bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurologic Manifestations of Muscle Relaxants and Drugs Used for Analgesia and Anesthesia in the Intensive Care Unit
Authors: Wijdicks Eelco F.M.
Published: June 2023

Sedation aside, many analgesic drugs are used in the ICU, predominantly in surgical ICUs. Neuromuscular-blocking agents are used frequently for brief procedures but can be administered for prolonged periods of time. Consulting neurologists often find that the combined use of opioids and benzodiazepines confounds the examination. Moreover, the duration of infusion of analogosedative drug combinations affect clearance, drugs do not clear well in critical illness, and drug-drug interactions are often underestimated. It is necessary to think through the absorption, distribution, and the two routes of drug elimination (metabolism and excretion) in patients and assess accurately the effect of drug interactions, body physique, or age. This chapter provides a full scope of drugs that may confound neurologic examination.
Seizures in the Intensive Care Unit
Authors: Wijdicks Eelco F.M.
Published: June 2023

Seizures in critically ill patients are a common reason for neurologic consultation. The causes and management of seizures are discussed in relation to this unique situation. Seizures may be more consequential in critical illness because they may impact on already unstable vital signs. Causes of seizures are discussed, including drug-induced seizure and seizures brought about by the withdrawal of certain drugs. Status epilepticus is major neuroemergency, and clinicians have an obligation to press on quickly with treatment, to correct metabolic abnormalities, and assess for structural abnormalities and lesions in the central nervous system. This chapter discusses how to manage recurrent seizures and the evolution to status epilepticus, including a transition to refractory status epilepticus.
Neurologic Complications of Invasive Procedures in the Intensive Care Unit
Authors: Wijdicks Eelco F.M.
Published: June 2023

Critically ill patients require support systems to maintain adequate circulation and oxygenation. Some need full life support to take over. Important procedures that are commonplace in surgical and medical intensive care units can be a cause of an unintended iatrogenic neurologic complications. The type of complications associated with invasive procedures can be categorized as either reaction to injected material (air or contrast medium) or mobilization of intravascular debris. Neurologic complications pertaining to invasive procedures and assisting devices are ischemic strokes and isolated peripheral nerve damage. This chapter concentrates on complications of invasive procedures and life support systems such as extracorporeal membrane oxygenation and left ventricular assist devices.
Neurologic Manifestations of Acute Bacterial Infections and Sepsis
Authors: Wijdicks Eelco F.M.
Published: June 2023

Patients with community-acquired bacterial infections comprise a considerable proportion of intensive care unit admissions. Within this cohort of admission are those patients with fever, agitation, and neurologic signs suggesting a primary neurologic infection. This chapter focuses on selected disorders associated with bacterial infection, chosen largely because they are potential reasons for neurologic consultation, and many intensive care specialists seek early help with the management of bacterial meningitis, epidural abscess, complications of endocarditis, and, occasionally, clostridial syndromes. Treatment of sepsis is common in any ICU, and patients can be seriously affected. The controversies of septic encephalopathy diagnosis are also discussed.
Neurologic Complications of Cardiac Arrest
Authors: Wijdicks Eelco F.M.
Published: June 2023

Cardiac arrest often leads to coma post-resuscitation, and this state may be devastating and result in persistent coma or severe disability. The distribution of causes of coma changes when patients are seen in the hospital or intensive care units, when structural causes of brain injury are then more frequent. Neurologic examination can determine the cause and severity of coma, but there might also be clues from a general physical examination that may point toward a certain cause. Treatable coma, however, can be due to mass effect and its remote effect or edema that may displace the brainstem; these comas can be reversed by neurosurgical intervention. This chapter discusses the evaluation of coma, how to interpret neurologic findings, how to grade coma, and which treatment actions to consider.
Neurologic Manifestations of Acid–Base Derangements, Electrolyte Disorders, and Endocrine Crises
Authors: Wijdicks Eelco F.M.
Published: June 2023

Critically ill patients display a gamut of homeostatic imbalances, and it is difficult to predict the ultimate clinical response in any given patient with any degree of acute metabolic abnormality. The clinical spectrum associated with acute metabolic or endocrine derangements ranges from transient and subtle neurologic manifestations to long-lasting damage to the central nervous system. Interpretation of laboratory derangements is important because several electrolyte and acid–base abnormalities are encountered regularly in the intensive care unit. In this chapter, the most representative clinical neurologic manifestations are selected to guide clinicians in their differential diagnosis and clarify the extent of the derangement on the nervous system.
Neurologic Complications Associated with Disorders of Thrombosis and Hemostasis
Authors: Wijdicks Eelco F.M.
Published: June 2023

Disorders of hemostasis may be part of organ dysfunction in patients presenting to the intensive care unit (ICU), or patients may be admitted with a primary hematologic disorder causing hemorrhage or thrombus. For these patients, the primary objective is to control a life-threatening hemorrhage and immediate hemostasis, but this may not be without neurologic consequences.

