bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual dysfunction in female patients with multiple sclerosis: relationship with functional status, fatigue, depression, sleep quality, and quality of life
Authors: Yeni Kübra , Tulek Zeliha , Terzi Murat
Published: January 2025

Background

Although sexual dysfunction is one of the most common symptoms in patients with multiple sclerosis (MS), there are relatively few studies on this topic.

Aim

The aim of this study was to assess sexual function in female MS patients and investigate its association with functional state, fatigue, depression, sleep, and quality of life.

Methods

This descriptive cross-sectional study was conducted between May and November 2019 with MS patients attending an MS outpatient clinic at a university hospital. Patients' sexual function was assessed using the Female Sexual Function Index (FSFI). Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), and Multiple Sclerosis Quality of Life Scale (MSQoL-54) were used to determine their relationship to sexual function.

Outcomes

Sexual function, functional status, depression, sleep quality, and quality of life.

Results

The mean age of the 83 patients included in the study was 41.8 (±8.5) years, and all were married. The mean FSFI score of the patients was 21.1 (±8.9) and 26.55, 72.3% of patients were found to have sexual dysfunction. FSFI scores were found to have a negative correlation with age (r = −0.398, P = .001), duration of diagnosis (r = −0.338, P = .001), and EDSS scores (r = −0.326, P = 0.040). Patients taking symptomatic medication (P = .032) and antidepressants (P = .012) had lower mean FSFI scores. Additionally, the FSFI score showed a significant negative correlation with the FSS (r = −0.368, P = .001), the BDI (r = −0.423, P < .001), the PSQI (r = −0.314, P = .004), and the MSQoL-54 (physical health: r = 0.509, P < .001 and mental health: r = 0.431, P < .001).

Clinical implications

A comprehensive evaluation of sexual dysfunction and the development of tailored treatment plans, taking into account associated factors, will be beneficial for female patients with MS.

Strengths and Limitations

Small sample size and assessment of sexual function by a generic scale are the limitations of this study.

Conclusion

Considering the multifactorial nature of sexual dysfunction in female MS patients, it is recommended that patients be assessed multidimensionally during outpatient follow-up visits.
Medication Management
Authors: Montejano Julio , Selzer Angela
Published: January 2025

Annually, 600,000 percutaneous coronary stent procedures are performed in the United States. Up to 7% of these will undergo noncardiac surgery within the first year following stent placement and 22.5% within 2 years. The management of these patients in the perioperative period is complex and must consider the indication for placement, timing of placement, location of stent(s), and type of stent(s) placed. In addition, interruption of dual antiplatelet therapy (DAPT) needs to be considered, taking into account the urgency of surgery and balancing risks of surgical bleeding with stent rethrombosis. This is often a complex management decision which should be made collaboratively with surgeons, cardiologists, and anesthesiologists and must involve a detailed risk discussion with the patient. This chapter describes a challenging patient with a recent myocardial infarction with drug-eluting stent placement who must proceed with a semi-urgent craniotomy just 2 months after stent placement. The guidelines for interruption of DAPT following stent placement are reviewed.
Prehabilitation Before Total Hip Replacement
Authors: Belloni Olivia , Gogue Rashwan , Beretta Luigi , Maria Minnella Enrico
Published: January 2025

Total hip replacement (THR) surgery is an intervention that involves exposing the patient to a major stress. Prehabilitation is a preoperative intervention that aims to enhance the functional capacity of the patient prior to surgery, thus minimizing the effect of surgical stress to facilitate the recovery. This program acts on the three main aspects of functional capacity: physical, nutritional, and psychological status. This chapter presents the most recent evidence in literature about the effectiveness of prehabilitation in the context of THR. These studies predominantly focused on physical intervention and patient education; preoperative nutritional therapy is still under investigation. While multimodal prehabilitation is increasingly recognized as an important component of enhanced recovery perioperative pathways, further studies are essential to foster knowledge of the topic and support its clinical implementation.
Geriatric Assessment
Authors: Willham Kaitlin , Nye Heather E.
Published: January 2025

More than one in three surgical procedures in the United States is performed on a patient 65 years or older. Older adults experience higher rates of mortality and morbidity following surgery than do younger adults. This has generated a call to better optimize older adults prior to surgery and employ risk reduction strategies when possible, using an expanded preoperative assessment prior to intermediate- or high-risk surgery in older adults. This assessment should include all features of a standard preoperative evaluation and screening for age-related syndromes known to contribute to poor surgical outcomes, such as functional and cognitive impairment. Discussions with the patient should elicit goals and expectations for the surgery—and ensure they align with likely outcomes. With this information, the perioperative clinical team is better able to guide the individual in careful planning and decision-making around their surgical treatment plan and reduce modifiable risk factors to every extent possible.
Echo Shows Elevated Pulmonary Artery Pressure
Authors: Pulley Debra D. , Lakshminarasimhachar Anand
Published: January 2025

