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Background: Models of care that are culturally responsive, trauma-informed and provide continuity of care(r), are important components of care for Aboriginal and Torres Strait Islander parents during the broad perinatal period (pregnancy to 2 years after birth; first 1000 days). Many health services do aim to incorporate these concepts in care provision, but often focus on only one., Aim: To identify practical toolkits that guide implementation of culturally responsive care, trauma-informed care, or continuity of care(r) in the perinatal period, and map the key elements., Methods: A scoping review was conducted. Relevant databases and grey literature were searched to identify toolkits that guided implementation of any one of the aforementioned concepts in the perinatal period. Toolkit context, principles, core components and processes were extracted and synthesised., Findings: Thirteen toolkits, from both Indigenous and non-Indigenous contexts, met the inclusion criteria. Six related to culturally responsive care, nine to trauma-informed care, and eight to continuity of care(r), with some overlap. Key principles included continuity of carer, collaboration, woman (or family) centred care, safety and holistic care. Individualised care, team work, having a safe service environment and continuity of care/r were highlighted as core components. Key processes related to planning, implementation, monitoring and evaluation, and sustainability., Discussion: There are no available resources that support holistic implementation of all three concepts of culturally responsive, trauma-informed continuity of care(r), spanning the first 1000 days, for Aboriginal and Torres Strait Islander families. A synthesised toolkit of key principles, core components and key processes would assist implementation of this., Statement of Significance: Problem: Aboriginal and Torres Strait Islander families experience health inequalities and poorer perinatal outcomes due to a legacy of colonisation and ongoing discrimination., What Is Already Known: Culturally responsive care, trauma-informed care and continuity of care(r) are elements of perinatal care shown to improve outcomes and experiences., What This Paper Adds: This review synthesises key aspects of culturally responsive, trauma-informed and continuity of care(r) models. It highlights the lack of resources to support services implementing models pertaining to these three concepts across the full First 1000 days, for Aboriginal and Torres Strait Islander families., Competing Interests: Declaration of Competing Interest There are no competing interests to declare., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Objectives: We previously demonstrated the potential of radiomics for the prediction of severe histological placenta accreta spectrum (PAS) subtypes using T2-weighted MRI. We aim to validate our model using an additional dataset. Secondly, we explore whether the performance is improved using a new approach to develop a new multivariate radiomics model., Methods: Multi-centre retrospective analysis was conducted between 2018 and 2023. Inclusion criteria: MRI performed for suspicion of PAS from ultrasound, clinical findings of PAS at laparotomy and/or histopathological confirmation. Radiomic features were extracted from T2-weighted MRI. The previous multivariate model was validated. Secondly, a 5-radiomic feature random forest classifier was selected from a randomized feature selection scheme to predict invasive placenta increta PAS cases. Prediction performance was assessed based on several metrics including area under the curve (AUC) of the receiver operating characteristic curve (ROC), sensitivity, and specificity., Results: We present 100 women [mean age 34.6 (±3.9) with PAS], 64 of whom had placenta increta. Firstly, we validated the previous multivariate model and found that a support vector machine classifier had a sensitivity of 0.620 (95% CI: 0.068; 1.0), specificity of 0.619 (95% CI: 0.059; 1.0), an AUC of 0.671 (95% CI: 0.440; 0.922), and accuracy of 0.602 (95% CI: 0.353; 0.817) for predicting placenta increta. From the new multivariate model, the best 5-feature subset was selected via the random subset feature selection scheme comprised of 4 radiomic features and 1 clinical variable (number of previous caesareans). This clinical-radiomic model achieved an AUC of 0.713 (95% CI: 0.551; 0.854), accuracy of 0.695 (95% CI 0.563; 0.793), sensitivity of 0.843 (95% CI 0.682; 0.990), and specificity of 0.447 (95% CI 0.167; 0.667)., Conclusion: We validated our previous model and present a new multivariate radiomic model for the prediction of severe placenta increta from a well-defined, cohort of PAS cases., Advances in Knowledge: Radiomic features demonstrate good predictive potential for identifying placenta increta. This suggests radiomics may be a useful adjunct to clinicians caring for women with this high-risk pregnancy condition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Objective: To assess internet usage among new patients seen by urologists and impact on post-consultation understanding for 4 common conditions: kidney stones, elevated prostate-specific antigen, male voiding, and female voiding., Methods: We performed a prospective study of new urology patients at our diverse urban, academic urology practice for the above conditions over a 1-year period. A voluntary questionnaire assessed patients' internet use related to referred conditions prior to encounters. Questions evaluated quality of information and patient understanding of symptoms/condition at baseline, after online searches, and after their urology visit. A patient-reported Likert scale of 1 (poor) to 10 (excellent) was used and internet "searchers" were compared to "non-searchers.", Results: Two hundred fifteen patients participated. Most respondents were Latino (41%) or Black (35%) and English-speaking (81%). Cohorts comprised 130 searchers (60%) and 85 non-searchers (40%). Searchers were significantly younger (median 53 vs 63 years, P <.001), more likely to have home internet access (P <.001), and more general medical internet use (P <.001). Overall, patients' understanding of visit diagnoses increased after their encounters (median pre-visit rating 5 vs post-visit rating 10). Searchers reported a greater post-visit understanding compared to non-searchers (median rating 10 vs 9, P <.001), and a greater change in understanding from baseline (median +4 vs +3, P = .02)., Conclusion: Internet use is common amongst younger patients referred to urologists and may be associated with improved understanding of their condition after urologic consultation. Continued investigation of patient uses and attitude towards popular online resources can help urologists curate resources to benefit patients and providers alike., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The European Working Group for Abnormally Invasive Placenta proposed a checklist of ultrasound features for the antenatal detection of placenta accreta spectrum (PAS). This study aims to assess the performance of the checklist in identifying histopathologically confirmed PAS cases in a cohort with a high pre-test probability of PAS, and identify if particular features are associated with PAS., Material and Methods: This is a prospective multi-site cohort study conducted between 2018 and 2023. Consecutive patients who underwent ultrasound assessment for suspicion of PAS were included, and the sonographic checklist was completed at the time of ultrasound. Cases were defined as PAS where they had intraoperative findings as described by the International Federation of Gynecology and Obstetrics (FIGO) grading, and histopathological findings for hysterectomy and myometrial resection cases. All non-PAS cases in this study had placenta previa and at least one prior cesarean delivery., Results: Seventy-eight participants met inclusion criteria, of whom 63 (80.7%) were diagnosed with PAS. Cesarean hysterectomy was performed in 49 cases (62.8%). Overall, third-trimester ultrasound performed at a median gestational age of 32 weeks (IQR 30-34 weeks) had a sensitivity of 0.84 (95% CI 0.73 to 0.92) and specificity of 0.73 (95% CI 0.45 to 0.92) for detecting PAS, with a positive and negative likelihood ratio of 3.15 (95% CI 1.35 to 7.35) and 0.22 (95% CI 0.11 to 0.41), respectively. Features most associated with PAS were abnormal placental lacunae (Odds Ratio [OR] 5.40 [95% CI 1.61 to 18.03] and myometrial thinning OR 6.87 [95% CI 1.93 to 24.4]). While many of the ultrasound features seen in PAS were also present in cases of placenta previa with prior Cesarean section, the median (IQR) number of features present in PAS cases was significantly higher than in the non-PAS placenta previa group (six features [3-8] vs. two features [0-3] p = 0.001). No case of non-PAS placenta previa had more than five features present., Conclusions: The use of a standardized sonographic checklist had a high sensitivity and good specificity for the detection of PAS in this prospective cohort of well-classified PAS cases., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Purpose: To document the 2-year mortality and seizure recurrence rate of a prospective cohort of patients identified with status epilepticus (SE)., Methods: Patients presenting to any hospital in the Auckland region between April 6 2015, and April 5 2016, with a seizure lasting 10 min or longer were identified. Follow up was at 2 years post index SE episode via telephone calls and detailed review of clinical notes., Results: We identified 367 patients with SE over the course of one year. 335/367 (91.3 %) were successfully followed up at the 2-year mark. Two-year all-cause mortality was 50/335 (14.9 %), and 49/267 (18.4 %) when febrile SE was excluded. Two-year seizure recurrence was 197/335 (58.8 %). On univariate analyses, children (preschoolers 2 to < 5 years and children 5 to < 15 years), Asian ethnicity, SE duration <30 mins and acute (febrile) aetiology were associated with lower mortality, while older age >60 and progressive causes were associated with higher mortality on both univariate and multivariate analyses. Age < 2 years and acute aetiology were associated with lower seizure recurrence, while non convulsive status epilepticus (NCSE) with coma and a history of epilepsy were associated with higher seizure recurrence. On multivariate analyses, a history of epilepsy, as well as having both acute and remote causes were associated with higher seizure recurrence., Conclusions: All-cause mortality in both the paediatric and adult populations at 2 years was lower than most previous reports. Older age, SE duration ≥30 mins and progressive aetiologies were associated with the highest 2-year mortality, while febrile SE had the lowest mortality. A history of epilepsy, NCSE with coma, and having both acute and remote causes were associated with higher seizure recurrence at 2 years. Future studies should focus on functional measures of outcome and long-term quality of life., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter S Bergin reports financial support was provided by Health Research Council of New Zealand. Stuart R Dalziel reports financial support was provided by Health Research Council of New Zealand. Stuart R Dalziel reports financial support was provided by Cure Kids New Zealand. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Splenic vein aneurysm (SVA) rupture is a rare clinical entity, with few case reports detailing its occurrence during pregnancy. We describe a case of a SVA rupture and present a systematic review of the literature in relation to splenic vein rupture, with or without aneurysm. Our case was of a 30-year-old woman, Para 4 at 37 weeks' gestation who presented with significant abdominal pain and subsequent maternal collapse. Massive intra-abdominal hemorrhage was identified, with splenic vessel rupture suspected. A splenectomy and partial pancreatectomy were performed along with massive blood product transfusion. There was both maternal and fetal survival with no long-term sequelae at follow-up. Histological examination of the spleen and its vessels noted a SVA rupture. In a subsequent systematic review of the literature, we identified 10 cases of splenic vein rupture with only two previously documented cases of SVA rupture in pregnancy. Maternal and fetal survival has only been reported in two cases of splenic vein rupture, with ours being a third., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objectives: The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome., Design: Observational cohort study., Setting: Neurocritical care unit, Cambridge, United Kingdom., Patients: Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS])., Intervention: None., Measurements and Main Results: The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome., Conclusions: Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired., Competing Interests: Dr. Begiri received funding from the Medical Research Council (grant MR N013433-1) and the Gates Cambridge Scholarship. Dr. Bögli received funding from the Swiss National Science Foundation (grant 210839). Dr. Helmy’s institution received funding from the Medical Research Council; they received support for article research from the Research Councils UK. Dr. Smielewski receives part of the licensing fees for ICM+ software, licensed by Cambridge Enterprise Ltd, University of Cambridge, Cambridge. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Pulmonary embolism (PE) is a leading cause of pregnancy-related mortality. CT pulmonary angiogram (CTPA) is the first-line advanced imaging modality for suspected PE in pregnancy at institutes offering low-dose techniques; however, a protocol balancing safety with low dose remains undefined. The wide range of CTPA doses reported in pregnancy suggests a lack of confidence in implementing low-dose techniques in this group., Purpose: To define and validate the safety, radiation dose and image quality of a low-dose CTPA protocol optimised for pregnancy., Materials and Methods: The OPTICA study is a prospective observational study. Pregnant study participants with suspected PE underwent the same CTPA protocol between May 2018 and February 2022. The primary outcome, CTPA safety, was judged by the reference standard; the 3-month incidence of venous thromboembolism (VTE) in study participants with a negative index CTPA. Secondary outcomes defined radiation dose and image quality. Absorbed breast, maternal effective and fetal doses were estimated by Monte-Carlo simulation on gestation-matched phantoms. Image quality was assessed by signal-to-noise and contrast-to-noise ratios and a Likert score for pulmonary arterial enhancement., Results: A total of 116 CTPAs were performed in 113 pregnant women of which 16 CTPAs were excluded. PE was diagnosed on 1 CTPA and out-ruled in 99. The incidence of recurrent symptomatic VTE was 0.0% (one-sided 95% CI, 2.66%) at follow-up. The mean absorbed breast dose was 2.9 ± 2.1mGy, uterine/fetal dose was 0.1 ± 0.2mGy and maternal effective dose was 1.4 ± 0.9mSv. Signal-to-noise ratio (SNR) was 11.9 ± 3.7. Contrast-to-noise ratio (CNR) was 10.4 ± 3.5., Conclusion: The OPTICA CTPA protocol safely excluded PE in pregnant women across all trimesters, with low fetal and maternal radiation., Clinical Relevance: OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) is the first prospective study to define the achievable radiation dose, image-quality and safety of a low-dose CT pulmonary angiogram protocol optimised for pregnancy (NCT04179487). It provides the current benchmark for safe and achievable CT pulmonary angiogram doses in the pregnant population., Key Points: • Despite the increased use of CT pulmonary angiogram in pregnancy, an optimised low-dose protocol has not been defined and reported doses in pregnancy continue to vary widely. • The OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) study prospectively defines the achievable dose, image quality and safety of a low-dose CT pulmonary angiogram protocol using widely available technology. • OPTICA provides a benchmark for safe and achievable CT pulmonary angiogram doses in the pregnant population., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days (DAOH-90), which measures survival, time spent in hospital or rehabilitation settings, readmission and institutionalization, is an objective outcome measure that can be obtained from large administrative data sets without the need for patient contact. We aimed to assess the comparability of DAOH with mRS and its relationship with other prognostic variables after acute stroke reperfusion therapy., Methods and Results: Consecutive patients with ischemic stroke treated with intravenous thrombolysis or endovascular thrombectomy were analyzed. DAOH-90 was calculated from a national minimum data set, a mandatory nationwide administrative database. mRS score at day 90 (mRS-90) was assessed with in-person or telephone interviews. The study included 1278 patients with ischemic stroke (714 male, median age 70 [59-79], median National Institutes of Health Stroke Scale score 14 [9-20]). Median DAOH-90 was 71 [29-84] and median mRS-90 score was 3 [2-5]. DAOH-90 was correlated with admission National Institutes of Health Stroke Scale score (Spearman rho -0.44, P <0.001) and Alberta Stroke Program Early CT [Computed Tomography] Score (Spearman rho 0.24, P <0.001). There was a strong association between mRS-90 and DAOH-90 (Spearman rho correlation -0.79, P <0.001). Area under receiver operating curve for predicting mRS score >0 was 0.86 (95% CI, 0.84-0.88), mRS score >1 was 0.88 (95% CI, 0.86-0.90) and mRS score >2 was 0.90 (95% CI, 0.89-0.92)., Conclusions: In patients with stroke treated with reperfusion therapies, DAOH-90 shows reasonable comparability to the more established outcome measure of mRS-90. DAOH-90 can be readily obtained from administrative databases and therefore has the potential to be used in large-scale clinical trials and comparative effectiveness studies.

