bluuebunny/crossref_metadata_2025 huggingface dataset:
Principles of Animal Research Ethics
Authors: DeGrazia David , Beauchamp Tom L.
Published: May 2020

The centerpiece section of this book on animal research ethics presents a new moral framework of general principles. It is preceded in the front matter by a preamble that explains the overall project in the book as well as in the sections specifically on the six principles. The centerpiece section first discusses the essential place of ethical justification in the animal research arena and then presents the framework of three principles of social benefit and three principles of animal welfare. Next it examines both the critical role played by ethics committees in a well-functioning system of ethical review of animal research and the idea of scientific necessity as a justification for harming animal subjects. The section closes with an analysis of the influential Three-Rs framework, as presented in Russell and Burch’s Principles of Humane Experimental Technique. Despite the Three Rs’ important advance in the promotion of animal welfare, it does not adequately address the costs and benefits of animal research to human beings and lacks a comprehensive program of animal-subjects protection.
Some Reflections on Primates in Research
Authors: de Waal Frans B. M.
Published: May 2020

This commentary offers refinements and extensions of Beauchamp and DeGrazia’s recommendations in Principles of Animal Research Ethics. The code of ethics that we apply to other species is grounded in our estimation of their mental lives, which affects our respect for them. Much in animal research ethics boils down to how much gain justifies how much pain, presented by Beauchamp and DeGrazia as the principle of sufficient value to justify harm. This pain-to-gain balance is affected by how much consciousness and sentience we attribute to other species. Another major issue is how animals should be housed. Ideally, research facilities would move toward permitting primates to be in the company of familiar others all the time. This enlightened approach would be complemented by Beauchamp and DeGrazia’s more careful ethical justification of research.
Preamble
Authors: DeGrazia David , Beauchamp Tom L.
Published: May 2020

Research involving animals has advanced since its inception without the aid of a framework of general moral principles. The need for such a framework might therefore be doubted, but several developments call for a reconsideration and reconstruction of animal research ethics. First, public concerns about animal welfare have increased substantially in recent decades and continue to increase. Second, the scientific study of animals has afforded a wealth of new insights into their behaviors, mental lives, and basic needs. Third, animal ethics emerged in the last quarter of the twentieth century as an important field of interdisciplinary scholarship and has expanded for several decades, frequently challenging traditional ways of thinking about animals’ moral status and human responsibilities for their care and use....
Clinical Assessment Including Bedside Diagnosis
Authors: Bhaumik Sabyasachi , Tromans Samuel , Gumber Rohit , Gangavati Shweta
Published: May 2020

People with intellectual disability (ID) have a range of different abilities and means of communication, and it is important to be flexible in one’s approach clinically in order to best meet the needs of the specific patient being assessed. Neurodevelopmental conditions, such as Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are more prevalent in individuals with intellectual disability, and common mental health conditions such as depression and schizophrenia often present differently within this patient group. It is important to maintain the person with ID as the central focus of the assessment and help make the consultation as beneficial an experience for them as possible. Other issues to consider are the setting for the consultation, the presence of other individuals important to the patient and taking a thorough history, with additional focus to development and functioning. Those with ID are at a greater risk of physical and psychiatric comorbidities relative to the general population, and such comorbidities may or may not be associated with a specific syndrome, such as Down syndrome. These syndromes can have classically associated patterns of behaviours (so called ‘behavioural phenotypes’), though it is important to recognize that considerable within-syndrome variation exists between individuals. Additionally, one must be mindful of the risks and potential implications of diagnostic overshadowing, whereby symptoms are attributed to the person’s ID and/or pre-existing mental illness, when they actually represent an additional physical or psychiatric comorbid condition.
Alcohol and Substance Misuse and People with Intellectual and/or Developmental Disabilities
Authors: Buxton Tobias , Chester Verity , Arackal Bijil , Devulapally Divya , Lunsky Yona
Published: May 2020

The independence and freedoms associated with deinstitutionalization and increasing community residence has correlated with an increase in the use of both illicit and legal intoxicants among people with intellectual and/or developmental disability (IDD). While alcohol and substance use can be an important aspect of social inclusion in many cultures, the IDD population are at disproportionate physical side effects and psychosocial risks. Treatments and interventions have largely been designed to benefit the general population, and the IDD group experience a range of barriers to appropriate care, due to issues of accessibility, a lack of direct focus and research. This chapter reviews the prevalence, risk factors, physical, and psychological risks, treatment approaches, guidance. and research focusing on this multiply disadvantaged group. A number of recommendations are made, relating to the need for local and national development and evaluation of accessible interventions, service provision, and public health initiatives.
Psychological Therapies with People who have Intellectual Disabilities
Authors: Langdon Peter E. , Kehinde Tawakalitu , Parkes Georgina
Published: May 2020

