bluuebunny/crossref_metadata_2025 huggingface dataset:
Dabigatran
Authors: Benz Alexander P. , Hohnloser Stefan H.
Published: October 2023

Dabigatran is a direct oral anticoagulant that acts through specific and reversible inhibition of thrombin. It has been developed as a fixed-dose, modern alternative to vitamin K antagonists such as warfarin. Dabigatran does not require frequent blood testing or dose adjustments. The main indication for dabigatran is the prevention of stroke and systemic embolism in patients with atrial fibrillation and risk factors for stroke. Furthermore, there is high-quality evidence supporting its use in patients with atrial fibrillation undergoing percutaneous coronary intervention or catheter ablation. Dabigatran has also received approval for the prevention of venous thromboembolism after major orthopaedic surgery and recurrent venous thromboembolism, and the treatment of venous thromboembolism. Dabigatran is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min), and in patients with moderate-to-severe mitral stenosis or with a mechanical heart valve prosthesis. Idarucizumab is a monoclonal antibody fragment that specifically reverses the anticoagulant activity of dabigatran.
Antithrombotic strategies in primary cardiovascular prevention
Authors: Michelotti Erica , Ridker Paul M. , De Caterina Raffaele
Published: October 2023

Antithrombotic strategies in primary cardiovascular prevention essentially revolve around the use of aspirin. This chapter provides an update and guidance for the use of aspirin in patients without previous clinical evidence of vascular disease. In contrast to secondary prevention, aspirin in primary prevention is widely debated in part because early trials predated the statin era. furthermore, because prevention of cardiovascular outcomes demonstrated in several trials was counterbalanced by increased risk for bleeding, a net clinical benefit has not clearly been shown in pooled estimates. Using data from the most recent trials, and performing a meta-regression of benefits and risks associated with aspirin use as related to the 10-year risk of major adverse cardiovascular events (MACEs), a tailored approach to aspirin prescription in primary prevention is proposed. In patients aged less than 70 years with optimal risk factor control, individual cardiovascular risk should be carefully evaluated, while also considering bleeding risk and patient preferences. Absolute MACE reduction appears superior to the hazard of haemorrhagic events in patients at intermediate–high cardiovascular risk without a prohibitive bleeding risk, and this category of individuals, as well as those with documented evidence of subclinical carotid, coronary, or peripheral atherosclerotic vascular disease, appear to be a proper target population. Treatment of other cardiovascular risk factors, such as high cholesterol, should, however, be prioritized prior to aspirin administration, and this should be accompanied, especially in the elderly, by the concurrent administration of gastroprotective agents.
Antithrombotic strategies in patients undergoing elective percutaneous coronary interventions and in chronic coronary syndromes without interventions
Authors: Greco Antonio , Capodanno Davide
Published: October 2023

Antithrombotic therapy plays a key role in the treatment and secondary prevention of coronary artery disease. After elective percutaneous coronary intervention or chronic coronary syndrome, dual antiplatelet therapy (DAPT) is usually indicated for 6 months. However, a risk stratification approach considering both the ischaemic and bleeding risks is of the utmost importance. Different antithrombotic regimens can be adopted, including strategies aimed at minimizing the risk of bleeding (i.e. shortening DAPT duration) or at enhancing antithrombotic protection (i.e. prolonging DAPT duration, switching to more potent P2Y12 inhibitors, or adding a low-dose anticoagulant to aspirin). The choice is even more challenging among patients who require, per se, long-term oral anticoagulation, in whom a triple therapy is theoretically indicated but unfeasible over the long term due to the excess bleeding risk. The aim of this chapter is to review the evidence supporting guideline recommendations in the field of antithrombotic therapy for patients with chronic coronary syndrome.
Antithrombotic therapy in ST-elevation acute myocardial infarction and non-ST elevation acute coronary syndromes
Authors: Parker William A.E. , De Caterina Raffaele , Moliterno David J. , Kristensen Steen Dalby , Storey Robert F.
Published: October 2023

Atherothrombosis is the central pathological process in acute coronary syndromes (ACS). Antithrombotic therapy is, therefore, a cornerstone of ACS treatment. As soon as ACS is suspected, aspirin should be commenced to reduce the risk of major adverse cardiovascular events. Addition of an oral P2Y12 inhibitor further reduces risk. Parenteral anticoagulation is indicated for any patient undergoing percutaneous coronary intervention (PCI) or thrombolysis, and for patients with non-ST elevation ACS where an early invasive treatment strategy is not pursued. In some cases of PCI for ST-elevation myocardial infarction, a platelet glycoprotein inhibitor may be utilized. Where timely primary PCI cannot be performed for ST-elevation myocardial infarction, thrombolysis with a tissue plasminogen activator may be recommended. Where there is an additional requirement for oral anticoagulation, in general patients treated by PCI should receive a short period of aspirin plus P2Y12 inhibitor plus oral anticoagulation before stopping aspirin, and then receive oral anticoagulation alone from 1 year.
Antithrombotic therapy for patients with prosthetic valves and during structural percutaneous interventions
Authors: Misumida Naoki , Alkhouli Mohamad , Moliterno David J.
Published: October 2023

