bluuebunny/crossref_metadata_2025 huggingface dataset:
Price of Regulations: Regulatory Costs and the Cross-section of Stock Returns
Authors: Ince Baris , Ozsoylev Han
Published: January 2024

Regulations introduce significant fixed costs and add to operating leverage. Fixed regulatory costs that contribute to operating leverage should generate a risk premium. To explore whether such a premium exists, we introduce a measure of “regulatory operating leverage” that reflects the importance of fixed regulatory costs in a firm’s cost structure. Regulatory operating leverage predicts stock returns in the cross-section, and a zero-cost high-low regulatory operating leverage strategy generates positive and significant risk-adjusted return. Finally, the impact of regulatory operating leverage on returns is due to the (systematic) risk contribution of fixed regulatory costs.
Altered sleep architecture following consecutive nights of presleep alcohol
Authors: McCullar Katie S , Barker David H , McGeary John E , Saletin Jared M , Gredvig-Ardito Caroline , Swift Robert M , Carskadon Mary A
Published: January 2024

Study Objectives

Alcohol consumption before sleep decreases sleep latency, explaining the common use of alcohol as a sleep aid. The full impact of alcohol on sleep architecture is not well understood, particularly the potential cumulative effects of presleep alcohol consumption across consecutive nights. Here, we describe the effects of presleep alcohol on sleep architecture across three consecutive nights.

Methods

Thirty adult participants took part in a crossover, within-participants study consisting of two sets of three consecutive nights of in-lab polysomnography. For each series of nights, participants drank one of the two beverages: a mixer only or a mixer plus alcohol (targeting a BrAC of 0.08 mg/L), ending 1 hour before lights out. Polysomnography (PSG) was used to stage sleep, and standard sleep variables were extracted. Linear mixed-effect analysis and generalized additive modeling were used to examine the effect of alcohol on sleep architecture.

Results

Alcohol before sleep increased the rate of slow wave sleep (SWS) accumulation across all three nights and decreased the rate of rapid eye movement (REM) sleep accumulation at the start of each night. Alcohol also decreased the total amount of REM sleep but did not affect the total amount of SWS each night.

Conclusions

These data indicate that drinking alcohol before sleep substantially affects sleep architecture, including changes to the rate of accumulation of SWS and REM sleep. We show that alcohol disrupts normal sleep architecture, leading to a significant decrease in REM sleep; thus, the use of alcohol as a sleep aid remains a public health concern.
Management of Soybean Cyst Nematode and Sudden Death Syndrome with Nematode-Protectant Seed Treatments Across Multiple Environments in Soybean
Authors: Bissonnette Kaitlyn M. , Barizon Jefferson , Adee Eric , Ames Keith A. , Becker Talon , Biggs Meghan , Bradley Carl A. , Brown Mariama , Byamukama Emmanuel , Chilvers Martin I. , Faske Travis R. , Harbach Chelsea J. , Jackson-Ziems Tamra A. , Kandel Yuba R. , Kleczewski Nathan M. , Koehler Alyssa M. , Markell Samuel G. , Mueller Daren S. , Sjarpe Daniel A. , Smith Damon L. , Telenko Darcy E. P. , Tenuta Albert U.
Published: January 2024

As soybean (Glycine max) production continues to expand in the United States and Canada, so do pathogens and pests that directly threaten soybean yield potential and economic returns for farmers. One such pathogen is the soybean cyst nematode (SCN; Heterodera glycines). SCN has traditionally been managed using SCN-resistant cultivars and rotation with nonhost crops, but the interaction of SCN with sudden death syndrome (SDS; caused by Fusarium virguliforme) in the field makes management more difficult. Nematode-protectant seed treatments have become options for SCN and SDS management. The objectives of this study were to evaluate nematode-protectant seed treatments for their effects on (i) early and full season SCN reproduction, (ii) foliar symptoms and root-rot caused by SDS, and (iii) soybean yield across environments accounting for the above factors. Using a standard protocol, field trials were implemented in 13 states and one Canadian province from 2019 to 2021 constituting 51 site-years. Six nematode-protectant seed treatment products were compared with a fungicide + insecticide base treatment and a nontreated check. Initial (at soybean planting) and final (at soybean harvest) SCN egg populations were enumerated, and SCN females were extracted from roots and counted at 30 to 35 days postplanting. Foliar disease index (FDX) and root rot caused by the SDS pathogen were evaluated, and yield data were collected for each plot. No seed treatment offered significant nematode control versus the nontreated check for in-season and full-season nematode response, no matter the initial SCN population or FDX level. Of all treatments, ILEVO (fluopyram) and Saltro (pydiflumetofen) provided more consistent increases in yield over the nontreated check in a broader range of SCN environments, even when FDX level was high.
GRK5 promoted renal fibrosis via HDAC5/Smad3 signaling pathway
Authors: Xiang Huiling , Huang Jing , Song Anni , Liu Feng , Xiong Jing , Zhang Chun
Published: January 2024

Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD), poses a significant burden in the aging population, and is a major cause of end‐stage renal disease (ESRD). In this study, we investigated the role of G protein‐coupled receptor kinases (GRKs) 5 in the pathogenesis of renal fibrosis. GRK5 is a serine/threonine kinase that regulates G protein‐coupled receptor (GPCR) signaling. GRK5 has been shown to play a role in various diseases including cardiac disorders and cancer. However, the role of GRK5 in renal fibrosis remains largely unknown. Our finding revealed that GRK5 was significantly overexpressed in renal fibrosis. Specifically, GRK5 was transferred into the nucleus via its nuclear localization sequence to regulate histone deacetylases (HDAC) 5 expression under renal fibrosis. GRK5 acted as an upstream regulator of HDAC5/Smad3 signaling pathway. HDAC5 regulated and prevented the transcriptional activity of myocyte enhancer factor 2A (MEF2A) to repress the transcription of Smad7 which leading to the activation of Smad3. These findings first revealed that GRK5 may be a potential therapeutic target for the treatment of renal fibrosis. Inhibition of GRK5 activity may be a promising strategy to attenuate the progression of renal fibrosis.
Imaging of chronic rhinosinusitis with nasal polyps in the era of biological therapies
Authors: Poto Remo , Pelaia Corrado , di Salvatore Antonio , Saleh Hesham , Scadding Guy W. , Varricchi Gilda
Published: January 2024

Purpose of review

Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of the sinonasal cavities classified into two major phenotypes: CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). The diagnosis of CRS is based on clinical symptoms associated with imaging and/or nasal endoscopy findings of mucosal inflammation.

Recent findings

Recently, novel biological therapies have emerged as therapeutic options for CRSwNP. Imaging is helpful in deciding whether surgery is likely to be beneficial and in guiding surgery. It can also help demonstrate a clinical response to medical therapy. However, specific guidelines concerning the role of imaging in CRwNP are lacking.

This article provides a comprehensive and critical multidisciplinary review of the role of conventional radiology, computed tomography (CT), and magnetic resonance imaging (MRI) in the diagnosis and characterization of CRSwNP. Since the complete characterization of nasal polyps on CT or MR images is very challenging, we provide a critical review of the best imaging methods and essential reporting elements used to assess nasal polyps.
Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires
Authors: He Jingui , Wilson Jenna M. , Fields Kara G. , Zachos K. Mikayla Flowers , Franqueiro Angelina R. , Reale Sharon C. , Farber Michaela K. , Bateman Brian T. , Edwards Robert R. , Rathmell James P. , Soens Mieke , Schreiber Kristin L.
Published: January 2024

Background

Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models.

Methods

In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery.

Results

A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain.

Conclusions

The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

Editor’s Perspective

What We Already Know About This Topic

What This Article Tells Us That Is New
Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine
Authors: Ribeiro Bruno M. , Tucci Mauro R. , Victor Júnior Marcus H. , Melo Jose R. , Gomes Susimeire , Nakamura Maria A. M. , Morais Caio C. A. , Beraldo Marcelo A. , Lima Cristhiano A. S. , Alcala Glasiele C. , Amato Marcelo B. P.
Published: January 2024

Background

Lower fractional inspired oxygen tension (Fio2
) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2
(0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis.

Methods

In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2
in three combinations: high PEEP with low Fio2
(Fio2
= 0.4), zero PEEP (PEEP0) with low Fio2
(Fio2
= 0.4), and PEEP0 with high Fio2
(Fio2
= 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2
= 0.21) and low aerated (Fio2
= 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography.

Results

During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2
in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2
. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007).

Conclusions

PEEP0 with low Fio2
, compared with high Fio2
, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2
= 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Urethral Bulking With Polyacrylamide Hydrogel Compared With Other Treatments for Stress Urinary Incontinence
Authors: Chang Olivia H. , Shepherd Jonathan P. , Cadish Lauren A. , Wallace Shannon L. , St Martin Brad , Sokol Eric R.
Published: January 2024

Our objective was to perform a cost-effectiveness analysis comparing polyacrylamide hydrogel urethral bulking with other surgical and nonsurgical treatments for stress urinary incontinence (SUI). We created a cost-effectiveness analysis using TreeAge Pro, modeling eight SUI treatments. Treatment with midurethral sling (MUS) had the highest effectiveness (1.86 quality-adjusted life-years [QALYs]), followed by polyacrylamide hydrogel (1.82 QALYs), with a difference (Δ 0.02/year) less than the minimally important difference for utilities of 0.03 annually. When the proportion of polyacrylamide hydrogel urethral bulking procedures performed in the office setting is greater than 58%, polyacrylamide hydrogel is a cost-effective treatment for SUI, along with pessary, pelvic floor physical therapy, and MUS. Although MUS is more effective and, therefore, the preferred SUI treatment, polyacrylamide hydrogel is a reasonable alternative depending on patient preferences and treatment goals.
Geographic Access to Early Pregnancy Loss Management
Authors: Krashin Jamie W. , Black Patricia , Brannen Eric , Gard Charlotte C. , Lin Yan , Greenwood-Ericksen Margaret , Trujillo Victoria Y. , Burkhardt Gillian , Schreiber Courtney A.
Published: January 2024

