bluuebunny/crossref_metadata_2025 huggingface dataset:
The Vulnerable Patient
Authors: Mossey Jana M.
Published: May 2024

This chapter addresses the occurrence, risk factors for, and consequences of pain across the life span with a focus on identification of groups vulnerable to chronic pain conditions in six age-specific groups: newborns, preschool children, preadolescent and adolescent youth, young adults, middle-aged adults, and elderly individuals. Despite the absence of a common chronic pain assessment tool used across studies, several findings regarding chronic pain vulnerability and impact have emerged from review of the relevant pain literature. First, due to frequent receipt of medically indicated, painful neonatal intensive care unit procedures, lifelong chronic pain vulnerability begins at birth for preterm infants. Second, most chronic pain risk factors are relevant for all age-specific groups. Excluding age, sex, and genetic makeup, most chronic pain risk factors—including persistent exposure to racial discrimination and/or poverty, personal maltreatment, physical inactivity, obesity, nonrestorative sleep, multiple comorbid medical conditions, anxiety and/or depression, and behaviors such as smoking—are preventable or modifiable. Third, experienced chronic pain increases the likelihood of future chronic pain episodes. Fourth, the negative impacts of risk factors that become persistent (e.g., racial discrimination, physical inactivity, and obesity) accumulate over time. Finally, with aging, most risk factors increase in strength. Falling and fear of falling emerge as additional chronic pain risk factors. These findings emphasize the potential benefits of aggressive primary prevention efforts and the importance of monitoring those whose chronic pain occurs early in life. Recommendations to achieve these aims are provided.
Vulnerable Populations
Authors: Mossey Jana M. , Haozous Emily A.
Published: May 2024

This chapter addresses the long-standing, uncomfortably predictable disparate pain care provided to “minoritized” individuals, those who have limited resources or are any population other than non-Hispanic White, who are female, and/or who are members of the LGBTQ community. Following a summary of the extensive literature pertinent to the topic, etiologic components driving the persistent delivery of inequitable pain care are presented within an “injustice” framework. Cultural, institutional, and interpersonal injustices that contribute to disparate pain care delivery are identified, and the intrapersonal responses of minoritized persons to experienced injustices are described. With a clear understanding that the reversal of disparate pain care practices will require dedicated, focused, and potentially uncomfortable work and a recognition of the importance of cultural and institutional injustices to the perpetuation of health care disparities, steps to achieve the circumstances under which pain care practitioners are capable of and insistent upon providing equitable care are proposed.
Diagnostic Reasoning: What’s the Lesion? (Why We Localize)
Authors: Albers James W. , Gelb Douglas J.
Published: May 2024

This chapter describes a systematic approach to determining the type of disease process causing a patient’s symptoms, based on the time course and whether the process is focal or diffuse. Definitions are provided for acute, subacute, and chronic time courses. Each type of underlying disease process—degenerative, neoplastic, vascular, inflammatory, toxic/metabolic, traumatic, and congenital/developmental—is briefly discussed, especially with reference to its typical time course and whether it is focal or diffuse.
Neuromuscular Disorders
Authors: Bromberg Mark B. , Gelb Douglas J.
Published: May 2024

This chapter reviews the functional divisions of the peripheral nervous system (PNS) and the symptoms associated with them. It then discusses the clinical syndromes associated with disorders of the peripheral nervous system, proceeding in a proximal-to-distal order, and it provides a flowchart for identifying these disorders. It explains the diagnostic tests used to help in diagnosing PNS disorders, especially electromyography (EMG) and nerve conduction studies. It presents the clinical features, pathophysiology, and principles of diagnosis and management for major PNS diseases: motor neuron diseases—especially amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), radiculopathies, plexopathies, neuropathies—including mononeuropathies, polyneuropathies, and mononeuropathy multiplex, neuromuscular junction disorders—especially myasthenia gravis, and myopathies—especially muscular dystrophies and inflammatory myopathies.
Dizziness and Disequilibrium
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with a discussion of the approach to dizziness, with a focus on the vestibular pathway and the distinction between disorders of the CNS portion of the pathway and the PNS portion. Most of the ensuing discussion concerns disorders of the peripheral portion of the vestibular pathway. Recurrent episodes of vertigo are discussed first: especially benign paroxysmal peripheral vertigo (BPPV), with a detailed description of the relevant diagnostic and therapeutic maneuvers, but also Ménière disease, perilymphatic fistula, dehiscence of the superior semicircular canal, and vestibular paroxysmia. This is followed by a discussion of a single episode of vertigo, focusing on acute labyrinthitis and acute idiopathic unilateral peripheral vestibulopathy. The chapter concludes with a discussion of the various abnormalities that can contribute to disequilibrium.
Pediatric Neurology
Authors: Gelb Douglas J.
Published: May 2024