Due to increased recognition and treatment success, an increasing number of patients with pulmonary hypertension are undergoing surgery/procedures. Unfortunately, PH is a risk factor for perioperative morbidity/mortality especially in patients with PAH and chronic thromboembolic PH. To help reduce the risk and guide perioperative decision making, it is imperative to have processes to identify the higher-risk PH patients, optimize preoperatively if needed, and manage intraoperatively and immediately postoperatively to reduce PH crisis and right ventricular failure. In the past few years, several organizations and experts have published useful statements and guidelines. Ways to identify higher-risk patients include focused clinical assessment, functional class, and right ventricular function. High-risk patients especially need multidisciplinary input into the perioperative plan. As the field of PH evolves, future research will be able to guide individualized care improving perioperative outcomes.
Severe OSA in the Ambulatory Setting
Authors: Love Sean , Santino Chelsey , Tran Tina
Published: January 2025

Patients with comorbidities commonly undergo surgery at ambulatory surgery centers (ASC). These ASCs might have limited resources available, and most ASCs do not have the ability to admit patients overnight. It is important to screen patients and confirm that they are appropriate candidates to undergo surgery in the ASC setting. Obstructive sleep apnea (OSA) is an important issue when determining a patient’s appropriateness for ASC procedures. OSA is prevalent in the adult population, is often undiagnosed, and, when untreated, can lead to a higher risk of perioperative complications. With appropriate diagnosis, treatment, and careful planning, patients with OSA can safely receive surgery in the ASC setting.
Respiratory
Authors: Raine Tim , Collins George , Brown Fraser , Howarth Sophie
Published: January 2025

This chapter covers the diagnosis and treatment of respiratory conditions. It discusses emergencies in the case of breathlessness and low sats or stridor in a conscious adult patient. It also covers the causes of coughs, and the treatment of respiratory conditions such as asthma, COPD, pneumonia, spontaneous pneumothorax, and pulmonary embolism.
Psychiatry
Authors: Raine Tim , Collins George , Brown Fraser , Howarth Sophie
Published: January 2025

This chapter discusses the treatment of psychological disturbances and psychiatric illness. It covers emergency protocol in the case of aggressive behaviour caused by psychiatric distress. It also includes discussion of the Mental Health Act, alcoholism, aggression and violence, acute confusion, dementia, mood disturbance, psychosis, anxiety disorders, neuroses, and insomnia.
Haematology
Authors: Raine Tim , Collins George , Brown Fraser , Howarth Sophie
Published: January 2025

This chapter discusses haematology, including coverage of anaemia, transfusion of blood products, clotting emergencies, bleeding disorders, and anticoagulation.
Skin and eyes
Authors: Raine Tim , Collins George , Brown Fraser , Howarth Sophie
Published: January 2025

This chapter covers the treatment of conditions and diseases of the skin and eyes. It includes discussion of emergencies pertaining to rashes and acute red eye. It also discusses bacterial, viral, and fungal infections causing a rash, infestations causing a rash, chronic inflammatory rashes, and other causes of rash. The chapter goes on to cover skin lumps, skin cancers, and leg ulcers as well as sudden visual loss, gradual visual loss, and other visual disturbances.
Genetic Methodologies and Applications
Authors: Neale Benjamin M.
Published: January 2025

The genetic investigation into mental illnesses has progressed rapidly since the mapping of the human genome. Driven by advances in genomic profiling technology, massive genomic datasets are powering the discovery of genetic variation associated to complex traits, including mental illness. From severe neurodevelopmental disorders to schizophrenia and depression, genetic variation plays some role in risk. This chapter provides an overview and introduction to the genetic investigation of severe mental illnesses. The major topics and themes of the chapter center on how to assess evidence for a genetic contribution to risk via twin and family studies; approaches to measure genetic variation in people; methods for associating genetic variation to traits such as disorders (e.g., schizophrenia) or disease-relevant traits (e.g., treatment response); methods that incorporate information from across the genome to inform on individual risk (i.e., polygenic risk scores); as well as the development of novel biological hypotheses.
Methods for In Vivo Circuit Analysis
Authors: Johnson Micah , Filali Yassine , Velamuri Radha , Dzirasa Kafui , Hultman Rainbo
Published: January 2025

Breakthroughs in understanding neural circuit activity hold much promise for developing next-generation therapeutics for psychiatric disorders. Determination of how dynamic activity is coordinated across brain regions to effect specific behavioral function (or dysfunction) has the capacity to enable the development of therapeutics with increased specificity and fewer side effects. This chapter discusses the advantages and limitations of different methodologies for measuring and manipulating neural circuit activity in humans and in animal models. Methodologies that can be carried out in humans include functional magnetic resonance imaging; functional near-infrared spectroscopy; positron emission tomography; magnetoencephalography; and electroencephalography, including scalp and intracranial electroencephalography. Methodologies used specifically in animal models include in vivo electrophysiology, fiber photometry, and microendoscopy. Targeted neural circuit manipulations combined with these measurements are already being applied to a wide range of experimental and therapeutic strategies that illuminate routes to circuit-based treatments for complex brain disorders.
Magnetic Resonance Methodologies
Authors: Lu Hanzhang , Bandettini Peter A.
Published: January 2025

