Seven Strategies to Integrate Equity within Translational Research in Neurology.

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.

Effect of Alteplase on Ischemic Stroke Mortality Is Dependent on Stroke Severity.

OBJECTIVE: Although intravenous alteplase (IV-tPA) has a beneficial effect on functional outcome after ischemic stroke (IS), prior studies of IV-tPA's impact on post-stroke mortality did not have sufficient representation of more severe stroke. METHODS: We determined if the interaction between the baseline National Institutes of Health (NIH) Stroke Scale (NIHSS) and IV-tPA modified the risk of mortality after IS in two cohorts: (1) National Inpatient Sample 2016-2020, and (2) a harmonized cohort of IS patients from the NINDS IV-tPA, ALIAS part 2, SHINE, FAST-MAG, IMS-III, POINT, and DEFUSE 3 trials. We fit logistic regression models to the outcome of in-hospital mortality (National Inpatient Sample [NIS] cohort) or mortality within 90 days (harmonized cohort), adjusted for baseline variables. RESULTS: We included 198,668 patients in the NIS cohort, of which 14.0% received IV-tPA and 3.4% died in hospital. We included 7,138 patients in the harmonized cohort, of which 33.2% received IV-tPA and 9.4% died by 90 days. Mortality in the NIS cohort was associated with older age, female sex, non-Hispanic white race, atrial fibrillation, and higher NIHSS. In the harmonized cohort, mortality was associated with older age, diabetes, atrial fibrillation, and higher NIHSS. In both cohorts, the interaction between NIHSS and IV-tPA was significant. In the NIS cohort, the separation became significant at NIHSS 15 and in the harmonized cohort at NIHSS 23, at which point, IV-tPA began to have a significant benefit for both in-hospital and 90-day mortality, respectively. INTERPRETATION: IV-tPA is associated with a reduction in both in-hospital and 90-day mortality for patients with more severe IS. ANN NEUROL 2023;93:1106-1116.

Relapse Rates With Paliperidone Palmitate in Adult Patients With Schizophrenia: Results for the 6-Month Formulation From an Open-label Extension Study Compared to Real-World Data for the 1-Month and 3-Month Formulations.

BACKGROUND: The 3 paliperidone palmitate (PP) long-acting injectable antipsychotic formulations, PP 1-month (PP1M), PP 3-month (PP3M), and PP 6-month (PP6M), have shown to reduce the risk of relapse in schizophrenia. The current phase-4 study constructed external comparator arms (ECAs) using real-world data for PP3M and PP1M and compared relapse prevention rates with PP6M from an open-label extension (OLE) study in adult patients with schizophrenia. METHODS: PP6M data were derived from a single-arm, 24-month, OLE study (NCT04072575), which included patients with schizophrenia who completed a 12-month randomized, double-blind, noninferiority, phase-3 study (NCT03345342) without relapse. Patients in the PP3M and PP1M ECAs were identified from the IBM® MarketScan® Multistate Medicaid Database based on similar eligibility criteria as the PP6M cohort. RESULTS: A total of 178 patients were included in each cohort following propensity score matching. Most patients were men (>70%; mean age: 39-41 years). Time to relapse (primary analysis based on Kaplan-Meier estimates) was significantly delayed in the PP6M cohort (P < .001, log-rank test). The relapse rate was lower in the PP6M cohort (3.9%) vs PP3M (20.2%) and PP1M (29.8%) cohorts. Risk of relapse decreased significantly (P < .001) by 82% for PP6M vs PP3M (HR = 0.18 [95% CI = 0.08 to 0.40]), 89% for PP6M vs PP1M (HR = 0.11 [0.05 to 0.25]), and 35% for PP3M vs PP1M (HR = 0.65 [0.42 to 0.99]; P = .043). Sensitivity analysis confirmed findings from the primary analysis. Although the ECAs were matched to mimic the characteristics of the PP6M cohort, heterogeneity between the groups could exist due to factors including prior study participation, unmeasured confounders, variations in data capture and quality, and completeness of clinical information. CONCLUSIONS: In a clinical trial setting, PP6M significantly delayed time to relapse and demonstrated lower relapse rates compared with PP3M and PP1M treatments in real-world settings among adult patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.

'Letting it be': a grounded theory about dementia care in Fiji.