This chapter starts with a summary of some general principles of normal development. It then proceeds to discuss some common clinical manifestations of nervous system dysfunction in the pediatric population. The first example is the hypotonic infant. The distinction between central and peripheral causes of hypotonia is emphasized. The next examples are developmental delay and developmental regression. It is noted that the most common inherited cause of global developmental delay is fragile X syndrome, the most common reason for isolated language delay is reduced hearing, and the most common cause of delayed social development is autism spectrum disorder. Attention deficit hyperactivity disorder (ADHD), cerebral palsy, and periventricular leukomalacia are discussed. The next examples are paroxysmal disorders: migraine, seizures, breath-holding spells, and benign paroxysmal vertigo. The final discussion concerns gait disorders, focusing on conditions that cause spasticity, weakness, and ataxia.
Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro
Authors: Doroudian Maryam , Gailer Jürgen
Published: May 2024

Red blood cells (RBCs) constitute ∼50% of the bloodstream and represent an important target for environmental pollutants and bacterial/viral infections, which can result in their rupture. In addition, diseases such as sickle cell anaemia and paroxysmal nocturnal haemoglobinuria can also result in the rupture of RBCs, which can be potentially life-threatening. With regard to the release of cytosolic metalloproteins from RBCs into the blood-organ system, the biochemical fate of haemoglobin is rather well understood, while comparatively little is known about another highly abundant Zn-metalloprotein, carbonic anhydrase (CA I). To gain insight into the interaction of CA I with human blood plasma constituents, we have employed a metallomics tool comprised of size-exclusion chromatography (SEC) coupled online with an inductively coupled plasma atomic emission spectrometer (ICP-AES), which allows to simultaneously observe all Cu, Fe, and Zn-metalloproteins. After the addition of CA I to human blood plasma incubated at 37°C, the SEC-ICP-AES analysis using phosphate buffered saline (pH 7.4) after 5 min, 1 h, and 2 h revealed that CA I eluted after all endogenous Zn-metalloproteins in the 30 kDa range. Matrix-assisted laser desorption-time of flight mass spectrometry analysis of the collected Zn-peak confirmed that CA I eluted from the column intact. Our in vitro results suggest that CA I released from RBCs to plasma remains free and may be actively involved in health-relevant adverse processes that unfold at the bloodstream-endothelial interface, including atherosclerosis and vision loss.
Engineering catalytic defects via molecular imprinting for high energy Li-S pouch cells
Authors: Zhao Yufei , Geng Chuannan , Wang Li , Cao Yun , Yang Haotian , Peng Linkai , Jiang Xin , Guo Yong , Ye Xiaolin , Lv Wei , Yang Quan-Hong
Published: May 2024

Heterogeneous catalysis promises to accelerate sulfur-involved conversion reactions in lithium-sulfur batteries. Solid-state Li2S dissociation remains as the rate-limiting step because of the weakly matched solid-solid electrocatalysis interfaces. We propose an electrochemically molecular-imprinting strategy to have a metal sulfide (MS) catalyst with imprinted defects in positions from which the pre-implanted Li2S has been electrochemically removed. Such tailor-made defects enable the catalyst to bind exclusively to Li atoms in Li2S reactant and elongate the Li–S bond, thus decreasing the reaction energy barrier during charging. The imprinted Ni3S2 catalyst shows the best activity due to the highest defect concentration among the MS catalysts examined. The Li2S oxidation potential is substantially reduced to 2.34 V from 2.96 V for the counterpart free of imprinted vacancies, and an Ah-level pouch cell is realized with excellent cycling performance. With a lean electrolyte/sulfur ratio of 1.80 μL mgS–1, the cell achieves a benchmarkedly high energy density beyond 500 Wh kg–1.
Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer
Authors: Mansoor Wasat , Joo Seongjung , Norquist Josephine M , Kato Ken , Sun Jong-Mu , Shah Manish A , Enzinger Peter , Adenis Antoine , Doi Toshihiko , Kojima Takashi , Metges Jean-Philippe , Li Zhigang , Kim Sung-Bae , Cho Byoung Chol , Sunpaweravong Patrapim , Alsina Maria , Goekkurt Eray , Suryawanshi Shailaja , Shah Sukrut , Shen Lin
Published: May 2024

Background

In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and objective response rate compared with chemotherapy, with a manageable safety profile in patients with advanced esophageal cancer. Prespecified health-related quality-of-life (HRQoL) outcomes are reported.

Materials and Methods

Change from baseline to week 18 in the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/QoL (GHS/QoL) and QLQ–Esophageal cancer module (OES18) dysphagia, pain, and reflux scales were evaluated.

Results

The HRQoL analysis included 730 patients who received treatment and completed ≥1 HRQoL assessment. Least squares mean (LSM) change from baseline to week 18 was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 reflux scales. The QLQ-OES18 dysphagia (LSM difference, −5.54; 95% CI, −10.93 to −0.16) and pain (LSM difference, −2.94; 95% CI, −5.86 to −0.02) scales favored pembrolizumab plus chemotherapy over placebo plus chemotherapy. Median time to confirmed deterioration (TTD) was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 dysphagia and reflux scales. Compared with chemotherapy, pembrolizumab plus chemotherapy prolonged median TTD, as seen on the QLQ-OES18 pain scale (HR, 0.69; 95% CI, 0.51 to 0.95).