This chapter reviews the major disorders of thrombosis or hemostasis most commonly encountered in ICUs and their neurologic manifestations. These manifestations may affect both the central and peripheral nervous systems. The disorders that most often generate a neurologic consult are intravascular coagulation with intracranial hemorrhage, complications of thrombolysis, and thrombotic thrombocytopenic purpura. Assessment, management, and therapeutic options are discussed.
Neurologic Complications of Acute Vasculitis Syndromes
Authors: Wijdicks Eelco F.M.
Published: June 2023

Several clinical entities may lead to the admittance of a patient with a necrotizing vasculitis to a medical or surgical intensive care unit. With every visceral and organ involvement comes a potentially life-threatening condition, and often they occur simultaneously. These conditions are ischemic ulceration of the gut, pulmonary hemorrhage due to small vessel vasculitis or capillaritis, necrotizing nephritis, and myocarditis. Vasculitis of cerebral vessels may produce intracranial hemorrhages or multiple-territory cerebral infarcts. The peripheral nervous system becomes involved in severe forms of acute vasculitis syndromes, with acute respiratory or renal failure. A number of vasculitis disorders are discussed, along with their management.
Neurologic Complications of Acute Environmental Injuries
Authors: Wijdicks Eelco F.M.
Published: June 2023

Certain types of environmental injuries can produce specific neurologic manifestations. Although these injuries have a propensity for pulmonary, cardiovascular, and renal involvement, morbidity is commonly determined by an additional injury to the brain or spinal cord. Every circumstance is different, and confounding factors, such as acute drug intoxication or an unexpected acute structural CNS lesion that has led to the injury, should be excluded. Long-term data are also not available to reach a degree of certainty with prognostication. This chapter presents an overview of the most common neurologic presentations in environmental injuries severe enough to have resulted in intensive care admission.
Neurologic Complications of Drug Overdose, Poisoning, and Terrorism
Authors: Wijdicks Eelco F.M.
Published: June 2023

The treatment of intoxications and poisoning is common in emergency departments and the care of these patients is continued in the intensive care unit. The neurologist can be useful in an assessment of the severity of the intoxication, but also in the management of the patient, particularly when there are recurrent seizures or permanent unexplained unconsciousness. The consulting neurologist should have a good working knowledge of the pharmacodynamics of ingested drugs in large quantities and how to interpret neuroimaging, and this chapter provides that information. A section on the weaponized use of poisons in biological and chemical warfare and the necessary emergency response is also provided.
Neurologic Complications of Organ Transplantation
Authors: Wijdicks Eelco F.M.
Published: June 2023

Despite the scarcity of organs and the substantial cost to society, transplantation has become firmly established as a viable cure for vital organ failure. After transplantation, patients are admitted to specially equipped surgical intensive care units. Most academic institutions have meticulously organized transplantation programs with several specialties sharing the responsibility for care of the transplant recipient. Any patient with a recent solid organ or hematopoietic stem cell transplantation may develop graft-versus-host disease, multiorgan failure, and shock. In these patients’ neurologic complications are an expected outcome. These neurologic complications may be major when they involve recurrent seizures, postoperative failure to awaken, immunosuppression neurotoxicity, or acute disabling neuromuscular disease, all of which are addressed in this chapter.
The Neurologist and ICU Ethical Dilemmas
Authors: Wijdicks Eelco F.M.
Published: June 2023

A number ethical situations can arise in the intensive care unit in which the consulting neurologist may be closely involved. These situations usually resolve around end-of-life care, futility of further treatment, and the decision to withdraw or withhold other than palliative treatments. Neurologists are not required to continue futile treatment in any patient nor to continue or escalate treatment in the devastatingly injured neurologic patient. Similarly, clinicians are not required to discontinue aggressive management if a clear benefit can be achieved. Discordances between the wishes of family and the views of the healthcare team in the ICU are usually avoidable when there is clear, open, and frequent communication. This chapter discusses a number of major neuroethical topics.
Mental disorders in forensic psychiatry
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán , Williams Hannah Kate
Published: June 2023

This chapter covers different mental disorders and their prevalence in both the general and offending populations, specific symptoms and their relationship to violence or risk of offending, comorbidities, and assessing risk. The chapter includes functional psychosis, alcohol and drug misuse, personality disorders, psychopathy, biopolar disorder, depression and other affective disorders, post-traumatic stress disorder, anxiety, dissociative and conversion disorders, and paraphilias. It goes on to autism spectrum disorders, ADHD, conduct disorders, intellectual disability, acquired brain injury, epilepsy and sleep disorders, and organic disorders. It ends with malingering and factitious disorders.
Forensic psychiatric services
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán , Williams Hannah Kate
Published: June 2023