Aim: Private practice is one of the most rapidly growing, but under-researched employment sectors for graduate dietitians in Australia, limiting evidence-based workforce development. This scoping review examines existing international literature to gain an understanding of the current private practice workforce size, distribution, demography and workforce development considerations, including competencies, supply and demand, remuneration and professional development activities., Methods: The databases MEDLINE, EMBASE, CINAHL, EMCARE, PsycInfo (Ovid) and grey literature were systematically searched in August 2023 using key search terms to identify studies for inclusion. Articles were included if they related to private practice dietetics and described an aspect of workforce. Original research, government and organisational reports, statements of practice and websites providing governmental or organisational statistics were included. A directed content analysis and qualitative constant comparison technique were used to deductively map intelligence sources against a workforce development framework. A gap analysis was also conducted to provide a focus for future workforce development research., Results: A total of 72 peer-reviewed and grey literature sources were included, with 65% of the studies being Australian-based publications. Private practice dietetics research interest has increased in the last decade. Despite a breadth of published sources, this review found little published data on workforce size, distribution, demography, supply, demand, continued professional development and remuneration, indicating a significant gap in the evidence base. Existing literature focuses on workforce challenges and barriers, the work of private practice dietitians, with limited exploration of competency requirements for graduate private practitioners., Conclusions: The literature on the private practice dietetics workforce is lacking worldwide, which constrains evidenced-based workforce development initiatives. Workforce development research across all workforce aspects is warranted to address current evidence gaps., (© 2024 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.)