Prosthetic heart valves are effective in alleviating symptoms of dysfunctional native valves. However, prosthetic valves are inherently inferior to native valves regarding haemodynamics, durability, and thrombogenicity. Antithrombotic therapy reduces the long-term risk of prosthetic valve thrombosis after mechanical valve replacement and can potentially mitigate the risk of acute or subacute leaflet thrombosis after bioprosthetic valve replacement. With the increasing complexity of patient undergoing valve replacement and the advent and growing use of direct oral anticoagulants, antithrombotic management among patients with valvular heart disease and prosthetic valves has become more intricate. This chapter reviews the current prophylactic and therapeutic strategies for the prevention and treatment of valve thrombosis and discusses future directions in this field.
Atrial fibrillation: current and forthcoming antithrombotic therapies
Authors: De Caterina Raffaele , Marcucci Rossella
Published: October 2023

Atrial fibrillation is the most common sustained arrhythmia, involving up to 1 out of 10 patients beyond 80 years of age. Its prevalence is increasing, only partly explained by the ageing of the population. Atrial fibrillation is a thrombogenic condition, with blood stasis in the left atrium/left atrial appendage and local structural abnormalities in the atrial walls favouring thrombus formation and distal embolization in the arterial circulation, causing 20–25% of ischaemic strokes. The risk of stroke in patients with atrial fibrillation is widely variable, from less than 1/100 patient-years (indistinguishable from the risk of the average population without the arrhythmia) to greater than 10/100 patient-years, depending on well-characterized risk factors, some of which are modifiable. Risk scores, such as the CHA2DS2-VASc, help in stratifying ischaemic risk, but are even more useful to identify patients who do not derive benefit—and possibly derive harm—from antithrombotic treatments. Anticoagulants are here the antithrombotic treatment of choice, and are clearly superior to aspirin for stroke prevention. In recent years, with few exceptions, the non-vitamin K antagonist oral anticoagulants have largely replaced vitamin K antagonists such as warfarin for stroke prevention, being at least equally effective and safer. An emerging role for stroke prevention is that of left atrial appendage occlusion, either percutaneous or surgical.
Antithrombotic therapies in inherited or acquired thrombophilia
Authors: Pengo Vittorio , Denas Gentian
Published: October 2023

The treatment of thrombophilias and their related clinical events is based on antithrombotic agents. Testing for inherited thrombophilia generally does not alter the clinical management of patients with venous or arterial thrombosis or pregnancy complications. An exception may be the presence of severe inherited thrombophilia that is usually rare and comprises deficiency of natural coagulation inhibitors (antithrombin, protein C, and protein S) or homozygosity and compound heterozygosity of factor V Leiden and prothrombin variant G20210A. In contrast, the presence of acquired thrombophilia guides antithrombotic treatment in affected patients. Appropriate treatment is important in patients with the antiphospholipid syndrome, heparin-induced thrombocytopenia, paroxysmal nocturnal haemoglobinuria, polycythaemia vera/essential thrombocythaemia, and sickle cell disease. Other common conditions of acquired thrombophilia, such as combined oral contraceptives and cancer-associated thrombosis, deserve special attention. Finally, the correct differential diagnosis of thrombotic microangiopathies is the basis of correct antithrombotic treatment.
Prevention and treatment of bleeding related to antithrombotic drugs
Authors: Mehran Roxana , Spirito Alessandro , Cao Davide , Dangas George
Published: October 2023

Antiplatelet and anticoagulant therapy reduce the occurrence of ischaemic events both in primary and secondary prevention in different cardiovascular conditions. However, these benefits come at the expense of higher bleeding complications, especially when different types of antithrombotic medications are combined. For decades, bleeding was thought to be an unavoidable side effect of antithrombotic therapy and of marginal relevance compared to ischaemic events. Yet, in recent years, major bleeding has been proven to impact mortality to a similar extent as ischaemic events. For these reasons, adoption of bleeding avoidance strategies is pivotal in the management of patients on antithrombotic therapy. These include an upfront bleeding risk assessment, accurate selection of candidates for invasive procedures, prevention of vascular access-related bleeding, modulation of antithrombotic therapy, and regular monitoring follow-up visits to reassess the bleeding risk and adjust the treatment. In case of bleeding, prompt treatment including reversal of antithrombotic treatment is required.
Management of patients treated with antithrombotic drugs undergoing surgery
Authors: Maeng Michael , Kristensen Steen Dalby , Siller-Matula Jolanta M.
Published: October 2023

Many patients with cardiovascular disease need surgery while on treatment with antiplatelet or anticoagulant drugs. Patient-related factors (severity of cardiovascular disease, comorbidities, age, and the type and combination of antithrombotic agents) and procedure-related factors (urgency, duration, and type of procedure) determine the risk of ischaemic and bleeding complications. Since major cardiovascular and bleeding events both occur frequently in the perioperative setting, the decision to interrupt or continue an antithrombotic agent must be carefully considered for each individual patient. Importantly, cardiovascular and bleeding events are interlinked since bleeding often leads to interruption of antithrombotic agents or transfusion of blood products, which may induce platelet hyperactivity. Also, surgery induces a prothrombotic state with enhanced risk of arterial and venous thrombosis. This chapter focuses on timing and duration of perioperative drug discontinuation, reversal for antiplatelet and antithrombotic agents, and when to resume antithrombotic therapy.
Antithrombotic therapy in patients with atrial fibrillation and recent coronary stenting, with or without an acute coronary syndrome
Authors: Fanaroff Alexander C. , Lopes Renato D. , Alexander John H.
Published: October 2023