Magnetic resonance imaging (MRI) is a versatile imaging technique that is widely used to study mental illnesses. This chapter reviews major MRI techniques that have the potential to make an impact on psychiatric diseases. Although anatomic MRI has been available for many years, technical advances have allowed images to be acquired at higher spatial resolution and with less scan time. Functional MRI has gradually shifted to resting-state fMRI, which permits the assessment of brain functional connectivity across the entire brain. However, task-evoked fMRI still has a place in human brain mapping. Perfusion MRI is valuable in psychiatric disease because it provides a surrogate marker of basal neural activity based on the concept of neurovascular coupling. More advanced physiological parameters, such as brain metabolism, cerebrovascular reactivity, and brain waste clearance system, can also be assessed by MRI. MR spectroscopy provides important information on metabolites and neurotransmitter concentrations.
Emerging Treatments for Bipolar Disorder
Authors: Yalin Nefize , Young Allan H. , Zarate Jr. Carlos A.
Published: January 2025

Various medication options with good efficacy are currently available for bipolar disorder treatment, but there are some major pitfalls regarding these agents. Therefore, improving the treatment outcome in bipolar disorder is a pressing issue, and it involves both optimizing the available interventions and pursuing novel treatment options. Multiple pharmacological and nonpharmacological therapies acting through different mechanisms have been investigated as potential therapeutic targets for bipolar disorder. Studies on some of these treatments have shown promising results for the most challenging areas in bipolar disorder, including depressive episodes and cognitive and functional impairment. Nevertheless, most of them still need to be tested in larger samples with rigorously designed randomized controlled trials before they can confidently be transferred to the clinical practice. Future studies should follow enriched protocols with further stratification of bipolar disorder samples to allow homogeneous groups for the tested modalities.
Genetics of Depression
Authors: Levey Daniel F. , Gelernter Joel
Published: January 2025

Major depressive disorder (MDD) is moderately heritable and polygenic, meaning that there are many risk gene variants each with a small effect on risk. One contributing factor to this moderate heritability is trait heterogeneity; many symptom permutations can contribute to diagnosis. We review some of the historic family and epidemiologic studies of MDD. We discuss new trends, particularly biobanking and the emergence of the well-powered genome-wide association study (GWAS). We examine the status of studies in under-studied ancestries, and how it is useful to improve population diversity in recruitment to ensure better scientific knowledge and equitable benefits from new insights. We follow-up by seeing how the outcomes of GWAS studies are being leveraged to understand the genetic relationship between MDD and other traits, the underlying biology, and potential clinical implications.
Immune Mechanisms of Depression
Authors: Hodes Georgia E. , Ménard Caroline , Pfau Madeline L. , Russo Scott J.
Published: January 2025

Depression is among the most prevalent psychiatric disorders, yet it is inadequately treated in many patients. Recent evidence suggests that there are subsets of depression patients who exhibit immune-related abnormalities, including elevated levels of proinflammatory cytokines, monocytes, and neutrophils in the peripheral circulation; dysregulation of microglia; and disruption of the blood–brain barrier function. Animal models of stress, which have been used to mimic depressive-like symptomatology in humans, have confirmed links between stressful experience, disrupted immune–brain interactions, and the emergence of depressive-like behaviors. This chapter discusses the most prominent changes identified in humans with depression confirmed in animal stress models. It also discusses the possibility of targeting the immune system to treat depression in humans.
Genetics of Anxiety and Trauma-Related Disorders
Authors: Benstock Sarah E. , Hettema John M.
Published: January 2025

This chapter provides a broad overview of the state of research in the genetics of the primary anxiety and trauma-related disorders. These disorders exhibit moderate familial aggregation and heritability due to genetic risk factors that are shared between them as well as those that are disorder-specific. Although many candidate gene association studies have been published, their value is being rapidly superseded by the wealth of novel genetic variants emerging from genome-wide association studies. Epigenetic studies are testing key hypotheses about the combined role of stress and genetics in trauma-related disorders, but they are still in their infancy for the primary anxiety disorders. Animal studies provide a promising complimentary approach that demonstrates concurring evidence across species and allows deeper investigation into the genetic mechanisms of these disorders.
Anxiety and Trauma-Related Disorders
Authors: Jia Caroline , Li Hao , Tye Kay
Published: January 2025

