Academic hospitalist perspectives on the benefits and challenges of secure messaging: A mixed methods analysis.

BACKGROUND: Hospitals and patients rely on effective clinician communication. Asynchronous electronic secure messaging (SM) systems are a common way for hospitalists to communicate, but few studies have evaluated how hospitalists are navigating the adoption of SM and the benefits and challenges they are encountering. OBJECTIVES: The objective of this study is to assess academic hospitalist perspectives on SM to guide future research and quality improvement initiatives. METHODS: This was a mixed methods study utilizing an embedded REDCap survey and six virtual semistructured focus groups. It took place during a Hospital Medicine ReEngineering Network Zoom meeting on October 13, 2023. Rapid qualitative methods were used to define major themes. RESULTS: There were 28 hospitalists and one patient representative across 24 separate academic institutions. There was a 71% survey completion rate (N = 20). SM was felt to be an effective and efficient communication modality but was associated with a large amount of multitasking and interruptions. Perspectives around SM clustered around three main themes: SM has been widely but variably adopted; there is a lack of institutional guidance about how to best engage with SM; and SM is changing the landscape of hospitalist work by increasing ease but decreasing depth of communication, increasing cognitive load, and changing interpersonal relationships. Recommendations for SM improvements included the need for institutions to work with frontline workers to develop and implement clear usage guidelines. CONCLUSION: SM is likely contributing to both positive and negative effects for clinicians and patients. Understanding hospitalist perspectives on SM will help guide future research and quality improvement initiatives.

Estrogen receptor alpha (ERα) regulates PARN-mediated nuclear deadenylation and gene expression in breast cancer cells.

The estrogen signalling pathway is highly dynamic and primarily mediated by estrogen receptors (ERs) that transcriptionally regulate the expression of target genes. While transcriptional functions of ERs have been widely studied, their roles in RNA biology have not been extensively explored. Here, we reveal a novel biological role of ER alpha (ERα) in mRNA 3' end processing in breast cancer cells, providing an alternative mechanism in regulating gene expression at the post-transcriptional level. We show that ERα activates poly(A) specific ribonuclease (PARN) deadenylase using in vitro assays, and that this activation is further increased by tumour suppressor p53, a factor involved in mRNA processing. Consistent with this, we confirm ERα-mediated activation of nuclear deadenylation by PARN in samples from MCF7 and T47D breast cancer cells that vary in expression of ERα and p53. We further show that ERα can form complex(es) with PARN and p53. Lastly, we identify and validate expression of common mRNA targets of ERα and PARN known to be involved in cell invasion, metastasis and angiogenesis, supporting the functional overlap of these factors in regulating gene expression in a transactivation-independent manner. Together, these results show a new regulatory mechanism by which ERα regulates mRNA processing and gene expression post-transcriptionally, highlighting its contribution to unique transcriptomic profiles and breast cancer progression.

Using Multilevel Models and Generalized Estimating Equation Models to Account for Clustering in Neurology Clinical Research.

In clinical and health services research, clustered data (also known as data with a multilevel or hierarchical structure) are frequently encountered. For example, patients may be clustered or nested within hospitals. Understanding when data have a multilevel structure is important because clustering of individuals can induce a homogeneity in outcomes within clusters, so that, even after adjusting for measured covariates, outcomes for 2 individuals in the same cluster are more likely to be similar than outcomes for 2 individuals from different clusters. Using conventional statistical regression models to analyze clustered data can result in incorrect conclusions being drawn. In particular, estimated CIs may be artificially narrow, and significance levels may be artificially low. As a result, one may conclude that there is a statistically significant association when there is none. To avoid this problem, investigators should ensure that their analyses use techniques that account for clustering of data. Generalized linear models estimated using generalized estimating equation (GEE) methods and multilevel regression models (also known as hierarchical regression models, mixed-effects models, or random-effects models) are two such techniques. We provide an introduction to clustered or multilevel data and describe how GEE models or multilevel models can be used for the analysis of multilevel data.

Information exchange, responsibilities and expectation management in interhospital transfers: a qualitative study of hospital medicine physicians and advanced practice providers.

