Confusional State Research Articles

The Inferiority Complex after Being Accused and Its Enlightenment to Judicature

"The inferiority complex after being accused" is one of the typical cultural psychologies of some people currently in the judicial field at the grassroots society in China. It is mainly manifested in their reluctance to be sued or cooperated with the investigation, and keep away from grass-roots judicial field as far as possible in terms of geographical location and behavior. Once someone else are called by the real judiciary or individuals or organizations pretending to the judiciary, it is easy to trigger the illusion that they may have done something wrong in past times, then they can easily fall into a state of depression and confusion, and even be deceived by other malicious people. Obviously, similar psychology is not conducive to the rule by law and modernization of grassroots society, and it is not conducive to the construction of a harmonious police-civilian relationship. Based on humanistic care and universal law, it is necessary to achieve fine justice based on the perspectives of language culture, costume culture, public psychology, etc., and gradually guide the traditional people to correctly face the phenomenon of the “inferiority complex after being accused”, so it can help they integrate themselves into the modern society ruled by law smoothly.

An Individualized Risk Mitigation Approach for Safety: Experience from the Mosunetuzumab (CD20/CD3 Bispecific Antibody) Development Program in Relation to Neurotoxicity Risk

An Individualized Risk Mitigation Approach for Safety: Experience from the Mosunetuzumab (CD20/CD3 Bispecific Antibody) Development Program in Relation to Neurotoxicity Risk

Neurological Adverse Events Following CAR-T Cell Therapy: A Real-World Analysis of Adult Patients Treated with Axicabtagene Ciloleucel or Tisagenlecleucel

Introduction: Neurotoxicity is a major adverse event (AE) of CAR-T therapy with diverse presentation. When severe, it can be fatal, and may lead to neurologic sequelae as well as contribute to increased health care utilization, driving up cost of therapy. In clinical trials, the most common neurologic AEs with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) included encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia and anxiety. Fatal and serious cases of cerebral edema, leukoencephalopathy and/ or seizures have been reported with both agents. In this real-world analysis, we reviewed post-marketing case reports from the FDA Adverse Events Reporting System (FAERS). Database involving axi-cel or tis-cel for large B cell lymphoma (LBCL), with the dual objectives of characterizing the various components of neurotoxicity and assessing the association of neurological (neuro) AEs with demographic and treatment factors as well as with other AEs reported with CAR-T cell therapy use. Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The FAERS database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if patient age was unknown or if the case was reported outside the US. Of all patients reported to have neuro AEs, the frequency of various components was collected. The association of neuro AEs with patient age, concomitant AEs and key lab abnormalities were evaluated by Fisher's exact test, using a two-sided α=0.05 to determine statistical significance. Median age in each subgroup was compared using the Mann-Whitney U test. Results: In the 397 case reports identified, the majority of reactions (376, 95%) were classified as serious. Overall, 258 (65%) were reported to have neuro AEs, with "neurotoxicity" reported in 170 cases (66%); encephalopathy including CAR-T cell-related, metabolic and toxic in 92 cases (36%); seizures including status epilepticus, myoclonus and partial seizures in 12 cases (5%); stroke including cerebrovascular accident, hemiparesis, basal ganglia, brain stem, cerebellar and cerebral infarcts, motor dysfunction, facial and cranial nerve paralysis in 13 cases (5%); speech disorders including terms of aphasia, dysarthria, speech and language impairment in 55 cases (21%); amnesia and memory impairment in 18 cases (7%); brain or spinal cord edema and increased intracranial pressure in 6 cases (2%). Peripheral neuropathy was reported in 5 cases (2%). Symptoms of headache, tremors, dizziness and somnolence were reported in 30 (12%), 41 (16%) 3 (1%) and 34 (13%) cases respectively. Confusional state, delirium or agitation were reported in 61 cases (24%). Neuro AEs were associated with use of axi-cel vs. tis-cel (69% vs. 24%, p <0.01) and with age ≥65 years (43% vs. 36% in age <65, p=0.02) but did not impact death or hospitalization (Table). Neuro AEs were associated with cytokine release syndrome (CRS, 67% vs. 49% without, p<0.01) as well as with cardiac AEs including tachycardia (p<0.01). There was an association of psychiatric AEs with neuro AEs though some (delirium, agitation, hallucination) may be considered a part of the neuro AEs. There were no associations of febrile neutropenia, thrombocytopenia, serum ferritin and C-reactive protein with neuro AEs (all p values>0.05). Conclusions: Neuro AEs were common with CAR-T cell therapy in the real world and largely resembled those reported in clinical trials. Neuro AEs were associated with the agent used, age ≥65 as well as the presence of CRS, cardiac and psychiatric AEs but not with any of the laboratory values studied. The limitations of this study include its retrospective nature, potential under-reporting to FAERS and the relatively small number of patients in the tis-cel group due to its later approval and shorter time available for uptake compared to axi-cel. Despite these limitations, our findings can serve to inform clinicians' decision making when treating adult patients with CAR-T cell therapy. Further research is needed to better discern the etiopathology and biomarkers of neuro AEs in CAR-T cell therapy. Disclosures Gajra: Cardinal Health: Employment. Zettler:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients (Pts) With Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Results of the Phase 2 ZUMA-2 Study

KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients (Pts) With Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Results of the Phase 2 ZUMA-2 Study

Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines

Schuster: Novartis: Honoraria, Patents & Royalties: Combination CAR-T and PD-1 Inhibitors, Research Funding; Nordic Nanovector: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Genentech: Consultancy, Honoraria, Research Funding. Bartlett:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Kite Pharma: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Gilead: Research Funding; Immune Design: Research Funding; Incyte: Research Funding; Janssen: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Research Funding; Autolus: Research Funding; Forty Seven: Research Funding; Genentech, Inc.: Research Funding. Assouline:Janssen: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau. Yoon:Kyowa Hako Kirin: Research Funding; Genentech, Inc.: Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; MSD: Consultancy; Janssen: Consultancy; Yuhan Pharma: Research Funding. Bosch:Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Sehn:Acerta: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Apobiologix: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Janssen-Ortho: Honoraria; TG Therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Cheah:Janssen: Honoraria; Acerta: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; AbbVie: Research Funding; Celgene: Research Funding; Gilead: Honoraria; Loxo: Honoraria. Shadman:Mustang Biopharma: Research Funding; Gilead: Research Funding; AbbVIe: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; AstraZeneca: Consultancy; Sound Biologics: Consultancy; Pharmacyclics: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Atara: Consultancy; Bigene: Research Funding; Celgene: Research Funding; TG Therapeutics: Research Funding; Verastem: Consultancy; Acerta: Research Funding; Emergent: Research Funding; Sunesis: Research Funding; Merck: Research Funding. Gregory:MSD: Other: grant pending, Research Funding; Beigene: Other: Grant pending, Research Funding; Celgene: Other: grant pending, Research Funding; Monash University: Research Funding; Roche: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: grant pending, Research Funding; Janssen: Other: grant pending, Research Funding; Melbourne Haematology: Consultancy, Honoraria, Other: Travel fees and conference support, Speakers Bureau. Wei:Genentech, Inc./F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Yin:Genentech, Inc: Employment, Equity Ownership. Kwan:Genentech, Inc: Employment, Equity Ownership. Yousefi:F. Hoffmann-La Roche Ltd: Employment. Hernandez:Genentech, Inc.: Employment, Equity Ownership. Li:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. O'Hear:F. Hoffmann-La Roche Ltd: Equity Ownership; Genentech, Inc.: Employment. Budde:F. Hoffmann-La Roche Ltd: Consultancy. Mosunetuzumab (RG7828) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.