This chapter covers different aspects of psychiatric services in the forensic setting, and the relationships between them. It begins with the structure of forensic services, and goes on to secure hospital settings, and special provisions within secure settings. Gender identity issues in secure care are explained. Rehabilitation and recovery, community services, and diversion services are all outlined, as are prison psychiatric services. Service development is described, and then population needs assessment is covered.
Conflicting ethical values
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán , Williams Hannah Kate
Published: June 2023

This chapter covers the issues that arise when a forensic psychiatrist encounters a situation that may result in conflicting ethical values. It covers working in multi-disciplinary teams, with other agencies, non-public bodies, and when a psychiatrist works in a non-therapeutic context. It goes on to legal and ethical issues surrounding confidentiality and disclosure, then covers ethical risk assessment and management. Finally, the philosophy and ethics of coercion are discussed.
The interface between psychiatry and law
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán , Williams Hannah Kate
Published: June 2023

This chapter introduces the interface between psychiatry and the law. It begins with the objectives of both the psychiatric and legal systems, then the associated constructs and models. Different uses of information are covered, and negotiating the interface between psychiatry and the law is outlined.
The psychiatrist in court
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán , Williams Hannah Kate
Published: June 2023

This chapter covers the role of the psychiatrist in court. It starts with witnesses, experts, and expert evidence, then expands on this with the principles and law around expert evidence (including specific legal rules). It then also outlines the codes of practice for expert, and then consent and confidentiality in the court.
Clinical cases
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán
Published: June 2023

This chapter provides twenty-seven clinical cases and discusses how the forensic psychiatrist should approach these difference scenarios, with self-reflection questions and discussion included for each case. It begins with setting up the concept of a forensic case, and the use of behaviour without conviction with risk assessment, and risk assessment as a whole. It also includes cases on hospital-to-prison transfer, worked examples of structured risk-assessment, and location of the patient in the presence of psychosis, personality disorders, and substance misuse. It goes on to cases with brain injury, risk assessment in sexual offending, and associated transcultural issues, complex violence, cases where there are patient threats against staff, and how to manage requests for transfer to higher security. It also contains cases on the management of violent behaviour in the absence of current mental illnesses, management of self-harm, covert treatment of violence, and remission from hospital back to prison in the case of the prisoner with a life sentence. It closes with the cases relating to social and occupational therapies in forensic psychiatry, how to work with public protection arrangements, the professional relationship with the justice ministry, recall of CTOs, supporting a court diversion scheme via consultation, and how to make a professional judgement on whether prison or hospital would be a more appropriate setting for a patient.
Mental capacity and mental health law cases
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán
Published: June 2023

This chapter features five cases that relate to mental capacity and mental health law cases. The first explores mental capacity in the context of refusal of a Caesarean section. In the second case ‘appropriate treatment’ tests in personality disorders are explored. The third case is focused on choosing between mental health and capacity law in the contexts of autism and mild learning difficulties. The fourth case is on performing assessments at the police station of a person with psychosis who is facing murder charges. The fifth case regards residual common law powers such as a delay in emergency situations. Each case raises relevant questions for the practitioner to consider. Clinical, legal, clinico-legal, ethical issues are discussed for each of the five cases.
The critique matrix
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán
Published: June 2023

We can perhaps most easily address external critiquing of decisions by considering a ‘matrix’ with two dimensions. First, is the ‘level’ of critique (i.e. the subject matter an individual case, a case type, or a whole are of practice). Second, is the ‘method’ of critique: for example, clinical, legal, professional regulatory, internal service inquiry, external inquiry, or peer review. Various methods can be applied to the different levels of critique; albeit some methods do not fit some levels (e.g. the clinical method of audit only operates on case types or areas of practice, not individual cases). This chapter introduces the critique matrix as a way of elaborating on varying methods of how to critique one’s own decisions, including their nature and limitations, and how to choose a valid form of self-critique for specific types of cases.
Conclusion
Authors: Eastman Nigel , Adshead Gwen , Fox Simone , Latham Richard , Whyte Seán
Published: June 2023

The destination we have arrived at after reviewing a range of critique paradigms is, perhaps in a somewhat self-serving fashion for the casebook, that individual self-reflection represents the gold standard. And that the very best guardian of good practice, be it clinical, clinico-legal, or ethical, and potentially even the greatest safety from external critique, is via learning the habit of self-reflection: that is, awareness and constant vigilance throughout daily practice in regard to the thinking and values we apply to cases. We hope that addressing the cases in Part B of the casebook will assist colleagues in pursuit of such good practice. This chapter provides a conclusion on the chapters in Section C.
What is a clinical trial?
Authors: Cook Jonathan A.
Published: June 2023

This chapter sets the scene for the rest of the book by giving a brief history of clinical trials, their purposes, and the motivation behind their conduct. The key ethical considerations and the role of regulatory bodies and related legislation are also covered. Within this chapter the main types of clinical trials are described and how they differ in their focus and design is addressed using examples. Differences between clinical trials that evaluate drug and non-drug treatments are also covered. Finally, the role of clinical trials today is considered, followed by a short outline of the rest of the book.
Alternative randomized controlled trial designs
Authors: Cook Jonathan A.
Published: June 2023

