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Marya D Zilberberg,1 Brian H Nathanson,2 Kate Sulham,3 John F Mohr,3 Matthew Goodwin,3 Andrew F Shorr4 1EviMed Research Group, LLC, Goshen, MA, USA; 2OptiStatim, LLC, Longmeadow, MA, USA; 3scPharmaceuticals, Burlington, MA, USA; 4Washington Hospital Center, Washington, DC, USACorrespondence: Marya D Zilberberg, Department of Health Services Research, EviMed Research Group, LLC, PO Box 303, Goshen, MA, 01032, USA, Email evimedgroup@gmail.comBackground: Two-thirds of the 1 million annual US CHF hospitalizations are for diuresis only; some may be avoidable. We describe a population of low-severity short-stay ( 2. We compared baseline characteristics, processes of care, and outcomes in low-severity (CHF-L) to CHF-H.Results: Among 301,672 short-stay CHF patients, 135,304 (44.8%) were CHF-L. Compared to CHF-H, CHF-L was younger (70.5 ± 14.1 vs 72.1 ± 13.6 years, p < 0.001), more commonly female (48.6% vs 45.8%, p < 0.001), and more likely to receive IV ACE-I/ARB agents (0.5% vs 0.4%, p = 0.003). Most other IV medications were more common in CHF-H, and anticoagulation was the most prevalent non-diuretic IV therapy in both groups (23.8% vs 33.3%, p < 0.001). Hospital mortality (0.2% vs 1.5%, p < 0.001) and CHF-related 30-day readmissions (8.1% vs 10.5%, p < 0.001) were lower in CHF-L than CHF-H.Conclusion: Among short-stay CHF patients, nearly &half; meet criteria for CHF-L, and are mainly admitted for fluid management. Avoiding these admissions could result in substantial savings.Keywords: congestive heart failure, epidemiology, outcomes, hospital, costs

Anthony D Andre,1 John F Mohr,2 Barbara W Cornelius,2 Matthew M Goodwin,2 Carson P Whitaker,1 Bhavini H Patel,2 Jessica A Huckleberry,3 Michael D Hassman2 1Interface Analysis Associates LLC, Saratoga, CA, USA; 2scPharmaceuticals, Inc, Burlington, MA, USA; 3Heart Group of the Eastern Shore, P.C, Fairhope, AL, USACorrespondence: Michael D Hassman, scPharmaceuticals, Inc, 25 Mall Road, Suite 203, Burlington, MA, 01803, USA, Tel +1 781 301 7373, Email mhassman@scpharma.comPurpose: Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs).Methods: Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation.Results: Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity.Conclusion: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.Keywords: heart failure, furosemide, subcutaneous furosemide, on-body infusor, human factors

Relatively limited work has been performed to quantify how internal curing influences curing specifications. This paper examines the performance of internally cured mixtures (made using fine lightweight aggregates) compared to conventional concrete cured with wet burlap and curing compounds. Mortar mixtures were prepared using ordinary portland cement (OPC), fly ash, and silica fume (SF) with water-cementitious materials ratios (w/c) of 0.35 and 0.45. Neutron radiography (NR) was used to determine the nonevaporable water content as a function of curing time and distance from the exposed surface. The curing-affected zone (CAZ) was determined using the nonevaporable water profiles. The CAZ was used to develop equivalent curing durations for conventionally cured and internally cured samples. Internally cured mixtures reduced the depth of the CAZ, especially in the samples with limited external curing durations (reduction up to 15 mm [0.6 in.]). The application of internal curing in all mixtures reduced the duration of external curing by 50 to 60%, except for the internally cured SF samples, which showed a slight reduction. This dramatically impacts the construction schedule. [ABSTRACT FROM AUTHOR]