INTRODUCTION: The transfer of patients between hospitals, known as interhospital transfer (IHT), is associated with higher rates of mortality, longer lengths of stay and greater resource utilisation compared with admissions from the emergency department. To characterise the IHT process and identify key barriers and facilitators to IHT care, we examined the experiences of physician and advanced practice provider (APP) hospital medicine clinicians who care for IHT patients transferred to their facility. METHODS: Qualitative descriptive study using semistructured interviews with adult medicine hospitalists from an academic acute care hospital that accepts approximately 4000 IHT patients annually. A combined inductive and deductive coding approach guided thematic analysis. RESULTS: We interviewed 30 hospitalists with a mean of 5.7 years of experience. Two-thirds of interviewees were physicians and one-third were APPs.They described IHTs as challenging when (1) exchanged information was incomplete, inaccurate, extraneous, and/or untimely, (2) uncertainty impacted care responsibilities and (3) healthcare team members and patients had differing care expectations. As a result, participants described patient safety issues such as delays in care and inappropriate triage of patients due to incomplete communication of clinical status changes.Recommended improvement strategies include (1) dedicated individuals performing IHT tasks to improve consistency of information exchanged and relationships with transferring clinicians, (2) standardised scripts and documentation, (3) bidirectional communication, (4) interdisciplinary training and (5) shared understanding of care needs and expectations. CONCLUSIONS: Physicians and APP hospital medicine clinicians at an accepting hospital found information exchange, care responsibilities and expectation management challenging in IHT. In turn, hospitalists perceived a negative impact on IHT patient care and safety. Highly reliable and timely information transfer, standardisation of IHT processes and clear interdisciplinary communication may facilitate improved care for IHT patients.

Dosimetric calibration of anatomy-specific ultra-high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments.

BACKGROUND: FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra-high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation. PURPOSE: We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate irradiation to two anatomic sites in mice and for cell-culture FLASH radiobiology experiments. METHODS: Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source-to-surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions. RESULTS: The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm2 for whole-abdomen and 1.5 × 1.5 cm2 for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement. CONCLUSION: We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications.

Association Between Neighborhood-Level Income and the Incidence of Cardiovascular Events Varies by Immigration Status: A Population-Based Cohort Study.

BACKGROUND: Neighborhood-level income is inversely associated with cardiovascular events; however, it is uncertain whether this association varies with immigration status. METHODS AND RESULTS: We conducted a population-based cohort study of 5.2 million (53% women, 19% immigrants) urban-dwelling people aged ≥40 years without a prior history of cardiovascular disease in Ontario, Canada. Neighborhood-level income was measured in quintiles from quintile 1 (lowest) to quintile 5 (highest), and immigrants were defined as those born outside of Canada who moved to Canada after 1985. We estimated the association between neighborhood-level income and the rate of incident cardiovascular events (hospitalization for stroke or myocardial infarction, or cardiovascular death) using multivariable cause-specific hazards models and added an interaction term to see if the association varies by immigration status. The absolute difference in the rate of cardiovascular events across income quintiles was less pronounced in immigrants than in long-term residents: age- and sex-adjusted rate per 1000 person-years in quintile 1 versus quintile 5: 5.69 versus 4.10 in immigrants and 8.37 versus 5.87 in long-term residents. In adjusted models, the interaction between immigration status and neighborhoodl evel was significant (Pinteraction <0.001). The hazard of cardiovascular events declined with increasing income among long-term residents (hazard ratio [HR]Q1vsQ5, 1.46 to HRQ4vsQ5, 1.10) and immigrants, albeit with a smaller gradient (HRQ1vsQ5, 1.43 to HRQ4vsQ5, 1.20). CONCLUSIONS: The association between neighborhood-level income and cardiovascular disease incidence varies by immigration status. Understanding the social and structural factors associated with residing in low-income neighborhoods can help with the development of prevention programs that improve health for all.

Rising out-of-hospital mortality in Canada during 2020‒2022: A striking impact observed among young adults.