Early pregnancy loss (EPL) is common, but patients face barriers to the most effective medication (mifepristone followed by misoprostol) and procedural (uterine aspiration) management options. This cross-sectional geospatial analysis evaluated access in New Mexico to mifepristone and misoprostol and uterine aspiration in emergency departments (comprehensive) and to uterine aspiration anywhere in a hospital (aspiration) for EPL. Access was defined as a 60-minute car commute. We collected data from hospital key informants and public databases and performed logistical regression to evaluate associations between access and rurality, area deprivation, race, and ethnicity. Thirty-five of 42 (83.3%) hospitals responded between October 2020 and August 2021. Two hospitals (5.7%) provided comprehensive management; 24 (68.6%) provided aspiration. Rural and higher deprivation areas had statistically significantly lower adjusted odds ratios for comprehensive management (0.03–0.07 and 0.3–0.4, respectively) and aspiration (0.03–0.06 and 0.1–0.3, respectively) access. Mifepristone and uterine aspiration implementation would address disparate access to EPL treatment.
Glycemic Variability As a Prognostic Factor for Mortality in Patients With Critical Illness: A Systematic Review and Meta-Analysis
Authors: Hryciw Brett N. , Ghossein Jamie , Rochwerg Bram , Meggison Hilary , Fernando Shannon M. , Kyeremanteng Kwadwo , Tran Alexandre , Seely Andrew J. E.
Published: January 2024

OBJECTIVES:

To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness.

DATA SOURCES:

We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023.

STUDY SELECTION:

We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU.

DATA EXTRACTION:

Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty of pooled estimates.

DATA SYNTHESIS:

We included 41 studies (n = 162,259). We demonstrate that increased sd, coefficient of variance, glycemic lability index, and decreased time in range are probably associated with increased mortality in critically ill patients (moderate certainty) and that increased mean absolute glucose, mean amplitude of glycemic excursion, and detrended fluctuation analysis may be associated with increased mortality (low certainty).

CONCLUSIONS:

We found a consistent association between increased measures of glycemic variability and higher short-term mortality in patient with critical illness. Further research should focus on standardized measurements of glycemic variation and complexity, along with their utility as therapeutic targets and prognostic markers.
Prevalence of Delirium After Abdominal Surgery and Association With Ketamine: A Retrospective, Propensity-Matched Cohort Study
Authors: Faisal Hina , Qamar Fatima , Hsu En Shuo , Xu Jiaqiong , Lai Eugene C. , Wong Stephen T. , Masud Faisal N.
Published: January 2024

IMPORTANCE:

Delirium is a common postoperative complication for older patients in the ICU. Ketamine, used primarily as an analgesic, has been thought to prevent delirium.

OBJECTIVE:

Determine the prevalence and association of delirium with low-dose ketamine use in ICU patients after abdominal surgery.

DESIGN:

Single-center, retrospective, propensity-matched cohort study.

SETTING:

Eight hospital academic medical center.

PATIENTS:

Cohort comprising 1836 patients admitted to the ICU after abdominal surgery between June 23, 2018 and September 1, 2022.

MAIN OUTCOMES AND MEASURES:

Propensity score matching (PSM) with a 3:1 ratio between no-ketamine use and ketamine use was performed through a greedy algorithm (caliper of 0.005). Outcomes of interest included: delirium (assessed by Confusion Assessment Method—ICU), mean pain score (Numeric Pain Scale or Critical Care Pain Observation Tool score as available), mean opioid consumption (morphine milligram equivalents), length of stay (d), and mortality.

RESULTS:

Prevalence of delirium was 47.71% (95% CI, 45.41–50.03%) in the cohort. Of 1836 patients, 120 (6.54%) used low-dose ketamine infusion. After PSM, the prevalence of delirium was 56.02% (95% CI, 51.05–60.91%) in all abdominal surgery patients. The ketamine group had 41% less odds of delirium (odds ratio [OR] = 0.59; 95% CI, 0.37–0.94; p = 0.026) than patients with no-ketamine use. Patients with ketamine use had higher mean pain scores (3.57 ± 2.86 vs. 2.21 ± 2.09, p < 0.001). In the subgroup analysis, patients in the ketamine-use group 60 years old or younger had 64% less odds of delirium (OR = 0.36; 95% CI, 0.13–0.95; p = 0.039). The mean pain scores were higher in the ketamine group for patients 60 years old or older. There was no significant difference in mortality and opioid consumption.

CONCLUSIONS AND RELEVANCE:

Low-dose ketamine infusion was associated with lower prevalence of delirium in ICU patients following abdominal surgery. Prospective studies should further evaluate ketamine use and delirium.
Point-of-Care Echocardiography in the Difficult-to-Image Patient in the ICU: A Narrative Review
Authors: Grotberg John C. , McDonald Rachel K. , Co Ivan N.
Published: January 2024

OBJECTIVES:

The objective of this narrative review was to address common obstacles encountered in the ICU to acquiring quality and interpretable images using point-of-care echocardiography.