OBJECTIVES: This research study aimed to discover how dementia affecting older people was perceived, experienced, and managed by stakeholders in the Pacific Island country of Fiji. METHOD: A transformational grounded theory approach was used. Semi-structured interviews and focus groups with key stakeholders in the major towns of Suva, Lautoka, and Nadi were carried out. Transcripts were analysed in line with transformational grounded theory methods. RESULTS: A total of 50 participants (40 service providers, eight family caregivers, one person with dementia, and one village elder) shared their views and experiences about dementia. A grounded theory about dementia care management was constructed. 'Letting it be' is the grounding socio-cultural construct that interweaves and binds together the processes of dementia care management. It expresses a compassionate approach to caring for older people with dementia that involves searching for knowledge and support, and application of traditional care practices within the strength of family and community networks. CONCLUSION: In Fiji, support for dementia centres on the integration of community understandings, and promotion of cultural values of wellbeing and care, with service provision. It also focuses on support for families and communities through social welfare, community networks, and education.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021.

BACKGROUND: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. METHODS: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. RESULTS: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). CONCLUSION: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Childhood Cancer Survivors' Reported Late Effects, Motivations for Seeking Survivorship Care, and Patterns of Attendance.

BACKGROUND: Childhood cancer survivors are vulnerable to long-term treatment-related health conditions, which can lead to poor quality of life. Little data exist on the overall health of long-term Australian and New Zealand childhood cancer survivors or on survivors' motivations for attending survivorship clinics. METHODS: This study administers a cross-sectional questionnaire to long-term survivors ≥5 years from their primary diagnosis. We compared participant-reported number of late effects by a cancer diagnosis, and identified clinical (eg, treatment) and demographic (eg, age) factors that were associated with late effects burden and engagement in cancer survivorship care. RESULTS: A total of 634 participants completed questionnaires (48% male, mean age = 21.7 years). Most participants (79%) reported at least one cancer-related late effect, most commonly fatigue (40%) and memory/learning difficulties (34%). Brain tumor survivors reported a higher total number of late effects than survivors with other diagnoses (mean = 5.7 vs. 3.2, P < .001). Participants' most commonly reported motivators for engaging in care were to understand problems that may occur later in life because of their cancer and/or treatment (98.5%) and to get reassurance about one's health (97.4%). The proportion of survivors endorsing each motivating factor was similar across cancer diagnoses, with the exception of learning more about insurance and pensions (highest in brain tumor survivors = 80%). In multivariable analyses, survivors were more likely to report being engaged in survivorship care if they were younger (P < .001), less time had elapsed since their diagnosis (P < .001), or they reported a higher number of motivating factors (P = .016). CONCLUSION: Survivors report a range of health problems decades after treatment completion. Understanding the burden of late effects, and motivators for seeking survivorship care to manage these health problems, is important for ensuring that tailored interventions or services are available to meet the needs of this growing population and to design effective models of survivorship care.

Multicomponent Chiral Quantification with Ultraviolet Circular Dichroism Spectroscopy: Ternary and Quaternary Phase Diagrams of Levetiracetam.

Chiral molecules are challenging for the pharmaceutical industry because although physical properties of the enantiomers are the same in achiral systems, they exhibit different effects in chiral systems, such as the human body. The separation of enantiomers is desired but complex, as enantiomers crystallize most often as racemic compounds. A technique to enable the chiral separation of racemic compounds is to create an asymmetry in the thermodynamic system by generating chiral cocrystal(s) using a chiral coformer and using the solubility differences to enable separation through crystallization from solution. However, such quaternary systems are complex and require analytical methods to quantify different chiral molecules in solution. Here, we develop a new chiral quantification method using ultraviolet-circular dichroism spectroscopy and multivariate partial least squares calibration models, to build multicomponent chiral phase diagrams. Working on the quaternary system of (R)- and (S)-2-(2-oxopyrrolidin-1-yl)butanamide enantiomers with (S)-mandelic acid in acetonitrile, we measure accurately the full quaternary phase diagram for the first time. By understanding the phase stabilities of the racemic compound and the enantiospecific cocrystal, the chiral resolution of levetiracetam could be designed due to a large asymmetry in overall solubility between both sides of the racemic composition. This new method offers improvements for chiral molecule quantification in complex multicomponent chiral systems and can be applied to other chiral spectroscopy techniques.

Increased stroke severity and mortality in patients with SARS-CoV-2 infection: An analysis from the N3C database.