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To compare loop gain (LG) before and during pharmacological increases in cerebral blood flow (CBF) at high altitude (HA). Loop gain (LG) describes stability of a negative-feedback control system; defining the magnitude of response to a disturbance, such as hyperpnea to an apnea in periodic breathing (PB). "Controller-gain" sensitivity from afferent peripheral (PCR) and central-chemoreceptors (CCR) plays a key role in perpetuating PB. Changes in CBF may have a critical role via effects on central chemo-sensitivity during sleep., Methods: Polysomnography (PSG) was performed on volunteers after administration of I.V. Acetazolamide (ACZ-10mg/kg) + Dobutamine (DOB-2-5 μg/kg/min) to increase CBF (via Duplex-ultrasound). Central sleep apnea (CSA) was measured from NREM sleep. The duty ratio (DR) was calculated as ventilatory duration (s) divided by cycle duration (s) (hyperpnea/hyperpnea + apnea), LG = 2π/(2πDR-sin2πDR)., Results: A total of 11 volunteers were studied. Compared to placebo-control, ACZ/DOB showed a significant increase in the DR (0.79 ± 0.21 vs 0.52 ± 0.03, P = 0.002) and reduction in LG (1.90 ± 0.23 vs 1.29 ± 0.35, P = 0.0004). ACZ/DOB increased cardiac output (CO) (8.19 ± 2.06 vs 6.58 ± 1.56L/min, P = 0.02) and CBF (718 ± 120 vs 526 ± 110ml/min, P < 0.001). There was no significant change in arterial blood gases, minute ventilation (VE), or hypoxic ventilatory response (HVR). However, there was a reduction of hypercapnic ventilatory response (HCVR) by 29% (5.9 ± 2.7 vs 4.2 ± 2.8 L/min, P = 0.1)., Conclusion: Pharmacological elevation in CBF significantly reduced LG and severity of CSA. We speculate the effect was on HCVR "controller gain," rather than "plant gain," because PaCO 2 and VE were unchanged. An effect via reduced circulation time is unlikely, as the respiratory-cycle length did not change., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

As large-scale disasters continue to become increasingly common worldwide, nursing homes, whose residents are more vulnerable to disaster-related health and psychosocial shocks, and their staff, are carrying progressively more responsibility for health care readiness practices. Implementation science is a research discipline that seeks to improve uptake of evidence-based practices, such as health care readiness planning, and thus has potential to improve nursing home care delivery during and after disasters. We describe the limited field of existing evidence-based strategies in the peer-reviewed literature that seek to advance health care readiness in the nursing home setting and illustrate how implementation science can better support health care readiness planning for nursing homes. We rest on 3 main themes: (1) implementation science frameworks can strengthen nursing home staff engagement around health care readiness; (2) implementation science can support tailoring of emergency preparedness plans to individual nursing homes' unique needs; and (3) implementation science can advance the integration of nursing homes into local, state, and federal health care readiness planning initiatives. Finally, research is urgently needed to both generate and disseminate implementation strategies that increase uptake of evidence-based health care readiness practices in the nursing home setting., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.)

Introduction: PRx can be used as surrogate measure of Cerebral Autoregulation (CA) in traumatic brain injury (TBI) patients. PRx can provide means for individualising cerebral perfusion pressure (CPP) targets, such as CPPopt. However, a recent Delphi consensus of clinicians concluded that consensus could not be reached on the accuracy, reliability, and validation of any current CA assessment method., Research Question: We aimed to quantify the short-term uncertainty of PRx time-trends and to relate this to other physiological measurements., Material and Methods: Intracranial pressure (ICP), arterial blood pressure (ABP), end-tidal CO 2 (EtCO 2 ) high-resolution recordings of 911 TBI patients were processed with ICM + software. Hourly values of metrics that describe the variability within modalities derived from ABP, ICP and EtCO 2 , were calculated for the first 24h of neuromonitoring. Generalized additive models were used to describe the time trend of the variability in PRx. Linear correlations were studied for describing the relationship between PRx variability and the other physiological modalities., Results: The time profile of variability of PRx decreases over the first 12h and was higher for average PRx ∼0. Increased variability of PRx was not linearly linked with average ABP, ICP, or CPP. For coherence between slow waves of ABP and ICP >0.7, the variability in PRx decreased (R = -0.47, p < 0.001)., Discussion and Conclusion: PRx is a highly variable parameter. PRx short-term dispersion was not related to average ICP, ABP or CPP. The determinants of uncertainty of PRx should be investigated to improve reliability of individualised CA assessment in TBI patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Smielewski, Marek Czosnyka has patent with royalties paid to Cambridge Enterprise Ltd, University of Cambridge, Cambridge., (© 2024 The Authors.)