Marya D Zilberberg,1 Brian H Nathanson,2 Katherine Sulham,3 John F Mohr,3 Matthew M Goodwin,3 Andrew F Shorr4 1EviMed Research Group, LLC, Goshen, MA, USA; 2Optistatim, LLC, Longmeadow, MA, USA; 3scPharmaceuticals, Burlington, MA, USA; 4Washington Hospital Center, Washington, DC, USACorrespondence: Marya D Zilberberg, EviMed Research Group, LLC, PO Box 303, Goshen, MA, 01032, USA, Email evimedgroup@gmail.comBackground: Congestive heart failure (CHF) hospitalizations cost the US &dollar;35 billion annually. Two-thirds of these admissions, generally requiring /=65 years: 68.3% vs 71.9%), less likely covered by Medicare (71.9% vs 75.4%), and had a lower comorbidity burden (Charlson: 3.9 [2.1] vs 4.5 [2.2) than patients with LLOS; they less frequently developed acute kidney injury (0.4% vs 2.9%) or a need for mechanical ventilation (0.7% vs 2.8%). A higher proportion with SLOS than with LLOS underwent no procedures (70.4% vs 48.4%). Mean LOS (2.2 [0.8] vs 7.7 [6.5]), direct hospital costs (&dollar;6150 [&dollar;4413]) vs &dollar;17,127 [&dollar;26,936]), and aggregate annual hospital costs &dollar;3,131,560,372 vs &dollar;11,359,002,072) were all lower with SLOS than LLOS. All comparisons reached alpha = 0.001.Conclusion: Among patients admitted for CHF, nearly &half; have LOS

Centrifugal-flow left ventricular assist devices (CF-LVADs) have improved morbidity and mortality for LVAD recipients. Hospital readmissions, however, remain common and affect quality of life and survival. We sought to identify factors associated with readmissions on LVAD support. Patients receiving a CF-LVAD between February 2011 and March 2021 were prospectively evaluated. Hospital readmissions were dichotomized into HF/LVAD-related or non-HF/LVAD-related. Multivariable logistic regression models augmented using the least absolute shrinkage and selection operator method for variable selection were used to estimate associations between ≥1 HF/LVAD-related readmissions and clinical variables. Our study cohort included 201 patients. Seventy percent (140/201) were readmitted for HF/LVAD-related reasons and accounted for 74% (489/657) of total readmissions. The main reasons for HF or LVAD-related readmission were major bleeding, major infection, heart failure exacerbation, and neurological dysfunction. Using pre-LVAD variables we built a multivariable model of HF/LVAD-related readmission. The variables associated with readmission were age, previous cardiac surgery, inotrope dependency, percutaneous LVAD/VA-ECMO support, duration of LVAD support, LVAD type, serum sodium and aspartate aminotransferase, and LV ejection fraction (Table). The area under the ROC curve (AUC) was 0.825. The inclusion of intra- and post-operative variables did not significantly increase accuracy (AUC=0.831) (Table). We created models accurately identifying patients with a high likelihood of readmissions after LVAD implant. Most variables associated with readmission can be identified pre-operatively. Our findings can guide the implementation of therapeutic strategies to mitigate readmission risk and further improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Individuals with sickle cell disease (SCD) experience poor clinical outcomes while transitioning from paediatric to adult care. Standards for SCD transition are needed. We established a Quality Improvement (QI) Collaborative that aimed to improve the quality of care for all young adults with SCD by establishing a standardised SCD transition process. This study evaluates the implementation of the Six Core Elements (6CE) of Health Care Transition, which was a fundamental component of the cluster-randomised Sickle Cell Trevor Thompson Transition Project (ST3P-UP) study., Methods: A central QI team trained 14 ST3P-UP study sites on QI methodologies, 6CE and Got Transition's process measurement tool (PMT). Site-level QI teams included a transition coordinator, clinic physicians/staff, patients/parents with SCD and community representatives. Sites completed the PMT every 6 months for 54 months and monthly audits of 10 randomly-selected charts to verify readiness/self-care