Historically, many people with intellectual disabilities (ID) were considered unable to take part in psychological therapies. This view has changed considerably, and there has been an increasing focus on the development of psychological therapies for people with ID, including methods to help improve the accessibility of treatment. Within this chapter, cognitive-behavioural therapy, mindfulness, dialectical behaviour therapy, behavioural therapy, and psychodynamic therapy are reviewed. There is emerging evidence to indicate that a range of psychological therapies are effective with people who have ID, but a lack of large-scale and well-designed clinical trials investigating a range of psychological interventions remains problematic.
Physical Health in People with Intellectual Disabilities
Authors: Chauhan Umesh , Courtenay Ken , Hoghton Matthew
Published: May 2020

The aim of this chapter is to outline the importance of good physical health for a person with intellectual disability (ID) on their mental health and wellbeing; the impact of the choice of psychotropic therapy on their physical health; the presentations of mental disorders in people with ID with health problems; what to include in assessment—good history taking, physical examination, and investigations. Other aspects covered are the management of health problems including health prevention and what to monitor; the role of guidelines; and importance of liaison with GPs and the Primary Care Team.
Epilepsy in People with Intellectual Disability
Authors: Shankar Rohit , Walker Matthew
Published: May 2020

It is well recognized that both Intellectual Disability (ID) and epilepsy individually have higher rates of premature mortality. Thus, the two conditions in combination will be more likely to lead to premature mortality than either individually. People with ID and epilepsy have a higher likelihood of communication, psychiatric, behavioural, and drug sensitivity problems that makes their treatment difficult. This is not a homogenous group. At one end of the spectrum are patients with mild ID, 10–12% of who have epilepsy and treatment is mainly focused on areas like compliance and risky behaviours. At the other end are patients with severe ID, up to 50% of who have epilepsy and treatment is more focused on factors such as the co-morbidity, impact of medications, recognition of side effects, treatment resistance, and informed consent. This chapter looks to collate and provide an overview of epilepsy diagnosis and management and the current good practice on its applicability to people with ID.
Behavioural Phenotypes
Authors: Holland Anthony
Published: May 2020

This chapter describes the concept of behavioural phenotypes with examples of genetically-determined neurodevelopmental syndromes which are associated with particular developmental trajectories and specific comorbid risks for challenging behaviour or mental ill-health. Potential neural and other mechanisms that might explain the observed genotype/phenotype associations are explored as are treatment modalities including a focus on novel syndrome specific treatments. The chapter is primarily aimed at trainees, clinicians, and clinical researchers and, for this reason, is about those aspects of the behavioural phenotypes that impinge negatively on a person’s health, well-being, and quality of life.
Visual and Hearing Impairments and their Impact on the Mental Health of Adults with Intellectual Disability
Authors: Kiani Reza , Bhaumik Sugato
Published: May 2020

Visual and hearing impairments, congenital or acquired, are much more common in people with intellectual disability (ID) than the general population. These can be missed or diagnosed with delay if professionals rely just on the subjective reports by the families/care givers rather than objective screening and assessment. People with ID might be unable to complain about a visual or hearing impairment due to their communication difficulties. Therefore, diagnostic overshadowing might occur whereby these conditions might present with atypical signs and symptoms (e.g. loss of skills, isolation, and challenging behaviours) which could be attributed to dementia, depression, or other mental health problems. There has also been an overrepresentation of autistic-like features and autism spectrum disorder reported in people with visual and hearing impairment. Raising awareness of these comorbidities in people with ID will therefore facilitate early diagnosis and implementation of appropriate management strategies that can improve service provision for this vulnerable population.
Current and Future Research Priorities in the Psychiatry of Intellectual Disability
Authors: Thurston Rupert , Tromans Samuel , Chester Verity , Cooper Sally-Ann , Strydom Andre , Bhaumik Sabyasachi , Rai Dheeraj
Published: May 2020

This chapter provides an overview of current areas of interest for research in the field of intellectual disability (ID) and consider future directions. It is divided into the following broad headings: understanding the causes of ID, outcomes and comorbidities of ID, pharmacological and psychological interventions, service models and health services research, and a final section on building capacity and overcoming barriers to research in ID. While it is impossible to provide an exhaustive summary within a single book chapter, focus is directed to areas most relevant to practice of ID psychiatry.
Models of Service Development and Delivery for People with Intellectual Disability
Authors: Jaydeokar Sujeet , Devapriam John , McCarthy Jane , Kapugama Chaya , Bhaumik Sabyasachi
Published: May 2020

