174.912013), hospital admissions (482.632019 vs 480.192013), and ALC days (1905.572019 vs 1443.032013) per 1000 individuals. Residents of assisted living facilities also had significantly higher rates of ED visits [rate ratio (RR) 3.30, 95% CI 3.20, 3.41), hospital admissions (RR 6.24, 95% CI 6.01, 6.47), and ALC days (RR 25.68, 95% CI 23.27, 28.35) relative to community-dwelling older adults. CONCLUSIONS AND IMPLICATIONS: The disproportionate use of ED visits, hospital admissions, and ALC days among residents of assisted living facilities may be attributed to the characteristics of the population and fragmented licensing and regulation of the sector, including variable models of care. The implementation of interdisciplinary, after-hours, team-based approaches to home and primary care in assisted living facilities may reduce the potentially avoidable use of ED visits, hospital admissions, and ALC days among this population and optimize resource allocation in health care systems.
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Instituciones de Vida Asistida , Humanos , Anciano , Estudios Transversales , Hospitalización , Servicio de Urgencia en Hospital , Hospitales , OntarioRESUMEN
OBJECTIVE: We investigate the changes in the sociodemographic characteristics, clinical comorbidities, and transitions between care settings among residents of assisted living facilities. DESIGN: Repeated cross-sectional study. SETTING AND PARTICIPANTS: Linked, individual-level health system administrative data on residents of assisted living facilities in Ontario, Canada, from January 1, 2013, to December 31, 2019. METHODS: Counts and proportions were calculated to describe the sociodemographic characteristics and clinical comorbidities. Relative changes and trend tests were calculated to quantify the longitudinal changes in the characteristics of residents of assisted living facilities between 2013 and 2019. A Sankey plot was graphed to display transitions between different care settings (ie, hospital admission, nursing home admission, died, or remained in the assisted living facility) each year from 2013 to 2019. RESULTS: There was a 34% relative increase in the resident population size of assisted living facilities (56,9752019 vs 42,6002013). These older adults had a mean age of 87 years, and women accounted for nearly two-thirds of the population across all years. The 5 clinical comorbidities that had the highest relative increases were renal disease (24.3%), other mental health conditions (16.8%), cardiac arrhythmias (9.6%), diabetes (8.5%), and cancer (6.9%). Nearly 20% of the original cohort from 2013 remained in an assisted living facility at the end of 2019, and approximately 10% of that cohort transitioned to a nursing home in any year from 2013 to 2019. CONCLUSIONS AND IMPLICATIONS: Residents of assisted living facilities are an important older adult population that has progressively increased in clinical complexity within less than a decade. Clinicians and policy makers should advocate for the implementation of on-site medical care that is aligned with the needs of these older adults.
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Instituciones de Vida Asistida , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Estudios Transversales , Casas de Salud , Hospitalización , OntarioRESUMEN
OBJECTIVES: To examine the practice patterns and trends of long-term care (LTC) physicians between 2019 and 2021 in Ontario, Canada. DESIGN: Population-level descriptive time trend study. SETTING AND PARTICIPANTS: Most responsible physicians (MRPs) of LTC residents of publicly funded LTC homes in Ontario, Canada, from September 2019 to December 2021. METHODS: We examined the number of MRPs in publicly regulated Ontario LTC homes before and during the COVID-19 pandemic using population-level administrative databases. Characteristics of MRPs and practice patterns were generated at baseline and across distinct time periods of the pandemic in descriptive tables. We created a Sankey diagram to visualize MRP practice changes over time. RESULTS: More than one-quarter of pre-pandemic MRPs were no longer MRPs by the end of 2021, although most continued to practice in non-LTC settings. There was a decrease from 1444 to 1266 MRPs over time. Other characteristics of MRPs remained stable over the pandemic time periods. At baseline, LTC physicians were MRP for an average of 57.3 residents. By the end of 2021, this caseload decreased to 53.3 residents per MRP. MRPs increasingly billed monthly management compensation fees over the fee-for-service model across the pandemic time periods. The number of MRPs working in an LTC home shifted to fewer MRPs per home. CONCLUSIONS AND IMPLICATIONS: MRP demographic characteristics did not change over the course of the pandemic. The observed shifts in practice patterns showed a reduction in the overall LTC MRP workforce, who delivered care to fewer residents on average in LTC homes with fewer colleagues to rely on. Future work can study how changes to LTC MRPs' practice patterns impact physician coverage, access and continuity of care, and health services and quality outcomes among residents.
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COVID-19 , Médicos , Humanos , Cuidados a Largo Plazo , Ontario/epidemiología , Pandemias , Casas de Salud , Recursos HumanosRESUMEN
Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements. We image fields of view up to 800 µm × 800 µm at resolutions down to 260 nm with sensitivities approaching single-molecule detection. We leverage these properties to interrogate intrapatient heterogeneity in tumor organization in triple-negative breast cancer, revealing regional variability in tumor cell phenotypes in contrast to a structured immune response. Given its versatility and sample back-compatibility, MIBI-TOF is positioned to leverage existing annotated, archival tissue cohorts to explore emerging questions in cancer, immunology, and neurobiology.
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Espectrometría de Masa de Ion Secundario/métodos , Anticuerpos/química , Anticuerpos/inmunología , Astrocitos/citología , Astrocitos/metabolismo , Proteína Ácida Fibrilar de la Glía/química , Proteína Ácida Fibrilar de la Glía/inmunología , Humanos , Metales/química , Proteínas de Microfilamentos/química , Proteínas de Microfilamentos/inmunología , Microglía/citología , Microglía/metabolismo , Tonsila Palatina/patología , Fenotipo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
An aerodynamic lens has been used to introduce polystyrene nanoparticles into an apparatus that combines laser vaporisation with mass spectrometric measurements of ion intensity. The particles have a mean diameter of 129 nm and are sterically-stabilised with poly(ethylene glycol) which coats the surface to a depth of approximately 5 nm. Measurements have been made at wavelengths of 266, 355, and 523 nm, and over a range of laser powers. The results provide clear evidence that depth profiling can be achieved by changing the wavelength of the ablating radiation, but that changes in power at a single wavelength have little influence on the range of ions observed. At 523 nm the mass spectra are predominantly derived from surface-bound material, whilst at 266 nm the dominant contribution is from ions related to the polystyrene core of the particles. It is proposed that these differences in behaviour can be equated with existing models of the laser ablation process.