This chapter explains the circumstances under which the standard randomized controlled trial design might not be a suitable design, or may not be feasible. Common alternative randomized controlled trial designs and trial modifications are considered using example clinical trials. Designs which vary the randomisation options (multi-arm), or what is randomised (within-person, crossover and cluster designs) are considered. The difference between an adaptive and fixed trial design is reviewed and the reasons for their use considered. Supra-trial designs are also covered. Why each of these designs might be used is addressed. How to choose an appropriate design is also considered.
Large-step neural network for learning the symplectic evolution from partitioned data
Authors: Li Xin , Li Jian , Xia Zhihong Jeff , Georgakarakos Nikolaos
Published: June 2023

In this study, we focus on learning Hamiltonian systems, which involves predicting the coordinate ($\boldsymbol q$) and momentum ($\boldsymbol p$) variables generated by a symplectic mapping. Based on Chen & Tao (2021), the symplectic mapping is represented by a generating function. To extend the prediction time period, we develop a new learning scheme by splitting the time series ($\boldsymbol q_i$, $\boldsymbol p_i$) into several partitions. We then train a large-step neural network (LSNN) to approximate the generating function between the first partition (i.e. the initial condition) and each one of the remaining partitions. This partition approach makes our LSNN effectively suppress the accumulative error when predicting the system evolution. Then we train the LSNN to learn the motions of the 2:3 resonant Kuiper belt objects for a long time period of 25 000 yr. The results show that there are two significant improvements over the neural network constructed in our previous work: (1) the conservation of the Jacobi integral and (2) the highly accurate predictions of the orbital evolution. Overall, we propose that the designed LSNN has the potential to considerably improve predictions of the long-term evolution of more general Hamiltonian systems.
Collision-induced excitation of ammonia in warm interstellar and circumstellar environments
Authors: Demes Sándor , Lique François , Loreau Jérôme , Faure Alexandre
Published: June 2023

Ammonia (NH3) is the first polyatomic molecule detected in the interstellar medium. Both its spectroscopic and collisional properties have been extensively studied earlier, and NH3 has often been used in laboratory astrophysics studies to compare high-level scattering calculations with state-of-the-art experiments. Nevertheless, some of its important collisional properties remain unresolved. In this paper, we report state-to-state and thermally averaged collisional data for the rotational excitation of NH3 by H2 calculated with the close-coupling quantum theory. Both nuclear spin symmetries (ortho/para) of the colliders are studied. Similar research has been carried out previously, providing rate coefficients up to a temperature of 200 K for rotational states with internal energy up to ∼420 cm−1. Here, we have computed cross sections for collision energies up to 4700 cm−1 and rate coefficients up to 500 K. Most of the rotation-inversion levels of ammonia have been considered below the first vibrational excitation threshold, leading to a total of 33 ortho- and 62 para-NH3 states. We have compared our results with the most accurate data for He and H atoms available in the literature. The propensity rules have also been analysed in the case of high rotational levels of NH3. The rate coefficients obtained by averaging over the thermal H2 relative populations exhibit significantly larger magnitudes than the state-to-state collisional data in the case of NH3 transitions with large internal energy difference, when the rotational energy transfer between the colliders is strong.
Conformational Dynamics of the D53−D3−D14 Complex in Strigolactone Signaling
Authors: Liu Simiao , Wang Jia , Song Bin , Gong Xinqi , Liu Huihui , Hu Qingliang , Zhang Junhui , Li Qianqian , Zheng Jie , Wang Hongwei , Xu H Eric , Li Jiayang , Wang Bing
Published: June 2023

Strigolactones (SLs) play fundamental roles in regulating plant architecture, which is a major factor determining crop yield. The perception and signal transduction of SLs require the formation of a complex containing the receptor DWARF14 (D14), an F-box protein D3 and a transcriptional regulator D53 in an SL-dependent manner. Structural and biochemical analyses of D14 and its orthologs DAD2 and AtD14, D3 and the complexes of ASK1−D3−AtD14 and D3CTH–D14 have made great contributions to understanding the mechanisms of SL perception. However, structural analyses of D53 and the D53−D3−D14 holo-complex are challenging, and the biochemical mechanism underlying the complex assembly remains poorly understood. Here, we found that apo-D53 was rather flexible and reconstituted the holo-complex containing D53, S-phase kinase-associated protein 1 (SKP1), D3 and D14 with rac-GR24. The cryo-electron microscopy (cryo-EM) structure of SKP1−D3−D14 in the presence of D53 was analyzed and superimposed on the crystal structure of ASK1−D3−AtD14 without D53. No large conformational rearrangement was observed, but a 9Å rotation appeared between D14 and AtD14. Using hydrogen–deuterium exchange monitored by mass spectrometry, we analyzed dynamic motifs of D14, D3 and D53 in the D53−SKP1−D3−D14 complex assembly process and further identified two potential interfaces in D53 that are located in the N and D2 domains, respectively. Together, our results uncovered the dynamic conformational changes and built a model of the holo-complex D53−SKP1−D3−D14, offering valuable information for the biochemical and genetic mechanisms of SL perception and signal transduction.
Building the Science of Physical Therapy: Conundrums and a Wicked Problem
Authors: Landers Merrill R , Deusinger Susan S
Published: June 2023