BACKGROUND: Studies from early in the COVID-19 pandemic showed that patients with ischemic stroke and concurrent SARS-CoV-2 infection had increased stroke severity. We aimed to test the hypothesis that this association persisted throughout the first year of the pandemic and that a similar increase in stroke severity was present in patients with hemorrhagic stroke. METHODS: Using the National Institute of Health National COVID Cohort Collaborative (N3C) database, we identified a cohort of patients with stroke hospitalized in the United States between March 1, 2020 and February 28, 2021. We propensity score matched patients with concurrent stroke and SARS-COV-2 infection and available NIH Stroke Scale (NIHSS) scores to all other patients with stroke in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most factors and exact matching was used for race/ethnicity and site. We modeled stroke severity as measured by admission NIHSS and the outcomes of death and length of stay. We also explored the temporal relationship between time of SARS-COV-2 diagnosis and incidence of stroke. RESULTS: Our query identified 43,295 patients hospitalized with ischemic stroke (5765 with SARS-COV-2, 37,530 without) and 18,107 patients hospitalized with hemorrhagic stroke (2114 with SARS-COV-2, 15,993 without). Analysis of our propensity matched cohort revealed that stroke patients with concurrent SARS-COV-2 had increased NIHSS (Ischemic stroke: IRR=1.43, 95% CI:1.33-1.52, p<0.001; hemorrhagic stroke: IRR=1.20, 95% CI:1.08-1.33, p<0.001), length of stay (Ischemic stroke: estimate = 1.48, 95% CI: 1.37, 1.61, p<0.001; hemorrhagic stroke: estimate = 1.25, 95% CI: 1.06, 1.47, p=0.007) and higher odds of death (Ischemic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001; hemorrhagic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001). We observed the highest incidence of stroke diagnosis on the same day as SARS-COV-2 diagnosis with a logarithmic decline in counts. CONCLUSION: This retrospective observational analysis suggests that stroke severity in patients with concurrent SARS-COV-2 was increased throughout the first year of the pandemic.

Collateral status, hyperglycemia, and functional outcome after acute ischemic stroke.

BACKGROUND: Mixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial. METHODS: In this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment. The primary analysis assessed the degree to which collateral status modified the effect between treatment group and functional outcome as defined by the 90-day modified Rankin Scale score. Logistic regression was used to model the data, with adjustments made for thrombectomy status, age, post-perfusion thrombolysis in cerebral infarction (TICI) score, tissue plasminogen activator (tPA) use, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Five SHINE trial centers contributed data for this analysis. Statistical significance was defined as a p-value < 0.05. RESULTS: Among the 1151 patients in the SHINE trial, 57 with angiographic data were included in this sub-analysis, of whom 19 had poor collaterals and 38 had good collaterals. While collateral status had no effect (p = 0.855) on the association between glucose control treatment group and functional outcome, patients with good collaterals were more likely to have a favorable functional outcome (p = 0.001, OR 5.02; 95% CI 1.37-16.0). CONCLUSIONS: In a post-hoc analysis using a subset of patients with angiographic data enrolled in the SHINE trial, collateral status did not modify the association between glucose control treatment group and functional outcome. However, consistent with prior studies, there was a significant association between good collateral status and favorable outcome in patients with large vessel occlusion stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier is NCT01369069. Registration date is June 8, 2011.

Quantification of hematoma and perihematomal edema volumes in intracerebral hemorrhage study: Design considerations in an artificial intelligence validation (QUANTUM) study.

BACKGROUND: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. METHODS/DESIGN: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method. DISCUSSION: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets.