OBJECTIVE: Out-of-hospital mortality rates surged during the early COVID-19 pandemic. While expecting a return to pre-pandemic levels, the evolving patterns of out-of-hospital mortality in Canada remain uncertain. We investigated whether these rates returned to pre-pandemic levels. METHODS: This retrospective study, employing linked administrative data, analyzed out-of-hospital mortality trends among adult residents in Ontario, Alberta, and Nova Scotia. Interrupted time series analysis assessed trends in age- and sex-standardized rates/100,000/quarter during pre-pandemic (April 2014-March 2020) and pandemic periods (April 2020-March 2022), while considering April to June 2020 as the pandemic onset period. Crude mortality rates were also examined, stratified by sex and age groups. RESULTS: Pre-pandemic, Ontario's standardized out-of-hospital mortality rates were rising, while Alberta's and Nova Scotia's remained stable. At the pandemic onset, all provinces experienced significant increases in standardized out-of-hospital mortality rates/100,000 (Ontario: ß 14.6, 95% CI [3.97, 25.22]; Alberta: 21.3, 95% CI [9.26, 33.34]; Nova Scotia: 10.5, 95% CI [1.06, 19.88]). During the pandemic, standardized out-of-hospital mortality rates/100,000/quarter remained above pre-pandemic levels, with no significant departure from the increased pandemic onset levels (Ontario: - 1.6, 95% CI [- 3.63, 0.52]; Alberta: 0.45, 95% CI [- 1.47, 2.36]; Nova Scotia: - 0.06, 95% CI [- 2.18, 2.06]). Crude out-of-hospital mortality rates increased most prominently among individuals aged 18 to 45 in Alberta and Ontario, and among males across all provinces. CONCLUSION: The sustained increase in out-of-hospital mortality, observed from the pandemic's onset, spanning more than 2 years, potentially suggests its persistent direct and indirect effects on population health in Canada.

RéSUMé: OBJECTIF: Les taux de mortalité non hospitalière ont bondi au début de la pandémie de COVID-19. Bien qu'un retour aux niveaux prépandémiques soit attendu, l'évolution des tendances de la mortalité non hospitalière au Canada demeure incertaine. Nous avons cherché à savoir si ces taux sont retournés à leurs niveaux prépandémiques. MéTHODE: Dans le cadre d'une étude rétrospective faisant appel à des données administratives liées, nous avons analysé les tendances de la mortalité non hospitalière chez les adultes vivant en Ontario, en Alberta et en Nouvelle-Écosse. Une analyse des séries chronologiques interrompues a permis d'estimer les tendances des taux normalisés selon l'âge et le sexe pour 100 000 par trimestre pendant la période prépandémique (avril 2014 ­ mars 2020) et pendant la pandémie (avril 2020 ­ mars 2022), la période d'avril à juin 2020 étant considérée comme le début de la pandémie. Les taux de mortalité brute ont aussi été examinés, puis stratifiés selon l'âge et le sexe. RéSULTATS: Avant la pandémie, les taux de mortalité non hospitalière normalisée de l'Ontario étaient en hausse, tandis que ceux de l'Alberta et de la Nouvelle-Écosse étaient stables. Au début de la pandémie, les trois provinces ont connu d'importantes augmentations des taux de mortalité non hospitalière normalisée pour 100 000 (Ontario: ß 14,6, IC de 95% [3,97, 25,22]; Alberta: 21,3, IC de 95% [9,26, 33,34]; Nouvelle-Écosse: 10,5, IC de 95% [1,06, 19,88]). Pendant la pandémie, les taux de mortalité non hospitalière normalisée pour 100 000 par trimestre sont demeurés au-dessus des niveaux prépandémiques, sans écart significatif par rapport aux niveaux accrus du début de la pandémie (Ontario: -1,6, IC de 95% [-3,63, 0,52]; Alberta: 0,45, IC de 95% [-1,47, 2,36]; Nouvelle-Écosse: -0,06, IC de 95% [-2,18, 2,06]). Les taux de mortalité non hospitalière brute ont surtout augmenté chez les personnes de 18 à 45 ans en Alberta et en Ontario, et chez les hommes dans les trois provinces. CONCLUSION: L'augmentation soutenue de la mortalité non hospitalière, observée dès le début de la pandémie et étalée sur plus de deux ans, pourrait indiquer que celle-ci a eu des effets directs et indirects persistants sur la santé des populations au Canada.

Understanding how organizational culture shapes the experiences of direct support professionals: A qualitative meta-synthesis from an organizational justice perspective.