Many patients with atrial fibrillation (AF) will ultimately undergo percutaneous coronary intervention (PCI) at some point in their lifetime. Though antithrombotic therapy is indicated for both conditions, anticoagulation is most effective for stroke prophylaxis in AF and dual antiplatelet therapy is most effective for prevention of stent thrombosis and myocardial infarction after PCI. However, the use of so-called triple therapy (oral anticoagulation + P2Y12 inhibitor + aspirin) in patients with AF who undergo PCI is associated with unacceptably high rates of major bleeding. Over the past decade, multiple clinical trials have tested alternate antithrombotic regimens in this patient population. Overall, these trials have indicated that the combination of a non-vitamin K antagonist oral anticoagulant plus clopidogrel, with only a short (7–30 days) course of aspirin, hits the sweet spot of limiting major bleeding while still providing acceptable protection from stroke, stent thrombosis, and myocardial infarction.
Antithrombotic agents and drug–drug interactions
Authors: Dunn Steven P. , Beavers Craig J. , Moliterno David J.
Published: October 2023

Drug–drug interactions affecting antiplatelet and anticoagulant medications are not uncommon, and among patients with cardiovascular disease, many receive polypharmacy thereby increasing the risk for important drug interactions. Such interactions may impact the efficacy or safety, or both, of antithrombotic medications. Since vitamin K antagonists have been widely used in clinical medicine for many years, drug interactions with agents such as warfarin are well known. Over recent years, newer and more potent antiplatelet and anticoagulant agents have been developed, and each of these has an identified potential to be impacted by other medications, primarily by affecting hepatic cytochromes involved with drug metabolism. While many interactions have been identified and alterations of plasma concentrations of drugs have been found, limited meaningful impacts on clinical outcomes have been discerned from large-scale trials. Drugs which importantly alter renal function may also pose a drug clearance issue for agents with a high proportion of the active compound being renally excreted. Lastly, the combination of anticoagulant agents poses the highest risk to patients as the antithrombotic impact is greatest as well as the risk for drug-related interactions among the antithrombotic agents and with other drugs. Recognition of these risks has led to increased scrutiny of anticoagulant safety by clinical care providers, pharmaceutical companies, health agencies, as well as accrediting bodies.
Personalized antithrombotic therapy: measuring individual variation and monitoring
Authors: van den Broek Wout W.A. , ten Berg Jur M. , Sibbing Dirk , Rizas Konstantinos D.
Published: October 2023

Antithrombotic drugs are frequently prescribed in patients with coronary artery disease, embolic stroke, or atrial fibrillation to prevent thrombosis. However, patients vary widely in their response to these drugs. This interindividual variability can be a result of genetic variation in enzymes that play a role in drug metabolism, though it can also be a consequence of other patient characteristics. A personalized antithrombotic treatment accounts for this interindividual variability with the aim of optimizing the balance between the risk of bleeding and thrombosis. Personalization of antithrombotic therapy might be done by testing for genetic polymorphisms or measuring the patient’s response on treatment, both of which have their advantages and disadvantages. This chapter describes the different ways that antithrombotic therapy can be personalized, provides the latest evidence for these strategies, and focuses on the treatment strategies with the most clinical impact.
Schizophrenia and the Error-Prediction Model of Thought Insertion
Authors: López-Silva Pablo , Cavieres Álvaro
Published: October 2023

Delusions of thought insertion (TI) are a severe symptom of psychosis with a higher prevalence in schizophrenia. People suffering from TI claim that external agents of different nature introduce thoughts into their minds in a generally altered experience of embodiment, external reality, and intersubjectivity. One of the most fundamental issues surrounding the clinical understanding of TI is the debate about how it is produced or, as it will be called in this chapter, the aetiological problem. Over the last years, the so-called error-prediction model of delusions has been gaining explanatory traction due to the way in which it brings together insights from neuroscience, computational psychiatry, and phenomenological psychopathology. This model claims that, in creating our conscious experience of reality, our brain uses prior learned predictions to infer the causes of incoming sensory data. Moreover, this process can be formalized as a type of Bayesian inference where probabilistic predictions are combined with observed sensory data to compute. After describing some of the most fundamental aspects of TI in the context of schizophrenia, this chapter examines a number of issues that applications of the prediction-error model to the aetiological problem face. Finally, in order to motivate further research in the field, we conclude with the description of a challenge that seems to remain open within the target debate.
What Can Magic and Science Tell Us About the Experience of Thought Insertion?
Authors: Pailhès Alice , Olson Jay , Kuhn Gustav
Published: October 2023