Despite the pervasiveness of anxiety and trauma-related disorders, there is no mechanistic explanation for their causes, and the search is ongoing for therapeutic interventions that are effective and do not cause undesirable side effects. Given the evolutionarily advantageous function of anxiety and fear responses, there are multiple redundant circuits. However, the robustness that this redundancy provides also represents a challenge for targeted anxiolytic therapies to penetrate the multiple layers of circuitry. To find new targets, preclinical models are required to delve into the neural underpinnings of anxiety. The most utilized preclinical models for anxiety have historically been demonstrated to have various degrees of face, predictive, and construct validity but only assess a limited range of behaviors. Broader use of multiple anxiety assays combined with unsupervised machine learning and discovery of behavioral motifs using computer vision tools will allow researchers to parse anxiety phenotyping into greater granularity.
Epidemiology of Substance Use Disorders
Authors: Kandel Denise B. , Griesler Pamela C. , Hu Mei-Chen , Melas Philippe A. , Kerridge Bradley T. , Grant Bridget F.
Published: January 2025

This chapter examines the epidemiology of substance use and substance use disorders based on data from two nationally representative surveys, the 2019 National Survey on Drug Use and Health and the 2013 National Epidemiological Survey on Alcohol and Related Conditions–III. The chapter reviews the prevalence of substance use and substance use disorders among adults and adolescents; substance use disorders and comorbidity of substance use disorders with psychiatric disorders among adults; and differences by age, gender, and race/ethnicity. The impact of marijuana legalization and the COVID-19 pandemic on substance use and mental health is briefly discussed. Drug use initiation sequences, including changing patterns involving e-cigarettes and marijuana, are defined in a national adolescent sample. Adolescence as a critical exposure period is reviewed.
Genetics of Substance Use Disorders
Authors: Goldman David , Sambo Danielle
Published: January 2025

Substance use disorders (SUDs) are influenced by genes, environment, and gene × environment interactions, leading to different levels and kinds of vulnerability. Some genes are substance specific, including genes that mediate drug metabolism or receptor binding. Others are nonspecific, including genes influencing reward, stress resiliency, or executive function, and are thus pleiotropic, leading to cross-transmission and comorbidity of SUDs and other disorders. Genome-wide association studies have revealed many SUD genes, including some in known pathways to addiction. Most functional loci are unknown, but polygenic scores are accounting for an increasing fraction of genetic liability. The identification of rare and uncommon variants with roles in SUDs is expanding, with some being “private” to certain populations, underscoring the need to increase diversity in SUD genetic studies. Together with multiomic data including transcriptome and epigenome, genomic studies are identifying new pathways to SUDs and generating novel targets for treatment and prevention.
Animal Models of Addiction
Authors: Evans Christopher J. , Jentsch J. David , Kieffer Brigitte L. , Maldonado Rafael J. , Cahill Catherine M.
Published: January 2025

Substance use disorders (SUDs) are characterized by chronic relapsing episodes of drug seeking and/or drug taking, often despite negative outcomes. Although animal models cannot recapitulate all aspects of SUDs because of the complexities of societal interactions and human-specific processing of rewards and affect, there are many components of SUDs that can be effectively modeled. This chapter reviews the key concepts, advantages, and caveats of using animal models to study initiation, maintenance, and escalation of drug taking, drug taking despite adverse consequences, and drug abstinence and relapse. The chapter discusses the models that have direct translational impact and where there are interpretation limitations. It also reviews the animal models used to interrogate both genetic and environmental factors influencing vulnerability at different stages of SUD. Animal models have made important contributions to the current knowledge of drug-mediated responses and adaptations to brain circuitry that could never have been acquired via human research.
Molecular and Cellular Mechanisms of Primary Tauopathies
Authors: Gong Shiaoching , Gan Li
Published: January 2025

Primary tauopathies are a diverse group of sporadic or genetic neurodegenerative diseases in which tau is the predominant pathology in neurons, glia, or both. They can be classified to 3R and 4R tauopathies with respect to major tau isoforms. There are different clinical syndromes associated with distinct isoforms of tau, type of cellular inclusions, and the regions of the brain affected. Neuropathological heterogeneities also suggest that each isoform of tauopathy may have distinct mechanism or tau conformers. Better understanding of biology and pathology of tau, the maladaptive innate immune response, the three-dimensional structures from cryo-electron microscopy studies, and the discoveries from human patients and animal models is important for the development of therapeutics for primary tauopathies.
Novel Approaches for Treating Pediatric Psychiatric Disorders
Authors: Sabetfakhri Niki P. , Cook Jr. Edwin H.
Published: January 2025

Ongoing gene discovery has led to the identification of numerous genes underlying pediatric psychiatric disorders. Neurodevelopmental disorders such as autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder have been associated with rare pathogenic variants of large effect. Studies that examine single-gene disorders that cause syndromic ASD have allowed scientists to investigate causative protein defects underlying key behavioral phenotypes. Scientists have utilized a combination of approaches to develop targeted treatments. In a mechanistic approach, knowledge of underlying pathophysiology is used to target disease mechanisms. Alternatively, unbiased drug screening has uncovered therapeutic compounds in the absence of such knowledge. Advances in new gene therapy methods have allowed for the targeting of dysfunctional genes directly. Together, these approaches have led to the discovery of novel therapeutics that can alleviate symptomatology in pediatric psychiatric disorders and shed light on the underlying disease mechanisms.
The NIMH Research Domain Criteria Project
Authors: Cuthbert Bruce N.
Published: January 2025