Don DeLillo's Great Jones Street: Commodification and Pandemonium

The future modern condition of humanity is at stake; the market economy rationalizes and mechanizes people; reduces them to objects that consume objects. Material value predominates human value. Meaning is lost; it is equal to the accumulation of tangible objects. The complexity of human condition in the 21st century has become one of the most widely explored topics among scholars, writers, and critics in American literature. Given that DeLillo's character Bucky Wunderlick exemplifies this complexity, this paper proposes to explore Wunderlick’s treatment to commodification imposed upon him by the crowds (audience/masses) and market economy. In this paper, these crowds and the economic system are reduced to the notion of Pandemonium. It denotes chaos, a state of extreme confusion and disorder. My reading of Wunderlick’s commodification in contemporary America grounds on Marx and Engels' definition of the concept. I strengthen my argument with Jean Baudrillard, Guy DeBord, Lucas, and Adorno. On the whole, this study aspires to further expand the understanding of the future plight of human beings in the post-contemporary (my italics) America.

GENERALIZABILITY OF CLINICAL TRIALS OF DELIRIUM INTERVENTIONS

Delirium, or acute confusional state, affects up to 7 million hospitalized older adults annually, and is associated with increased risk of mortality, institutionalization, and cognitive and functional impairment. There has been a proliferation of both pharmacological and nonpharmacological clinical trials to reduce the incidence and sequelae of delirium. In other neuropsychiatric disorders, exclusion criteria prevent up to 75% of individuals with the condition under study from participating. It is unclear how well these trial samples represent the population of older adults with delirium. We selected all intervention trials registered at ClinicalTrials.gov containing the keyword “delirium” (N=131), regardless of type of intervention. We manually examined study descriptions to restrict analysis to studies with delirium as a primary or secondary outcome (N=92). Of these 92 studies, 76% enrolled only adults, with 45% enrolling only older adults. 38% of studies were restricted to surgical units, 27% to intensive care units, and 7.6% to medical units. Only 1 study examined nursing homes and 4 studies examined palliative care. 50% of studies excluded individuals with pre-existing dementia, 28% excluded individuals with psychiatric disorders, and 30% excluded individuals with neurological disorders. 34% of studies excluded individuals with alcohol or drug abuse. Overall, many intervention studies for delirium are limited to the surgical and ICU populations, and they exclude individuals with common comorbidities associated with an increased risk of delirium. Similar to other neuropsychiatric disorders, these findings raise significant concerns about the generalizability of clinical trials in delirium to the hospitalized older adult population.

Advanced hemodynamic monitoring in critically ill neonates

The neonatal circulation is unique due to the presence of fetal shunts. With the advances in biomedical technology, the assessment of sick newborn infants has improved significantly. It allows to collect, store and analyze the complex physiometric data and provides a foundation for advances in diagnosis and management of neonatal cardiovascular compromise. This could allow the clinician to have objective information to compliment the clinical assessment. Additionally, serial assessments and trending of measured parameters provides longitudinal information on disease pathophysiology and the response to treatment.The advanced hemodynamic monitoring however has to be structured and focussed to get the relevant information to compliment clinical signs and symptoms. It however has an inherent risk of inappropriate or over-treatment leading to a state of confusion. The following questions should thus be addressed at the outset:1. Objectives of assessment and goal of therapy2. Available techniques and processing information3. Point assessment vs continuous assessment4. Invasive monitoring vs non-invasive monitoringThe goal of hemodynamic monitoring is to optimise end-organ perfusion. The delivery of oxygen (DO2) depends on gas exchange, haematocrit, macrocirculation (preload, cardiac function and afterload) and microcirculation (capillary and end organ perfusion) (Table 1)1. The point-of-care functional echocardiography is helpful for initial assessment to complement continuous assessment techniques such as non-invasive continuous hemodynamic monitoring and in emergency situations of hemodynamic instability.When utilising these techniques, the limitations of individual devices and the interaction between them should be known. As compared to point-of-care assessment, when non-invasive monitoring devices are used, the trending of data from them with simultaneous single screen longitudinal display of values is helpful for diagnosis of disease and assessing response to treatment (Figure 1).2 The examples are continuous cardiac output, blood pressure, central venous pressure, pulse oximetry and near infrared spectroscopy. The trending of heart rate monitoring has already been utilised for early detection of sepsis using HeRO monitor. There has been interest in continuous amplitude integrated EEG but so far it is limited to research trials.We compared measurement of cardiac output with echocardiography with non-invasive cardiac output monitoring. We observed that absolute values were different but the trend on longitudinal assessment was comparable. This could be due to the fact that non-invasive cardiac output assessment methods utilise indirect techniques such as electric velocimetry, arterial pulse contour analysis etc. Using an example of a baby with septic shock, one can understand how the hemodynamic monitoring can guide initial management.3 BP = cardiac output (CO) x systemic vascular resistance (SVR) (Figure 2) 4 If a patient has low CO, high SVR and normal BP, the choice of treatment is inodilators e.g., milrinone. If CO, SVR and BP are all low, commence treatment with norepinephrine and add epinephrine. If high CO and low BP and SVR, give fluid bolus initially and titrate therapy.The integration of advanced hemodynamic monitoring in clinical care is akin to whole genome sequencing where a large amount of information is gathered which requires processing. Utilising this information is a challenge at present but it has the potential to open gateways for precision medicine.5