DATA SOURCES:

Detailed searches were performed using PubMed and Ovid Medline using medical subject headings and keywords on topics related to patient positioning, IV echo contrast, alternative subcostal views, right ventricular outflow tract (RVOT) hemodynamics, and point-of-care transesophageal echocardiography. Articles known to the authors were also selected based on expert opinion.

STUDY SELECTION:

Articles specific to patient positioning, IV echo contrast, alternative subcostal views, RVOT hemodynamics, and point-of-care transesophageal echocardiography were considered.

DATA EXTRACTION:

One author screened titles and extracted relevant data while two separate authors independently reviewed selected articles.

DATA SYNTHESIS:

Impediments to acquiring quality and interpretable images in critically ill patients are common. Notably, body habitus, intra-abdominal hypertension, dressings or drainage tubes, postoperative sternotomies, invasive mechanical ventilation, and the presence of subcutaneous emphysema or lung hyperinflation are commonly encountered obstacles in transthoracic image acquisition in the ICU. Despite these obstacles, the bedside clinician may use obstacle-specific maneuvers to enhance image acquisition. These may include altering patient positioning, respiratory cycle timing, expanding the subcostal window to include multilevel short-axis views for use in the assessment of RV systolic function and hemodynamics, coronal transhepatic view of the inferior vena cava, and finally point-of-care transesophageal echocardiography.

CONCLUSIONS:

Despite common obstacles to point-of-care echocardiography in critically ill patients, the beside sonographer may take an obstacle-specific stepwise approach to enhance image acquisition in difficult-to-image patients.
Secure Messaging: Demonstration and Enrollment Patient Portal Program
Authors: Short-Russell Melinda , Thompson Julie , Waldrop Julee
Published: January 2024

Vulnerable populations face challenges gaining access to quality healthcare, which places them at a high risk for poor health outcomes. Using patient portals and secure messaging can improve patient activation, access to care, patient follow-up adherence, and health outcomes. Developing and testing quality improvement strategies to help reduce disparities is vital to ensure patient portals benefit all, especially vulnerable populations. This quality improvement initiative aimed to increase enrollment in a patient portal, use secure messages, and adhere to follow-up appointments. Before the project, no patients were enrolled in the portal at this practice site. Over 8 weeks, 61% of invited patients were enrolled in the patient portal. Eighty-five percent were Medicaid recipients, and the others were underinsured. Eight patients utilized the portal for secure messaging. The follow-up appointment attendance rate was better in the enrolled patients than in those who did not enroll. The majority of survey respondents reported satisfaction in using the patient portal. Patient portal utilization and adoption in vulnerable groups can improve when a one-on-one, hands-on demonstration and technical assistance are provided.
Treatment Patterns of Bone-targeting Agents Among Solid Tumor Patients With Bone Metastases
Authors: Nicholson Gina , Carlson Katherine B. , Hernandez Rohini K. , Schenfeld Jennifer , Cadieux Benoit , Henry David , De Sousa Barbosa Vitor Jose , Saad Hossam
Published: January 2024

Objectives:

This study evaluated real-world treatment patterns of approved bone-targeting agents (BTAs) with various mechanisms of action—pamidronate, zoledronic acid, and denosumab—for the prevention of skeletal-related events in patients with bone metastases (BM) from solid tumors.

Methods:

Adult patients with BM secondary to solid tumors between January 1, 2014, and December 31, 2018, were identified from the Flatiron Health Oncology Services Comprehensive Electronic Records database and categorized by BTA use and therapy type. Time from diagnosis to initiation, persistence (mean time on treatment), and compliance (≥12 administrations/year) with BTA with up to 4 years of follow-up were examined.

Results:

This study included 27,268 patients with BM (breast cancer, 32.7%; lung cancer, 16.5%; prostate cancer, 17.2%; and other solid tumors, 33.6%); of these, 41.4% initiated denosumab after BM diagnosis; 21.3%, zoledronic acid; 0.6%, pamidronate; and 36.7% had no treatment record. Mean (SD) time to initiation for denosumab or zoledronic acid was 68.6 (157.0) days (denosumab, 70.3 (160.4) days; zoledronic acid, 65.2 [150.2] days). Mean persistence and compliance (first year of treatment) were significantly higher for denosumab than for zoledronic acid (22.0 vs. 14.9 mo [P<0.0001] and 42.3% vs. 34.8% [P<0.0001], respectively). Treatment compliance was the highest in patients with breast cancer (denosumab, 48.2%; zoledronic acid, 39.1%).