Mentalism is a magic genre that deals with mind reading, clairvoyance, prophecies, and thought insertion. Magicians often proclaim (performances, lectures), that they can insert specific thoughts into people’s minds, or unconsciously manipulate their behaviour. For example, magicians may give the illusion that they influence a person’s thoughts through telepathy or psychological priming (e.g., Derren Brown). In most instances, these demonstrations rely on a secret method that simply mimics thought insertion. These fake demonstrations can misinform the public and researchers about what may or may not be possible. This chapter will present in three sections how magicians provide the illusion that there are inserting thoughts into people’s minds and the recent scientific studies showing (1) magicians’ techniques that significantly influence simple thoughts and behaviours and (2) why magic provides a useful tool to mimic thought insertion and (3) how to mimic thought insertion with magic. We will try to distinguish fact from fiction and provide some insight into the type of thoughts magicians can or cannot reliably insert in people’s minds, and discuss the benefits of using magic to induce thought insertion-like symptoms in non-clinical populations.
Thought Insertion and Commitment
Authors: Fernández Jordi
Published: October 2023

In thought insertion, subjects claim to have thoughts which are not their own. This chapter offers an account of the thought insertion delusion by utilizing the notion of commitment, that is, the experience of a conscious state as being appropriate or fitting. The proposed explanation of thought insertion relies on two main tenets. One is that the experience of a thought as being one’s own is the experience of regarding that thought as being correct. The other one is that subjects with thought insertion do not experience being committed to the thoughts that they disown. The account is then extended to the case of patient RB, who disowns some of his conscious memories, and to the case of anarchic hand syndrome, in which patients disown some of their conscious actions.
Cultural influences on placebo and nocebo effects
Authors: Cundiff-O’Sullivan Rachel L. , Oula Desai , Shafir Roni , Colloca Luana
Published: October 2023

The meaning of illness and the context of treatment and expectations are known to influence patients’ responses to treatments, including placebo and nocebo effects. These meanings and expectations are rooted in a person’s cultural beliefs, norms, values, worldview, and experience. This chapter discusses just a few of the elements of culture that can affect placebo and nocebo responses. Cultural differences underlie preferences for the physical or aesthetic elements of treatments and how treatments are marketed and presented in the media. Spiritual and religious beliefs inform coping and other health behaviors. Rituals within both traditional and modern medical belief systems are important contextual factors in eliciting treatment responses. The preferred qualities of a healthcare provider and the interpersonal relationship between patient and provider, shaped by verbal and nonverbal cues, play key roles in maximizing healing. These cultural factors can influence individuals’ responsiveness to placebos and nocebos.
Predictability of placebo responses and their clinical implications
Authors: Branco Paulo , Vachon-Presseau Etienne , Hall Kathryn T. , Wager Tor D. , Vania Apkarian A.
Published: October 2023

The bulk of research on the mechanisms underlying placebo effects has been conducted for painful stimuli in laboratory settings. Such studies identify a long list of learning mechanisms that can explain observed effects, as well as provide evidence that placebo analgesia is associated with reproducible patterns of brain activity. These studies also show that placebo effects are unstable across contexts, and the magnitude of a participant’s response in one setting does not generalize following subtle manipulations of the procedure, suggesting that placebo effects are primarily driven by immediate, context-specific expectations and, thus, remain essentially unpredictable. Recent studies challenge this notion by finding that clinical placebo effects in chronic pain patients can be predicted by genetics, brain properties and language use. If replicated, latter results suggest that placebo effects can be understood and harnessed in clinical treatment of chronic pain conditions and beyond.
Dynamic regulation of genes in placebo responsiveness in alcohol use disorder and co-occurring pain
Authors: Seneviratne Chamindi , Dorsey Susan G. , Colloca Luana
Published: October 2023

Research has shown a significant variation in neurobiological regulation in alcohol use or misuse and alcohol use disorder (AUD) influenced by environmental factors that constantly interact with biological underpinnings such as a person’s genetic background. These differences affect how individuals respond to treatment with pharmacological or behavioral therapies, including placebo responses. Here we discuss the dynamic nature of neurobiological dysregulation and highlight research conducted to identify specific genes whose expression alterations drive molecular level changes underlying placebo responses in AUD. Moreover, given that chronic pain and AUD are highly comorbid common conditions, we present similarities between the two conditions. A mechanistic understanding of the relationship between AUD and chronic pain is important for effective treatment and prevention of both conditions.
Placebos meet proteomics
Authors: Meissner Karin , von Toerne Christine , Lutter Dominik , Hauck Stefanie M. , Tschoep Matthias
Published: October 2023

The human proteome is defined as the overall set of proteins that can be expressed by genome, cells, tissues, or organisms at a given time. There are estimates that the proteome consists of over one hundred thousand proteins, not including posttranslational modifications. Translating genetic information onto the effector level, proteins are involved in numerous biological pathways in health and disease. Especially promising are plasma proteomics in combination with advanced computational tools, to identify potential biomarkers that enable the prediction and monitoring of the placebo components of any treatments in the context of clinical trials. In this chapter, we introduce plasma proteomics as a method and illustrate its implementation in a placebo study investigating nausea. We present typical statistical and bioinformatics approaches to analyze such complex data. Finally, we discuss the applicability of proteomics in clinical trials as well as for placebo research.
The role of sleep disturbance in endogenous pain modulation through opioidergic, placebo, and positive affective mechanisms
Authors: Finan Patrick H. , Colloca Luana , Iacovides Stella , Lavigne Gilles J.
Published: October 2023