The Research Domain Criteria (RDoC) project is an experimental framework for translational research on mental illness. The project was initiated in response to the increasing concern that contemporary scientific data in genetics, neurobiology, and behavior do not align with current diagnostic categories, thus constraining cutting-edge research. RDoC encourages new ways of studying psychopathology in terms of dysregulation in basic functions (e.g., working memory or reward valuation), with an emphasis on neurodevelopment and environmental effects that are recognized as key drivers of disorder risk. This chapter reviews ways in which RDoC has integrated multiple measures of dimensional functions to promote mechanistic studies that have already resulted in multiple proof-of-concept clinical trials. This transdiagnostic research has fostered a wide variety of computational methods that are shifting perspectives on mental illness toward a precision approach to psychiatry.
From Codes and Ethics to Professional Identity Formation and Beyond
Authors: de Groot Janet , Crowshoe Lynden (Lindsay) , Simpson Annie
Published: January 2025

Consistent with more inclusive medical education, professionalism is challenged to better address equity, diversity, inclusion, and accessibility (EDIA). This chapter identifies an Indigenous perspective on ethical space and ethical listening to support engaging with difference. With the used of an EDIA lens, the American Medical Association’s Code of Ethics is analyzed. A critical literature review assesses for EDIA integration into professional identity formation (PIF) in both adult psychological and development growth and the role of socialization. Literature on socialization in the current medical culture has begun to consider the role of relationships, including mentorship for PIF to support diverse personal identities and different lived experiences. Finally, professional resistance is described as valuable for medical education to affirmatively find solutions for injustices and health inequities within healthcare.
Ecosystems of Professionalism
Authors: Edgar Laura , Selden Nathan R. , Brigham Timothy P. , Inui Thomas S.
Published: January 2025

Objective: This chapter focuses on the way that professionalism can develop during graduate medical education and how it can be measured through milestones. Methods: Through use of the Accreditation Council for Graduate Medical Education’s milestones for professionalism (professional behavior, ethical principles, and accountability), the literature has been explored and vignettes have been developed to further demonstrate a developmental trajectory of attaining advanced levels of professionalism in these three areas. Results: Milestones data demonstrates the growth of professionalism during graduate medical education at both the residency and fellowship levels. Development and demonstration of these skills and attributes happen at different junctures in training. Conclusion: Professionalism is a competency that develops over time and through various experiences. As an individual moves from medical school to residency to fellowship and into practice, professionalism skills will continue to develop.
Special Considerations for Military and Veterans
Authors: Place Ronald , Sugden Steven G.
Published: January 2025

Military medicine serves the specific purpose of working to maintain the high-functioning capacity of the U.S. military complex, with the unique role to preserve the health of its Soldiers. This makes the provision of care in military medicine different from the care provided only to civilian populations and results in important differences in how medical professionalism is thought about and addressed within the provision of military medicine. This chapter addresses some of the historical aspects of military medicine, as well as how military medicine has helped advance medical care, while also addressing some of the specific differences in education and development of military medical professionals.
Health Law and Organizational Professionalism
Authors: Agris Julie L.
Published: January 2025

Fractions of the health sector continue to grapple with public skepticism about professionalism, on individual and organizational levels. This uncertainty has led to questions related to the ability to trust healthcare personnel at every level of the system. To foster healthcare organizations that prioritize organizational professionalism (OP), leaders, in addition to all stakeholders, within the entity must understand and consider the framework for realizing OP. One approach to purposefully incorporating OP principles into an organization’s culture may be to identify ongoing organizational behaviors and actions that promote professionalism. One area that is regularly implicated as an obstacle to achieving professionalism is the laws and associated policy requirements. To delve more deeply into the ways in which the law does or does not act as an impediment to prioritizing professionalism and OP, this chapter reviews the relevant domains of OP, identifies many of the areas on which they intersect with health law (HL), then concludes with a case study of the way in which the OP domains could be applied to an important aspect of HL: privacy and confidentiality of protected health information. The chapter identifies several of the commonly perceived areas of concern related to HL and its potential to impede the achievement of OP. The chapter concludes by suggesting preliminary strategies and recommendations for improving identified obstacles and ways in which the law can serve to support efforts to prioritize OP and bolster trust and trust building in the health sector.
Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department
Authors: Choi Alex , Morrison Laura
Published: January 2025