assessments and emergency care plans., Results: Of a possible 100, the aggregate mean (±SD) PMT score for paediatric clinics was 23.9 (±13.8) at baseline, 95.9 (±6.0) at 24 months and 98.9 (±2.1) at 54 months. The aggregate mean PMT score for adult clinics was 15.0 (±13.5) at baseline, 88.4 (±11.8) at 24 months and 95.8 (±6.8) at 54 months. The overall QI Collaborative PMT score improved by 402%. At baseline, readiness/self-care assessments were current for 38% of paediatric and 20% of adult patients; emergency care plans were current for 20% of paediatric and 3% of adult patients. Paediatric clinics had one median readiness assessment shift (76%) and four median emergency care plan shifts (65%, 77%, 79%, 84%). Adult clinics experienced three median self-care assessment shifts (58%, 63%, 70%) and two median emergency care plan shifts (57%, 70%)., Conclusions: The ST3P-UP QI Collaborative successfully embedded the 6CE of Health Care Transition into routine care and increased administration of assessments and emergency care plans for transition-aged patients with SCD., Competing Interests: Competing interests: IO received grant funding from HRSA and CDC and previously served as a consultant for Acceleron, Chiesi, Cyclerion, Emmaus, Forma Therapeutics, Global Blood Therapeutics and Novartis. PD received grant funding from CHL-Bhering, Forma, NIH, Novartis, Takeda, UPMC and UT Memphis and serves as an NMDP study monitor and Forma advisory board member. She has also consulted for Forma, Chiesi, Bluebird Bio and Vertex as an advisory member. RHL received grant funding from PCORI, served as a consultant for Novo Nordisk and Pfizer and served as a consultant for Forma Therapeutics. OAA was advisory board member of Novartis and Global Blood Therapeutics and receives grant funding from NIH, HRSA and CDC. All other authors have no relevant interests to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Residual host cell proteins (HCPs) in drug products may impact product quality, stability, efficacy and safety. To support consistent and accurate quantitative analysis for low levels of HCPs (≥ 1 ppm), the data-independent sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS/MS-based method provides unique advantages over data dependent acquisition (DDA) or targeted methods for HCP identification and quantification. However, SWATH MS/MS-based methods can generate biased quantitative results that are highly dependent on the selected reference protein. In this study, we enhanced the accuracy of SWATH-based HCP quantitation relative to a spiked-in reference protein by selecting appropriate reference proteins based on their ranking values. We developed a reliable SWATH-based method for quantifying specific HCPs by adding sodium deoxycholate (SDC) during digestion to enhance both protein detection and quantitation consistency. By combining SWATH-based quantitation with standard addition, we showed its use in measuring HCP levels with good accuracy and reproducibility, confirmed by both targeted MRM-MS/MS and ELISA. Additionally, we demonstrated an automated Spectronaut data analysis workflow can efficiently generate SWATH quantitative results for HCPs in different in-process pools. Using SWATH-based quantitation, we were able to measure specific HCPs (e.g. Peroxiredoxin-1) and support process development with good throughput and quantitation consistency., 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 © 2024. Published by Elsevier Inc.)

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis ( Mtb ) to look for inducible expression of antitubercular agents and identified five fungi that produced cidal antitubercular agents upon exposure to live Mtb . Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All three of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through three different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.