It is important to ensure that people with intellectual disability (ID) have access to high quality healthcare services. There is a wide variation in the availability of services and service delivery models globally for people with ID. Reasons for these variations are examined including availability of workforce resources and the development and availability of specialist resources. Tracing the development of services across the world, the chapter goes on to review the ongoing debate on access to generalized healthcare services versus the role of specialist services. We review advantages and disadvantages of different service delivery models. While these models have evolved in response to the political, cultural, and economic environment, it is important that any development of service delivery model signs up to basic underlying principles of person-centred, right-based, and outcome-focused approach. This should be undertaken in partnership with service users and carers in the spirit of co-production and with the underlying principles of choice, inclusion, rights, and independence. Any service development should also ensure that it would meet the complex health needs of people with ID as described in the tiered model of services with an efficient use of available resources. It should be sustainable through development of skills, competencies, and capabilities of the workforce and agencies that work with people with ID. There are number of examples across countries of innovative service provisions by public, private, and voluntary sectors as described in the chapter and it is important that we learn from those models. Advocating should be an integral aspect of any service delivery; we should be constantly advocating globally for high quality healthcare based on the best available evidence for people with ID.
Safeguarding and Ethical Practice for People with Intellectual Disability
Authors: Roy Meera , Roy Ashok , Tharian Priyanka , Retzer Ameeta
Published: May 2020

This chapter will outline the legal and practical principles that inform safeguarding and ethical practice for people with intellectual disability (ID) in the UK. The legal foundations for practice are discussed, drawing first on their foundations in international human rights law, the impact this has had on domestic law and the development of legislation to protect the rights of those with ID. Next, the current policy and principles that underpin ongoing practice are discussed, beginning with the particular history of people with ID and how understanding of ID has since evolved. Case examples are provided throughout to demonstrate these concepts in practice.
Leaving Hospital: A Step too Far for Risk-Based Regulation?
Authors: Moore Victoria L
Published: May 2020

Discharges from hospital are internationally recognised as a dangerous time in the care pathway of a patient, posing a risk to both their physical wellbeing and dignity. This article examines the effectiveness of risk-based regulation as a tool to address patient safety incidents linked to the hospital discharge process within the English National Health Service. It examines how the risk of this process is identified, conceptualised, and prioritised amongst the relevant statutory regulators, and argues that the risk is neither uniformly recognised by the statutory regulators within the English NHS, nor sufficiently addressed. Professional regulators in particular appear to have a poor awareness of the risk and their role in addressing it. Until these issues are resolved, patients leaving hospitals will continue to be exposed to patient safety incidents which should be avoidable.
What Would a Phenomenology of Logic Look Like?
Authors: Kinkaid James
Published: May 2020

The phenomenological movement begins in the Prolegomena to Husserl’s Logical Investigations as a philosophy of logic. Despite this, remarkably little attention has been paid to Husserl’s arguments in the Prolegomena in the contemporary philosophy of logic. In particular, the literature spawned by Gilbert Harman’s work on the normative status of logic is almost silent on Husserl’s contribution to this topic. I begin by raising a worry for Husserl’s conception of ‘pure logic’ similar to Harman’s challenge to explain the connection between logic and reasoning. If logic is the study of the forms of all possible theories, it will include the study of many logical consequence relations; by what criteria, then, should we select one (or a distinguished few) consequence relation(s) as correct? I consider how Husserl might respond to this worry by looking to his late account of the ‘genealogy of logic’ in connection with Gurwitsch’s claim that ‘[i]t is to prepredicative perceptual experience … that one must return for a radical clarification and for the definitive justification of logic’. Drawing also on Sartre and Heidegger, I consider how prepredicative experience might constrain or guide our selection of a logical consequence relation and our understanding of connectives like implication and negation.
HER2 antibody-drug conjugate controls growth of breast cancer brain metastases in hematogenous xenograft models, with heterogeneous blood–tumor barrier penetration unlinked to a passive marker
Authors: Gril Brunilde , Wei Debbie , Zimmer Alexandra S , Robinson Christina , Khan Imran , Difilippantonio Simone , Overstreet Michael G , Steeg Patricia S
Published: May 2020

Background

Brain metastases of HER2+ breast cancer persist as a clinical challenge. Many therapeutics directed at human epidermal growth factor receptor 2 (HER2) are antibodies or antibody-drug conjugates (ADCs), and their permeability through the blood–tumor barrier (BTB) is poorly understood. We investigated the efficacy of a biparatopic anti-HER2 antibody-tubulysin conjugate (bHER2-ATC) in preclinical models of brain metastases.

Methods

The compound was evaluated in 2 hematogenous HER2+ brain metastasis mouse models, SUM190-BR and JIMT-1-BR. Endpoints included metastasis count, compound brain penetration, cancer cell proliferation, and apoptosis.

Results

Biparatopic HER2-ATC 3 mg/kg prevented metastasis outgrowth in the JIMT-1-BR model. At 1 mg/kg bHER2-ATC, a 70% and 92% reduction in large and micrometastases was observed. For the SUM190-BR model, an 85% and 53% reduction, respectively, in large and micrometastases was observed at 3 mg/kg, without statistical significance. Proliferation was reduced in both models at the highest dose. At the endpoint, bHER2-ATC uptake covered a median of 4–6% and 7–17% of metastasis area in the JIMT-1-BR and SUM190-BR models, respectively. Maximal compound uptake in the models was 19% and 86% in JIMT-1-BR and SUM190-BR, respectively. Multiple lesions in both models demonstrated ADC uptake in the absence or low diffusion of Texas Red Dextran, a marker of paracellular permeability. Using in vitro BTB assays, the ADC was endocytosed into brain endothelial cells, identifying a potentially new mechanism of antibody permeability.