Sleep is a fascinating biological phenomenon that regulates learning effects and many behaviors. Poor sleep quality and sleep disturbance have been identified as risk factors with tangible consequences such as pain, impairments in executive functions, memory loss and/or low mood. In this chapter, we focus on the role of sleep disturbance in the context of chronic pain and pain management with a mechanistic emphasis on sleep as a potential regulator of endogenous pain modulation. Through that lens, we describe interactions between sleep and the opioid system, effects on positive affective analgesia, and the influence of sleep on the occurrence and consolidation of placebo effects and expectations of pain reduction in both healthy participants and chronic pain patients. Future areas of research are identified and discussed.
Placebo effects in cough
Authors: Eccles Ronald
Published: October 2023

Cough is subject to large placebo effects. What are the implications for clinical trials on cough and the development of new medicines? Placebo treatments can reduce cough by 40% in trials, and this large placebo effect confounds the outcome of these clinical trials. Over-the-counter (OTC) cough medicines are viscous sweet syrups, and the sweet taste may have antitussive effects by causing release of endogenous opioids. There is some doubt about the pharmacological efficacy of OTC cough medicines, but these medicines provide benefit by a powerful placebo effect. OTC cough medicines contain over 100 excipients that enhance the viscosity, taste, color, smell, and sensory effect of the medicine and enhance the placebo effects. With cough being subject to large placebo effects, research should be conducted on harnessing the placebo as a powerful treatment for all forms of cough while we wait for any breakthrough in the pharmacological treatment of cough.
Placebo and nocebo effects in depression
Authors: Rief Winfried , Kelley John M. , Nestoriuc Yvonne
Published: October 2023

This chapter reviews evidence for placebo and nocebo effects in depression, including their mechanisms of action. The authors then consider how these effects could be used clinically. Meta-analyses indicate that antidepressants provide only marginal benefits over placebos, which suggests that placebos could benefit patients nearly as much as antidepressants do, but without medication side effects. Open-label placebos are a promising avenue for evoking these effects. It is also presented evidence for expectancy as an important mechanism underlying placebo and nocebo effects. It is discussed how expectancies regarding treatment efficacy and side effects could be manipulated to reduce side effects and improve clinical outcomes. In particular, the authors discuss how communication strategies such as contextualizing informed consent and framing treatment information can optimize treatment expectations, improve clinical outcomes, and reduce nocebo-related side effects. Finally, implications that such expectancy manipulations might have for clinical trial design are covered.
Why psychotherapy is an open-label placebo and open-label placebos are psychotherapy
Authors: Gaab Jens
Published: October 2023

In recent years, placebos have undergone a rapid development from methodological chaff to therapeutic wheat. Hereby, the role of placebos as a deceptive control in clinical trials, as well as negative denomination for anything murky, changed to an innovative promise, an effective as well as ethical treatment. This surprising change in perception was achieved by disclosing the use of placebos, which is even the more surprising as the deceptive administration has been assumed to be necessary to delude patients into believing that their treatment is not just wishful thinking. By this turn, not only have open-label placebos become a new clinical trademark, but also their true nature as a psychological intervention has be revealed, aka psychotherapy. But how ready is psychotherapy to embrace its long-ostracized sibling? And how do open-label placebos fit into the psychotherapy scene? This chapter will attempt to consider the possibilities of open-label placebos as a psychotherapy, as well as how psychotherapy can benefit the use of open-label placebos.
Putting placebos into practice
Authors: Finniss Damien G. , Howick Jeremy , Babel Przemyslaw
Published: October 2023

Placebos have been part of the medical lexicon for over 200 years. Over these 2 centuries, there has been discussion about the use of placebos in clinical practice with various interpretations (positive and negative) from utility and ethical perspectives. The advent of the placebo-controlled trial in the 1950s, coupled with Beecher’s seminal meta-analysis in 1955, raised the profile of the topic area and arguably marked a new phase in research on placebos and placebo effects. The field of Placebo Research has evolved significantly over the past 70 years. Much work has been devoted to understanding how and why placebo effects arise; however, there is a relative lack of research on how to implement this research for patient benefit. This chapter calls for a shift in the Placebo Research field, one which dramatically increases implementation of the existing research for patient benefit and clinically applicable research. A sociopsychobiological framework for the application of placebo research is proposed as a way of harnessing and applying the research in routine clinical practice.
Using the person-based approach to implement placebo research into primary care
Authors: Bishop Felicity L. , Vennik Jane , Smith Kirsten A. , Morrison Leanne , Everitt Hazel A.
Published: October 2023