OBJECTIVES: Self-reported Black (SRB) Americans are approximately twice as likely to have a stroke as self-reported White (SRW) Americans. While social determinants of health and vascular risk factors account for some of the disparity, half the increased risk remains unexplained and may be related to unmeasured real-world factors of the racialized experience. MATERIALS: and Methods In this cohort study, we compared SRB and SRW participants in the Systolic Blood Pressure Intervention Trial (SPRINT) to the same groups in the observational Atherosclerosis Risk in Communities (ARIC) study to evaluate if clinical trial participation mitigates disparities in stroke risk. We set the ARIC baseline at visit 4 and excluded participants with prior stroke to create an ARIC cohort similar in age to SPRINT participants. The study outcome was incident primary stroke. We report hazard ratios from Cox models and inverse-probability weighted Cox models with propensity score matching on participant age, sex, diabetes, atrial fibrillation, and smoking. RESULTS: We included 10,094 patients from ARIC and 8,869 from SPRINT, of which 26.1% were SRB. The risk of stroke between SRW participants in SPRINT versus ARIC was not significantly different (IPW-Weighted HR 0.78 [0.52-1.19]). SRB ARIC participants were twice as likely to have a stroke as SRW ARIC participants (IPW-Weighted HR = 1.96 [1.41-2.71]). However, SRB SPRINT participants did not have higher stroke risk compared to SRW SPRINT or ARIC participants (IPW-Weighted HR 0.99 [0.68--1.77] and 0.95 [.57-1.59], respectively). SRB SPRINT participants in the intensive BP control group had a lower risk of stroke compared to SRB ARIC participants (IPW-Weighted HR = 0.39 [0.20-0.75]). CONCLUSIONS: SRB race, compared to SRW race, is associated with an increase in primary stroke risk in the ARIC study but not in the SPRINT trial. The absence of the racial disparity in stroke incidence in SPRINT indicates that aspects of the disparity are modifiable. Population-based interventions that test this hypothesis deserve further attention.

Effect of Adjusting for Baseline Stroke Severity in the National Inpatient Sample.

[Figure: see text].

Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.

Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol's pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.

Client perceptions of the BreastScreen Australia remote radiology assessment model.

BACKGROUND: Telehealth and teleradiology are increasingly used around the world to facilitate health care provision when the health care provider and clients are separated by distance. The BreastScreen Australia Remote Radiology Assessment Model (RRAM) is an initiative developed to address the challenges of inadequate access to a local radiological workforce in regional Australia. With the growth in telehealth innovations more broadly, the RRAM represents a departure from the traditional onsite model where a radiologist would be co-located with practice staff during assessment clinics. Understanding client satisfaction is an important consideration with new models. This article explores client perceptions of the RRAM including awareness, satisfaction with experiences, confidence in the quality of care being received, and preferences regarding models of service delivery. METHODS: Clients in four BreastScreen services across three Australian states and territories were invited to provide feedback on their experiences of the RRAM. Brief face-to-face interviews based on a survey were conducted at the conclusion of assessment clinic visits. Clients also provided feedback through surveys completed and returned by post, and online. RESULTS: 144 clients completed the survey regarding their experiences of the RRAM. The majority were aged between 50 and 59 years (55/144, 38.2%). Most had attended a BreastScreen service for either screening or assessment on a total of two to five occasions (85/142, 59.9%) in the past. Nearly all women who attended a RRAM clinic expressed satisfaction with their experience (142/143, 99.3%). Clients were aware that the radiologist was working from another location (131/143, 91.6%) and the majority believed there wouldn't be any difference in the care they received between the RRAM and the onsite model (120/142, 84.5%). Clients generally had no particular preference for either the onsite or RRAM model of service delivery. CONCLUSIONS: Clients' high satisfaction with their clinic experiences, high confidence in care being received, and the majority having no preference for either the onsite or remote model indicates their acceptance of the RRAM. Client acceptance of the model supports continuation of the RRAM at these sites and expansion. Findings may inform future telehealth innovations where key health care team members are working remotely.

Black Patients with Ischemic Stroke and Hyperglycemia have Worse outcome than Whites if given Intensive Glucose Control.

BACKGROUND: Hyperglycemia is common after acute ischemic stroke and is associated with worse outcome, but intensive glucose control has not improved outcome. There is also a racial disparity in outcome after stroke, with Black patients more likely to have functional impairment than whites. We aimed to evaluate if there were racial differences in outcomes in acute ischemic stroke patients treated with intensive glucose control. METHODS: We performed a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial to determine if Black patients had worse functional outcome than whites and if standard versus intensive glucose control modified that association. We included non-Hispanic white and Black patients. The primary outcome was excellent functional outcome (90-day modified Rankin Score of 0-1). To account for patient clustering by study site, we fit mixed-effects logistic regression models to our outcome and tested the interaction of treatment and race. RESULTS: We included 895 patients, of which 304 (34%) were Black and 591 (66%) were white. The rate of excellent outcome was 31.6% in Black patients versus 41.0% in white patients (p=0.006). After adjusting for potential confounders, the odds ratio for excellent outcome in Black patients was 0.54 (95% CI 0.38-0.77). The interaction term between treatment and race was significant (p=0.067). In the intensive treatment arm, Black patients had a predicted probability of excellent outcome of 26.4% (20.1-32.8) versus 42.7% (37.6-47.9) for white patients (p<0.001), while in the standard treatment arm the difference was not significant. CONCLUSIONS: Black patients with acute ischemic stroke and hyperglycemia had worse functional outcome at 90 days than white patients, particularly if given intensive glucose control. These findings are from a post-hoc analysis and may be confounded, thus warrant additional study.