Conclusions

Biparatopic HER2-ATC significantly prevented JIMT-1-BR brain metastasis outgrowth and showed activity in the SUM190-BR model. The bHER2-ATC penetration into metastases that are impermeable to fluorescent dye suggested an endocytic mechanism of brain penetration.
Hand-Held Stereovision System for Image Updating in Open Spine Surgery
Authors: Fan Xiaoyao , Durtschi Maxwell S , Li Chen , Evans Linton T , Ji Songbai , Mirza Sohail K , Paulsen Keith D
Published: May 2020

BACKGROUND

Image guidance in open spinal surgery is compromised by changes in spinal alignment between preoperative images and surgical positioning. We evaluated registration of stereo-views of the surgical field to compensate for vertebral alignment changes.

OBJECTIVE

To assess accuracy and efficiency of an optically tracked hand-held stereovision (HHS) system to acquire images of the exposed spine during surgery.

METHODS

Standard midline posterior approach exposed L1 to L6 in 6 cadaver porcine spines. Fiducial markers were placed on each vertebra as “ground truth” locations. Spines were positioned supine with accentuated lordosis, and preoperative computed tomography (pCT) was acquired. Spines were re-positioned in a neutral prone posture, and locations of fiducials were acquired with a tracked stylus. Intraoperative stereovision (iSV) images were acquired and 3-dimensional (3D) surfaces of the exposed spine were reconstructed. HHS accuracy was assessed in terms of distances between reconstructed fiducial marker locations and their tracked counterparts. Level-wise registrations aligned pCT with iSV to account for changes in spine posture. Accuracy of updated computed tomography (uCT) was assessed using fiducial markers and other landmarks.

RESULTS

Acquisition time for each image pair was <1 s. Mean reconstruction time was <1 s for each image pair using batch processing, and mean accuracy was 1.2 ± 0.6 mm across 6 cases. Mean errors of uCT were 3.1 ± 0.7 and 2.0 ± 0.5 mm on the dorsal and ventral sides, respectively.

CONCLUSION

Results suggest that a portable HHS system offers potential to acquire accurate image data from the surgical field to facilitate surgical navigation during open spine surgery.
Intraoperative Rerupture and Surgical Clipping of a Small Superiorly Projecting Anterior Communicating Artery Aneurysm: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: May 2020

Anterior communicating artery (ACoA) aneurysms are prone to rupture even at smaller sizes. The surgical management of ACoA aneurysms is highly dependent on the spatial orientation of the saccular projection, categorized as inferior, superior, anterior, or posterior. Superior projecting aneurysms constitute approximately one-third of all aneurysms involving the ACoA. These aneurysms commonly project within the interhemispheric fissure; however, if the aneurysm is not high-riding, it can often be approached via a transsylvian trajectory. The patient presented after subarachnoid hemorrhage with a 3-mm superiorly projecting ACoA aneurysm. The lesion was approached via a right modified orbitozygomatic craniotomy with a transsylvian trajectory. The aneurysm reruptured after minimal manipulation of the dome. Mitigation of the intraoperative rupture was achieved through temporary clip application to bilateral A1 vessels. Bipolar coagulation and placement of 2 permanent clips facilitated final aneurysm occlusion. Postoperative imaging demonstrated patent bilateral A2 flow and no residual aneurysm filling. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Clipping of Basilar and Middle Cerebral Artery Aneurysms: 2-dimensional operative video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: May 2020

Careful preoperative planning for patients with multiple intracranial aneurysms is paramount given the importance of an appropriate trajectory and exposure for each aneurysm that will be clipped. The general principle is to clip aneurysms in a retrograde manner, such that more distal aneurysms are clipped earlier, and more superficial aneurysms are clipped later. This patient had unruptured middle cerebral artery (MCA) and basilar artery (BA) apex aneurysms and elected for surgical clipping of both lesions. An orbitozygomatic craniotomy ipsilateral to the MCA aneurysm was performed to permit clipping of both lesions. The dissection initially focused on exposure of the MCA aneurysm and then focused on the carotid-oculomotor triangle to permit basilar apex exposure and aneurysm clipping. The MCA aneurysm was clipped second. Postoperative imaging demonstrated complete obliteration of both aneurysms. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Aiding shared decision making in lung cancer screening: two decision tools
Authors: Sferra Shelby R , Cheng Joyce S , Boynton Zachary , DiSesa Verdi , Kaiser Larry R , Ma Grace X , Erkmen Cherie P
Published: May 2020

Background

Shared decision making (SDM) preceding lung cancer screening is important for populations that are underrepresented in lung cancer screening trials. Current evidence-based guidelines; however, do not address personal risk and outcomes in underrepresented populations. This study compared two SDM decision aids (Option Grids and Shouldiscreen.com) for SDM efficacy, decision regret and knowledge.