Mechanistic studies of placebo effects and clinical trials comparing placebo to no-treatment controls suggest the potential for patient benefit in certain conditions and symptoms. However, translating the findings from placebo studies into clinical practice for patient benefit is not straight forward. In particular, there are contextual differences between research and practice that need to be identified and considered. Systematic and sensitive approaches are therefore needed to develop ways of implementing placebo research into medical practice. This chapter illustrates and reflects on the use of one such approach—the person-based approach—to develop a digital intervention for primary care practitioners based on findings from placebo research.
Sharing online clinical notes with patients
Authors: Blease Charlotte
Published: October 2023

In around 20 countries worldwide, patients are now offered online access to at least some of their medical records, a practice referred to as “open notes.” Access includes test results, medication lists, referral information, and/or the very words written by clinicians. In this chapter, focusing in particular on patients’ access to the narrative summaries or free text notes written by clinicians in the United States. The chapter reviews recent survey findings and analyses of electronic medical records that point to a complex picture about how open notes might differentially facilitate placebo and nocebo effects among patients along the lines of race/ethnicity. The chapter also briefly reflects on the ethical implications for clinical practice, with an emphasis on what open notes might mean for justice and equity in clinical care for Black and other minority patients.
The rise of digital health and digital medicine
Authors: Brown Ellenor , Persky Susan , Franklin Patricia D. , Seneviratne Chamindi , Noel Jason , Colloca Luana
Published: October 2023

The global COVID-19 pandemic limited or prevented traditional in-person interactions with healthcare providers, placing greater emphasis on remote solutions. This crisis came in the midst of the already increasing development of digital health technologies that have transformed healthcare and the patient-provider relationship. The new digitally enhanced landscape of healthcare will undoubtedly present new considerations for patient care, including processes related to placebo effects. With the proliferation of digital health technologies along with expanded understanding and use of placebo and nocebo effect in clinical care, there is a growing need to identify, understand, and harness placebo and nocebo effects in the digital health space. This chapter provides a brief review of extant applications of digital technologies, discusses the significance of the study and application of placebo and/or nocebo effects in digital health care, and looks to the future of digital medicine while considering the potential challenges of isolating and identifying placebo effects.
A glimpse of the multiple applications of virtual reality
Authors: Wang Yang , Massalee Rachel , Beebe Kris , Latham William , Putnam Lance , Westendorp Janine , Evers Andrea , Testa Marco , Silber Denise , Trost Zina , Colloca Giancarlo , Colloca Luana
Published: October 2023

A growing number of clinical trials and laboratory studies have examined the role of immersive virtual reality (VR) in medical and nonmedical contexts, especially in pain management. By creating a sense of presence and immersion, in addition to an experience of embodiment and interactivity, VR has excellent potential for improving clinical outcomes. Evidence from laboratory studies and clinical trials supports VR capability to enhance experimental pain tolerance as well as reduce clinical acute pain, chronic pain, and anxiety. By applying the principles of embodiment, virtual rehabilitation programs can facilitate adaptive body movements in chronic pain patients. Applying VR to educational contexts, VR-enhanced training allows students and healthcare professionals to be trained in realistic contexts prior to interacting with patients and real-world circumstances. Future advances in VR-based technology, group counseling, monitoring, and educational training will result in more widespread applications of VR in medical and nonmedical environments.
The growth of the gargantuan black holes powering high-redshift quasars and their impact on the formation of early galaxies and protoclusters
Authors: Bennett Jake S , Sijacki Debora , Costa Tiago , Laporte Nicolas , Witten Callum
Published: October 2023

High-redshift quasars (z ≳ 6), powered by black holes (BHs) with large inferred masses, imply rapid BH growth in the early Universe. The most extreme examples have inferred masses of ∼109 M⊙ at z = 7.5 and ∼1010 M⊙ at z = 6.3. Such dramatic growth via gas accretion likely leads to significant energy input into the quasar host galaxy and its surroundings, however, few theoretical predictions of the impact of such objects currently exist. We present zoom-in simulations of a massive high-redshift protocluster, with our fiducial fable model incapable of reproducing the brightest quasars. With modifications to this model to promote early BH growth, such as earlier seeding and mildly super-Eddington accretion, such ‘gargantuan’ BHs can be formed. With this new model, simulated host dust masses and star formation rates are in good agreement with existing JWST and ALMA data from ultraluminous quasars. We find the quasar is often obscured as it grows, and that strong, ejective feedback is required to have a high probability of detecting the quasar in the rest-frame UV. Fast and energetic quasar-driven winds expel metal-enriched gas, leading to significant metal pollution of the circumgalactic medium (CGM) out to twice the virial radius. As central gas densities and pressures are reduced, we find weaker signals from the CGM in mock X-ray and Sunyaev–Zeldovich maps, whose detection – with proposed instruments such as Lynx, and even potentially presently with ALMA – can constrain quasar feedback.
Formation of giant planets around intermediate-mass stars
Authors: Johnston Heather F , Panić O , Liu B
Published: October 2023