Conclusion

The use of pembrolizumab plus chemotherapy maintained HRQoL at week 18 relative to baseline and was comparable with placebo plus chemotherapy. These HRQoL results together with published reports of efficacy, support the use of pembrolizumab plus chemotherapy as first-line therapy for advanced/metastatic esophageal cancer.

ClinicalTrials.gov ID

NCT03189719
The CVA Process from Preparation to Decision
Authors: Harley Gabe
Published: May 2024

This chapter discusses the preparation and decision of the CVA process. In line with the Cork Committee recommendations, the nominee in a CVA must be qualified to act as an insolvency practitioner. The CVA proposal is a document that establishes the terms of the proposed compromise and arrangement with creditors. Additionally, the proposal is typically put together by directors of the company with the assistance of the proposed nominee, legal, and other professional advisors. The chapter also looks into the legal commencement and notice requirements of the CVA before the process of the creditor's making decisions through a physical meeting, virtual meeting, electronic voting, or correspondence.
Unraveling the Concept of Childhood Adversity in Psychosis Research: A Systematic Review
Authors: Sætren Sjur S , Bjørnestad Jone R , Ottesen Akiah A , Fisher Helen L , Olsen Daniel A S , Hølland Kari , Hegelstad Wenche ten Velden
Published: May 2024

Background

During the last decades, an abundance of studies has investigated childhood adversity in relation to psychosis. This systematic review critically examines the methodologies employed to investigate childhood adversity in psychosis over the past decade, including operational definitions, measurement tools and characteristics, and psychometric properties of instruments used in these studies.

Study Design

This systematic review followed the PRISMA guidelines (registration number CRD42022307096), and the search used the following electronic databases: PsychINFO, SCOPUS, Web of Science, African Index Medicus (AIM), LILACS, CINAHL, EMBASE, and MEDLINE. The search included variations and combinations of the terms targeting childhood adversity and psychosis.

Study Results

Out of 585 identified studies published between 2010 and 2023, 341 employed a validated instrument to investigate childhood adversity. Our findings show “childhood trauma” being the most frequently examined construct, followed by “child maltreatment” or “child abuse.” The short version of the Childhood Trauma Questionnaire was the dominant instrument. Physical abuse, emotional abuse, and sexual abuse were most frequently investigated, and indeed the field appears generally to focus on child abuse and neglect over other adversities. Significant psychometric heterogeneity was observed in the selection and summarization of instrument items, with only 59% of studies documenting original psychometric validation and 22% reporting reliability in their datasets.

Conclusion

This review highlights substantial methodological heterogeneity in the field, pointing out biases in the research on childhood adversity and psychosis. These findings underline the need for standardized definitions and high-quality measurement tools to enhance the validity of future research in this area.
Wireless wearable sensors can facilitate rapid detection of sleep apnea in hospitalized stroke patients
Authors: Sindorf Jacob , Szabo Alison L , O’Brien Megan K , Sunderrajan Aashna , Knutson Kristen L , Zee Phyllis C , Wolfe Lisa , Arora Vineet M , Jayaraman Arun
Published: May 2024

Study Objectives

To evaluate wearable devices and machine learning for detecting sleep apnea in patients with stroke at an acute inpatient rehabilitation facility (IRF).

Methods

A total of 76 individuals with stroke wore a standard home sleep apnea test (ApneaLink Air), a multimodal, wireless wearable sensor system (ANNE), and a research-grade actigraphy device (ActiWatch) for at least 1 night during their first week after IRF admission as part of a larger clinical trial. Logistic regression algorithms were trained to detect sleep apnea using biometric features obtained from the ANNE sensors and ground truth apnea rating from the ApneaLink Air. Multiple algorithms were evaluated using different sensor combinations and different apnea detection criteria based on the apnea–hypopnea index (AHI ≥ 5, AHI ≥ 15).

Results

Seventy-one (96%) participants wore the ANNE sensors for multiple nights. In contrast, only 48 participants (63%) could be successfully assessed for obstructive sleep apnea by ApneaLink; 28 (37%) refused testing. The best-performing model utilized photoplethysmography (PPG) and finger-temperature features to detect moderate-severe sleep apnea (AHI ≥ 15), with 88% sensitivity and a positive likelihood ratio (LR+) of 44.00. This model was tested on additional nights of ANNE data achieving 71% sensitivity (10.14 LR+) when considering each night independently and 86% accuracy when averaging multi-night predictions.

Conclusions

This research demonstrates the feasibility of accurately detecting moderate-severe sleep apnea early in the stroke recovery process using wearable sensors and machine learning techniques. These findings can inform future efforts to improve early detection for post-stroke sleep disorders, thereby enhancing patient recovery and long-term outcomes.