This randomized, double-blinded, placebo-controlled trial investigated whether inhaled isopropyl alcohol reduces nausea compared to inhaled normal saline. Eighty adults who presented to the emergency department with the chief complaint of nausea/vomiting were randomized to either inhaled isopropyl alcohol or inhaled normal saline. Investigators measured verbal scores of nausea and pain at fixed intervals, overall satisfaction, and coadministration of rescue antiemetics. The intervention group had a lower median nausea score at 10 minutes compared to the placebo group (P < .01) and higher overall satisfaction. These findings suggest inhaled isopropyl alcohol as a potential effective treatment for acute nausea.
Methadone Versus Morphine as a First-Line Strong Opioid for Cancer Pain
Authors: Allen Jennifer , Gans Brian
Published: January 2025

This chapter reviews a study that compares the effectiveness and side effects of methadone and morphine as first-line opioid treatment for cancer pain. Patients in multiple international palliative care clinics with cancer pain were randomly assigned to receive methadone or morphine over the duration of a 4-week study. Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared to morphine. This is the first double-blind study that uses methadone as a first-line strong opioid for patients with advanced cancer pain.
Octreotide in Malignant Bowel Obstruction
Authors: Latuga Natalie M. , Luczkiewicz Debra L. , Davis Mellar P.
Published: January 2025

This chapter reviews a large, double-blind, placebo-controlled, randomized trial examining the effects of adding octreotide to standardized supportive therapy in the setting of malignant bowel obstruction. The study was rigorously designed and adequately powered for the primary endpoints and found no significant difference between octreotide and placebo, which is contrary to current practice and other reports of efficacy. This chapter describes the basics of the study and briefly reviews the study limitations and criticisms. The implications of this study are illustrated by a short clinical case.
Safety and Benefit of Discontinuing Statin Therapy in Advanced Life-Limiting Illness
Authors: Nymeyer Jessica
Published: January 2025

This multicenter, unblinded, randomized clinical trial evaluated the impact of discontinuation of statin therapy for individuals with a life expectancy of less than 1 year without active cardiovascular disease and found no significant difference in survival or cardiovascular events. The study found that statin discontinuation may be associated with improved quality of life, decreased use of nonstatin medications, and reduced medication cost.
Safety of Morphine Delivered via Patient-Controlled Analgesia Devices in the Pediatric Population
Authors: Urban Sophia S. , Higgins Elizabeth A.
Published: January 2025

Although the use of patient-controlled analgesia (PCA) in the pediatric population is widely accepted as an effective and preferable method of pain control, there have been no large-scale studies conducted to examine the safety of these devices in children. This study compared the delivery of morphine either via PCA device or intravenous (IV) administration in a retrospective cohort and assessed the short-term risk of cardiopulmonary resuscitation (CPR) or need for mechanical ventilation (MV). Results showed that patients who received morphine via PCA were not at increased risk of requiring CPR or MV, leading to the conclusion that PCA usage in pediatric patients is at least as safe as conventional IV analgesia.
Migraine
Authors: Kernick David , Davies Brendan
Published: January 2025

Migraine is the most common headache diagnosis in all clinical settings. It has significant impact upon the lives of sufferers and their families with decrease in health-related quality of life and negative impact on functioning. This chapter gives an overview of epidemiology, pathophysiology, and diagnosis. It includes complications and comorbidities.
Migraine management
Authors: Kernick David , Davies Brendan
Published: January 2025

This chapter gives a n overview of migraine management. The identification of triggers and the influence of environmental factors are an important starting point. Lifestyle factors are also important such as diet and exercise. The pharmacological treatment of the acute attack and migraine prevention are described together with other approaches where evidence is limited, overrated or contested.
Headache and sleep
Authors: Nesbitt Alex
Published: January 2025

A strong bidirectional relationship exists between sleep and headache disorders. This relationship exists at many levels, including neuroanatomical, physiological, pharmacological, homeostatic, and therapeutic. Disturbances in sleep, and sleep disorders, impact many of the primary headache disorders.

This chapter provides an overview of these relationships, and a practical approach to modifying and optimizing sleep to aid in the management of headache.
Headache in children
Authors: Abu-Arafeh Ishaq
Published: January 2025

Headache is one of the most common complaints in children. Recurrent headache can negatively impact a child’s life in a number of ways, including school absences, decreased academic performance, social stigma, and impaired ability to establish and maintain peer relationships.