Producing science that supports the physical therapist profession in all its endeavors is critical to ensure that the best evidence is used in practice and education. In this Perspective, numerous conundrums are discussed that can constrain efforts to be productive in research in the academic institutions that serve as the intellectual centers of the discipline. Taken together, these conundrums and the conditions that create them collectively contribute to the wicked problem of how to generate sufficient evidence to support the practice of physical therapy. In response, this Perspective recommends changes in the Standards and Elements of the Commission on Accreditation in Physical Therapy Education to support the importance of faculty research, reconfigure the rules for faculty composition, and introduce a new metric of productivity that reinforces the need of all programs to produce evidence for the profession, while still allowing flexibility and institutional prerogative to govern how this need is expressed.
A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures
Authors: Ling Stephanie F , Yap Chuan Fu , Nair Nisha , Bluett James , Morgan Ann W , Isaacs John D , Wilson Anthony G , Hyrich Kimme L , Barton Anne , Plant Darren
Published: June 2023

Objectives

Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs.

Methods

Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis.

Results

A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit η with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses.

Conclusion

This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort.
Comparative effectiveness of sodium-glucose co-transporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on cardiorenal function and treatment adherence: a prevalent new-user design study in tertiary hospitals
Authors: Sim Ruth , Chong Chun Wie , Loganadan Navin Kumar , Adam Noor Lita , Hussein Zanariah , Lee Shaun Wen Huey
Published: June 2023

Objectives

Data on the long-term effects comparing sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are scarce, especially from middle-income countries. To examine the effects of SGLT2i and DPP4i on the cardiorenal function and treatment adherence for people with type 2 diabetes (T2D) using prevalent new-user design in real-world setting.

Methods

We conducted a retrospective cohort study in two tertiary hospitals in Malaysia and matched T2D patients initiated on SGLT2i or DPP4i from 2010 to 2021 using time-conditional propensity score. Outcomes of interest included cardiovascular and renal outcomes, as well as clinical lab outcomes, adherence and non-persistence. The hazard ratios for cardiorenal outcomes were inferred using Cox proportional hazards model.

Key findings

The cohort included 1528 patients, with 406 SGLT2i users matched with 406 DPP4i users. Over a median follow-up of 1.52 years, no differences in cardiorenal outcomes were observed. Patients initiated with SGLT2i had lower HbA1c at 12 months (−0.79%, P < 0.001) compared with DPP4i (−0.49%, P < 0.05; difference: −0.30%, P < 0.05). No differences in the renal, lipid, weight and blood pressure parameters were observed between both groups. Higher medication persistence was noted among SGLT2i users compared with DPP4i users (92% vs 87%, P = 0.03).

Conclusions

Both medications were comparable in exerting distinct effects on cardiorenal risk factors, with better HbA1c control and medication persistence among SGLT2i users. The long-term cardiorenal outcomes remain undetermined.
Bridging the Gap: Sustained Treatment Effect of Glabellar Lines With Twice-A-Year Treatment With DaxibotulinumtoxinA
Authors: Dover Jeffrey S. , Solish Nowell , Gross Todd M. , Gallagher Conor J. , Brown Jessica
Published: June 2023

BACKGROUND

To achieve natural-looking outcomes when treating dynamic lines with botulinum toxin (BoNT), retreatment must be timed such that the patient maintains a relatively constant aesthetic outcome. Although first-generation BoNT products require retreatment with 3- to 4-month frequency to avoid discontinuous correction, the average patient returns for treatment every 6 months, when these toxins have generally fully worn off.

OBJECTIVE

To discuss the number of days a typical patient treated with daxibotulinumtoxinA for injection (DAXI) or legacy BoNT products will spend undertreated or uncorrected in a given calendar year.

MATERIALS AND METHODS

Median time for maintaining glabellar lines in the “none” or “mild” severity range was compared for approved doses of onabotulinumtoxinA (ONA; 120 days) and DAXI (168 days).

RESULTS

The average patient treated with 40U of DAXI every 6 months can expect to be uncorrected (with “moderate” or “severe” glabellar lines) for 14.5 days between visits compared with 61.5 days for 20U of ONA.