Conclusions:

Real-world BTA treatment patterns in the United States suggest that over one-third of patients with BM secondary to solid tumors remain untreated and less than 50% of the patients received ≥12 administrations/year of BTA therapy.
Histological features of chronic hepatitis B patients with normal alanine aminotransferase according to different criteria
Authors: Huang Rui , Liu Jiacheng , Wang Jian , Qiu Yuanwang , Zhu Li , Li Yiguang , Liu Yilin , Zhan Jie , Xue Ruifei , Jiang Suling , Geng Yu , Wan Yawen , Li Ming , Mao Minxin , Gao Dongmei , Gu Yan , Zhang Yao , Yin Shengxia , Tong Xin , Xia Juan , Yan Xiaomin , Ding Weimao , Chen Yuxin , Li Jie , Zhu Chuanwu , Wu Chao
Published: January 2024

Background:

The upper limits of normal (ULNs) for alanine aminotransferase (ALT) are different among international guidelines for chronic hepatitis B (CHB). We aimed to investigate the proportion of significant histological disease in Asian patients with CHB with detectable hepatitis B virus (HBV) DNA under diverse ALT ULNs.

Methods:

Consecutive patients with CHB and detectable HBV DNA who underwent liver biopsy were retrospectively included from four tertiary hospitals. Above grade 2 inflammation and stage 2 fibrosis were defined as significant inflammation and significant fibrosis, respectively. Significant histological disease was defined as above grade 2 inflammation or stage 2 fibrosis.

Results:

Among the 414 patients with detectable HBV DNA and normal ALT, the proportion of those with significant histological disease was lower (59.7%) according to the ULN for ALT at 30/19 U/L (male/female), while the corresponding proportions were 66.7% and 62.3% according to the ULNs of 40 U/L and 35/25 U/L (male/female), respectively. In patients with detectable HBV DNA and normal ALT levels without significant fibrosis, the proportions of significant inflammation were comparable among different ULNs of ALT at 40 U/L (30.7%), 35/25 U/L (27.3%) and 30/19 U/L (25.0%). The proportion of significant histological disease was significantly lower in patients with normal ALT for 2 determinations at least 6 months apart compared to patients with normal ALT once.

Conclusions:

Although a more stringent ALT ULN may reduce the risk of the presence of significant histological disease in patients with detectable HBV DNA, the rates of significant histological disease remain high. Persistently normal ALT levels are more important for excluding patients with CHB with a high probability of significant histological disease.
Post-operative Photoreceptor Integrity and Anatomic Outcomes Based on Presenting Morphologic Stage of Rhegmatogenous Retinal Detachment
Authors: El-Sehemy Ahmed , Melo Isabela Martins , Pecaku Aurora , Zajner Chris , Naidu Sumana , Motekalem Yasmin , Muni Rajeev H.
Published: January 2024

Purpose:

To evaluate outer retinal recovery on post-operative optical coherence tomography (OCT) based on presenting morphologic stage of rhegmatogenous retinal detachment (RRD).

Methods:

Retrospective cohort of consecutive primary fovea-involving RRDs, referred from January 2012-September 2022. Baseline OCTs were assessed for morphologic stage of RRD. Post-operative OCTs were graded at 3, 6 and 12 months for external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IDZ) discontinuity, epiretinal membrane (ERM) formation and severity, and residual subfoveal fluid.

Results:

351 patients were included. Increasing baseline morphologic stage of RRD was significantly associated with ELM, EZ and IDZ discontinuity at all time points post-operatively(p<.001) and was shown to be an independent predictor of foveal photoreceptor integrity after adjusting for height of detachment, time to surgery and duration of fovea involvement(p<.001). Earlier stages were associated with subfoveal fluid(p<.001). There was no association between the stages of RRD and ERM severity. However, late stages presented with earlier development of ERM(p=.012).

Conclusion:

Increasing morphologic stage of RRD is associated with delayed recovery of outer retinal bands in the first year and faster development of ERM following RRD repair. Our results suggest that the stages may serve as a prognostic biomarker for postoperative photoreceptor recovery.
Efficacy of Micropulse Laser Cyclophotocoagulation Therapy in Primary Angle Closure Glaucoma
Authors: Chauhan Divya , Midha Neha , Mahalingam Karthikeyan , Angmo Dewang , Sihota Ramanjit , Gupta Shikha , Chawla Rohan , Dada Tanuj
Published: January 2024

Précis:

In primary angle closure glaucoma (PACG), micropulse cyclophotocoagulation resulted in a significant reduction in intraocular pressure (IOP), and the number of antiglaucoma medications without any sight-threatening complications. However, the IOP lowering efficacy decreased over time.

Purpose:

The purpose of this study was to evaluate the efficacy and safety of micropulse trans-scleral cyclophotocoagulation (MP-TSCPC) in PACG.

Patients and Methods:

Thirty-three phakic PACG eyes with patent laser peripheral iridotomy and IOP uncontrolled on maximum tolerable antiglaucoma medications (AGMs), scheduled for trabeculectomy, were given a trial of MP-TSCPC (810 nm laser, 2000 mw power for 180 seconds, 360 degrees). The primary outcome measure was a success at 1 year with IOP ≤18 mm Hg and ≤15 mm Hg with (qualified success) or without (absolute success) AGMs after a single session of MP laser. Secondary outcome measures were changes in pupillary diameter, visual acuity, central macular thickness, and subjective pain perception.