Patients with benign upper gastrointestinal (UGI) conditions such as achalasia, gastroparesis and refractory gastroesophageal reflux disease often suffer from debilitating symptoms. These conditions can be complex and challenging to diagnose and treat, making them well suited for discussion within a multidisciplinary meeting (MDM). There is, however, a paucity of data describing the value of a benign UGI MDM. The aim of this study was to assess the impact of our unit's benign UGI MDM service and its outcomes. This was a retrospective analysis of prospectively collected data for all consecutive patients reviewed in the monthly benign UGI MDM between July 2021 and February 2024. The primary outcome was the incidence that MDM review changed clinical treatment. Secondary outcomes included change in diagnosis, additional investigations and referrals to subspecialists. A total of 104 patients met inclusion criteria. A total of 73 (70.2%) patients had a change in their overall management following MDM review; 25 (24.0%), 31 (29.8%) and 48 (46.2%) patients had changes in pharmacological, endoscopic and surgical interventions respectively. Most changes in pharmacological and endoscopic intervention involved treatment escalation, whereas most changes in surgical intervention involved treatment de-escalation. A total of 84 (80.8%) patients had a documented diagnosis post-MDM with 44 (42.3%) having a change in their pre-MDM diagnosis. 50 (48.1%) patients had additional investigation/s requested and 49 (47.1%) had additional referral pathway/s recommended. Over two thirds of patients had at least one aspect of their management plan changed following MDM review. These changes occurred across pharmacological, endoscopic, and surgical interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The prevalence of isotopes of radioxenon in the atmosphere poses a problem for the International Monitoring System (IMS) of the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The atmospheric radioxenon background has accumulated due to emissions from civil nuclear facilities and as a result, the IMS frequently detects isotopes that might be considered a signal of a nuclear explosion. The UK National Data Centre (NDC) at the Atomic Weapons Establishment (AWE) analyses all data from the IMS radionuclide network and through a new 'event analysis' pipeline, works to determine the source of each detection of interest. The pipeline consists of sample screening, sample association and source reconstruction methods. There are various methods to determine which detections are worthy of further analysis, such as activity concentration magnitude, number of isotopes detected, isotopic activity ratios or consecutive detections. Once the detections have been identified, atmospheric transport and dispersion modelling (ATDM) simulations can be used to identify and characterise the source. Not all sources are known to the Treaty-verification community so work to identify new emitters and their impact on the IMS is critical to the international effort to monitor for nuclear explosions. This work presents a study of the phenomenon of consecutive 133 Xe detections (here referred to as 'plumes'), which are frequently identified on the IMS. We consider the likelihood of a plume from various radionuclide release scenarios and conduct an analysis of a database of IMS measurement data, using the outputs of the automatic Radionuclide (RN) and Event Analysis Pipelines., 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., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS., Methods: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models., Results: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm -5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm -5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P =0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P <0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P =0.003)., Conclusions: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynes•s•cm -5 , high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed., Competing Interests: Dr Drakos served as a consultant to Abbott. The other authors report no conflicts.

Objectives: The addition of fluoride to community drinking water supplies has been a long-standing public health intervention to improve dental health. However, the evidence of cost-effectiveness in the UK currently lacks a contemporary focus, being limited to a period with higher incidence of caries. A water fluoridation scheme in West Cumbria, United Kingdom, provided a unique opportunity to study the contemporary impact of water fluoridation. This study evaluates the cost-effectiveness of water fluoridation over a 5-6 years follow-up period in two distinct cohorts: children exposed to water fluoridation in utero and those exposed from the age of 5., Methods: Cost-effectiveness was summarized employing incremental cost-effectiveness ratios (ICER, cost per quality adjusted life year (QALY) gained). Costs included those from the National Health Service (NHS) and local authority perspective, encompassing capital and running costs of water fluoridation, as well as NHS dental activity. The measure of health benefit was the QALY, with utility determined using the Child Health Utility 9-Dimension questionnaire. To account for uncertainty, estimates of net cost and outcomes were bootstrapped (10 000 bootstraps) to generate cost-effectiveness acceptability curves and sensitivity analysis performed with alternative specifications., Results: There were 306 participants in the birth cohort (189 and 117 in the non-fluoridated and fluoridated groups, respectively) and 271 in the older school cohort (159 and 112, respectively). In both cohorts, there was evidence of small gains in QALYs for the fluoridated group compared to the non-fluoridated group and reductions in NHS dental service cost that exceeded the cost of fluoridation. For both cohorts and across all sensitivity analyses, there were high probabilities (>62%) of water fluoridation being cost-effective with a willingness to pay threshold of £20 000 per QALY., Conclusions: This analysis provides current economic