Methods

We conducted a prospective trial of lung cancer screening patients (N = 237) randomized to SDM with Option Grids or Shouldiscreen.com. To evaluate the SDM process after lung cancer screening, patients answered two questionnaires: CollaboRATE and Decision Regret. Patients also completed a questionnaire to test their knowledge of lung cancer screening.

Results

Patients were predominantly African American (61.6%), though multiple races, varying education levels and equal genders were represented. Patients in both Option Grids and Shouldiscreen.com groups reported favorable SDM experiences (P = 0.60) and equivalent knowledge about lung cancer screening (P = 0.43). Patients using Shouldiscreen.com had less knowledge regarding the potential complications of subsequent testing (P = 0.02). Shouldiscreen.com patients had increased regret regarding their decision to pursue screening (P = 0.02).

Conclusions

Option Grids and Shouldiscreen.com both facilitated a meaningful SDM process. However, Option Grids patients experienced decreased decision regret and enhanced knowledge of the potential complications of screening.
Hepatitis B or C prevalence in waste pickers from South America: a systematic review
Authors: Souza-Silva Gabriel , Mol Marcos Paulo Gomes
Published: May 2020

Background

Waste pickers are considered a vulnerable population at risk for potential health damage. Taking into account the risk of hepatitis B or C infection in this population, the aim of this study was to show the prevalence of these diseases in waste pickers from South America, through a systematic review.

Methods

The search covered publications until February 2020, accessed through Google Scholar database. Epidemiological studies on hepatitis B or C focused on waste pickers in South America were included. All selected papers were evaluated for quality.

Results

Six studies composed this systematic review, all conducted in Brazil and using cross-sectional study. The prevalence of all makers (HBsAg or anti-HBc) for hepatitis B varied from 4.3 to 33.4% while for hepatitis C varied from 1.6 to 12.4%.

Conclusion

The lack of results showed the requirement for more research about hepatitis including this informal workers group. High prevalences of hepatitis B and C in waste pickers highlighted the need of increase preventive health protection as vaccination against hepatitis B; training on working conditions; and the use of individual protection.
COVID-19: Insights from innovation economists
Authors: Abi Younes George , Ayoubi Charles , Ballester Omar , Cristelli Gabriele , de Rassenfosse Gaétan , Foray Dominique , Gaulé Patrick , Pellegrino Gabriele , van den Heuvel Matthias , Webster Elizabeth , Zhou Ling
Published: May 2020

The present document provides the take of innovation economists on the COVID-19 pandemic. It targets the general public and focuses on questions related to the Science, Technology, and Innovation ecosystem. It provides a reading of current real-world developments using economic reasoning and relying on existing economic research.
Guilty until proven innocent! Unexplained Wealth Orders: what are they and could they affect you and your clients?
Authors: Brassey John , Burns Rosalind
Published: May 2020

Unexplained Wealth Orders (a.k.a. The “McMafia Law”) entered the UK’s anti-criminal arsenal on 31 January 2018 to huge fanfare. However, after a great deal of noise, only four have actually been issued to date…. Are they a legitimate concern for the Ultra-High-Net-Worth adviser? Or is the UK government just paying lip service to appease its international friends…?
Postweaning mortality in commercial swine production II: review of infectious contributing factors
Authors: Gebhardt Jordan T , Tokach Mike D , Dritz Steve S , DeRouchey Joel M , Woodworth Jason C , Goodband Robert D , Henry Steve C
Published: May 2020

Postweaning mortality is extremely complex with a multitude of noninfectious and infectious contributing factors. In the current review, our objective is to describe the current state of knowledge regarding infectious causes of postweaning mortality, focusing on estimates of frequency and magnitude of effect where available. While infectious mortality is often categorized by physiologic body system affected, we believe the complex multifactorial nature is better understood by an alternative stratification dependent on intervention type. This category method subjectively combines disease pathogenesis knowledge, epidemiology, and economic consequences. These intervention categories included depopulation of affected cohorts of animals, elimination protocols using knowledge of immunity and epidemiology, or less aggressive interventions. The most aggressive approach to control infectious etiologies is through herd depopulation and repopulation. Historically, these protocols were successful for Actinobacillus pleuropneumoniae and swine dysentery among others. Additionally, this aggressive measure likely would be used to minimize disease spread if either a foreign animal disease was introduced or pseudorabies virus was reintroduced into domestic swine populations. Elimination practices have been successful for Mycoplasma hyopneumoniae, porcine reproductive and respiratory syndrome virus, coronaviruses, including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus, swine influenza virus, nondysentery Brachyspira spp., and others. Porcine circovirus type 2 can have a significant impact on morbidity and mortality; however, it is often adequately controlled through immunization. Many other infectious etiologies present in swine production have not elicited these aggressive control measures. This may be because less aggressive control measures, such as vaccination, management, and therapeutics, are effective, their impact on mortality or productivity is not great enough to warrant, or there is inadequate understanding to employ control procedures efficaciously and efficiently. Since there are many infectious agents and noninfectious contributors, emphasis should continue to be placed on those infectious agents with the greatest impact to minimize postweaning mortality.
Resting heart rate control and prognosis in coronary artery disease patients with hypertension previously treated with bisoprolol: a sub-group analysis of the BISO-CAD study
Authors: Chen Yun-Dai , Yang Xin-Chun , Pham Vinh Nguyen , Huang Shi-An , Fu Guo-Sheng , Chen Xiao-Ping , Truong Binh Quang , Yang Yu , Liu Shao-Wen , Ma Tian-Rong , Kim Dong-Soo , Kim Tae-hoon
Published: May 2020