Venous thromboembolism (VTE) is still reported as the leading cause of direct maternal death in pregnancy in serial international reports in developed countries. VTE risk is higher during pregnancy but is further increased by additional well-characterized risk factors. International guidelines recommend that formal VTE risk assessment should be conducted at least in early pregnancy, at delivery and when risk factors change. High quality data supporting optimal VTE prevention strategies are lacking, outside the setting of prevention of VTE recurrence. Moreover, recent high-quality studies have provided much-needed data on diagnostic strategies for pulmonary embolism (PE) in pregnancy. In this review, we summarize knowledge gaps and recently published data in the prevention and diagnosis of VTE in pregnancy. Moreover, we describe ongoing high-quality randomised trials and prospective clinical management studies in this area. High quality clinical studies and trials in pregnancy can be done and must be prioritised, through international network efforts and national funding advocacy. Ultimately, translation of study results to impact upon guidelines and policy will deliver better care to and will protect the lives and health of pregnant people and those contemplating pregnancy throughout the world., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FNA: IIS awarded to institution (current); Bayer, Daiichi-Sankyo. Consultancy (paid to institution); Boston Scientific. FNA, JD and BC: Grant funding through HRB Definitive Interventions and Feasibility Awards (DIFA) 2017 (DIFA-2017-040)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background Mirai, a state-of-the-art deep learning-based algorithm for predicting short-term breast cancer risk, outperforms standard clinical risk models. However, Mirai is a black box, risking overreliance on the algorithm and incorrect diagnoses. Purpose To identify whether bilateral dissimilarity underpins Mirai's reasoning process; create a simplified, intelligible model, AsymMirai, using bilateral dissimilarity; and determine if AsymMirai may approximate Mirai's performance in 1-5-year breast cancer risk prediction. Materials and Methods This retrospective study involved mammograms obtained from patients in the EMory BrEast imaging Dataset, known as EMBED, from January 2013 to December 2020. To approximate 1-5-year breast cancer risk predictions from Mirai, another deep learning-based model, AsymMirai, was built with an interpretable module: local bilateral dissimilarity (localized differences between left and right breast tissue). Pearson correlation coefficients were computed between the risk scores of Mirai and those of AsymMirai. Subgroup analysis was performed in patients for whom AsymMirai's year-over-year reasoning was consistent. AsymMirai and Mirai risk scores were compared using the area under the receiver operating characteristic curve (AUC), and 95% CIs were calculated using the DeLong method. Results Screening mammograms ( n = 210 067) from 81 824 patients (mean age, 59.4 years ± 11.4 [SD]) were included in the study. Deep learning-extracted bilateral dissimilarity produced similar risk scores to those of Mirai (1-year risk prediction, r = 0.6832; 4-5-year prediction, r = 0.6988) and achieved similar performance as Mirai. For AsymMirai, the 1-year breast cancer risk AUC was 0.79 (95% CI: 0.73, 0.85) (Mirai, 0.84; 95% CI: 0.79, 0.89; P = .002), and the 5-year risk AUC was 0.66 (95% CI: 0.63, 0.69) (Mirai, 0.71; 95% CI: 0.68, 0.74; P < .001). In a subgroup of 183 patients for whom AsymMirai repeatedly highlighted the same tissue over time, AsymMirai achieved a 3-year AUC of 0.92 (95% CI: 0.86, 0.97). Conclusion Localized bilateral dissimilarity, an imaging marker for breast cancer risk, approximated the predictive power of Mirai and was a key to Mirai's reasoning. © RSNA, 2024 Supplemental material is available for this article See also the editorial by Freitas in this issue.

In response to growing concerns surrounding the relationship between climate change and escalating flood risk, there is an increasing urgency to develop precise and rapid flood prediction models. Although high-resolution flood simulations have made notable advancements, they remain computationally expensive, underscoring the need for efficient machine learning surrogate models. As a result of sparse empirical observation and expensive data collection, there is a growing need for the models to perform effectively in 'small-data' contexts, a characteristic typical of many scientific problems. This research combines the latest developments in surrogate modelling and physics-informed machine learning to propose a novel Physics-Informed Neural Network-based surrogate model for hydrodynamic simulators governed by Shallow Water Equations. The proposed method incorporates physics-based prior information into the neural network structure by encoding the conservation of mass into the model without relying on calculating continuous derivatives in the loss function. The method is demonstrated for a high-resolution inland flood simulation model and a large-scale regional tidal model. The proposed method outperforms the existing state-of-the-art data-driven approaches by up to 25 %. This research demonstrates the benefits and robustness of physics-informed approaches in surrogate modelling for flood and hydroclimatic modelling problems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Amyloid precursor protein (APP) is a brain-rich, single pass transmembrane protein that is proteolytically processed into multiple products, including amyloid-beta (Aβ), a major driver of Alzheimer disease (AD). Although both overexpression of APP and exogenously delivered Aβ lead to changes in sleep, whether APP processing plays an endogenous role in regulating sleep is unknown. Here, we demonstrate that APP processing into Aβ40 and Aβ42 is conserved in zebrafish and then describe sleep/wake phenotypes in loss-of-function appa and appb mutants. Larvae with mutations in appa had reduced waking activity, whereas larvae that lacked appb had shortened sleep bout durations at night. Treatment with the γ-secretase inhibitor DAPT also shortened night sleep bouts, whereas the BACE-1 inhibitor lanabecestat lengthened sleep bouts. Intraventricular injection of P3 also shortened night sleep bouts, suggesting that the proper balance of Appb proteolytic processing is required for normal sleep maintenance in zebrafish., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature., Objective: To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS., Methods: From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing., Results: For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted., Conclusion: In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function of neurons as well as of myelin sheaths. Accumulated evidence shows that aerobic type of exercise can enhance neuroplasticity in mouse models of AD. However, whether and how aerobic exercise can affect myelin sheath repair and neuroprotection in the AD models remains unclear. In this study we tested the hypotheses that 1) myelin structural alterations in 3xTg-AD mice would be related to abnormalities in oligodendrocyte lineage cells, resulting in impaired learning and memory, and 2) a 6-month aerobic exercise intervention would have beneficial effects on such alterations. Two-month-old male 3xTg-AD mice were randomly assigned to a control (AC) or an exercise (AE) group, and age-matched male C57BL/6;129 mice were also randomly assigned to a normal control (NC) or an exercise (NE) group, with n = 12 in each group. Mice in the exercise groups were trained on a motor-drive treadmill, 60 min per day, 5 days per week for 6 months. Cognitive function was assessed at the end of the intervention period. Then, brain specimens were obtained for assessments of morphological and oligodendrocyte lineage cell changes. The results of electron microscopy showed that myelin ultrastructure demonstrated a higher percentage of loose and granulated myelin sheath around axons in the temporal lobe in the AC, as compared with the NC group, along with greater cognitive dysfunction at 8-months of age. These differences were accompanied by significantly greater myelin basic protein (MBP) expression and less neuron-glial antigen-2 (NG2) protein and mRNA levels in the AC, compared to the NC. However, there were no significant between-group differences in the G-ratio (the ratio of axon diameter to axon plus myelin sheath diameter) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) protein and mRNA levels. The aerobic exercise ameliorated cognitive deterioration and appeared to keep components of myelin sheath and oligodendrocyte precursor cells stabilized, resulting in a decrease in the percentage of loose and granulated myelin sheath and MBP protein, and an increase in NG2 protein and mRNA levels in the AE group. Therefore, the 6-month exercise intervention demonstrated beneficial effects on myelin lesions, abnormal differentiation of oligodendrocytes and general brain function in the 3xTg-AD mice, providing further insights into the role of aerobic exercise in management of neurodegeneration in AD by maintaining intact myelination., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adolescents with intellectual and developmental disabilities (IDD) experience overweight and obesity (OW/OB) up to 1.8 times the rate of their typically developing peers. Parents may influence adolescent weight management behaviors in this population, but the association between parent factors and adolescent weight management behaviors is unclear., Objective: To examine the associations between parent BMI and sociodemographic characteristics with adolescents' BMI, diet quality, daily energy intake, moderate to vigorous physical activity (MVPA), and sedentary behavior., Methods: This study analyzed baseline data from an 18-month randomized controlled weight loss trial for adolescents with IDD. We assessed parent BMI (kg/m 2 ) and sociodemographic factors, and adolescent BMI z-score, MVPA, sedentary time, daily energy intake, and diet quality. Associations between parent and adolescent factors were assessed with Pearson, Spearman or Kendall Tau-b correlations; mean differences for categorical outcomes were assessed with independent samples t-tests/Mann-Whitney U tests or ANOVA/Kruskall-Wallis tests., Results: Ninety-five adolescent and parent dyads were included. Parent BMI was positively correlated with adolescent BMI z-score (n = 94: r s  = 0.37, p < 0.01). Household income was inversely correlated with adolescent BMI z-score (n = 95: T b  = -0.18, p = 0.02). Parents with less than a bachelor's degree had adolescents with higher BMI z-scores than those with bachelor's or higher (2.1 ± 0.5 vs. 1.8 ± 0.5, p = 0.02) as well as higher sedentary behavior (n = 28, 515.2 ± 102.6 min/day vs. n = 40, 463.9 ± 148.1 min/day, p = 0.02)., Conclusion: We found parent BMI, income, and education associated with adolescent BMI z-score. These findings contribute to the sparse literature on parental factors associated with OW/OB in this population., Clinical Trials Number: NCT02561754., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Placenta accreta spectrum (PAS) is a rare, life-threatening complication of pregnancy. Predicting PAS severity is critical to individualise care planning for the birth. We aim to explore whether radiomic analysis of T2-weighted magnetic resonance imaging (MRI) can predict severe cases by distinguishing between histopathological subtypes antenatally., Methods: This was a bi-centre retrospective analysis of a prospective cohort study conducted between 2018 and 2022. Women who underwent MRI during pregnancy and had histological confirmation of PAS were included. Radiomic features were extracted from T2-weighted images. Univariate regression and multivariate analyses were performed to build predictive models to differentiate between non-invasive (International Federation of Gynecology and Obstetrics [FIGO] grade 1 or 2) and invasive (FIGO grade 3) PAS using R software. Prediction performance was assessed based on several metrics including sensitivity, specificity, accuracy and area under the curve (AUC) at receiver operating characteristic analysis., Results: Forty-one women met the inclusion criteria. At univariate analysis, 0.64 sensitivity (95% confidence interval [CI] 0.0-1.00), specificity 0.93 (0.38-1.0), 0.58 accuracy (0.37-0.78) and 0.77 AUC (0.56-.097) was achieved for predicting severe FIGO grade 3 PAS. Using a multivariate approach, a support vector machine model yielded 0.30 sensitivity (95% CI 0.18-1.0]), 0.74 specificity (0.38-1.00), 0.58 accuracy (0.40-0.82), and 0.53 AUC (0.40-0.85)., Conclusion: Our results demonstrate a predictive potential of this machine learning pipeline for classifying severe PAS cases., Relevance Statement: This study demonstrates the potential use of radiomics from MR images to identify severe cases of placenta accreta spectrum antenatally., Key Points: • Identifying severe cases of placenta accreta spectrum from imaging is challenging. • We present a methodological approach for radiomics-based prediction of placenta accreta. • We report certain radiomic features are able to predict severe PAS subtypes. • Identifying severe PAS subtypes ensures safe and individualised care planning for birth., (© 2023. European Society of Radiology (ESR).)