CONCLUSION

An extended duration BoNT product can be expected to create greater consistency in aesthetic outcome and minimize the discontinuous correction commonly seen with first-generation BoNT products for patients treated twice a year, without requiring a change in patient behavior regarding visit frequency.
Survival Outcomes and Prognostic Factors of Dermatofibrosarcoma Protuberans: A Population-Based Retrospective Cohort Analysis
Authors: Chen Shijing , Xiong Lidan , Zhao Lingyun , Li Yiming , Li Li
Published: June 2023

BACKGROUND

Limited information is available regarding survival outcomes and risk factors of dermatofibrosarcoma protuberans (DFSP).

OBJECTIVE

To investigate the clinicopathologic characteristics and survival outcomes of DFSP.

MATERIALS AND METHODS

The study cohort (7,567 patients) was selected from the Surveillance, Epidemiology, and End Results Program (2000–2018). Demographic and clinicopathologic variables, survival outcomes, and prognostic factors were analyzed.

RESULTS

A total of 5,640 (74.53%) and 1,927 (25.47%) tumors were located in the skin and soft tissue, respectively. The median follow-up duration was 92 months. Median follow-up times were similar between patients with lymph node (107 months) and distant (102 months) metastases; the median survival time of the 89 patients (1.18%) who died of DFSP was significantly short (41 months, p < .001). Independent risk factors for cancer-specific mortality included age at diagnosis, histologic grade, and tumor size. Patients with tumors ≥10 cm in size or histologic grade III had significantly higher DFSP-specific mortality (7.07% and 10.08%, respectively, p < .001). Tumor locations and surgical procedures did not significantly influence survival.

CONCLUSION

Dermatofibrosarcoma protuberans has a favorable survival prognosis, even in patients with node-positive or distant metastases. Dermatofibrosarcoma protuberans-specific mortality is significantly higher in patients with grade III or large (≥10 cm) tumors.
Sleep apnea and cardiovascular risk
Authors: Rajachandran Manu , Nickel Nils , Lange Richard A.
Published: June 2023

Purpose of review

Obstructive sleep apnea (OSA) is associated with several cardiovascular risk predictors that have only recently begun to be studied in detail. The strong association between OSA and hypertension, coronary artery disease, congestive heart failure, and sudden cardiac death underscores its significant impact on cardiovascular health. This brief review considers the links between OSA and cardiovascular risk.

Recent findings

OSA is an important contributor to endothelial dysfunction and damage, while repetitive hypoxia and hypercarbia contribute to autonomic dysfunction and sympathetic stimulation. In turn, these derangements have deleterious hematologic effects, including hypercoagulability and abnormal platelet aggregability, which are important in the pathogenesis of atherothrombotic disease.

The varied deleterious effects of OSA on cardiovascular health stem from a unique ‘perfect storm’ of hypoxic oxidative stress, autonomic dysregulation, endothelial damage, and inflammation occurring at the microvascular level. Further research may disentangle these multiple etiologic threads and provide a better understanding of the underlying pathophysiological relationship between OSA and cardiovascular disease.
Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats
Authors: Salman Ibrahim M.
Published: June 2023

Background:

Altered baroreflex function is well documented in hypertension; however, the female sex remains far less studied compared with males. We have previously demonstrated a left-sided dominance in the expression of aortic baroreflex function in male spontaneously hypertensive rats (SHRs) and normotensive rats of either sex. If lateralization in aortic baroreflex function extends to hypertensive female rats remains undetermined. This study, therefore, assessed the contribution of left and right aortic baroreceptor afferents to baroreflex modulation in female SHRs.

Method:

Anesthetized female SHRs (total n = 9) were prepared for left, right and bilateral aortic depressor nerve (ADN) stimulation (1–40 Hz, 0.2 ms, 0.4 mA for 20 s) and measurement of reflex mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR) and femoral vascular resistance (FVR). All rats were also matched for the diestrus phase of the estrus cycle.

Results:

Reflex (%) reductions in MAP, HR, MVR and FVR were comparable for both left-sided and right-sided stimulation. Bilateral stimulation evoked slightly larger (P = 0.03) reductions in MVR compared with right-sided stimulation; however, all other reflex hemodynamic measures were similar to both left-sided and right-sided stimulation.

Conclusion:

These data show that female SHRs, unlike male SHRs, express similar central integration of left versus right aortic baroreceptor afferent input and thus show no laterization in the aortic baroreflex during hypertension. Marginal increases in mesenteric vasodilation following bilateral activation of the aortic baroreceptor afferents drive no superior depressor responses beyond that of the unilateral stimulation. Clinically, unilateral targeting of the left or right aortic baroreceptor afferents may provide adequate reductions in blood pressure in female hypertensive patients.
Longitudinal microvascular and neuronal retinal evaluation in patients with diabetes mellitus type 1 and 2 and good glycemic control
Authors: Vujosevic Stela , Toma Caterina , Villani Edoardo , Nucci Paolo , Brambilla Marco , Torti Emanuele , Prof Francesco Leporati , De Cillà Stefano
Published: June 2023

Purpose:

To evaluate microvascular and neuronal changes over 3 years in patients with type 1/2 diabetes mellitus (DM1/DM2), good metabolic control and no signs of diabetic retinopathy (DR).