Clinical Trial

SIESTA (Sleep of Inpatients: Empower Staff to Act) for Acute Stroke Rehabilitation, https://clinicaltrials.gov/study/NCT04254484?term=SIESTA&checkSpell=false&rank=1, NCT04254484
EPHA2 is a novel cell surface marker of OCT4-positive undifferentiated cells during the differentiation of mouse and human pluripotent stem cells
Authors: Intoh Atsushi , Watanabe-Susaki Kanako , Kato Taku , Kiritani Hibiki , Kurisaki Akira
Published: May 2024

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) possess the intrinsic ability to differentiate into diverse cellular lineages, marking them as potent instruments in regenerative medicine. Nonetheless, the proclivity of these stem cells to generate teratomas post-transplantation presents a formidable obstacle to their therapeutic utility. In previous studies, we identified an array of cell surface proteins specifically expressed in the pluripotent state, as revealed through proteomic analysis. Here we focused on EPHA2, a protein found to be abundantly present on the surface of undifferentiated mouse ESCs and is diminished upon differentiation. Knock-down of Epha2 led to the spontaneous differentiation of mouse ESCs, underscoring a pivotal role of EPHA2 in maintaining an undifferentiated cell state. Further investigations revealed a strong correlation between EPHA2 and OCT4 expression during the differentiation of both mouse and human PSCs. Notably, removing EPHA2+ cells from mouse ESC-derived hepatic lineage reduced tumor formation after transplanting them into immune-deficient mice. Similarly, in human iPSCs, a larger proportion of EPHA2+ cells correlated with higher OCT4 expression, reflecting the pattern observed in mouse ESCs. Conclusively, EPHA2 emerges as a potential marker for selecting undifferentiated stem cells, providing a valuable method to decrease tumorigenesis risks after stem-cell transplantation in regenerative treatments.
Meaning-centered psychotherapy training program for cancer care clinicians: Efficacy and impact of the first 5 years
Authors: Pessin Hayley , Dustin Ashley , Behrens Mia R , Saracino Rebecca M , Lichtenthal Wendy G , Applebaum Allison J , Roberts Kailey E , Breitbart William
Published: May 2024

Meaning-Centered Psychotherapy (MCP) is a manualized, evidence-based intervention designed to help cancer patients to find meaning and alleviate distress. Meaning-Centered Psychotherapy Training (MCPT) is a multicomponent program for cancer care clinicians that consists of didactics, group experiential learning, and role-plays with simulated patients to learn MCP and acquire skills to deliver it in real-world oncology settings. The efficacy and impact of MCPT for multidisciplinary cancer care clinicians to learn and disseminate MCP is described and evaluated. A multilevel evaluation based on the RE-AIM framework was utilized to assess the efficacy of the MCPT program over the initial 5 years of the program. The outcomes of the evaluation supported MCPT goals. Three hundred forty-two participants attended MCPT. Overall satisfaction measured in the post-training assessment was high. Significant increases in MCP skills were demonstrated by participants over the course of the role-play sessions, and participants showed significant improvements in pre/post-training MCP knowledge assessment scores, as well as significant increases in self-reported overall MCP skills and core competencies. Follow-up survey responses indicate that MCP trainees were utilizing MCP, had made changes to their clinical practice, and progressed on individual implementation goals. During the first 5 years, the MCPT program was successfully developed, established, implemented, and shown to be effective in the dissemination of MCP across the RE-AIM domains. Future directions for training and implementation research include increasing diversity of providers and investigating the impact of the program on patient outcomes.
Therapeutic effects of vitamin B17 against anabolic steroid Trenorol induced testicular toxicity, injury, DNA damage and apoptosis in male rats
Authors: Al-Otaibi Aljohara M
Published: May 2024

Several anabolic androgenic steroids (ASSs) are a group of synthetic molecules derived from testosterone and developed mainly for veterinary use that classed as a Schedule III and sometimes utilized by athletes to enlarge their muscles. Abuse of anabolic androgenic steroids can result in severe organ damage that cannot be repaired. Therefore; the objective of the current investigation was to examine the therapeutic effects of vitamin B17 (VitB17) on the testicular toxicity caused by the anabolic steroid Trenorol in male rats. Rats were randomly assigned into control, VitB17 (50 mg/kg b.wt./day, orally), Trenorol (received 10 mg/kg b.wt./week, IM) and Trenorol + VitB17 treated groups. At the end of experiment, hormonal assay, semen evaluation, testicular enzymes, and DNA damage were assessed. Besides, the histopathological and immunohistochemical investigations of the P53 expression were performed. Current results revealed that; Trenorol induced significant depletion in relative weights of testis (RWT), total testosterone follicle stimulating hormone (FSH), and luteinizing hormone (LH), sperm count, morphology index, viability, progressive motility, and testicular injury and a significant increase sperm abnormalities, testicular DNA damage and P53 experssions. Treatment of rats with Trenorol + VitB17 decreased the testicular toxicity, sperm parameters, DNA damage and apoptosis. We can conclude that; Trenorol induced toxicity, DNA damage and apoptosis in rat testis and treatments with VitB1 improved these parameters.
A Comparison of Three Automated Root-Knot Nematode Egg Counting Approaches Using Machine Learning, Image Analysis, and a Hybrid Model
Authors: Fraher Simon P. , Watson Mark , Nguyen Hoang , Moore Savannah , Lewis Ramsey S. , Kudenov Michael , Yencho G. Craig , Gorny Adrienne M.
Published: May 2024