To understand giant planet formation, we need to focus on host stars close to $M_{\star }{=}1.7\, \rm M_\odot$, where the occurrence rate of these planets is the highest. In this initial study, we carry out pebble-driven core accretion planet formation modelling to investigate the trends and optimal conditions for the formation of giant planets around host stars in the range of $1\!-\!2.4\ \rm {\rm M}_{\odot }$. We find that giant planets are more likely to form in systems with a larger initial disc radius; higher disc gas accretion rate; pebbles of ∼millimeter in size; and birth location of the embryo at a moderate radial distance of ∼10 au. We also conduct a population synthesis study of our model and find that the frequency of giant planets and super-Earths decreases with increasing stellar mass. This contrasts the observational peak at $1.7\, \rm M_\odot$, stressing the need for strong assumptions on stellar mass dependencies in this range. Investigating the combined effect of stellar mass dependent disc masses, sizes, and lifetimes in the context of planet population synthesis studies is a promising avenue to alleviate this discrepancy. The hot-Jupiter occurrence rate in our models is $\sim 0.7\!-\!0.8~{{\ \rm per\ cent}}$ around $1\, \rm M_\odot$ – similar to RV observations around Sun-like stars, but drastically decreases for higher mass stars.
The Galactic neutron star population – II. Systemic velocities and merger locations of binary neutron stars
Authors: Gaspari Nicola , Levan Andrew J , Chrimes Ashley A , Nelemans Gijs
Published: October 2023

The merger locations of binary neutron stars (BNSs) encode their galactic kinematics and provide insights into their connection to short gamma-ray bursts (SGRBs). In this work, we use the sample of Galactic BNSs with measured proper motions to investigate their kinematics and predict their merger locations. Using a synthetic image of the Milky Way and its Galactic potential we analyse the BNS mergers as seen from an extragalactic viewpoint and compare them to the location of SGRBs on and around their host galaxies. We find that the Galactocentric transverse velocities of the BNSs are similar in magnitude and direction to those of their Local Standards of Rest, which implies that the present-day systemic velocities are not isotropically oriented and the peculiar velocities might be as low as those of BNS progenitors. Both systemic and peculiar velocities fit a lognormal distribution, with the peculiar velocities being as low as ∼22–157 km s−1. We also find that the observed BNS sample is not representative of the whole Galactic population, but rather of systems born around the Sun’s location with small peculiar velocities. When comparing the predicted BNS merger locations to SGRBs, we find that they cover the same range of projected offsets, host-normalized offsets, and fractional light. Therefore, the spread in SGRB locations can be reproduced by mergers of BNSs born in the Galactic disc with small peculiar velocities, although the median offset match is likely a coincidence due to the biased BNS sample.
Survival in the Neptune desert: LTT 9779 b kept its atmosphere thanks to an unusually X-ray faint host star
Authors: Fernández Fernández Jorge , Wheatley Peter J , King George W , Jenkins James S
Published: October 2023

The Neptunian desert is a region in period-radius parameter space with very few Neptune-sized planets at short orbital periods. Amongst these, LTT 9779 b is the only known Neptune with a period shorter than 1 d to retain a significant H–He atmosphere. If the Neptune desert is the result of X-ray/EUV-driven photoevaporation, it is surprising that the atmosphere of LTT 9779 b survived the intense bombardment of high-energy photons from its young host star. However, the star has low measured rotational broadening, which points to the possibility of an anomalously slow spin period and hence a faint X-ray emission history that may have failed to evaporate the planet’s atmosphere. We observed LTT 9779 with XMM-Newton and measured an upper limit for its X-ray luminosity that is a factor of 15 lower than expected for its age. We also simulated the evaporation past of LTT 9779 b and found that the survival of its atmosphere to the present day is consistent with an unusually faint XUV irradiation history that matches both the X-ray and rotation velocity measurements. We conclude that the anomalously low X-ray irradiation of the one Neptune seen to survive in Neptunian desert supports the interpretation of the desert as primarily a result of photoevaporation.
The updated BaSTI stellar evolution models and isochrones – IV. α-Depleted calculations
Authors: Pietrinferni Adriano , Salaris Maurizio , Cassisi Santi , Savino Alessandro , Mucciarelli Alessio , Hyder David , Hidalgo Sebastian
Published: October 2023

This is the fourth paper of our new release of the BaSTI (a Bag of Stellar Tracks and Isochrones) stellar model and isochrone library. Following the updated solar-scaled, α-enhanced, and white dwarf model libraries, we present here α-depleted ([α/Fe] = −0.2) evolutionary tracks and isochrones, suitable to study the α-depleted stars discovered in Local Group dwarf galaxies and in the Milky Way. These calculations include all improvements and updates of the solar-scaled and α-enhanced models, and span a mass range between 0.1 and 15 M⊙, and 21 metallicities between [Fe/H] = −3.20 and +0.45 with a helium-to-metal enrichment ratio ΔY/ΔZ  = 1.31, homogeneous with the solar-scaled and α-enhanced models. The isochrones – available in several photometric filters – cover an age range between ∼20 Myr and 14.5 Gyr, including the pre-main-sequence phase. We have compared our isochrones with independent calculations of α-depleted stellar models, available for the same α-element depletion adopted in the present investigation. We have also discussed the effect of an α-depleted heavy element distribution on the bolometric corrections in different wavelength regimes. Our α-depleted evolutionary tracks and isochrones are publicly available at our BaSTI website.
Dealing with broad-band X-ray spectra of faint AGN: a case study
Authors: Molina M , Malizia A , Bassani L
Published: October 2023