Results:

Thirty-two out of 33 PACG patients completed 12 months of follow-up. The mean age of patients was 54.7±8.9 years; male:female ratio was 1:1. The baseline IOP was 25.7±5.3 mm Hg, which reduced to 17.9±4.6 mm Hg at the end of 12 months (P<0.0001). Twenty eyes (62.5%) achieved qualified success, and 1 eye (3.125%) had absolute success at 12 months for IOP ≤18 mm Hg; 6 eyes (18.75%) had qualified success, and 1 eye (3.125%) had absolute success for IOP ≤15 mm Hg at 12 months follow-up. A significant reduction was also observed in the number of AGMs (4.4±0.8 at baseline to 2.9±1.1 at 12 months; P <0.0001). Five eyes (15.6%) received additional treatment—3 eyes (9.4%) requiring a subsequent filtering procedure, and 2 eyes (6.2%) requiring an additional MP-TSCPC session. No significant change in pupillary diameter (P=0.489) or central macular thickness (P=0.938) was noted at 12 months. There was a transient drop of visual acuity >2 lines in 1 patient due to cystoid macular edema, and no major postlaser complications were noted.

Conclusions:

MP-TSCPC can be used as an interim procedure to reduce IOP in PACG eyes and delay the need for invasive surgery. Most patients require continued use of glaucoma medications, and target IOPs achieved are in the high teens.
Access to Eye Care Providers and Glaucoma Severity in the National Institutes of Health All of Us Research Program
Authors: Paul Megan , Kitayama Ken , Yu Fei , Tseng Victoria L. , Coleman Anne L.
Published: January 2024

Précis:

In the “All of Us (AoU) Research Program,” individuals with access to vision care were more likely to have mild, moderate, or severe glaucoma and undergo incisional surgery compared with those without vision care access.

Purpose:

To examine the associations between access to eye care, glaucoma severity, and incisional glaucoma surgery using data from the National Institute of Health AoU Research Program.

Materials and Methods:

Individuals with International Classification of Diseases Ninth or 10thRevision codes and who answered the survey question about eye care access in AoU were included in the study. The exposure variable was access to eye care services, with outcome variables (1) glaucoma severitys and (2) likelihood of incisional surgery. Unadjusted multinomial logistic regression compared access to eye care services and glaucoma severity. In addition, unadjusted logistic regression models compared access to eye care and the likelihood of incisional surgery. These were repeated using adjusted analyses, controlling for sex assigned at birth, race and ethnicity, and age.

Results:

Compared with individuals without access to eye care services, those with access were more likely to have all levels of glaucoma severity [mild adjusted odds ratio (aOR): 5.81, 95% CI: 3.15–10.73, moderate aOR: 4.44, 95% CI: 2.45–8.02, severe aOR: 6.95, 95% CI: 2.69–17.93, and unspecified aOR: 3.06, 95% CI: 2.72, 3.45]. Access to eye care was associated with increased odds of any incisional glaucoma surgery (aOR: 3.00, 95% CI: 1.24–9.90) and of trabeculectomy (aOR: 3.30, 95% CI: 1.02–20.28) but not of tube shunt procedures (aOR: 2.65, 95% CI: 0.80–16.38).

Conclusions:

This study demonstrated that access to eye care services was associated with a higher prevalence of all levels of glaucoma severity; those with access to eye care services were more likely to undergo incisional surgery than those without access. Future research should focus on methods to best encourage eye care to limit glaucoma progression.
Long-term outcomes in very young patients with myocardial infarction with non-obstructive coronary arteries
Authors: Ipek Gokturk , Nural Ali , Cebeci Ahmet Ceyhun , Yucedag Furkan Fatih , Bolca Osman
Published: January 2024

Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) covers an expanding group of patients over recent years. Previous studies showed considerable risks of outcomes in this group. However, there is a lack of evidence in young patients with MINOCA. In this study, we aimed to investigate the long-term outcomes in very young patients with MINOCA. We retrospectively compared the features and predictors of 183 very young (≤40-year-old) patients to >40-year-old patients with MINOCA. We compared the baseline characteristics and major adverse cardiac events (total MI, revascularization and mortality) rates between the groups during a median follow-up of 7.3 years. We performed the Cox regression analysis to investigate the risk factors for mortality. We found that the ≤40-year-old group with MINOCA had 12% mortality rates during the follow-up. They had significantly lower rates of diabetes and hypertension and higher rates of male gender and smoking compared to the older group. The very young group also had lower rates of CRF, previous MI and atrial fibrillation. The ≤40-year-old groups received significantly lower rates of medications. Ejection fraction (EF) <30% was independently associated with 6-fold increases in total mortality [hazard ratio (HR) = 6.23, 95% confidence interval (CI) 1.42–27.2, P = 0.02] in the ≤40-year-old group. In conclusion, the ≤40-year-old patients with MINOCA have substantial long-term mortality rates. EF <30% was independently associated with total mortality in this group. Moreover, the ≤40-year-old group also received less intense medical therapy compared to their older counterparts.
The Effect of Benson’s Relaxation Technique on Coping Strategies Among Informal Caregivers of Cancer Patients
Authors: Barghbani Hamid , Heshmatifar Narjes , Mahdavifar Neda , Ansari Mojgan , Sahebkar Mohammad
Published: January 2024

Background

Informal caregivers of cancer patients often experience high levels of stress and burden, leading to the adoption of ineffective coping strategies. This can result in psychological problems for the caregivers and inadequate care provision.