evidence that water fluoridation is likely to be cost-effective. The findings contribute valuable contemporary evidence in support of the economic viability of water fluoridation scheme., (© 2024 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Objectives: The objective was to assess the effectiveness of a Water Fluoridation program on a contemporary population of children., Methods: The study used a longitudinal prospective cohort design. In Cumbria, England, two groups of children were recruited and observed over a period of 5-6 years. The Birth Cohort consisted of families recruited from two hospitals in Cumbria where children were conceived after water fluoridation was reintroduced. The systemic and topical effects of community water fluoridation were evaluated in the Birth Cohort. The Older Cohort were approximately 5 years old and recruited from primary schools in Cumbria, shortly after water fluoridation was reintroduced. The predominantly topical effects of fluoridated water were evaluated in the Older Cohort. The primary outcome was the proportion of children with clinical evidence of caries experience in their primary (Birth Cohort) or permanent teeth (Older Cohort). Unadjusted and adjusted regression models were used for analysis., Results: The final clinical examinations for the Birth Cohort involved 1444 participants (mean age 4.8 years), where 17.4% of children in the intervention group were found to have caries experience, compared to 21.4% in the control group. A beneficial effect of water fluoridation was observed adjusting for deprivation (a socioeconomic measure), sex, and age, (adjusted odds ratio 0.74 95% CI 0.55 to 0.98). The final Older Cohort clinical examinations involved 1192 participants (mean age 10.8 years) where 19.1% of children in the intervention group were found to have caries experience compared to 21.9% in the control group (adjusted odds ratio 0.80, 95% CI 0.58 to 1.09). For both the Birth Cohort and Older Cohort there was evidence of a beneficial effect on dmft/DMFT count (IRR 0.61, 95% CI 0.44, 0.86) and (IRR 0.69, 95% CI 0.52, 0.93) respectively. No conclusive proof was found to indicate that the effectiveness of water fluoridation differed across area deprivation quintiles., Conclusions: In the contemporary context of lower caries levels and widespread use of fluoride toothpaste, the impact of water fluoridation on the prevalence of caries was smaller than previous studies have reported. It is important to consider the clinical importance of the absolute reduction in caries prevalence against the use of other dental caries preventive measures., (© 2024 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

The utilization of continuous wave (CW) near-infrared spectroscopy (NIRS) device to measure non-invasively muscle oxygenation in healthy and disease states is limited by the uncertainties related to the differential path length factor (DPF). DPF value is required to quantify oxygenated and deoxygenated heme groups' concentration changes from measurement of optical densities by NIRS. An integrated approach that combines animal and computational models of oxygen transport and utilization was used to estimate the DPF value in situ. The canine model of muscle oxidative metabolism allowed measurement of both venous oxygen content and tissue oxygenation by CW NIRS under different oxygen delivery conditions. The experimental data obtained from the animal model were integrated in a computational model of O 2 transport and utilization and combined with Beer-Lambert law to estimate DPF value in contracting skeletal muscle. A 2.1 value was found for DPF by fitting the mathematical model to the experimental data obtained in contracting muscle (T3) (Med.Sci.Sports.Exerc.48(10):2013-2020,2016). With the estimated value of DPF, model simulations well predicted the optical density measured by NIRS on the same animal model but with different blood flow, arterial oxygen contents and contraction rate (J.Appl.Physiol.108:1169-1176, 2010 and 112:9-19,2013) and demonstrated the robustness of the approach proposed in estimating DPF value. The approach used can overcome the semi-quantitative nature of the NIRS and estimate non-invasively DPF to obtain an accurate concentration change of oxygenated and deoxygenated hemo groups by CW NIRS measurements in contracting skeletal muscle under different oxygen delivery and contraction rate., Competing Interests: Declaration of Competing Interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic liver disease is responsible for significant morbidity and mortality worldwide. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) can fully visualise the liver and adjacent structures in the upper abdomen providing a reproducible assessment of the liver and biliary system and can detect features of portal hypertension. Subjective interpretation of CT and MRI in the assessment of liver parenchyma for early and advanced stages of fibrosis (pre-cirrhosis), as well as severity of portal hypertension, is limited. Quantitative and reproducible measurements of hepatic and splenic volumes have been shown to correlate with fibrosis staging, clinical outcomes, and mortality. In this review, we will explore the role of volumetric measurements in relation to diagnosis, assessment of severity and prediction of outcomes in chronic liver disease patients. We conclude that volumetric analysis of the liver and spleen can provide important information in such patients, has the potential to stratify patients' stage of hepatic fibrosis and disease severity, and can provide critical prognostic information. CRITICAL RELEVANCE STATEMENT: This review highlights the role of volumetric measurements of the liver and spleen using CT and MRI in relation to diagnosis, assessment of severity, and prediction of outcomes in chronic liver disease patients. KEY POINTS: Volumetry of the liver and spleen using CT and MRI correlates with hepatic fibrosis stages and cirrhosis. Volumetric measurements correlate with chronic liver disease outcomes. Fully automated methods for volumetry are required for implementation into routine clinical practice., (© 2024. The Author(s).)