Objectives: There is substantial immunological evidence that vaccination following natural infection increases protection. We compare the humoral immune response developed in initially seropositive individuals (naturally infected) to humoral hybrid immune response (developed after infection and vaccination) in the same population group after one year., Methods: The study included 197 male individuals who were naturally infected with SARS-CoV-2 and then vaccinated with SARS-CoV-2 vaccine. Trimeric spike, nucleocapsid, and ACE2-RBD blocking antibodies for SARS-CoV-2 were measured. Nasal swabs were collected for SARS-CoV-2 PCR testing. Information on vaccination against SARS-CoV-2 and PCR verified infection was retrieved from official databases (Abu Dhabi Health Data Services- SP LLC. ("Malaffi"), including number of vaccine doses received, date of vaccination, and type of the received vaccine., Results: All the study population were tested PCR-Negative at the time of sample collection. Our results showed that there was a significant rise in the mean (SD) and median (IQR) titers of trimeric spike, nucleocapsid and ACE2-RBD blocking antibodies in the post-vaccination stage. The mean (± SD) and median (IQR) concentration of the anti-S antibody rose by 3.3-fold (+230% ± 197% SD) and 2.8-fold (+185%, 220-390%, p<0.001), respectively. There was an observed positive dose-response relationship between number of the received vaccine doses and having higher proportion of study participants with higher than median concentration in the difference between the measured anti-S and ACE2-RBD blocking antibodies in the post-vaccination compared to pre-vaccination., Conclusion: Our study demonstrates that COVID-19 vaccination post natural infection elicits a robust immunological response with an impressive rise of SARS-CoV-2 antibodies, especially the ACE2-RBD blocking antibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 AbdelWareth, Alhousani, Abuyadek, Donnelly, Leinberger-Jabari, Atef and Al-Rifai.)

Background: Psychosocial factors have been informally associated with Chronic Spontaneous Urticaria (CSU); however, the relationship between psychosocial factors and CSU remains relatively unexplored in the scientific literature., Objective: This review aims to provide an evaluation of peer reviewed studies exploring psychosocial factors and CSU., Methods: A systematic search was performed over four databases identifying studies exploring psychosocial factors in relation to CSU published between the years 1995 and 2022., Results: Eighteen studies were included for narrative analysis, and 33 psychosocial factors were identified. These were split into two subgroups: psychosocial factors that were associated with CSU symptoms aggravation/onset (n = 20), and psychosocial factors expected to be impacted by CSU symptoms (n = 13)., Conclusion: This review has highlighted a need for more research and interventions to support individuals with psychosocial factors involved in CSU., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The primary objective was to determine the financial resources allocated to docusate at a representative U.S. tertiary care center. Secondary objectives included comparing docusate utilization between two tertiary care centers, and exploring alternative uses for the funds spent on docusate., Methods: The study population included all patients 18 years and older admitted to University Hospital in Newark, New Jersey. Every scheduled docusate prescription for the study population between January 1 st , 2015 and December 31 st , 2019 was collected. The annual total cost associated with docusate use per year was calculated. The 2015 data from this study and a 2015 McGill University Health Centre study were compared. Also, alternative uses for the money utilized on docusate were assessed., Results: Over the study period, 37,034 docusate prescriptions and 265,123 docusate doses were recorded. The average cost of prescribing docusate was $25,624.14 per year and $49.37 per hospital bed per year. A comparison between the 2015 data of University Hospital and McGill showed that McGill prescribed 107 doses and spent $10.09 more per hospital bed than University Hospital. Finally, alternative uses for the average yearly spending on docusate equated to 0.35 the salary of a nurse, 0.51 the salary of a secretary, 20.66 colonoscopies, 27.00 upper endoscopies, 186.71 mammograms, 1,399.37 doses of polyethylene glycol 3350, 3,826.57 doses of lactulose, or 4,583.80 doses of psyllium., Conclusion: A single average size tertiary care hospital spent about $25,000 yearly on docusate despite its lack of clinical effectiveness. While this amount is small compared to an overall hospital budget, when considering likely comparable docusate use at the U.S's 6,090 hospitals, the economic burden of docusate becomes significant. The funds currently being used on docusate could be redirected to alternative, more cost-effective purposes.