Headache in young people is associated with a high risk of comorbidities, particularly anxiety and depression, sleep disorders, and attention deficit hyperactivity disorder. It invariably persists into adulthood, so timely diagnosis is an opportunity for early understanding and control of headache and its associated problems. This chapter offers an overview of the management of headache in children.
Psychological approaches to headache conditions
Authors: White Sophie
Published: January 2025

The psychological needs of people with headache conditions are frequently defined in terms of high rates of mental health comorbidities, such as anxiety, depression, and suicidality. Psychological factors may also maintain illness behaviour that leads to higher levels of disability. This chapter describes a range of assessment and screening tools and an overview of current approaches to the psychological management of the person with headache.
Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting
Authors: Jaiswal Rahul , Braud Brandon , Hernandez-Ramirez Karen C , Santosh Vishaka , Washington Alexander , Escalante Carlos R
Published: January 2025

The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states. In the nucleotide-free state, Rep68 forms a heptameric complex around DNA, with three origin-binding domains (OBDs) bound to the Rep-binding element sequence, while three remaining OBDs form transient dimers with them. The AAA+ domains form an open ring without interactions between subunits and DNA. We hypothesize that the heptameric structure is crucial for loading Rep68 onto double-stranded DNA. The ATPγS complex shows that only three subunits associate with the nucleotide, leading to a conformational change that promotes the formation of both intersubunit and DNA interactions. Moreover, three phenylalanine residues in the AAA+ domain induce a steric distortion in the DNA. Our study provides insights into how an SF3 helicase assembles on DNA and provides insights into the DNA melting process.
RNA G-quadruplex structure-based PROTACs for targeted DHX36 protein degradation and gene activity modulation in mammalian cells
Authors: Zhang Kun , Nie Qichang , Li Maolin , Chen Xiaona , Zhong Liting , Dai Tianle , Guo Xiaofan , Zhao Haizhou , Lau Terrence Chi-Kong , Wang Huating , Chen Shuo-Bin , Kwok Chun Kit
Published: January 2025

RNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development. Generating innovative tools to disrupt rG4-G4BP interactions will provide a unique opportunity to explore new biological mechanisms and potentially treat related diseases. Here, we have rationally designed and developed a series of rG4-based proteolytic targeting chimeras (rG4-PROTACs) aimed at degrading G4BPs, such as DHX36, a specific G4BP that regulates gene expression by binding to and unraveling rG4 structures in messenger RNAs (mRNAs). Our comprehensive data and systematic analysis reveals that rG4-PROTACs predominantly and selectively degrade DHX36 through a proteosome-dependent mechanism, which promotes the formation of the rG4 structure in mRNA, leading to the translation inhibition of rG4-containing transcripts. Notably, rG4-PROTACs inhibit rG4-mediated APP protein expression, and impact the proliferative capacity of skeletal muscle stem cells by negatively regulating Gnai2 protein expression. In summary, rG4-PROTACs provide a new avenue to understand rG4-G4BP interactions and the biological implications of dysregulated G4BPs, promoting the development of PROTACs technology based on the non-canonical structure of nucleic acids.
Job-exposure matrix (JEM) validity on crystalline silica among systemic sclerosis patients
Authors: Touchard M , Bourgeois A , Thoreau B , Fadel M , Zavarsky B , Diot E , Lescoat A , Le Roux G , Descatha A
Published: January 2025

Background

Systemic sclerosis (SSc) is the connective tissue disease with the highest individual mortality. Crystalline silica is known to be an occupational risk factor for SSc. To assess past crystalline silica exposure, we aimed to study the validity of a job exposure matrix (JEM) to assess occupational exposure to crystalline silica compared to specific occupational interviews in two populations of SSc patients.

Aims

To demonstrate the reliability of JEM for the assessment of occupational exposure to hazards such as silica, in severe rare disorders like SSc.

Methods

Patients from two university hospital centres underwent standardized assessment of occupational silica exposure and collected job histories through face-to-face interviews. A JEM from the French program Matgéné was used to assess silica exposure and compared to the standardized interview results. Standard metrics were computed for evaluate the accuracy of JEM.

Results

67 participants from Rennes, and 119 from Tours were included, with respectively 10.5% and 18.0% of patients with silica exposure based on the results of the interview. The JEM with 50% probability cut-off had a good performance when compared with the classic assessment method. A cumulative exposure index from JEM over 250 had an area under the curve between 0.76 and 0.79 and also a very high positive likelihood ratio (17.14 and 10.29).

Conclusions

Despite limitations inherent to JEMs and associated validation methods, the JEM used in this setting provided accurate results to assess occupational exposure to crystalline silica for clinical purposes such as in SSc patients, especially to detect positive cases.
579. Safety and Immunogenicity of Mpox Vaccination in Adolescents
Authors: Healy C Mary , Creech C Buddy , Frey Sharon E , Lerner Andrea , Tomashek Kay , Beigel John H
Published: January 2025

Background

Monkeypox (Mpox) is a global public health threat. In the current Democratic Republic of Congo (DRC) mpox outbreak, children < 15 years of age comprise 70% of cases and 88% of deaths. Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is a live attenuated, non-replicating orthopoxvirus vaccine licensed in the US to prevent smallpox and mpox. MVA-BN is not approved in persons < 18 years of age (though is available in some countries under emergency use authorization).