Elevated arousal in anxiety is thought to affect attention control. To test this, we designed a visual short-term memory (VSTM) task to examine distractor suppression during periods of threat and no-threat. We hypothesized that threat would impair performance when subjects had to filter out large numbers of distractors. The VSTM task required subjects to attend to one array of squares while ignoring a separate array. The number of target and distractor squares varied systematically, with high (four squares) and low (two squares) target and distractor conditions. This study comprised two separate experiments. Experiment 1 used startle responses and white noise as to directly measure threat-induced anxiety. Experiment 2 used BOLD to measure brain responses. For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. For Experiment 2, we found that accuracy was affected by threat, such that the distractor load negatively impacted accuracy only in the threat condition. We also found threat-related differences in parietal cortex activity. Overall, these findings suggest that threat affects distractor susceptibility, impairing filtering of distracting information. This effect is possibly mediated by hyperarousal of parietal cortex during threat., (Published by Oxford University Press 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: Extracellular volume fraction (fECV) and liver and spleen size have been correlated with liver fibrosis stages and cirrhosis. The purpose of the current study was to determine the predictive value of fECV alone and in conjunction with measurement of liver and spleen size for severity of liver fibrosis., Methods: This was a retrospective study of 95 subjects (65 with liver biopsy and 30 controls). Spearman rank correlation coefficient was used to assess correlation between radiological markers and fibrosis stage. Receiver operating characteristic analysis was performed to assess the discriminative ability of radiological markers for significant (F2+) and advanced (F3+) fibrosis and cirrhosis (F4), by reporting the area under the curve (AUC)., Results: The cohort had a mean age of 51.4 ± 14.4 years, and 52 were female (55%). There were 36, 5, 6, 9, and 39 in fibrosis stages F0, F1, F2, F3, and F4, respectively. Spleen volume alone showed the highest correlation (r = 0.552, P < 0.001) and AUCs of 0.823, 0.807, and 0.785 for identification of significant and advanced fibrosis and cirrhosis, respectively. Adding fECV to spleen length improved AUCs (0.764, 0.745, and 0.717 to 0.812, 0.781, and 0.738, respectively) compared with splenic length alone. However, adding fECV to spleen volume did not improve the AUCs for significant or advanced fibrosis or cirrhosis., Conclusions: Spleen size (measured in length or volume) showed better correlation with liver fibrosis stages compared with fECV. The combination of fECV and spleen length had higher accuracy compared with fECV alone or spleen length alone., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Women's Health Needs Study (WHNS) collected information on the health characteristics, needs, and experiences, including female genital mutilation (FGM) experiences, attitudes, and beliefs, of women aged 18 to 49 years who were born, or whose mothers were born, in a country where FGM is prevalent living in the US. The purpose of this paper is to describe the WHNS design, methods, strengths and limitations, as well as select demographic and health-related characteristics of participants., Methods: We conducted a cross-sectional survey from November 2020 -June 2021 in four US metropolitan areas, using a hybrid venue-based sampling (VBS) and respondent-driven sampling (RDS) approach to identify women for recruitment., Results: Of 1,132 participants, 395 were recruited via VBS and 737 RDS. Most were born, or their mothers were born, in either a West African country (Burkina Faso, Guinea, Mali, Mauritania, Sierra Leone, The Gambia) (39.0%) or Ethiopia (30.7%). More than a third were aged 30-39 years (37.5%) with a majority who immigrated at ages ≥13 years (86.6%) and had lived in the United States for ≥5 years (68.9%). Medicaid was the top health insurer (52.5%), followed by private health insurance (30.5%); 17% of participants had no insurance. Nearly half of women reported 1-2 healthcare visits within the past 12 months (47.7%). One in seven did not get needed health care due to cost (14.8%). Over half have ever used contraception (52.1%) to delay or avoid pregnancy