Metabolic Encephalopathy - Part I

Encephalopathy can range from the acute confusional state to frank coma, and is broadly defined as a constellation of symptoms and signs reflecting diffuse cerebral dysfunction. The potential causes of encephalopathy are vast requiring a thorough initial assessment and systematic diagnostic approach. Obtaining a comprehensive history may be challenging and ancillary sources of information are often helpful in narrowing the differential diagnosis. The general examination may provide hints as to the cause of encephalopathy and the neurologic examination can guide both acute management and focus the diagnostic investigations on specific etiologies which fit the clinical presentation. The systemic manifestations of infection and toxic exposures are common causes of encephalopathy. In sepsis, not only is brain perfusion compromised, multi system dysfunction is common and additional factors related to the specific infection such as hypoxia in pneumonia or secondary CNS involvement can complicate management. An understanding of the common physical examination findings of toxic exposures can aid in the diagnosis and rapid treatment of reversible toxic encephalopathies such as narcotics, benzodiazepines or environmental toxins. Cardiopulmonary dysfunction can lead to hypoxic-ischemic encephalopathy and advances in critical care, and particularly targeted temperature management following cardiac arrest, have improved the neurologic outcome in these patients. This review contains 2 figures, 3 tables, and 25 references. Key words: encephalopathy, delirium, ascending reticular activating system, acute confusional state, subclinical seizures, Glasgow Coma Scale, Full Outline of Unresponsiveness (FOUR) Score , hypoxic-ischemic encephalopathy, neuroleptic malignant syndrome, serum neuron-specific enolase

Metabolic Encephalopathy - Part I

Encephalopathy can range from the acute confusional state to frank coma, and is broadly defined as a constellation of symptoms and signs reflecting diffuse cerebral dysfunction. The potential causes of encephalopathy are vast requiring a thorough initial assessment and systematic diagnostic approach. Obtaining a comprehensive history may be challenging and ancillary sources of information are often helpful in narrowing the differential diagnosis. The general examination may provide hints as to the cause of encephalopathy and the neurologic examination can guide both acute management and focus the diagnostic investigations on specific etiologies which fit the clinical presentation. The systemic manifestations of infection and toxic exposures are common causes of encephalopathy. In sepsis, not only is brain perfusion compromised, multi system dysfunction is common and additional factors related to the specific infection such as hypoxia in pneumonia or secondary CNS involvement can complicate management. An understanding of the common physical examination findings of toxic exposures can aid in the diagnosis and rapid treatment of reversible toxic encephalopathies such as narcotics, benzodiazepines or environmental toxins. Cardiopulmonary dysfunction can lead to hypoxic-ischemic encephalopathy and advances in critical care, and particularly targeted temperature management following cardiac arrest, have improved the neurologic outcome in these patients. This review contains 2 figures, 3 tables, and 25 references. Key words: encephalopathy, delirium, ascending reticular activating system, acute confusional state, subclinical seizures, Glasgow Coma Scale, Full Outline of Unresponsiveness (FOUR) Score , hypoxic-ischemic encephalopathy, neuroleptic malignant syndrome, serum neuron-specific enolase

Mining on communal land as a new frontier –a case study of the Kunene Region, Namibia