Meloidogyne spp. (root-knot nematodes [RKNs]) are a major threat to a wide range of agricultural crops worldwide. Breeding crops for RKN resistance is an effective management strategy, yet assaying large numbers of breeding lines requires laborious bioassays that are time-consuming and require experienced researchers. In these bioassays, quantifying nematode eggs through manual counting is considered the current standard for quantifying establishing resistance in plant genotypes. Counting RKN eggs is highly laborious, and even experienced researchers are subject to fatigue or misclassification, leading to potential errors in phenotyping. Here, we present three automated egg counting models that rely on machine learning and image analysis to quantify RKN eggs extracted from tobacco and sweet potato plants. The first method relied on convolutional neural networks trained using annotated images to identify eggs (M. enterolobii R2 = 0.899, M. incognita R2 = 0.927, M. javanica R2 = 0.886), whereas a second contour-based approach used image analysis to identify eggs from their morphological characteristics and did not rely on neural networks (M. enterolobii R2 = 0.977, M. incognita R2 = 0.990, M. javanica R2 = 0.924). A third hybrid model combined these approaches and was able to detect and count eggs nearly as well as human raters (M. enterolobii R2 = 0.985, M. incognita R2 = 0.992, M. javanica R2 = 0.983). These automated counting protocols have the potential to provide significant time and resource savings annually for breeders and nematologists and may be broadly applicable to other nematode species.
New evidence in food allergies treatment
Authors: Ghelli Chiara , Costanzo Giovanni , Canonica Giorgio Walter , Heffler Enrico , Paoletti Giovanni
Published: May 2024

Purpose of review

To acknowledge, the newly available treatments for food allergy described in the latest scientific literature, such as oral immunotherapy (OIT), biologics and the combination of them in managing patients with IgE-mediated food allergies.

Recent findings

Recent studies suggest that OIT and biologics, alone or together, can have a role as disease-modifying treatments for food allergies. The FDA has recently approved omalizumab as a treatment for food allergy. Other biologics are currently under evaluation and further studies are needed to assess the efficacy and safety of these therapies.

The allergology scenario is rapidly evolving, the recent introduction and approval of new therapeutic strategies such as biotechnological drugs and allergen immunotherapy is changing the therapeutic paradigm: we are witnessing a shift from a strategy based on avoiding the trigger and reversing an allergic reaction already in progress, to one that aims to modify the natural history of the disease by acting on the immunological mechanisms that determine it. This approach is consistent with the modern perspective of a personalized patient-tailored medicine. In this opinion review, we will provide a brief analysis of current and future therapeutic options for IgE-mediated food allergy, focusing on OIT, biologics and their combination.
Management and treatment of perioperative hypersensitivity
Authors: Littlejohns Anna , Savic Louise
Published: May 2024

Purpose of review

Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and poststabilization management of suspected reactions, alongside practical advice for anaesthetists who may be faced with these events.

Recent findings

Prompt treatment is essential but may be hampered by delay in recognition. This can occur because there are multiple differential diagnoses for the observed clinical signs as well as variations in clinical presentation. Resuscitation is dependent on the use of adrenaline and fluids. Adrenaline should be administered in small, titrated intravenous boluses. Low-dose infusions should be commenced early if the response to boluses is poor. Large volume fluid resuscitation may be required to maintain adequate circulating volume. Chest compressions are recommended when there is evidence of inadequate perfusion, rather than waiting until cardiac arrest is confirmed. Antihistamines and corticosteroids are no longer recommended in the immediate management phase. Once the patient has been stabilized, it is important to obtain serial tryptase concentrations to aid the subsequent clinic investigation. The decision to proceed or abandon surgery will be based on an individual risk-benefit analysis. All cases of suspected perioperative hypersensitivity, including fatal cases, must be referred for formal investigation.

There have been recent updates to management guidelines in perioperative hypersensitivity. Treatment algorithms, treatment packs and referral packs can all help the anaesthetist manage these complex cases, aid the subsequent investigation and ensure patient safety in the future.
Integration of Clinical Trial Development in Hematology-Oncology Fellowship Training
Authors: Auberle Christine , Wu Ningying , Dipersio John F. , Waqar Saiama N. , Ratner Lee
Published: May 2024

Problem

Several barriers to physicians becoming clinical investigators exist, including inexperience, lack of available mentors, and inconsistent instructive approaches with varying degrees of participation during training. These barriers cause fewer hematology-oncology fellows to pursue academic careers. A consensus is needed on structuring education in clinical investigation paired with active participation in development of a clinical trial guided by a mentor with the goal of increasing fellow interest in clinical research and pursuit of careers in academic medicine.