In this work, we analyse three average-luminosity hard X-ray selected AGN: ESO 506-G27, IGR J19039+3344, and NGC 7465. They have simultaneous Swift/XRT and NuSTAR data never published before and have been poorly studied at X-ray energies. These sources make for interesting targets both from a methodological and scientific point of view. Scientifically, they are of interest since they are possibly heavily absorbed objects, belong to a peculiar class and are variable both in flux and in spectral shape. Methodologically, because it is an interesting exercise to understand how existing spectral models can be applied to faint sources and how the use of NuSTAR data alone and then simultaneous and/or average data impacts on the spectral parameters determination. In this work, we demonstrate that simultaneous data are not sufficient if their statistical quality is poor. Moreover, we show that also the use of time-averaged data when dealing with faint AGN does not always provide confident results as for brighter AGN. Regardless of the poor data quality employed in our analysis, we are able to provide insights into the spectral characteristics of each source. We analyse in detail for the first time the iron line complex of ESO 506-G27, finding not only the presence of the iron K α and K β lines, but also of the iron K edge around 7 keV in the NuSTAR data. We also highlight changes in the absorption properties of IGR J19039+3344 and confirm NGC 7465 to be an unabsorbed type 1 LINER.
The monopole and quadrupole moments of the epoch of reionization (EoR) 21-cm bispectrum
Authors: Gill Sukhdeep Singh , Pramanick Suman , Bharadwaj Somnath , Shaw Abinash Kumar , Majumdar Suman
Published: October 2023

We study the monopole ($\bar{B}^0_0$) and quadrupole ($\bar{B}^0_2$) moments of the 21-cm bispectrum (BS) from EoR simulations and present results for squeezed and stretched triangles. Both $\bar{B}^0_0$ and $\bar{B}^0_2$ are positive at the early stage of EoR where the mean neutral hydrogen (${\rm H\, {\small I}}$) density fraction $\bar{x}_{\rm {\rm H\, {\small I}}}\approx 0.99$. The subsequent evolution of $\bar{B}^0_0$ and $\bar{B}^0_2$ at large and intermediate scales (k = 0.29 and $0.56 \, {\rm Mpc}^{-1}$, respectively) is punctuated by two sign changes which mark transitions in the ${\rm H\, {\small I}}$ distribution. The first sign flip where $\bar{B}^0_0$ becomes negative occurs in the intermediate stages of EoR $(\bar{x}_{\rm {\rm H\, {\small I}}}\gt 0.5)$, at large scale first followed by the intermediate scale. This marks the emergence of distinct ionized bubbles in the neutral background. $\bar{B}^0_2$ is relatively less affected by this transition, and it mostly remains positive even when $\bar{B}^0_0$ becomes negative. The second sign flip, which affects both $\bar{B}^0_0$ and $\bar{B}^0_2$, occurs at the late stage of EoR $(\bar{x}_{\rm {\rm H\, {\small I}}}\lt 0.5)$. This marks a transition in the topology of the ${\rm H\, {\small I}}$ distribution, after which we have distinct ${\rm H\, {\small I}}$ islands in an ionized background. This causes $\bar{B}^0_0$ to become positive. The negative $\bar{B}^0_2$ is a definite indication that the ${\rm H\, {\small I}}$ islands survive only in underdense regions.
The influence of globular cluster evolution on the specific frequency in dwarf galaxies
Authors: Moreno-Hilario Elizabeth , Martinez-Medina Luis A , Li Hui , Souza Stefano O , Pérez-Villegas Angeles
Published: October 2023

Dwarf galaxies are known to exhibit an unusual richness in numbers of globular clusters (GCs), property quantified by the specific frequency (SN), which is high for dwarf and giant elliptical galaxies, but with a minimum for intermediate-mass galaxies. In this work we study the role that GC evolution has in setting this trend, for which we use N-body simulations to evolve GCs in dwarf galaxies and quantify their disruption efficiency. We selected five individual dwarf galaxies from a high-resolution cosmological simulation, which includes GC formation and follow-up of their paths inside the host galaxy. Then, the tidal history of each GC is coupled to nbody6++gpu to produce N-body models that account for both, the interaction of GCs with their galactic environment and their internal dynamics. This results in a GC mass-loss parametrization to estimate dissolution times and mass-loss rates after a Hubble time. GC evolution is sensitive to the particular orbital histories within each galaxy, but the overall result is that the amount of mass that GC systems lose scales with the mass (and density) of the host galaxy, i.e. the GC mass-loss efficiency is lowest in low-mass dwarfs. After a 12 Gyr evolution all simulated GC systems retain an important fraction of their initial mass (up to 25 per cent), in agreement with the high GC to field star ratios observed in some dwarfs, and supports the scenario in which GC disruption mechanisms play an important role in shaping the GC specific frequency in dwarf galaxies.