Fully Automated Segmentation Algorithm for Perihematomal Edema Volumetry After Spontaneous Intracerebral Hemorrhage.

Background and Purpose- Perihematomal edema (PHE) is a promising surrogate marker of secondary brain injury in patients with spontaneous intracerebral hemorrhage, but it can be challenging to accurately and rapidly quantify. The aims of this study are to derive and internally validate a fully automated segmentation algorithm for volumetric analysis of PHE. Methods- Inpatient computed tomography scans of 400 consecutive adults with spontaneous, supratentorial intracerebral hemorrhage enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) were separated into training (n=360) and test (n=40) datasets. A fully automated segmentation algorithm was derived from manual segmentations in the training dataset using convolutional neural networks, and its performance was compared with that of manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric dice similarity coefficients for the fully automated segmentation algorithm were 0.838±0.294 and 0.843±0.293 with manual and semiautomated segmentation methods as reference standards, respectively. PHE volumes derived from the fully automated versus manual (r=0.959; P<0.0001), fully automated versus semiautomated (r=0.960; P<0.0001), and semiautomated versus manual (r=0.961; P<0.0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 18.0±1.8 seconds/scan) quantified PHE volumes at a significantly faster rate than both of the manual (mean 316.4±168.8 seconds/scan; P<0.0001) and semiautomated (mean 480.5±295.3 seconds/scan; P<0.0001) segmentation methods. Conclusions- The fully automated segmentation algorithm accurately quantified PHE volumes from computed tomography scans of supratentorial intracerebral hemorrhage patients with high fidelity and greater efficiency compared with manual and semiautomated segmentation methods. External validation of fully automated segmentation for assessment of PHE is warranted.

A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development.

As part of on-going efforts to control hookworm infection, the "human hookworm vaccine initiative" has recognised blood feeding as a feasible therapeutic target for inducing immunity against hookworm infection. To this end, molecular approaches have been used to identify candidate targets, such as Necator americanus (Na) haemoglobinase aspartic protease-1 (APR-1), with immunogenicity profiled in canine and hamster models. We sought to accelerate the immune analysis of these identified therapeutic targets by developing an appropriate mouse model. Here we demonstrate that Nippostrongylus brasiliensis (Nb), a phylogenetically distant strongylid nematode of rodents, begins blood feeding early in its development and that immunisation with Na-APR-1 can block its growth and completion of its life cycle. Furthermore, we identify a new haem detoxification pathway in Nb required for blood feeding that can be blocked by drugs of the quinolone family, reducing both infection burden and the associated anaemia in rodents. Collectively, our findings show that haem metabolism has potential as a checkpoint for interrupting hookworm development in early stages of the hookworm life cycle and that the Nippostrongylus brasiliensis rodent model is relevant for identifying novel therapeutic targets against human hookworm.

Re-Engage: A Novel Nurse-Led Program for Survivors of Childhood Cancer Who Are Disengaged From Cancer-Related Care.

BACKGROUND: Survivors of childhood cancer often experience treatment-related chronic health conditions. Survivorship care improves survivors' physical and mental health, yet many are disengaged from care. Innovative models of care are necessary to overcome patient-reported barriers to accessing survivorship care and to maximize survivors' health. METHODS: We piloted a novel survivorship program, called "Re-engage," a distance-delivered, nurse-led intervention aiming to engage, educate, and empower survivors not receiving any cancer-related care. Re-engage involves a nurse-led consultation delivered via telephone/online to establish survivors' medical history and needs. Participants completed questionnaires at baseline, 1 month postintervention, and 6-month follow-up. RESULTS: A total of 27 survivors who had not accessed survivorship care in the last 2 years participated (median age, 31 years; interquartile range [IQR], 27-39 years); of which, 82% were at high-risk for treatment-related complications. Participation in Re-engage was high (75%) and there was no attrition once survivors enrolled. At 1 month postintervention, 92% of survivors reported that Re-engage was "beneficial," which all survivors reported at 6-month follow-up. Survivors' overall satisfaction with their care increased from 52% before Re-engage to 84% at 1 month postintervention. Survivors' mean self-efficacy scores remained similar from baseline to 1 month postintervention (b = -0.33, 95% CI, -1.31 to 0.65), but increased significantly from baseline to 6-month follow-up (b = 1.64, 95% CI, 0.28-3.00). At 6-month follow-up, 73% of survivors showed an increase in health-related self-efficacy compared with baseline. CONCLUSIONS: Re-engage is a highly acceptable and feasible intervention and promotes health-related self-efficacy, which is integral to survivors being advocates for their own health. Further empirical work is needed to evaluate the long-term efficacy of Re-engage. TRIAL REGISTRATION: ACTRN12618000194268.