Medicines stewardship refers to coordinated strategies and interventions to optimise medicines use, usually within a specific therapeutic area. Medicines stewardship programs can reduce variations in practice and improve patient outcomes. Therapeutic domains for medicines stewardship are chosen to address frequently used drug classes associated with a high risk of adverse outcomes. Some examples include antimicrobial, opioid analgesic, anticoagulation and psychotropic stewardship. Common elements of successful stewardship programs include multidisciplinary leadership, stakeholder engagement, tailored communication strategies, behavioural changes, implementation science methodologies, and ongoing program monitoring, evaluation and reporting. Medicines stewardship is a continual quality improvement process that requires ongoing support and resources, as well as clinician and consumer engagement, to remain sustainable. It is critical for hospital-based medicines stewardship programs to consider impacts on care in the community when making and communicating changes to patient therapy. This ensures that stewardship efforts are sustained across transitions of care., Competing Interests: Conflicts of interest: David Liew is a member of the Drug Utilisation Subcommittee of the Pharmaceutical Benefits Advisory Committee., ((c) Therapeutic Guidelines.)

Objective: Cerebrovascular autoregulation impairment has been associated with stroke risk in cardiac surgery. We hypothesized that greater arterial emboli exposure in open-chamber surgery might promote dysautoreguation., Methods: Forty patients underwent closed or open-chamber surgery. Transcranial Doppler detected emboli and measured bilateral middle cerebral artery flow velocities. Cerebral autoregulation was assessed by averaging the mean velocity index ("Mx," a continuous moving correlation between cerebral blood flow velocity and mean arterial pressure) over 30 min before and after aortic cross-clamp removal., Results: Median (interquartile range) emboli counts were 775 (415, 1211) and 2664 (793, 3734) in the closed-chamber and open-chamber groups. Most appeared after the removal of the aortic cross-clamp (open-chamber 1631 (606, 2296)), (closed-chamber 229 (142, 384)), with emphasis on the right hemisphere (open-chamber: 826 (371, 1622)), (closed-chamber 181 (66, 276)). Linear mixed model analyses of mean velocity index change showed no significant overall effect of group (0.08, 95% CI: -0.04, 0.21; p = 0.19) or side (0.01, 95% CI: -0.03, 0.05; p = 0.74). There was an interaction between group and side ( p = 0.001), manifesting as a greater increase in mean velocity index in the right hemisphere in the open than the closed group (mean difference: 0.15, 95% CI: 0.02, 0.27; p = 0.03)., Conclusions: Overall, change in mean velocity index before and after cross-clamp removal did not differ between groups. However, most emboli entered the right cerebral hemisphere where this change was significantly greater in the open-chamber group, suggesting a possible association between embolic exposure and dysautoregulation.

Background: A previous retrospective single-centre study suggested that the percentage of time spent with cerebral perfusion pressure (CPP) below the individual lower limit of reactivity (LLR) is associated with mortality in traumatic brain injury (TBI) patients. We aim to validate this in a large multicentre cohort., Methods: Recordings from 171 TBI patients from the high-resolution cohort of the CENTER-TBI study were processed with ICM+ software. We derived LLR as a time trend of CPP at a level for which the pressure reactivity index (PRx) indicates impaired cerebrovascular reactivity with low CPP. The relationship with mortality was assessed with Mann-U test (first 7-day period), Kruskal-Wallis (daily analysis for 7 days), univariate and multivariate logistic regression models. AUCs (CI 95%) were calculated and compared using DeLong's test., Results: Average LLR over the first 7 days was above 60 mmHg in 48% of patients. %time with CPP < LLR could predict mortality (AUC 0.73, p =  < 0.001). This association becomes significant starting from the third day post injury. The relationship was maintained when correcting for IMPACT covariates or for high ICP., Conclusions: Using a multicentre cohort, we confirmed that CPP below LLR was associated with mortality during the first seven days post injury., (© 2023. The Author(s).)

Background Cystic Fibrosis (CF) is an autosomal recessive inherited multi-system disease that primarily affects the lungs and digestive system. New drug therapies and treatments are improving the lives of many people with CF. With improved life expectancy and increased quality of life, many people with CF are now contemplating parenthood and becoming pregnant, an aspiration that decades ago was almost unheard of. Given this quickly evolving and more positive health landscape, it is vital to understand how people with CF experience the care they receive whilst accessing and utilising fertility and maternity services. It is also important to explore the experiences of healthcare professionals involved in providing care during this period. The overall aim of the mixed-methods systematic review will be to explore the barriers and enablers experienced by people with CF and the healthcare professionals involved in their care in the pre-conception to post-partum period. Methods The proposed review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for convergent integrated mixed methods systematic reviews. A systematic search of Medline (Ebsco), Cinahl, Embase, APA PsychINFO and Cochrane Library from inception to February 2022 will be conducted. Quantitative, qualitative and mixed methods studies pertaining to the experience of pre-conception to post-partum care for people with CF and their healthcare professionals will be included. Two independent reviewers will screen titles, abstracts and full texts with disagreements being resolved by a third reviewer. Conclusion This review will help to determine the potential barriers and facilitators experienced by people with Cystic Fibrosis and the health care professionals involved in their care during the pre-conception to post-partum period. The results will be of benefit specifically to the CF population and their healthcare providers when planning further studies in the area of fertility and pregnancy for this population and when delivering care., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Balfe J et al.)

Objective: to evaluate fetal growth in pregnancies complicated by placenta accreta spectrum (PAS) and to compare fetal growth between cases stratified by ultrasound stage of PAS., Methods: This was a prospective multicenter cohort study of women diagnosed with PAS between January 2018 and December 2021. We grouped participants into cases by ultrasound stage (PAS stage 1-3) and controls (PAS0). Fetal growth centiles at three timepoints with median gestational ages of 21 ± 1 weeks (interquartile range [IQR], 20 ± 1-22 ± 0 weeks), 28 ± 0 weeks (IQR, 27 ± 0-28 ± 5 weeks), and 33 ± 0 weeks (IQR, 32 ± 1-34 ± 0 weeks) and birth weight centiles were compared between cases and controls and between those with PAS stratified by ultrasound stage., Results: A total of 53 women met inclusion criteria, with a mean age of 37 years (standard deviation, ±4.0 years) and body mass index of 27 kg/m 2 (standard deviation, ±5.8 kg/m 2 ). Median (IQR) fetal weight centiles were around the 50th centile at each timepoint, with no difference between groups. The incidence of small for gestational age (birth weight ≤ 10th percentile) and large for gestational age (birth weight ≥ 90th percentile) was 11.3% (n = 6) and 15.1% (n = 8), respectively, with no differences by ultrasound stage. The median birth weight centile was 64 (IQR, 26-85), with no differences between cases and controls or by ultrasound stage., Conclusions: In our cohort, a diagnosis of PAS was not associated with fetal growth restriction., (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Parturients with vascular Ehlers-Danlos syndrome are at particular risk of hemorrhage, and there is little evidence to guide prevention or management of hemorrhage in these patients. We present the case of a patient with vascular Ehlers-Danlos syndrome who had a cesarean delivery complicated by an intraoperative hemorrhage. Administration of desmopressin and tranexamic acid appeared to be of marked benefit in achieving hemostasis. To the best of our knowledge, this is the first report of the use of desmopressin during major obstetric hemorrhage in vascular Ehlers-Danlos syndrome., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