Approach

The clinical trial development (CTD) program was initiated at Washington University School of Medicine in St. Louis in 2002 as a hands-on learning experience for hematology and oncology fellows in the design, implementation, and publication of clinical trials. Each fellow was required to identify a mentor and propose at least 1 prospective investigator-initiated clinical trial.

Outcomes

At the time of data abstraction in July 2023, 118 fellows had participated in the CTD program and initiated protocols in a variety of areas according to their interests. Fellows were included in data abstraction if their fellowship began in 2002 through 2021; the program is ongoing, and the most recent class will graduate in 2024. Disease types were evenly distributed between solid tumor oncology (60 [51%]) or classic and malignant hematology (58 [49%]). Ninety-three fellows (79%) obtained institutional review board approval, and 60 (65%) published their results. Among graduating fellows, 67 (66%) secured an academic faculty appointment. Fellows with institutional review board–approved projects had significantly higher odds of obtaining an academic faculty appointment (odds ratio, 4.96; 95% confidence interval, 1.54–15.98; P = .007).

Next Steps

Next steps will be to further evaluate the effect of the mentorship network on early career productivity of trainees that graduate and the feasibility of extending the program to another institution.
Effects of White Noise on Pain Scores and Salivary Cortisol Levels in Surgical Neonates
Authors: Lin Siya , Li Li , Ren Xuyan , Zhong Chunxia , Wu Kai , Fang Xiaoling , Liang Shaocong , Chen Xuedong , Chen Jingxia , Yang Liucheng , Wang Xiaowu , Wang Bin
Published: May 2024

Background:

Neonates experience varying intensities of pain after surgery. While white noise has been used for postoperative pain relief in infants, its effects on neonates after surgery need further exploration.

Purpose:

This study aimed to evaluate the effects of white noise on pain scores and salivary cortisol levels in surgical neonates.

Methods:

In this randomized controlled trial, 64 neonates scheduled for surgery were recruited and assigned by block randomization into 2 groups. The intervention group listened to white noise at 50 dB, while the control group listened to white noise at 0 dB, for 30 minutes 6 times for 48 hours postoperatively. Pain scores, measured by the COMFORTneo Scale, and salivary cortisol levels were compared.

Results:

Although pain scores decreased after surgery in all subjects, no statistically significant difference was observed between the 2 groups (P = .937). There was a significant difference between pre- and postintervention pain scores in the intervention group only (P = .006). Salivary cortisol levels decreased after intervention in the intervention group, but there was no significant difference between pre- and postintervention levels in the 2 groups (P = .716).

Implications for Practice:

Given the reduction in pain scores and salivary cortisol concentrations after white noise intervention, white noise shows potential as an adjunctive soothing measure for neonates after surgery.

Implications for Research:

Future studies are needed to confirm the efficacy and utility of white noise intervention in clinical settings.
Hepatitis B Birth Dose Vaccination Improvement Initiative
Authors: Heidenreich Kaeli N. , Blair Shannon , Gillespie Hayley , Chang Amanda J. , Burns James L. , Shah Malika D.
Published: May 2024

Background:

An estimated 25,000 infants are born to mothers diagnosed with hepatitis B virus (HBV) each year in the United States. Administration of the birth dose HBV vaccine prevents transmission during delivery. Despite national guidelines promoting vaccination within 24 hours of birth, fewer than 70% of infants receive the dose in their first 3 days of life. To improve compliance with national recommendations, Northwestern Medicine implemented a bundled care initiative in the well newborn nursery, entitled the 24-hour baby bundle (24-HBB).

Purpose:

Evaluate the 24-HBB’s effect on improving time to HBV vaccine administration.

Methods:

The 24-HBB was created by an interdisciplinary team and implemented on February 17, 2020. Bundled care begins at 23 hours of life, starting with the HBV vaccine, followed by bath, weight, and congenital heart disease screening, and ending with metabolic screening. We conducted a retrospective cohort study of 22,057 infants born at Northwestern Medicine Prentice Women’s Hospital in Chicago, Illinois. Our sample included preintervention birthdates between February 16, 2019, and January 16, 2020, and postintervention birthdates between March 17, 2020, and February 16, 2021, with a 2-month washout education period between January 17, 2020, and March 16, 2020.

Results:

Hepatitis B virus immunization within 24 hours increased significantly from 43.83% to 66.90% (P < .0001). In addition, overall hepatitis B immunization prior to discharge significantly increased after implementation of the 24-HBB (98.18% vs 98.82%, P < .0001).

Implications for Practice and Research:

The 24-HBB is effective at increasing rates of HBV immunization within 24 hours of birth. Newborn nurseries may benefit from similar initiatives to prevent hepatitis B infection, satisfy national recommendations, and promote childhood vaccination compliance.
Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis
Authors: Tang Jia , Wang Ping , Liu Chenxi , Peng Jia , Liu Yubo , Ma Qilin
Published: May 2024

Background:

Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated.

Methods:

PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI).