Background

Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension.

Methods

We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value.

Results

A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19–15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients.

Conclusion

Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.
Imaging predictors for assessment of inferior vena cava wall invasion in patients with renal cell carcinoma and inferior vena cava tumor thrombus: a retrospective study
Authors: Wang Bin-Shuai , Li You-Zhao , Fang Yang-Yi , Zhang Shu-Dong , Ma Lu-Lin
Published: May 2020

Background

Renal cell carcinoma (RCC) has the propensity to lead to venous tumor thrombus (VTT). Nephrectomy with tumor thrombectomy is an effective treatment option but is a technically challenging surgical procedure that is accompanied by a high rate of complications. The aims of this study were to investigate pre-operative imaging parameters for the assessment of inferior vena cava (IVC) wall invasion due to a tumor thrombus in patients with RCC and to identify predictors from the intra-operative findings.

Methods

Clinical and imaging data were collected from 110 patients who underwent nephrectomy with IVC tumor thrombectomy (levels I–IV) for RCC and IVC tumor thrombus at the Peking University Third Hospital between May 2015 and March 2018. Univariable and multivariable logistic regression and receiver operating characteristic curves were used to assess the correlations between pre-operative imaging features and intra-operative macroscopic invasions of the IVC wall by tumor thrombus.

Results

Among the 110 patients, 41 underwent partial or segmental resection of IVC. There were univariate associations of pre-operative imaging parameters that could be used to predict the need for IVC resection, including those of the Mayo classification, maximum anterior-posterior (AP) diameter of the renal vein at the renal vein ostium (RVo), maximum AP diameter of the VTT at the RVo and IVC occlusion. For the multivariable analysis, the AP diameter of the VTT at the RVo and IVC occlusion were associated with a significantly increased risk of invasion of the IVC wall by tumor thrombus. The optimum imaging thresholds included an AP diameter of the VTT at the RVo larger than 17.0 mm and the presence of IVC occlusion, with which we predicted invasions of the IVC wall requiring IVC resection. The probabilities of intra-operative IVC resection for patients without both independent factors, with an AP diameter of the VTT at the RVo larger than 17.0 mm, with IVC occlusion, and with both concurrent factors were 5%, 23%, 56%, and 66%, respectively.

Conclusion

An increase in the AP VTT diameter at the RVo and the presence of complete occlusion of the IVC are independent risk factors for a high probability of IVC wall invasion by tumor thrombus.
Intraocular Pressure Reduction After Real-world Cataract Surgery
Authors: Leal Inês , Chu Colin J. , Yang Yit Y. , Manasses Demetri M. , Sebastian Rani T. , Sparrow John M.
Published: May 2020

Précis:

A large cohort undergoing cataract extraction was retrospectively analyzed to ascertain the degree of real-world intraocular pressure (IOP) reduction in normal eyes and those with glaucoma, and a predictive formula was developed.

Purpose:

The purpose of this study was to define the real-world degree of IOP reduction after cataract extraction to guide its role as an isolated intervention for glaucoma.

Materials and Methods:

A retrospective analysis was carried out of clinical data collected in 8 clinical sites in the United Kingdom from an electronic medical record system between January 2006 and May 2015. A total of 20,508 eyes without known pathology and 2251 eyes from patients with glaucoma undergoing phacoemulsification and intraocular lens insertion were included. Eyes with intraoperative complications, undergoing additional procedures, axial lengths outside 22 to 26.5 mm, preoperative IOP under 6 mm Hg or over 30 mm Hg, and copathology, except for amblyopia or glaucoma, were excluded. The main outcome measure was the change in preoperative IOP compared with the next recorded visit for up to 12 weeks.