We conducted a retrospective study to determine the incidence and frequency of different subtypes of encephalitis in patients aged 15 and older in the Auckland and Northland regions of New Zealand between 2009 and 2018. Residents in Auckland and Northland presenting with encephalitis between 2009 and 2018 were identified from three overlapping databases: positive cerebrospinal fluid (CSF) viral polymerase chain reaction (PCR) tests, CSF neuronal antibody requests, and CSF neuronal antibody tests sent overseas. A diagnosis of autoimmune encephalitis required fulfilment of diagnostic criteria published by Graus and colleagues (2016). One hundred and thirty-six (69, 50.7% female) patients met study inclusion criteria. The median age was 59 (range 15-92). The annual incidence was 1.10 cases per 100,000 person-years. Of these 136 patients, 56 (41.2%) had an infectious aetiology, with varicella zoster (26, 46.4%) and herpes simplex (23, 41.1%) being the most common agents. Autoimmune encephalitis was diagnosed in 32 patients (23.5%). LGI-1 antibody was the most commonly identified neuronal autoantibody (10 patients, 13.2%). Forty-eight patients (35.3%) had encephalitis of unknown cause. In-hospital mortality for infectious encephalitis was 12.5%, autoimmune encephalitis 6.3%, and encephalitis of unknown cause 10.4%. Compared to a previous analysis of encephalitis in adults in Auckland, the incidence of encephalitis and autoimmune encephalitis had increased. The proportion of patients with an unknown cause for encephalitis had decreased., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The objective of this multihospital study was to investigate how the intervention of coaching to bedside shift report (BSR) correlates with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) outcomes and relates to Centers for Medicare and Medicaid Services (CMS) Hospital Value-Based Purchasing (VBP) Program points over a 4-year period (2017-2020) for an acute care hospital health system., Background: Hospital leaders' responsibilities include intertwined areas of patient experience and fiscal accountability. Coaching to BSR is reported to have numerous benefits to the patient's experience. Published studies completed with hospital systems evaluating the intervention of coaching to BSR and how it correlated to patient experience and VBP are limited., Methods: Coaching to BSR was implemented at 16 adult acute care hospitals. Patient-reported BSR rates were collected in tandem with HCAHPS for 4 years. Statistical correlations were assessed between patient-reported BSR and HCAHPS and consequential effect on VBP dimension scores., Results: Coaching to BSR had a significant impact on top- and bottom-box "rate the hospital" HCAHPS scores at a system and hospital level. Value-based purchasing points and percentages increased over 2017-2020, potentially leading to lower CMS penalty claims over the period the BSR was implemented., Conclusions: Coaching is a key factor when creating a favorable patient experience. The implementation and sustainability of coaching to BSR may result in improved patient experience ratings and increase VBP point accumulation to hospital systems., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose., Objectives: The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH., Methods: In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH., Results: In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%)., Conclusion: With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection., (Copyright © 2022 International Society on Thrombosis and Haemostasis. All rights reserved.)

Objective: To investigate the financial toxicity (FT) related to kidney stone treatment., Methods: We performed a cross-sectional cohort study with multi-institutional in-person and online cohorts of stone formers.  Participants were surveyed using the validated COST tool (COmprehensive Score for financial Toxicity). The maximum score is 44 and lower scores indicate increased FT. "Moderate FT" was defined by COST scores between 25 and 14 points and "severe FT" for scores <14. Descriptive statistics, X 2 tests, T tests, Spearman correlation, and logistic regression were performed using SPSS v28., Results: Two hundred and forty-one participants were surveyed, including 126 in-person participants and 115 online. A total of 60% of participants reported at least moderate FT (COST score <26) and 26% reported severe FT (COST score <14). Patients who reported moderate to severe FT were younger than those with low FT by a median difference of 8 years (95%CI = 4, 12). There was a significant correlation between out-of-pocket expense and COST scores, such that as out-of-pocket expenses increased, COST scores decreased, (Spearman's rho =-0.406, P = <.001). Participants with moderate to severe FT tended to miss more workdays (P = .002), and their caretakers tended to miss more workdays (P = .007) due to their stone disease., Conclusion: Most participants reported moderate to severe FT. As prior studies have shown that patients with "moderate FT" employ cost-coping strategies (i.e., medication rationing) and those with "severe FT" have worse health outcomes, urologists need to be sensitive to the financial burdens of treatment experienced by such patients undergoing kidney stone treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain., Methods: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete., Findings: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09])., Interpretation: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism., Funding: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer., Competing Interests: Declaration of interests FNÁ reports grants as principal investigator from the Irish Health Research Board during the conduct of the study, and grants as principal investigator from Daiichi-Sankyo, Bayer, and Sanofi (investigator-initiated studies, fees paid to university) outside of the submitted work. AB reports grants from the French Ministry of Health, during the conduct of the study. JD reports grants as principal investigator from the Irish Health Research Board during the conduct of the study. NvE reports fees for scientific presentation from Bristol-Meyers Squibb (fee transferred to institution) and advisory board fees from LEO Pharma and Bayer (fees transferred to institution), outside of the submitted work. AFJ reports personal fees from Sanofi-Aventis outside of the submitted work. SM reports grants from GSK, Aspen, and Pfizer during the conduct of the study; grants and personal fees from Daiichi-Sankyo, Bayer, Pfizer, and Boehringer Ingelheim; and personal fees from Portola/Alexion, AbbVie, Pfizer/Bristol-Meyers Squibb, Norgine, Viatris, and Sanofi, outside of the submitted work. MTD reports personal fees from Sanofi Genzyme and Bioproducts Laboratory outside of the submitted work. PV reports grants and personal fees from LEO Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Bayer, and Pfizer/Bristol-Meyers Squibb and personal fees from Anthos and Portola/Alexion, outside of the submitted work. All other authors declare no competing interests, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Asians are the fastest growing racial and ethnic group in the United States, and in Michigan, Asians represent 3.4% of the state's population. Asians have long been aggregated as a homogeneous group and stereotyped as a "model minority." Asians, however, are very diverse, and each subgroup has different values, histories, beliefs, and dialects. The diversity among populations and variations in chronic disease risks demonstrate the importance of disaggregating Asian American ethnicities with respect to health promotion, which must be culturally and linguistically tailored to make the biggest impact. This article describes our challenges and successes in health communication messaging with Asian Americans during the 4 years of our Racial and Ethnic Approaches to Community Health (REACH) Cooperative Agreement.

Vitamin E, along with other vitamins and micronutrients play a range of physiologic roles in the homeostasis of the body. Moreover, they also have postulated therapeutic roles that are often incompletely studied and understood. In this scoping review, we explored the recent randomized control trials (RCTs) of Vitamin E in the context of cancer, to investigate whether Vitamin E has a therapeutic role. We searched major bibliographic electronic databases to identify sixteen RCTs studying the role of Vitamin E in cancer management that have been published in the last ten years. These studies had different methodological qualities, including some that used Vitamin E in combination with other treatments. Furthermore, due to the heterogenous results, it is difficult to make a consensus statement on the effectiveness of Vitamin E in cancer therapeutics. In some cases, there were even suggestion of detriment with Vitamin E supplementation. Therefore, well designed, large, prospective RCTs are needed studying pure isoforms of Vitamin E to establish the safety and efficacy of this dietary supplement.