Direct support professionals (DSPs) are critical to the quality of life of people with intellectual and developmental disabilities, yet high turnover rates significantly affect the quality and consistency of their services. A qualitative meta-synthesis could help understand how organizational culture shapes the experiences of DSPs. A systematic search found six articles that met all inclusion criteria. The initial findings show that although DSPs perceived their work as worthy and rewarding, they did not feel valued or supported by management either monetarily or professionally. The analysis revealed an overarching theme with elements congruent with the organizational justice literature. Findings suggest that cultivating a culture of justice and fairness is vital to retaining quality DSPs, promoting organizational outcomes, and improving the quality of life of people with intellectual and developmental disabilities.

An Interrupted Time-Series Analysis of the Impact of COVID-19 on Hospitalizations for Vascular Events in 3 Canadian Provinces.

Background: COVID-19 infection is associated with a pro-coagulable state, thrombosis, and cardiovascular events. However, its impact on population-based rates of vascular events is less well understood. We studied temporal trends in hospitalizations for stroke and myocardial infarction in 3 Canadian provinces (Alberta, Ontario, and Nova Scotia) between 2014 and 2022. Methods: Linked administrative data from each province were used to identify admissions for ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, and myocardial infarction. Event rates per 100,000/quarter, standardized to the 2016 Canadian population, were calculated. We assessed changes from quarterly rates pre-pandemic (2014-2020), compared to rates in the pandemic period (2020-2022), using interrupted time-series analysis with a jump discontinuity at pandemic onset. Age group- and sex-stratified analyses also were performed. Results: We identified 162,497 strokes and 243,182 myocardial infarctions. At pandemic onset, no significant step change in strokesper 100,000/quarter was observed in any of the 3 provinces. During the pandemic, stroke rates were stable in Alberta and Ontario, but they increased in Nova Scotia (0.44 per 100,000/quarter, P = 0.004). At pandemic onset, a significant step decrease occurred in myocardial infarctions per 100,000/quarter in Alberta (4.72, P < 0.001) and Ontario (4.84, P < 0.001), but not in Nova Scotia. During the pandemic, myocardial infarctions per 100,000/quarter decreased in Alberta (-0.34, P = 0.01), but they remained stable in Ontario and Nova Scotia. No consistent patterns by age group or sex were noted. Conclusions: Hospitalization rates for stroke or myocardial infarction across 3 Canadian provinces did not increase substantially during the first 2 years of the pandemic. Continued surveillance is warranted as the virus becomes endemic.

Contexte: L'infection par la COVID-19 est associée à un état procoagulant, à la thrombose et à des événements cardiovasculaires. Son incidence sur les taux d'événements vasculaires dans la population est cependant moins bien comprise. Nous avons étudié les tendances temporelles des hospitalisations pour un accident vasculaire cérébral (AVC) et un infarctus du myocarde dans trois provinces canadiennes (Alberta, Ontario et Nouvelle-Écosse) entre 2014 et 2022. Méthodologie: Des données administratives couplées provenant de chaque province ont été utilisées pour recenser les hospitalisations pour un AVC ischémique, une hémorragie intracérébrale, une thrombose veineuse cérébrale et un infarctus du myocarde. Nous avons calculé les taux d'événements pour 100 000 admissions/trimestre, uniformisés pour correspondre à la population canadienne de 2016. Nous avons évalué les variations par rapport aux taux trimestriels d'avant la pandémie (2014-2020), comparativement aux taux pendant la pandémie (2020-2022), à l'aide d'une analyse de séries chronologiques interrompues avec discontinuité à saut fini au début de la pandémie. Des analyses stratifiées selon le groupe d'âge et le sexe ont également été réalisées. Résultats: Nous avons recensé 162 497 AVC et 243 182 infarctus du myocarde. Au début de la pandémie, aucune variation progressive significative au niveau des AVC pour 100 000 admissions/trimestre n'a été observée dans aucune des trois provinces. Pendant la pandémie, les taux d'AVC sont demeurés stables en Alberta et en Ontario, mais ont augmenté en Nouvelle-Écosse (0,44 pour 100 000 admissions/trimestre; p = 0,004). Au début de la pandémie, une diminution graduelle significative du taux d'infarctus du myocarde pour 100 000 admissions/trimestre a été observée en Alberta (4,72; p < 0,001) et en Ontario (4,84; p < 0,001), mais pas en Nouvelle-Écosse. Durant la pandémie, le taux d'infarctus du myocarde pour 100 000 admissions/trimestre a diminué en Alberta (­0,34; p = 0,01), mais est demeuré stable en Ontario et en Nouvelle-Écosse. Aucune tendance constante n'a été observée selon le groupe d'âge ou le sexe. Conclusions: Les taux d'hospitalisation pour un AVC ou un infarctus du myocarde n'ont pas augmenté de manière substantielle dans les trois provinces canadiennes durant les deux premières années de la pandémie. Une surveillance continue s'impose alors que le virus devient endémique.