Results:

We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle “ACEI + BB + MRA” in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (–8.05 mL/m2, 95% CI: –14.88 to –1.23 mL/m2) and ACEI + BB + SGLT-2i (–18.94 mL/m2, 95% CI: –36.97 to –0.61 mL/m2) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (–3254.21 pg/mL, 95% CI: –6242.19 to –560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP.

Conclusions:

Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug “ARNI + BB + MRA + SGLT-2i” is superior to the golden triangle “ACEI + BB + MRA” in improving LVEF.

Registration:

PROSPERO; No. CRD42022354792.
Acute increases in physical activity and temperature are associated with hot flash experience in midlife women
Authors: Witkowski Sarah , White Quinn , Shreyer Sofiya , Garcia Randi L. , Brown Daniel E. , Sievert Lynnette Leidy
Published: May 2024

Objective

This study determined the association between acute changes in physical activity, temperature, and humidity and 24-hour subjective and objective hot flash experience.

Methods

Data collection occurred during the cooler months of the year in Western Massachusetts (October-April). Women aged 45-55 across three menopause stages (n = 270) were instrumented with ambulatory monitors to continuously measure hot flashes, physical activity, temperature, and humidity for 24 hours. Objective hot flashes were assessed via sternal skin conductance, and subjective hot flashes were recorded by pressing an event marker and data logging. Physical activity was measured with wrist-worn accelerometers and used to define sleep and wake periods. Logistic multilevel modeling was used to examine the differences in physical activity, humidity, and temperature in the 10 minutes preceding a hot flash versus control windows when no hot flashes occurred. The odds of hot flashes were considered separately for objective and subjective hot flashes as well as for wake and sleep periods.

Results

Data from 188 participants were included in the analyses. There was a significantly greater odds of a hot flash following acute increases in physical activity for objective waking hot flashes (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.17-1.47;P< 0.001) and subjective waking hot flashes (OR, 1.16; 95% CI, 1.0-1.33;P= 0.03). Acute increases in the actigraphy signal were associated with significantly higher odds of having an objective (OR, 1.17; 95% CI, 1.03-1.35;P< 0.01) or subjective (OR, 1.72; 95% CI, 1.52-2.01;P< 0.001) sleeping hot flash. Increases in temperature were significantly related to the odds of subjective sleeping hot flashes only (OR, 1.38; 95% CI, 1.15-1.62;P< 0.001). There was no evidence for a relationship between humidity and odds of experiencing any hot flashes.

Conclusion

These results indicate that acute increases in physical activity increase the odds of hot flashes that are objectively measured and subjectively reported during waking and sleeping periods. Temperature increases were only related to subjectively reported nighttime hot flashes.
Current trends in the management of corneal neovascularization
Authors: Rangu Neal , Dang Deanna H. , Riaz Kamran M.
Published: May 2024

Purpose of review

The aim of this study was to highlight recent developments in the medical and surgical management of corneal neovascularization (NV).

Recent findings

Improved understanding and diagnostic criteria among clinicians have led to advancements in the characterization of corneal NV and objective assessment of treatment response through ancillary imaging devices. Developments in corneal NV treatments, such as antivascular endothelial growth factor, fine needle diathermy, and photodynamic therapy, have improved treatment success rates and visual outcomes. More recent surgical treatment advancements include corneal cross-linking, endothelial keratoplasty, and mitomycin intravascular chemoembolization. Finally, a greater appreciation of the molecular pathogenesis and angiogenic factors involved in corneal NV has identified numerous potential targeted therapies in the future.

The management of corneal NV has evolved to include several standalone and combination medical and surgical options. Additionally, improvements in quantifying corneal NV and understanding its molecular basis have contributed to new management strategies with improved outcomes.
Test-Retest Reliability of Intraocular Pressure Measurements With Office-Based Versus Home-Based Rebound Tonometers
Authors: Realini Tony , Halenda Kevin , Palko Joel , McMillan Brian , Balasubramani Goundappa K.
Published: May 2024

Précis:

Intraocular pressure (IOP) measurements obtained with the HOME2 rebound tonometer are interchangeable with measurements obtained using the office-based IC100 and IC200 rebound tonometers, making characterization of circadian IOP achievable with no inter-device sources of variability.

Objective:

To evaluate test-retest reliability between IOP measurements obtained with a home rebound tonometer operated by patients and those obtained with office rebound tonometers operated by experienced clinical staff.

Methods:

After training and practice with a home rebound tonometer (iCare HOME2) in a randomly selected eye, patients with established or suspected open angle glaucoma underwent IOP measurement in the fellow eye as follows in randomized order: 3 good quality measurements with the iCare IC100 operated by experienced clinical staff, 3 good quality measurements with the iCare IC200 operated by experienced clinical staff, and 3 good quality measurements with the HOME2 operated by the patient. The Shrout-Fleisch intraclass correlation coefficient (ICC; 2,1) was the measure of reliability utilized based on the model using 2-way random effects, absolute agreement, and single measurement.