Objective

This study aimed to investigate the impact of Benson’s relaxation technique (BRT) on coping strategies among informal caregivers of cancer patients.

Interventions/Methods

This open-label randomized clinical trial enrolled 113 caregivers visiting the radiotherapy and chemotherapy departments of Vasei Hospital in Sabzevar, Iran, who scored ≥48 on the Novak and Guest Caregiver Burden Inventory. The participants were randomly allocated to either the intervention group or the control group. The intervention group received BRT, with participants performing the technique twice a day for 20 minutes each time over a 1-month period. The control group did not receive any intervention. Coping strategies were assessed using Endler and Parker’s coping strategies inventory.

Results

The findings of the study revealed that the intervention group showed an increase in the utilization of problem-oriented coping strategies (P = .076) and a decrease in the utilization of emotion-oriented coping strategies (P < .001) and avoidance-oriented coping strategies in the intervention group compared with the control group (P = .004).

Conclusions

Findings suggest that BRT, as a cost-effective and nonpharmacological intervention, effectively reduces the reliance on emotion-oriented and avoidance-oriented coping strategies among informal caregivers of cancer patients.

Implications for Practice

Healthcare professionals working in oncology settings are encouraged to incorporate BRT into their care practices.
HAF Prevents Hepatocyte Apoptosis and Hepatocellular Carcinoma through Transcriptional Regulation of the NF-κB pathway
Authors: Pilarte Karen Acuña , Reichert Ethan Conrad , Green Yangsook Song , Halberg Lily Marie-Therese , McFarland Sydney A. , Mimche Patrice N. , Golkowski Martin , Kamdem Severin Donald , Maguire Kathleen M. , Summers Scott. A. , Maschek J. Alan , Reelitz Jordan William , Cox James Eric , Evason Kimberley Jane , Koh Mei Yee
Published: January 2024

Background

Hepatocellular carcinoma (HCC) incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways that lead to MASH-HCC are poorly understood. We have previously reported that male mice with global haploinsufficiency of hypoxia-associated factor, HAF (SART1+/-) spontaneously develop MASH/HCC. However, the cell type(s) responsible for HCC associated with HAF loss are unclear.

Results

SART1-floxed mice were crossed with mice expressing Cre-recombinase within hepatocytes (Alb-Cre; hepS-/-) or macrophages (LysM-Cre, macS-/-). Only hepS-/-mice (both male and female) developed HCC suggesting that HAF protects against HCC primarily within hepatocytes. HAF-deficient macrophages showed decreased P-p65 and P-p50 and in many major components of the NF-κB pathway, which was recapitulated using HAF siRNAin vitro. HAF depletion increased apoptosis bothin vitroandin vivo, suggesting that HAF mediates a tumor suppressor role by suppressing hepatocyte apoptosis. We show that HAF regulates NF-κB activity by controlling transcription ofTRADDandRIPK1. Mice fed a high-fat diet (HFD) showed marked suppression of HAF, P-p65 and TRADD within their livers after 26 weeks, but manifest profound upregulation of HAF, P-65 and TRADD within their livers after 40 weeks of HFD, implicating deregulation of the HAF-NF-κB axis in the progression to MASH. In humans, HAF was significantly decreased in livers with simple steatosis but significantly increased in HCC compared to normal liver.

Conclusions

HAF is novel transcriptional regulator of the NF-κB pathway that protects against hepatocyte apoptosis and is a key determinant of cell fate during progression to MASH and MASH-HCC.
Predicting individual long-term prognosis of spatial neglect based on acute stroke patient data
Authors: Röhrig Lisa , Wiesen Daniel , Li Dongyun , Karnath Hans-Otto
Published: January 2024