Geographical Trends in Global Ophthalmology Research from 2002-2022.

PURPOSE: Characterize geographical trends in ophthalmology research between 2002-2022 and explore associations between study locations, designs, and funding sources DESIGN: Trend study METHODS: Analysis of 4199 publications from American Journal of Ophthalmology, British Journal of Ophthalmology, Investigative Ophthalmology and Visual Science, JAMA Ophthalmology, and Ophthalmology. All original full-length publications from 2002, 2012, and 2022 were included. Exclusion criteria were meta-analyses, literature reviews, and case reports. Main outcome measures were publication years, locations, study designs, and funding sources. RESULTS: Publications from North America (45.8%), Europe (30.7%), and Asia (28.9%) were the most common, whereas Africa (0.8%) and South America (1.4%) were least represented. North American research decreased by 10.6% (p < 0.001), whereas Asian research increased by 25.4% (p < 0.001). The USA contributed 42.3% of research but experienced a 11.3% decline from 2002-2022 (p < 0.001). USA publications received 5.8% more industry funding from 2002-2022 (p = 0.006). China's research grew by 17.0% and had the highest proportion of government (83.1%) or intramural (24.2%) funding (p < 0.001), with government-funded studies increasing by 46.7% (p < 0.001). Japan was less associated with all funding types (p ≤ 0.001). Singapore, Iceland, and Switzerland were top performers when adjusted for population size. CONCLUSIONS: Within the examined journals, the USA remains the primary research contributor, with China witnessing rapid growth and Japan facing stagnation. Despite the USA's declining research proportion, North America and Europe continue to maintain a disproportionately high presence in prestigious academic journals. Publications from Africa and South America are limited.

Quantum modeling simulates nutrient effect of bioplastic polyhydroxyalkanoate (PHA) production in Pseudomonas putida.

Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida's preference in channeling carbon towards PHA production as part of the bacterium's adaptative behavior to nutrient stress using quantum formalism. Generic parameters (kD, kN and theta θ) obtained based on such quantum formulation, representing P. putida's PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses.

Interhospital Transfer for Endovascular Stroke Treatment in Canada: Results From the OPTIMISE Registry.

BACKGROUND: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. METHODS: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. RESULTS: Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. CONCLUSIONS: Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.

Association of oxaliplatin-containing adjuvant duration with post-treatment fall-related injury and fracture in patients with stage III colon cancer: a population-based retrospective cohort study.

PURPOSE: Oxaliplatin-containing adjuvant chemotherapy yields a significant survival benefit in stage III colon cancer and is the standard of care. Simultaneously, it causes dose-dependent peripheral neuropathy that may increase the risk of fall-related injury (FRI) such as fracture and laceration. Because these events carry significant morbidity and the global burden of colon cancer is on the rise, we examined the association between treatment with a full versus shortened course of adjuvant chemotherapy and post-treatment FRI and fracture. METHODS: In this overlap propensity score weighted, retrospective cohort study, we included patients aged ≥ 18 years with resected stage III colon cancer diagnosed 2007-2019 and treated with oxaliplatin-containing adjuvant chemotherapy (oxaliplatin plus a fluoropyrimidine; capecitabine [CAPOX] or 5-fluorouracil and leucovorin [FOLFOX]). Propensity score methods facilitate the separation of design from analysis and comparison of baseline characteristics across the weighted groups. Treatment groups were defined as 50% (4 cycles CAPOX/6 cycles FOLFOX) and > 85% (7-8 cycles CAPOX/11-12 cycles FOLFOX) of a maximal course of adjuvant chemotherapy to approximate the treatment durations received in the IDEA collaboration. The main outcomes were time to any FRI and time to fracture. We determined the subdistribution hazard ratios (sHR) estimating the association between FRI/fracture and treatment group, accounting for the competing risk of death. RESULTS: We included 3,461 patients; 473 (13.7%) received 50% and 2,988 (86.3%) received > 85% of a maximal course of adjuvant therapy. For post-treatment FRI, median follow-up was 4.6 years and total follow-up was 17,968 person-years. There were 508 FRI, 301 fractures, and 692 deaths. Treatment with > 85% of a maximal course of therapy conferred a sHR of 0.84 (95% CI 0.62-1.13) for post-treatment FRI and a sHR of 0.72 (95% CI 0.49-1.06) for post-treatment fracture. CONCLUSION: For patients with stage III colon cancer undergoing treatment with oxaliplatin-containing adjuvant chemotherapy, any potential neuropathy associated with longer durations of treatment was not found to result in greater rates of FRI and fracture. Within the limits of this retrospective study, our findings suggest concern about FRI, while mechanistically plausible, ought not to determine treatment duration.