Methods:

In this prospective, longitudinal study, 20 DM1, 48 DM2 and 24 controls underwent macular OCT ant OCT-A at baseline and after 3 years. Following parameters were considered: thickness of the central macula (CMT), retinal nerve fiber layer (NFL), ganglion cell (GCL+/GCL++) complex; perfusion and vessel density (PD/VD) and fractal dimension (FD) at the superficial and deep capillary plexuses (SCP/DCP); choriocapillaris flow deficits (CC-FD); foveal avascular zone (FAZ) metrics. MATLAB and ImageJ were used for OCT-A scans analyses.

Results:

Mean HbA1c was 7.4 ± 0.8% in DM1 and 7.2 ± 0.8% in DM2 at baseline, with no change at 3 years. No eye developed DR. In longitudinal analyses, PD at SCP (p=0.03) and FAZ area and perimeter (p<0.0001) significantly increased in DM2 compared to other groups. No longitudinal changes occurred in OCT parameters. In comparisons within groups, DM2 had a significant thinning of GCL++ in the outer ring, decreased PD at DCP and CC-FD, an increase in FAZ perimeter and area in DCP; DM1 had an increase in FAZ perimeter in DCP (p<0.001 for all comparisons).

Conclusion:

Longitudinal data showed significant microvascular retinal changes in DM2. No changes were detected in neuronal parameters and in DM1. Longer and larger studies are needed to confirm these preliminary data.
Impact of Adverse Events Associated With Acitretin Treatment of Moderate-to-Severe Plaque Psoriasis: Based on an Observational, Single-Center Study in Shanghai, China
Authors: Zhong Xiao-Yuan , Li Ying , Ma Rui , Wang Xin , Yu Ying-Yuan , Yu Ning , Ding Yang-Feng , Lu Jia-Jing , Shi Yu-Ling
Published: June 2023

Objective:

Acitretin is a widely used systemic retinoid that is to treat psoriasis but has significant variations in efficacy and adverse events (AEs) among individuals. This study aimed to determine the impact of AEs associated with acitretin treatment of moderate-to-severe plaque psoriasis on the Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression Scale (HADS) scores.

Methods:

This prospective, observational, single-center study was conducted from March 2021 to June 2022 and analyzed 116 patients with moderate-to-severe plaque psoriasis treated with acitretin who were followed up for 12 weeks. The primary outcome was the incidence of AEs related to acitretin, and the secondary objective was to investigate the effect of AEs on the DLQI and HADS scores. The generalized linear models were used to assess the association between AEs related to acitretin and DLQI scores or HADS scores, and the association between the involved system/tissue and DLQI scores or HADS scores.

Results:

A final total of 45 patients were included in the analysis, and a total of 157 treatment-related AEs involving nine organs or systems were reported in 41 patients. The most common AE was skin- or mucosa-related, with 72 cumulative events in 31 patients. AEs also commonly affected the endocrine, digestive, and genitourinary systems. Compared with the group with 0–2 AEs, the group with 3–5 AEs had a significantly increased DLQI score by 5.49 points (95% CI, 1.47–9.51) (P = 0.0089). Compared with AEs involving 0 to 1 system, AEs affecting 2 to 3 systems resulted in a significant increase in the DLQI score by 5.75 points (95% CI, 1.67–9.83) (P = 0.0071). Generalized linear models showed no statistically significant associations between AEs and the HADS scores.

Conclusion:

Our study demonstrates a high incidence of acitretin-related AEs. These AEs may affect quality of life but rarely cause psychological problems such as anxiety and depression.
The use of tissue clearing to study renal transport mechanisms and kidney remodelling
Authors: Saritas Turgay
Published: June 2023

Purpose of review

Tissue clearing enables examination of biological structures at subcellular resolution in three dimensions. It uncovered the spatial and temporal plasticity of multicellular kidney structures that occur during homeostatic stress. This article will review the recent development in tissue clearing protocols and how it facilitated the study of renal transport mechanisms and remodelling of the kidney.

Recent findings

Tissue clearing methods have evolved from primarily labelling proteins in thin tissue or individual organs to visualizing both RNA and protein simultaneously in whole animals or human organs. The use of small antibody fragments and innovative imaging techniques improved immunolabelling and resolution. These advances opened up new avenues for studying organ crosstalk and diseases that affect multiple parts of the organism. Accumulating evidence suggests that tubule remodelling can occur rapidly in response to homeostatic stress or injury, allowing for adjustments in the quantitative expression of renal transporters. Tissue clearing helped to better understand the development of tubule cystogenesis, renal hypertension and salt wasting syndromes, and revealed potential progenitor cells in the kidney.