Results:

In eyes without pathology, the mean reduction in IOP was 1.40 mm Hg (±3.74) compared with 1.03 (±5.02), P-value <0.001, in eyes with a diagnosis of glaucoma. A multiple linear regression model identified preoperative IOP, a glaucoma diagnosis, preoperative corrected visual acuity, age, and axial length as determinants of IOP reduction. The model was validated against an independent cohort.

Conclusions:

We quantify mean IOP reduction achieved in a real-world setting from cataract surgery alone. In glaucomatous eyes where angle closure is not differentiated, phacoemulsification alone yields only a modest reduction of IOP.
COVID-19 and Avoiding Ibuprofen. How Good Is the Evidence?
Authors: Kutti Sridharan Gurusaravanan , Kotagiri Rajesh , Chandiramani Vijay H. , Mohan Babu P. , Vegunta Rathnamitreyee , Vegunta Radhakrishna , Rokkam Venkata R. P.
Published: May 2020

Ibuprofen is an over-the-counter medication that is used widely for the treatment of pain and fever during COVID-19 pandemic. A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin–Angiotensin–Aldosterone system. ACE2 is the coreceptor for the entry of SARS-CoV-2 into cells, and so, a potential increased risk of contracting COVID-19 disease and/or worsening of COVID-19 infection was feared with ibuprofen use. However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease. At this time, there is no supporting evidence to discourage the use of ibuprofen.
Mediastinal 99mTc-Methylene Diphosphonate Accumulation in a Patient With Primary Mediastinal Soft Tissue Giant Cell Tumor
Authors: Chen Haotian , Fan Qiuping , Su Minggang
Published: May 2020

Soft tissue giant cell tumor (GCT) is rare. It usually involves the extremities. We report the case of a 37-year-old woman who was suspected of having mediastinal tumor on radiograph. Thoracic CT revealed the tumor had extensive calcification and invaded the adjacent vertebrae and spinal canal. It intensively accumulated 99mTc-methylene diphosphonate on bone scan. The tumor showed hypointensity on T1-weighted and mixed intensity on T2-weighted fat-saturated sagittal images. Finally, a soft tissue GCT was confirmed by pathology. The case cautions us soft tissue GCT should be in the differential diagnosis spectrum in a calcified posterior mediastinal mass with 99mTc-methylene diphosphonate accumulation.
Primary Neuroendocrine Tumor of the Ileostomy Stoma on 68Ga-DOTATATE PET/CT
Authors: Yu Lei , Braun Alexander , Hansen Neil J. , Downey Ryan T. , Johnson Craig M.
Published: May 2020

A 75-year-old man presented with bleeding ileostomy stoma 20 years after total colectomy and end ileostomy for chronic ulcerative colitis. On physical examination, the stoma was mass-like and firm with friable mucosa. Wedge biopsy of the ileostomy stoma revealed well-differentiated neuroendocrine tumor (intermediate grade). 68Ga-DOTATATE PET/CT showed mass-like focal radiotracer uptake at the ileostomy site without radiotracer-avid lymphadenopathy or distant metastatic disease. No additional sites of neoplasm in the gastrointestinal tract were further identified by endoscopy. The diagnosis of isolated primary neuroendocrine tumor of the ileostomy stoma was confirmed, an extremely rare entity.
Coronavirus Disease 2019 (COVID-19)
Authors: Xiang Kai Yan , Zu Zi Yue , Lu Guang Ming , Zhang Long Jiang
Published: May 2020

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has spread rapidly throughout China and other countries, and has been characterized as a pandemic. With the strict prevention and control measures implemented by the Chinese government, the spread of the epidemic in China has come under preliminary control by the end of February, 2020, whereas the situation of some countries outside China is not optimistic and raises great public concern. In fighting COVID-19, radiologic examinations played a critical role in the early diagnosis of COVID-19, and could also help assess disease course and severity. There is an urgent need to share useful experience and effective measures internationally. This article outlines the collaborative actions and efforts by the Chinese radiology field and the situation of front-line health care workers in radiology departments to present the world with experiences and examples of Chinese radiology during the COVID-19 outbreak.
The impact of non-neurological organ dysfunction on outcomes in severe isolated traumatic brain injury
Authors: Astarabadi Mariam , Khurrum Muhammad , Asmar Samer , Bible Letitia , Chehab Mohamad , Castanon Lourdes , Ditillo Michael , Douglas Molly , Joseph Bellal
Published: May 2020

INTRODUCTION

Organ dysfunction following traumatic brain injury (TBI) is common and has been associated with unpredictable outcomes. The aim of our study is to describe the incidence of non-neurological organ dysfunction (NNOD) and its impact on outcomes in patients with severe TBI admitted to our intensive care unit (ICU).

METHODS

We performed a 3-year (2015-2017) review of our Level 1 trauma center’s prospectively maintained TBI database and included all adult (age ≥18y) patients with isolated severe TBI (head abbreviated injury severity (AIS) ≥3 and other AIS <3) and an ICU stay >48 hours. Organ dysfunction (OD) was measured by multiple organ dysfunction scores. Organ system failure was defined as a non-neurological component score of ≥3 on any day during the ICU stay. Outcomes measured were the incidence of NNOD and its effect on outcomes. Multivariate regression analysis was performed.