and 76.9% had their last pelvic and/or Papanicolaou (pap) exam within the past 3 years. More than half experienced FGM (55.0%). Nearly all women believed that FGM should be stopped (92.0%)., Conclusion: The VBS/RDS approach enabled recruitment of a diverse study population. WHNS advances research related to the health characteristics, needs, and experiences of women living in the US from countries where FGM is prevalent., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: The aim was to assess the effectiveness of a distributed, targeted toothbrush and toothpaste programme on referrals for tooth extraction under Dental General Anaesthetic (DGA), in children of high-risk families compared to usual care., Methods: A recruiter and assessor-blinded, clustered parallel randomised control trial (RCT). Families with one or more children aged between 3 and 10 years having undergone a DGA operation for extraction of carious teeth, were approached within hospitals in the North West of England. Families were randomised at the cluster level in a 1:1 ratio. All eligible children within the family consented to the study. The primary outcome was participant referral for a DGA 6-24-month post-randomisation., Results: A total of 961 families (1,671 children) were randomised, 482 families (832 children) to the intervention, and 479 families (839 children) to the control group. Families (1,662 children, 955 families) were included in the final analysis (825 intervention, 837 control). Marginal regression models (generalised estimating equation approach) taking into account cluster membership were used to model the effectiveness of the intervention at 24 and 48 month follow-up, including the variables, age, sex, and IMD quintile. Seventy-six children (9.2%) in the intervention group had a DGA referral within 2 years compared to 57 children (6.8%) in the control group. The study found no effect of a clinically meaningful difference between the intervention group and usual care (risk ratio 1.36, 95% CI: 0.98-1.89) in reducing referral for DGA for a targeted postal toothpaste/toothbrush program in a contemporary, population with previous family experience of DGA residing in an area of high deprivation., Conclusion: The target of the intervention (families of children with a DGA) was the correct focus given the referrals observed over 2 and 4 years. The study can aid policymakers, local authorities and commissioners to understand repeat DGA within families and further need for intervention., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Long COVID (LC) is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment and monitoring of people with LC., Objectives: To evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with LC., Methods: 1314 patients attending 10 UK specialist LC clinics completed C19-YRSm and EuroQol 5D-5L (EQ-5D-5L) longitudinally. Scale characteristics were derived for C19-YRSm subscales (Symptom Severity (SS), Functional Disability (FD) and Overall Health (OH)) and internal consistency (Cronbach's alpha). Convergent validity was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale. Known groups validity was assessed for the Other Symptoms subscale as tertiles, as well as by hospitalisation and intensive care admission. Responsiveness and test-retest reliability was evaluated for C19-YRSm subscales and EQ-5D-5L. The minimal important difference (MID) and minimal clinically important difference (MCID) were estimated. Confirmatory factor analysis was applied to determine the instrument's two-factor structure., Results: C19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 and 0.65 (for SS and FD), with good internal reliability (Cronbach's alphas>0.8). Item correlations between subscales ranged between 0.46 and 0.72. Convergent validity with FACIT was good (-0.46 to -0.62). The three subscales discriminated between different levels of symptom burden (p<0.001) and between patients admitted to hospital and intensive care. There was moderate responsiveness for the three subscales ranging from 0.22 (OH) to 0.50 (SS) which was greater than for the EQ-5D-5L. Test-retest reliability was good for both SS 0.86 and FD 0.78. MID was 2 for SS, 2 for FD and 1 for OH; MCID was 4 for both the SS and FD. The factor analysis supported the two-factor SS and FD structure., Conclusions: The C19-YRSm is a condition-specific, reliable, valid and responsive patient-reported outcome measure for LC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)