One of the most pressing questions after a stroke is whether an individual patient will recover in the long-term. Previous studies demonstrated that spatial neglect – a common behavioral deficit after right hemispheric stroke – is a strong predictor for poor performance on a wide range of everyday tasks and for resistance to rehabilitation. The possibility of predicting long-term prognosis of spatial neglect is therefore of great relevance. The aim of the present study was to test the prognostic value of different imaging and non-imaging features from right hemispheric stroke patients: individual demographics (age, sex), initial neglect severity, and acute lesion information (size, location). Patients’ behavior was tested twice in the acute and the chronic phases of stroke and prediction models were built using machine learning-based algorithms with repeated nested cross-validation and feature selection. Model performances indicate that demographic information seemed less beneficial. The best variable combination comprised individual neglect severity in the acute phase of stroke, together with lesion location and size. The latter were based on individual lesion overlaps with a previously proposed chronic neglect region-of-interest (ROI) that covers anterior parts of the superior and middle temporal gyri and the basal ganglia. These variables achieved a remarkably high level of accuracy by explaining 66% of the total variance of neglect patients, making them promising features in the prediction of individual outcome prognosis.
Applying a Motivational Instructional Design Model to Stroke Rehabilitation: A Feasibility Study in Occupational Therapy and Swallowing Therapy Settings
Authors: Oyake Kazuaki , Watanabe Shota , Takeuchi Ayano , Yoshida Taiki , Shigematsu Takashi , Natsume Yuuki , Tsuzuku Shigeki , Kondo Kunitsugu , Fujishima Ichiro , Otaka Yohei , Tanaka Satoshi
Published: January 2024

OBJECTIVE

This feasibility study aimed to investigate the feasibility of applying a motivational instructional design model to stroke rehabilitation and its potential physical and mental health effects in occupational and swallowing therapy settings.

DESIGN

An open-label, single-arm, feasibility study.

SETTING

Convalescent rehabilitation hospitals.

PARTICIPANTS

Twenty-five patients with stroke (19 males; mean age 62.4 ± 11.9 years) were recruited from two convalescent rehabilitation hospitals.

INTERVENTIONS

The intervention was to motivate participants during rehabilitation sessions based on the motivational instructional design model and was delivered to 12 and 13 participants in two hospitals during occupational and swallowing therapy sessions, respectively. The intervention was given for 40–60 min daily, 5 days weekly for 4 weeks (25 sessions).

MAIN OUTCOME MEASURES

The primary outcome was feasibility, including the drop-out rate, an adverse event, and the participants’ acceptability of the intervention. Additionally, physical (activities of daily living, motor function of the paretic upper extremity, and swallowing ability) and mental health (depressive symptoms and apathy) outcomes were evaluated before and after the intervention.

RESULTS

No participants dropped out of the intervention or experienced an adverse event. Twenty-one participants (84%) were satisfied with the intervention, and 19 (76%) hoped to continue receiving it. After the intervention, statistically significant improvements with a large effect size were found in physical outcomes (Cohen’s r = 0.68–0.85) but not in mental health outcomes (Cohen’s r = 0.31–0.34).

CONCLUSIONS

The application of the motivational instructional design model to occupational and swallowing therapies after stroke was feasible with the potential to improve physical outcomes.
Knowledge is not all you need to generate trust in AI use in healthcare
Authors: Li Anson Kwok Choi , Rauf Ijaz A. , Keshavjee Karim
Published: January 2024

Background

Canada has invested significantly in artificial intelligence (AI) research and development over the last several years. Canadians’ knowledge of and attitudes towards AI in healthcare are understudied.

Objectives

To explore the relationships between age, gender, education level, and income on Canadians’ knowledge of AI, their comfort with its use in healthcare, and their comfort with using personal health data in AI research.

Methods

Ordinal logistics regression and multivariate polynomial regression were applied to data from the 2021 Canadian Digital Health Survey using RStudio and SigmaZone’s Design of Experiments Pro.

Results

Female and older Canadians self-report less knowledge about AI than males and other genders and younger Canadians. Female Canadians and healthcare professionals are less comfortable with use of AI in healthcare compared to males and people with other levels of education. Discomfort appears to stem from concerns about data security and the current maturity level of the technology.

Conclusion

Knowledge of AI and the use of AI in healthcare are inversely correlated with age and directly correlated with education and income levels. Overall, female respondents self-reported less knowledge and comfort with AI in healthcare and research than other genders. Privacy concerns should continue to be addressed as a major consideration when implementing AI tools. Canadians, especially older females, not only need more education about AI in healthcare, but also need more reassurance about the safe and responsible use of their data and how bias and other issues with AI are being addressed.

Author Summary

Artificial intelligence (AI) and its application has garnered significant public interest and excitement within healthcare in recent years. However, its successful integration and use in healthcare will depend on patient and user adoption. As a result, AI tools may be limited in healthcare when user concerns are not carefully addressed and if patients are not educated about how these technologies work. While there have been studies on the attitudes of clinicians and healthcare professionals toward AI, little is known about the general public’s perception of AI within the healthcare setting. Our study addresses this gap in the literature by analyzing data from the 2021 Canadian Digital Health Survey to understand the relationships between Canadians’ attitudes towards AI and various socioeconomic and demographic factors. Our results found that older Canadians, Canadians with less formal education and women need to be better informed about the safe and responsible use of AI and be reassured about good data security practices before it can be broadly accepted by them. In addition, the element of trust may be a factor that is contributing to the higher levels of discomfort with AI observed in middle-aged Canadians. The findings from this study will help stakeholders better implement and broaden the accessibility of AI technologies.