Secondary Stroke Prevention in People With Schizophrenia.

BACKGROUND: People with schizophrenia are less likely than those without to be treated for cardiovascular disease. We aimed to evaluate the association between schizophrenia and secondary preventive care after ischemic stroke. METHODS AND RESULTS: In this retrospective cohort study, we used linked population-based administrative data to identify adults who survived 1 year after ischemic stroke hospitalization in Ontario, Canada between 2004 and 2017. Outcomes were screening, treatment, and control of risk factors, and receipt of outpatient physician services. We used modified Poisson regression to model the relative risk of each outcome among people with and without schizophrenia, adjusting for age and other factors. Among 81 163 people with ischemic stroke, 844 (1.04%) had schizophrenia. Schizophrenia was associated with lower rates of screening for hyperlipidemia (60.5% versus 66.0%, adjusted relative risk [aRR] 0.88 [95% CI, 0.84-0.93]) and diabetes (69.4% versus 73.9%, aRR 0.93 [95% CI, 0.89-0.97]), prescription of antihypertensive medications (91.2% versus 94.7%, aRR 0.96 [95% CI, 0.93-0.99]), achievement of target lipid levels (low-density lipoprotein <2 mmol/L) (30.6% versus 34.6%, aRR 0.86 [95% CI, 0.78-0.96]), and outpatient specialist visits (55.3% versus 67.8%, aRR 0.78 [95% CI, 0.74-0.83]) or primary care physician visits (94.5% versus 98.5%; aRR 0.96 [95% CI, 0.95-0.98]) within 1 year. There were no differences in prescription of antilipemic, antiglycemic, or anticoagulant medications, or in achievement of target hemoglobin A1c ≤7%. CONCLUSIONS: People with stroke and schizophrenia are less likely than those without to receive secondary preventive care. This may inform interventions to improve poststroke care and outcomes in those with schizophrenia.

Reducing Depressive Symptoms Among Latina Mothers of Autistic Children: A Randomized Controlled Trial.

This study examines the intervention effect of a culturally tailored parent education program in reducing depressive symptoms among Latina mothers of autistic children. In this two-site randomized waitlist-control study (n = 109 mother-child dyads), a peer-to-peer mentoring (promotora) model was used to deliver an intervention that was designed to increase mothers' self-efficacy and use of evidence-based strategies. We assessed mothers' depressive symptom (CES-D) scores at three time points and used linear mixed models to determine whether their scores significantly changed from baseline to postintervention (Time 2) and at 4 months postintervention (Time 3). Results show that mothers in the intervention group reported a significant decrease in mean depressive symptom scores at Time 2 and that the effect was maintained at Time 3 with intermediate to medium effect sizes. There were no differences in results across sites. Findings suggest that Parents Taking Action, a culturally tailored intervention led by peer mentors, showed a significant effect both immediately after the intervention and 4 months postintervention in reducing depressive symptoms among Latina mothers of autistic children.

Association Between Immigration Status and Ambulatory Secondary Stroke Preventive Care in Ontario, Canada.