Results:

Thirty eyes of 30 patients were evaluated. The Pearson correlation coefficient (r) for IOP measurements taken with the IC100 and HOME2 was 0.97, with the IC200 and HOME2 was 0.96, and with the IC100 and IC200 was 0.97. Test-retest reliability between HOME2 and IC100 (ICC: 0.90), HOME2 and IC200 (ICC: 0.92), and IC100 and IC200 (ICC: 0.94) all reflected excellent test-retest reliability.

Conclusion:

The test-retest reliability of IOP measurements taken by patients using the iCare HOME2 self-tonometer compared with IOP measurements taken by trained operators using the iCare IC100 and IC200 tonometers was uniformly excellent (ICCs all ≥0.9). These findings indicate that these three devices should be considered interchangeable for the clinical assessment of circadian IOP.
Cystic plate approach combined with ICG fluorescence in laparoscopic anatomical hepatectomy
Authors: Chen Hao , Shen Kefeng , Shen Xiayong , Liu Wenbin , Ge Yongsheng , Yu Jihai , Jia Weidong , Ma Jinliang , Yuan Peng , Zhang Chuanhai
Published: May 2024

Background:

The in-depth understanding of the fine anatomy of the liver has promoted the development of modern liver surgery. With the rapid popularity of laparoscopic hepatectomy, the membrane structure of the liver and its ability to dissect the intrahepatic and extrahepatic vascular system more conveniently and accurately has been gradually emphasized.

Objective:

Exploring the value of extrahepatic sheath dissection of the hepatic pedicle in minimally invasive anatomical hepatectomy with cystic plate approach. This study aims to assess the benefits of integrating the cystic plate approach with real-time guided laparoscopic anatomical hepatectomy, in comparison with conventional laparoscopic anatomical hepatectomy.

Materials and methods:

Based on the theory of cystic plate and hepatic portal plate, the authors have pioneered the fluorescence real-time guided cystic plate approach in hepatectomy. The article focuses on the anatomical knowledge and technical difficulties of anatomical hepatectomy with fluoroscopic laparoscopic cystic plate approach and explores the safety and practicality of the cystic plate approach in laparoscopic anatomical hepatectomy. Additionally, a retrospective cohort study was also conducted to compare the operation time, intraoperative blood loss, and postoperative complications between the cystic plate approach and the conventional approach during fluoroscopic laparoscopic hepatectomy.

Results:

A total of 38 patients who met the inclusion criteria underwent laparoscopic hepatectomy between January 2019 and November 2022. No significant disadvantages were found in terms of operation time and intraoperative blood loss during the surgeries. Furthermore, the postoperative indications, including liver function indexes on the first postoperative day, WBC, and the postoperative hospital stay, were also not affected, thus proving the safety of the cystic approach. Importantly, through the cystic plate approach, the target liver pedicle was fully freed, and then the segments to be resected were precisely marked by positive or negative staining, followed by hepatectomy under real-time fluoroscopic guidance. This approach is extremely advantageous in anatomical liver segment resections, especially in right posterior lobe or hemi-hepatectomy, without increasing intraoperative bleeding or postoperative complication rates.

Conclusion:

This technique allows for easy and safe freeing of the target liver pedicle using membrane structures, and also allows for precise anatomical hepatectomy in combination with real-time fluoroscopic laparoscopic navigation.
Risk factors for nephrolithiasis formation: an umbrella review
Authors: Ma Yucheng , Cheng Chao , Jian Zhongyu , Wen Jun , Xiang Liyuan , Li Hong , Wang Kunjie , Jin Xi
Published: May 2024

Objective:

Nephrolithiasis is prevalent and burdensome worldwide. At present, evidence on the risk factors for nephrolithiasis is unconsolidated and the associations remain uncertain. The authors systematically evaluate the robustness of the meta-analytic evidence and aid more reliable interpretations of the epidemiological relationships.

Methods:

The authors conducted a comprehensive review of the meta-analyses, screened the included studies with the aid of the AMSTAR 2 evaluation tool, and then used R (4.1.1) software to perform data analysis to evaluate the association between candidate risk factors and kidney stones, and evaluated the credibility of the evidence of the association between risk factors and kidney stones according to the GRADE classification, and finally obtained the strength and effectiveness of the association.

Results:

The authors finally included 17 meta-analyses regarding 46 risk factors, 34 of which (73.9%) showed statistically significant association with nephrolithiasis. Among the significant associations, the authors found that waist circumference, BMI, dietary intake and fructose intake were positively correlated with the occurrence and development of nephrolithiasis. Caffeine, dietary fiber and DASH-diet showed a tendency to reduce kidney stones. Interestingly, calcium supplementation, dietary calcium, and vitamin D, which are widely believed to be responsible for stone formation, made no difference or even reduced the risk of nephrolithiasis.

Conclusions:

The authors’ study demonstrates the suggestive causal (central obesity, type 2 diabetes, gout, dietary sodium, fructose intake and higher temperatures) risk factors of nephrolithiasis. The authors also demonstrate the suggestive causal (coffee/alcohol/beer intake, dietary calcium and DASH-diet) protective factors of nephrolithiasis. To provide epidemiological basis for the treatment and prevention of nephrolithiasis.