"From the technology came the idea": safe implementation and operation of a high quality teleradiology model increasing access to timely breast cancer assessment services for women in rural Australia.

Breast cancer is the most commonly diagnosed cancer in Australian women. Providing timely diagnostic assessment services for screen-detected abnormalities is a core quality indicator of the population-based screening program provided by BreastScreen Australia. However, a shortage of local and locum radiologists with availability and appropriate experience in breast work to attend onsite assessment clinics, limits capacity of services to offer assessment appointments to women in some regional centres. In response to identified need, local service staff developed the remote radiology assessment model for service delivery. This study investigated important factors for establishing the model, the challenges and enablers of successful implementation and operation of the model, and factors important in the provision of a model considered safe and acceptable by service providers. METHODS: Semi-structured interviews were conducted with service providers at four assessment services, across three jurisdictions in Australia. Service providers involved in implementation and operation of the model at the service and jurisdictional level were invited to participate. A social constructivist approach informed the analysis. Deductive analysis was initially undertaken, using the interview questions as a classifying framework. Subsequently, inductive thematic analysis was employed by the research team. Together, the coding team aggregated the codes into overarching themes. RESULTS: 55 service providers participated in interviews. Consistently reported enablers for the safe implementation and operation of a remote radiology assessment clinic included: clinical governance support; ability to adapt; strong teamwork, trust and communication; and, adequate technical support and equipment. Challenges mostly related to technology and internet (speed/bandwidth), and maintenance of relationships within the group. CONCLUSIONS: Understanding the key factors for supporting innovation, and implementing new and safe models of service delivery that incorporate telemedicine, will become increasingly important as technology evolves and becomes more accessible. It is possible to take proposed telemedicine solutions initiated by frontline workers and operationalise them safely and successfully: (i) through strong collaborative relationships that are inclusive of key experts; (ii) with clear guidance from overarching bodies with some flexibility for adapting to local contexts; (iii) through establishment of robust teamwork, trust and communication; and, (iv) with appropriate equipment and technical support.

Understandings of dementia in low and middle income countries and amongst indigenous peoples: a systematic review and qualitative meta-synthesis.

Objectives: Dementia is a growing health priority, particularly in less resourced countries and amongst indigenous populations. Understanding cultural meanings ascribed to dementia is an important aspect of policy development and the provision of culturally congruent care and support for people with dementia, their families and the caring professions. This review investigates conceptualizations of dementia amongst indigenous peoples and populations living in low and middle income countries (LMIC), who experience limited diagnosis and formal care for dementia, and how these shape responses to dementia.Methods: A systematic search was conducted for qualitative studies, reported in English, that investigated the perceptions, attitudes or understandings of dementia in LMIC and amongst indigenous populations. A qualitative analysis and meta-synthesis was carried out.Findings: Nineteen articles were included in the review following quality assessment. Dementia was rarely conceptualized as a defined, pathological condition characterized by progressive cognitive decline. Rather, notions of dementia existed within conceptualizations of aging, mental illness, traditional cultural beliefs and the trauma of colonization. Responses to dementia were influenced and perpetuated by community and health providers, and cultural norms for caregiving.Conclusions: There is a need to understand conceptualizations of dementia from the perspective of all stakeholders within a setting, and the dynamic responses that exist between key stakeholders. Community knowledge systems could facilitate understanding about appropriate and acceptable health and community care responses to dementia, and approaches to stigma reduction. Inclusive discussions about dementia are essential if awareness campaigns are to improve the wellbeing of people with dementia and caregivers.