BACKGROUND AND OBJECTIVES: Secondary stroke preventive care includes evaluation and control of vascular risk factors to prevent stroke recurrence. Our objective was to evaluate the quality of ambulatory stroke preventive care and its variation by immigration status in adult stroke survivors in Ontario, Canada. METHODS: We conducted a population-based administrative database-derived retrospective cohort study in Ontario, Canada. Using immigration records, we defined immigrants as those immigrating after 1985 and long-term residents as those arriving before 1985 or those born in Canada. We included community-dwelling stroke survivors 40 years and older with a first-ever stroke between 2011 and 2017. In the year following their stroke, we evaluated the following metrics of stroke prevention: testing for hyperlipidemia and diabetes; among those with the condition, control of diabetes (hemoglobin A1c ≤7%) and hyperlipidemia (low-density lipoprotein <2 mmol/L); medication use to control hypertension, diabetes, and atrial fibrillation; and visit to a family physician and a specialist (neurologist, cardiologist, or geriatrician). We determined age and sex-adjusted absolute prevalence difference (APD) between immigrants and long-term residents for each metric using generalized linear models with binomial distribution and an identity link function. RESULTS: We included 34,947 stroke survivors (median age 70 years, 46.9% women) of whom 12.4% were immigrants. The receipt of each metric ranged from 68% to 90%. Compared with long-term residents, after adjusting for age and sex, immigrants were slightly more likely to receive screening for hyperlipidemia (APD 5.58%; 95% CI 4.18-6.96) and diabetes (5.49%; 3.76-7.23), have visits to family physicians (1.19%; 0.49-1.90), receive a prescription for antihypertensive (3.12%; 1.76-4.49) and antihyperglycemic medications (9.51%; 6.46-12.57), and achieve control of hyperlipidemia (3.82%; 1.01-6.63). By contrast, they were less likely to achieve diabetes control (-4.79%; -7.86 to -1.72) or have visits to a specialist (-1.68%; -3.12 to -0.24). There was minimal variation by region of origin or time since immigration in immigrants. DISCUSSION: Compared with long-term residents, many metrics of secondary stroke preventive care were better in immigrants, albeit with small absolute differences. However, future work is needed to identify and mitigate the factors associated with the suboptimal quality of stroke preventive care for all stroke survivors.

Association Between Time to Treatment With Endovascular Thrombectomy and Home-Time After Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Home-time is a patient-prioritized stroke outcome that can be derived from administrative data linkages. The effect of faster time-to-treatment with endovascular thrombectomy (EVT) on home-time after acute stroke is unknown. METHODS: We used the Quality Improvement and Clinical Research registry to identify a cohort of patients who received EVT for acute ischemic stroke between 2015 and 2022 in Alberta, Canada. We calculated days at home in the first 90 days after stroke. We used ordinal regression across 6 ordered categories of home-time to evaluate the association between onset-to-arterial puncture and higher home-time, adjusting for age, sex, rural residence, NIH Stroke Scale, comorbidities, intravenous thrombolysis, and year of treatment. We used restricted cubic splines to assess the nonlinear relationship between continuous variation in time metrics and higher home-time, and also reported the adjusted odds ratios within time categories. We additionally evaluated door-to-puncture and reperfusion times. Finally, we analyzed home-time with zero-inflated models to determine the minutes of earlier treatment required to gain 1 day of home-time. RESULTS: We had 1,885 individuals in our final analytic sample. There was a nonlinear increase in home-time with faster treatment when EVT was within 4 hours of stroke onset or 2 hours of hospital arrival. There was a higher odds of achieving more days at home when onset-to-puncture time was <2 hours (adjusted odds ratio 2.36, 95% CI 1.77-3.16) and 2 to <4 hours (1.37, 95% CI 1.11-1.71) compared with ≥6 hours, and when door-to-puncture time was <1 hour (aOR 2.25, 95% CI 1.74-2.90), 1 to <1.5 hours (aOR 1.89, 95% CI 1.47-2.41), and 1.5 to <2 hours (1.35, 95% CI 1.04-1.76) compared with ≥2 hours. Results were consistent for reperfusion times. For every hour of faster treatment within 6 hours of stroke onset, there was an estimated increase in home-time of 4.7 days, meaning that approximately 1 day of home-time was gained for each 12.8 minutes of faster treatment. DISCUSSION: Faster time-to-treatment with EVT for acute stroke was associated with greater home-time, particularly within 4 hours of onset-to-puncture and 2 hours of door-to-puncture time. Within 6 hours of stroke onset, each 13 minutes of faster treatment is associated with a gain of 1 day of home-time.

How Do Quantitative Tissue Imaging Outcomes in Acute Ischemic Stroke Relate to Clinical Outcomes?

BACKGROUND AND PURPOSE: Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0-2). METHODS: Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. RESULTS: A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6-92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0-2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0-2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. CONCLUSION: There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.