Geometric Mean Titers of Vaccinia-Specific PRNT by Time Point and Age Group

Methods

We conducted a Phase 2, open-label, multisite clinical trial to evaluate the safety and immunogenicity of two 1x108 TCID50 doses of MVA-BN vaccine administered subcutaneously 28 days apart in adolescents aged 12-17 years compared to adults aged 18-50 years (NCT05740982). A planned interim analysis evaluated safety through Day 210 (180 days post dose 2) and immunogenicity through Day 43 (14 days post dose 2).

Results

Three hundred fifteen adolescents (161 [51%] aged 12-14 years, 160 [51%] male, 216 [69%] white, 251 [80%] not Hispanic or Latino) were compared to 211 adults (94 [45%] male, 145 [69%] white, 149 [71%] not Hispanic or Latino). Solicited systemic and local events, and unsolicited adverse events (AEs), were similar in both groups. Dizziness was more common in adolescents (9 events in 8/315 (3%) versus none in adults) but similar to rates reported after other adolescent vaccines. Overall, MVA-BN was well tolerated. Day 43 antibody responses, based on vaccinia virus (Western Reserve strain) plaque-reduction neutralization titer (PRNT) assay geometric mean titer (GMT), elicited by MVA-BN in adolescents (470.3 [95% CI: 422.3, 523.8]) were non-inferior to the response in adults (293.2 [95% CI: 249.8, 344.2]); GMT ratio: 1.60 [95% CI: 1.32, 1.95]) (Figure).

Conclusion

The interim data demonstrate MVA-BN vaccine is well-tolerated and the peak GMT met prespecified non-inferiority criteria for adolescents as compared to adults. These findings are relevant to adolescents in the US and in areas where Mpox is endemic. Evaluations in younger children are urgently needed to extend protection to those who are most vulnerable.

Disclosures

C. Mary Healy, MD, FIDSA, Dexcom Inc: Stocks/Bonds (Public Company)|Hillevax, Inc: Member of Advisory board|Intuitive Surgical Inc: Stocks/Bonds (Public Company)|Quidel Corporation: Stocks/Bonds (Public Company)|Vapotherm: Stocks/Bonds (Public Company) C. Buddy Creech, MD, MPH, CommenseBio: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|TDCowen: Advisor/Consultant|UpToDate: Honoraria|Vedanta: Grant/Research Support Sharon E. Frey, MD, Bavarian Nordic: Grant/Research Support|Saint Louis University (SLU): Grant/Research Support
170. Intrapartum Antibiotic Exposure and Infectious Diseases in Childhood - A Population-based Cohort Study
Authors: Hakkola Mikael , Ainonen Sofia , Ronkainen Eveliina , Honkila Minna , Paalanne Marika , Pokka Tytti , Kajantie Eero , Paalanne Niko , Ruuska Terhi
Published: January 2025

Background

Universal maternal screening for group B streptococcus (GBS) colonization and subsequent use of intrapartum antibiotics is currently recommended practice in many high-income countries. This strategy has reduced the occurrence of early-onset GBS diseases in infants significantly. However, this practice exposes up to 30% of infants to antibiotics at birth. Intrapartum antibiotics have been shown to alter the gut microbiome composition in the offspring, which may be associated with long-term clinical outcomes. We hypothesized that maternal use of intrapartum antibiotics increases the risk of infectious diseases in the offspring.Table 1.Baseline characteristics of the study cohort

Methods

In a cohort study of 45 575 vaginally delivered newborn infants in Finland, there were 9733 children exposed to intrapartum antibiotics and 35 842 unexposed children. Intrapartum antibiotic exposure was defined as antibiotics administered to mother 24 hours or less before birth of the child. The data used in the study were retrieved from high quality national registers and electronic medical records. Primary outcome was the annual number of infectious disease episodes leading to hospitalization, emergency department visit, or other outpatient visit in specialized health care during the first five years of life.Table 2.Number of infectious disease episodes during the first five years of life.

Results

Intrapartum antibiotic exposure was associated with increased risk of any infectious disease episode at ages 7-28 days (adjusted incidence rate [aIR)] 1.32, 95% CI 1.12−1.57), 1−2 years (aIR 1.09, 95% CI 1.03−1.15), and 2−3 years (aIR 1.08, 95% CI 1.00−1.17). Intrapartum antibiotic exposure was also associated with an increased cumulative incidence of at least one infectious disease episode, increased number of urinary tract infection episodes, and increased number of antibiotic courses received. We found no association with severe infections. Intrapartum antibiotics protected offspring from severe infections caused by pathogens susceptible to penicillin beyond neonatal period.Table 3.Number of severe infection episodes, number of antibiotics courses used and number of infection related surgical operations performed during the first five years of life.,

Conclusion

Intrapartum antibiotics were associated with a long-term altered risk of infectious diseases in childhood. The observed associations appeared to depend on the causative pathogens and their susceptibility to penicillin. Previously observed changes in gut microbiome might explain the findings.Figure 1.Cumulative incidence of at least one infectious disease episode during the first five years of life.

Disclosures

All Authors: No reported disclosures