The continued evolution and improvement of tissue clearing methods can help to gain deep biological insights into the structure and function of the kidney, which will have clinical implications.
Traumatic Experiences and Obsessive-Compulsive Symptoms
Authors: Santoro Gianluca , Sideli Lucia , Gugliemucci Fanny , Terrone Grazia , Schimmenti Adriano
Published: June 2023

Accumulating evidence suggests that obsessive-compulsive symptoms (OCSs) are positively associated with exposure to traumatic experiences and dissociative symptoms in both clinical and community samples. The current study was aimed at investigating the relationships between traumatic experiences, dissociation, and OCSs. A sample of 333 community adults (56.8% females) aged from 18 to 56 years (mean [SD], 25.64 [6.70] years) completed measures on traumatic experiences, dissociative symptoms, and OCSs. A structural equation modeling (SEM) framework was used to test if dissociative symptoms mediated the relationship between traumatic experiences and OCSs. SEM analyses showed that dissociation fully mediated the predictive association between traumatic experiences of emotional neglect and abuse and OCSs in the sample. Accordingly, some individuals suffering from OCSs might benefit from clinical interventions aimed at processing and integrating traumatic experiences.
The Impact of Family Functioning on Help-Seeking Behavior and Symptom Severity in Obsessive-Compulsive Disorder
Authors: Swisher Valerie S. , Ricketts Emily J. , Rogers Steven A.
Published: June 2023

Poor family functioning is associated with higher symptom severity in pediatric obsessive-compulsive disorder (OCD) and delayed help-seeking behavior in other forms of psychopathology. However, little is known about the impact of family functioning on help-seeking behavior and symptom severity in adults with OCD. The present study investigated the association between family functioning and both treatment delay and symptom severity in adults with obsessive-compulsive symptoms. Participants were 194 adults who self-identified as having OCD and completed an internet survey, including measures assessing family functioning, obsessive-compulsive symptom severity, help-seeking behavior, and depression symptom severity. Poorer family functioning was associated with higher obsessive-compulsive and depression symptom severity, after controlling for significant demographic variables. With respect to domains of family functioning, poorer general functioning, problem solving, communication skills, role functioning, affective involvement, and affective responsiveness were associated with higher obsessive-compulsive and depression symptom severity, after controlling for demographics. Poorer problem solving and communication were not significantly associated with treatment delay after controlling for demographics. Findings highlight the need for family intervention within the treatment framework for adult OCD and suggest targets (e.g., communication) to be addressed.
Spiritually Integrated Cognitive Processing Therapy for Moral Injury in the Setting of PTSD
Authors: O'Garo Keisha-Gaye N. , Koenig Harold G.
Published: June 2023

After defining the syndrome of moral injury (MI), reviewing its relationship to posttraumatic stress disorder (PTSD), and examining its psychological consequences and impact on functioning, we describe a new psychotherapeutic treatment for MI called spiritually integrated cognitive processing therapy (SICPT). SICPT builds on cognitive processing therapy (CPT), a commonly used trauma-focused treatment for PTSD. To our knowledge, SICPT is the first one-on-one individualized psychotherapeutic treatment that integrates a person's spiritual and religious beliefs into the treatment for MI, using the latter to work through and process the psychological, spiritual, and religious symptoms of this condition. Here, we describe the initial results obtained from a single-group experimental study examining the treatment of three patients with significant symptoms of both MI and PTSD. Given the effects of SICPT on reducing both MI and PTSD symptoms, we have decided to report these early results before study completion to alert the scientific community about this potentially effective new treatment.
Recruiting New Talent for Public Health Jobs With Evidence-Based Job Descriptions and Attractive Job Postings
Authors: Krasna Heather , Kulik Phoebe K. G. , Karnik Harshada , Leider Jonathon P.
Published: June 2023

Context:

With $7.4 billion from the American Rescue Plan funding new hires in the public health workforce, health departments could benefit from well-written, accurate job descriptions and job postings/advertisements to attract candidates.

Program:

We wrote accurate job descriptions for 24 jobs common in governmental public health settings.

Implementation:

We searched the gray literature for existing templates of job descriptions, job task analyses, lists of competencies, or bodies of knowledge; synthesized several currently posted job descriptions per occupation; utilized the 2014 National Board of Public Health Examiners' job task analysis data; and gathered feedback from current public health professionals in each field. We then engaged a marketing specialist to change the job descriptions into advertisements.

Discussion:

Several occupations examined did not have available job task analyses, while others had multiple. This project appears to be the first time that a list of existing job task analyses have been compiled together. Health departments have a special opportunity to replenish their workforce. Having evidence-based and vetted job descriptions that can be tailored for specific health departments' usage will accelerate their recruitment efforts and attract more qualified candidates.