RESULTS

A total of 285 patients were included. The mean age was 48 ± 22 years, 72% were males, median [IQR] Glasgow Coma Scale (GCS) was 8[5-10], and median Injury Severity Score (ISS) was 17[10-26]. Epidural hematoma was the most common intracranial hemorrhage (49%) followed by subdural hematoma (46%). The overall incidence of NNOD was 33%, with the most common dysfunctional organ system being the respiratory (23%) followed by the cardiovascular (12%) and hepatic system (8%). The overall in-hospital mortality rate was 19% (NNOD:36% vs. No-NNOD:9%,p< 0.01). On regression analysis, NNOD was associated with higher in-hospital mortality (aOR: 2.0 [1.6-2.7]), discharge to skilled nursing facility (SNF) (aOR: 1.8 [1.4-2.2]), and Glasgow Outcome Scale-Extended (GOS-E) ≤4 (OR: 1.7 [1.3-2.3]) andp-values <0.01.

CONCLUSION

One in every three isolated severe TBI patients develop NNOD. NNOD is independently associated with worse outcomes. Understanding the mechanisms associated with NNOD in the setting of TBI may promote prevention practices and improve outcomes in TBI.

LEVEL OF EVIDENCE

Prognostic, level III.
Comparative validation of the BOADICEA and Tyrer-Cuzick breast cancer risk models incorporating classical risk factors and polygenic risk in a population-based prospective cohort
Authors: Choudhury Parichoy Pal , Brook Mark N. , Wilcox Amber N. , Lee Andrew , Mulder Charlotta , Coulson Penny , Schoemaker Minouk J. , Jones Michael E. , Swerdlow Anthony J. , Chatterjee Nilanjan , Antoniou Antonis C. , Garcia-Closas Montserrat
Published: May 2020

Purpose

The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer models have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative validation of the extended models including a recently developed 313-variant PRS in a population-based prospective cohort.

Methods

We used data from a nested case-control sample of 1,337 women of European ancestry (619 incident breast cancer cases) aged 23-75 years from the Generations Study. Models were evaluated for calibration of five-year absolute risk and risk discrimination.

Results

The extended BOADICEA model with risk factors and PRS was well calibrated across risk deciles: expected-to-observed ratio (E/O) at the highest risk decile = 0.97 (95% Cl = 0.51 to 1.86) for women younger than 50 years and 1.09 (0.66 to 1.80) for women 50 years or older. Adding risk factors and PRS to the BOADICEA model improved discrimination modestly in younger women (Area Under the Curve (AUC): 69.7% vs. 69.1%) and substantially in older women (AUC: 64.6% vs. 56.8%). The Tyrer-Cuzick model with PRS had similar discrimination as the extended BOADICEA model for both age groups; but showed evidence of overestimation at the highest risk decile: E/O=1.54 (0.81 to 2.92) for younger and 1.73 (1.03 to 2.90) for older women.

Conclusion

The extended BOADICEA model identified women in a European ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. These analyses can inform choice of risk models for risk stratified breast cancer prevention for women of European ancestry.
Rise and Regional Variations in Schedule II Stimulant Use in the United States
Authors: Vaddadi Sneha M. , Czelatka Nicholas J. , Gutierrez Belsy D. , Maddineni Bhumika C. , Torres-Teran Carlos D. , Tron Daniel N. , McCall Kenneth L. , Piper Brian J.
Published: May 2020

Objective

There is a need to better understand recent trends in stimulant usage. This report compares the pharmacoepidemiology of three Schedule II stimulants in the United States from 2010 – 2017.

Methods

Drug weights were extracted from the Automated Reports and Consolidated Ordering Systems (ARCOS) for amphetamine, methylphenidate, and lisdexamfetamine. Total grams per drug were averaged across all states and compared from 2010–2017. Median stimulant daily dosage per patient user was determined from electronic medical records for a regional analysis.

Results

There was a rise in amphetamine (+67.5%) and lisdexamfetamine (+76.7%) use from 2010–2017. The change in methylphenidate (−3.0%) was modest. Regional analysis indicated that persons/day usage of stimulants in the west was lower than that of other US regions from 2014–2017. There was a negative correlation (r(48) = −0.43 to −0.65, p < .05) between the percent Hispanic population per state and the daily dose/population per stimulant.

Conclusion

The increasing amphetamine and lisdexamfetamine, but not methylphenidate, use may be explained by a rise in adult ADHD diagnoses and treatment. Regional analysis indicates that the use of stimulants in the west may be distinct from that in other regions. The lower stimulant use in areas with greater Hispanic population may reflect socioeconomic factors. Further research is needed on social factors impacting stimulant use and reasons for the pronounced regional variance.