The computational limitations of complex numerical models have led to adoption of statistical emulators across a variety of problems in science and engineering disciplines to circumvent the high computational costs associated with numerical simulations. In flood modelling, many hydraulic and hydrodynamic numerical models, especially when operating at high spatiotemporal resolutions, have prohibitively high computational costs for tasks requiring the instantaneous generation of very large numbers of simulation results. This study examines the appropriateness and robustness of Gaussian Process (GP) models to emulate the results from a hydraulic inundation model. The developed GPs produce real-time predictions based on the simulation output from LISFLOOD-FP numerical model. An efficient dimensionality reduction scheme is developed to tackle the high dimensionality of the output space and is combined with the GPs to investigate the predictive performance of the proposed emulator for estimation of the inundation depth. The developed GP-based framework is capable of robust and straightforward quantification of the uncertainty associated with the predictions, without requiring additional model evaluations and simulations. Further, this study explores the computational advantages of using a GP-based emulator over alternative methodologies such as neural networks, by undertaking a comparative analysis. For the case study data presented in this paper, the GP model was found to accurately reproduce water depths and inundation extent by classification and produce computational speedups of approximately 10,000 times compared with the original simulator, and 80 times for a neural network-based emulator., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Exposure to cerebral emboli is ubiquitous and may be harmful in cardiac surgery utilizing cardiopulmonary bypass. This was a prospective observational study aiming to compare emboli exposure in closed-chamber with open-chamber cardiac surgery, distinguish particulate from gaseous emboli and examine cerebral laterality in distribution., Methods: Forty patients underwent either closed-chamber procedures ( n  = 20) or open-chamber procedures ( n  = 20). Emboli (gaseous and solid) were detected using transcranial Doppler in both middle cerebral arteries in two monitoring phases: 1, initiation of bypass to the removal of the aortic cross-clamp; and 2, removal of aortic cross-clamp to 20 minutes after venous decannulation., Results: Total (median (interquartile range)) emboli counts (both phases) were 898 (499-1366) and 2617 (1007-5847) in closed-chamber and open-chamber surgeries, respectively. The vast majority were gaseous; median 794 (closed-chamber surgery) and 2240 (open-chamber surgery). When normalized for duration, there was no difference between emboli exposures in closed-chamber and open-chamber surgery in phase 1: 6.8 (3.6-15.2) versus 6.4 (2.0-18.1) emboli per minute, respectively. In phase 2, closed-chamber surgery cases were exposed to markedly fewer emboli than open-chamber surgery cases: 9.6 (5.1-14.9) versus 43.3 (19.7-60.3) emboli per minute, respectively. More emboli (total) passed into the right cerebral circulation: 985 (397-2422) right versus 376 (198-769) left., Conclusions: Patients undergoing open-chamber surgery are exposed to considerably higher numbers of cerebral arterial emboli after removal of the aortic cross-clamp than those undergoing closed-chamber surgery, and more emboli enter the right middle cerebral artery than the left. These results may help inform the evaluation of the pathophysiological impact of emboli exposure.

Background: Multimodal analgesia is a cornerstone of postoperative pain management. Different formulations of local anesthetics are available. Data to support these treatment options are limited., Objective: To determine the efficacy of liposomal bupivacaine compared with bupivacaine or ropivacaine in patients undergoing sternotomy for coronary artery bypass graft (CABG) and/or valve surgery., Methods: Single-center, retrospective, observational study at a community teaching hospital. Patients included were 18 years of age or older undergoing CABG and/or valve surgery via median sternotomy and received either liposomal bupivacaine or an active comparator. The primary outcome was opioid utilization in morphine milligram equivalent (MME) from 0 to 72 hours., Results: A total of 376 patients were included, 223 in the liposomal bupivacaine arm and 153 in the active comparator arm. There was no difference in the MME use from 0 to 72 hours among patients in the liposomal bupivacaine group compared with the comparator group (114.2 mg [75.55] vs 107.6 mg [68.4], P = 0.38). After Bonferroni correction, there was no difference in pain scores at individual time points. At 24- and 48-hour post-op, pain scores were higher with liposomal bupivacaine at 4.4 (2.7) vs 3.5 (2.8) ( P = 0.01) and 3.1 (2.9) vs 2.4 (2.6) ( P = 0.02)., Conclusion and Relevance: Based on these findings and previous studies, liposomal bupivacaine should not be routinely used for CABG and/or valve surgery through a median sternotomy given lack of superiority. This helps inform surgical practice to the role of anesthetics as part of the multimodal analgesia regimen.

In this Pro-Con commentary article, we discuss whether the lower limit of cerebral autoregulation is clinically relevant for anesthesiologists. The central question regarding this issue is whether mean arterial blood pressure below the lower limit of autoregulation is detrimental for the brain. The Pro side argues that continuous monitoring of cerebral autoregulation has revealed an association between going below the lower limit and mortality in the critically ill patient. Conversely, the Con side argues that cerebral autoregulation is only one of various defense mechanisms of the brain that protect against cerebral hypoperfusion, and that cerebral autoregulation may be more important to protect against intracranial hypertension., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

The past two years have prompted significant changes with regards to how healthcare is both taught and delivered. There has been a shift towards remote healthcare interventions where appropriate. As we return towards pre-pandemic practice, we must recognise that the healthcare environment has permanently changed. It is vital that safeguards and 'pandemic proofing' are built into healthcare provision.The prevalence of personal digital devices continues to increase, along with internet coverage. This technological revolution has also brought with it a plethora of free or cheap online platforms that allow individuals with limited IT skills to make mobile applications (apps). These factors create a perfect environment for considering mobile apps as viable, widespread healthcare interventions. There is also great potential for these to contribute to tackling inequality, reducing barriers and enhancing healthcare access. However, their use must be carefully considered.This article discusses the myriad of considerations pertaining to both developing and recommending mobile apps for healthcare. Examples of contemporaneous examples will be used, in conjunction with an app developed by the authors to demonstrate the process of creating bespoke resources., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility., (© 2022. The Author(s).)

As COVID-19 vaccines are readily available and most U.S. adults who are enthusiastic about the vaccine have received it, motivating those who have not been vaccinated to accept it has become a challenge. The purpose of this study was to understand the mechanisms behind COVID-19 vaccine acceptance in Asian American ethnic groups, including how sociodemographic characteristics and racism predict COVID-19 and vaccine perceptions. The study also examined associations between social vulnerability and COVID-19 and vaccine perceptions. Social vulnerability is defined as the degree to which a community is able to prepare and respond to a natural or man-made disaster. This cross-sectional study used community-based survey data collected from April to September 2021. Study measures included demographics, perceptions of COVID-19 and COVID-19 vaccines, and racism-related experiences. The results showed that, compared to Non-Asians, East Asians reported that they had significantly more challenges accessing COVID-19 vaccines, and South Asians reported significantly higher safety concerns about COVID-19 vaccines. Our study also found that racism experience mediates the association between race/ethnicity and safety concerns about COVID-19 vaccines. Three Asian subgroups (East Asians, South Asians, and Southeast Asians) experienced more racism (compared to Non-Asians), and more experience of racism was related to greater safety concerns. Geographical Information System (GIS) maps revealed that residents of lower social vulnerability index (SVI) areas reported fewer unfairness perceptions and that higher SVI areas had lower vaccine accessibility and trust in public health agencies. Our study advances the understanding of racism, social vulnerability, and COVID-19 vaccine-related perceptions among Asian Americans. The findings have implications for policymakers and community leaders with respect to tailoring COVID-19 program efforts for socially vulnerable populations and Asian American groups that experience greater challenges regarding vaccine safety concerns and accessibility.