ABSTRACT This paper is about mining under communal ownership which makes this kind of mining a new mining frontier. The newness of the frontier is that it has introduced a series of institutional complexities that is uncommon to artisanal and large-scale mining. Mining companies have to negotiate deals with communities and their leaders to be able to prospect for mineral resources. We also argue that the state’s environmental legislation is poorly harmonised with the prevalent conditions in communal areas where mining is gaining greater importance. Legislation remains silent on the rights of those living on communal land. These rights remain in a state of confusion with often negative effects on the local communities who are exposed to a number of duplicating development programmes and legislative structures. The aim of this paper is to explore the dynamics communal mining in the Kunene Region in north-western Namibia.

Seizure mimics in children- Awareness detects the abnormality

Though lot of seizure mimics are described in children very few publications about the clinical features and spectrum of diagnoses in children are available with acute paroxysmal events but without epileptic features. To describe children with seizure mimics and to determine the clinical characteristics predicting benign outcome. Paediatric Neuro team registered a cohort of 286 patients with acute/recurrent paroxysmal events suspicious for seizure like events out of 1286 seizures from January 2017 to December 2018. Cases reviewed for clinical and EEG features and were classified ";“benign";” if there was no clinical or EEG features and there was an anticipation of better outcome. Of the 286 cases evaluated for suspected seizure like events, 120(41.96%) had syncope.Of these. 55 had clonic or tonic seizure, 25 had post event headache, 5 had confusional states. History of migraine (Brainstem aura in 25, migraine with aura 40) in 80 and tension type of headache in 20 with syncope. Clustering seen in pubertal ages. 22 had gratification phenomenon, 18 had breath holding spells, 42 had pseudo-seizures and 4 had paroxysmal tonic up gaze. Narcolepsy(2), benign paroxysmal vertigo(18) and Sandifer syndrome(5) Paroxysmal dyskinesia(5) and severe tic disorders (9) were also seen. Except for clustering during December and March (school exam time) and parental disharmony a unifying risk factor was not seen. Parent recorded videos helped in the diagnosis (videos can be presented}. Care giver recorded video can distinguish conditions. Awareness and a thorough perusal of any case referred as “seizure. Disorder” for mimics will help in avoiding unnecessary anticonvulsants

Sporadic Creutzfeldt Jakob disease with fast progressive evolution – A challenging diagnosis – A case report

Creutzfeldt-Jakob disease (CJD), a spongiform encephalopathy, is a rare and fatal condition that affects the brain. It causes brain damage that worsens rapidly over time. We herein report the case of a 67 years old patient without pathological antecedents who was admitted to our department for visual and gait disturbances, coreo-athetotic movements and confusional state, symptomatology that had started about one month before and worsened progressively. The neurological exam pointed out: cortical blindness, coreoathetotic movements left more than right, hyperestesia. Laboratory test results revealed hyperglycemia. All others tests (B12 vitamin, B,C, hepatitis, HIV, FT4, TSH hormones, paraneoplastic and autoimmune markers – NMDA, GABA, VKGT) were physiologically within limits. The cerebrospinal fluid analysis revealed an intense 14-3-3 and TAU protein positivation. The CT scan that was performed did not reveal anything pathological. A cerebral MRI with contrast injection and an EEG were performed. The MRI, which was performed in general anesthesia, revealed: bicerebral cortical cortex hypersignal in diffusion sequence (except the left parietal lobe), with no FLAIR correspondence, without pathological contrast intakes,while EEG highlighted: slow dysrhythmia, delta waves with three phase paroxysmal discharge, Based on these examinations was established the final diagnosis: Probable Sporadic Creutzfeldt Jakob disease. The patient received treatment with valproic acid and clonazepam with no significant improvement.

Prevention as Intervention: Reducing Incident Delirium in Heart Failure.

Delirium, an acute confusional state, is a health problem complicating the course of illness of hospitalized and ICU patients, including acute decompensated heart failure patients. The use of prevention protocols will necessitate education of clinicians, as an interdisciplinary team is developed. Assess the impact of a 1-hour lecture and PowerPoint educational program on delirium and prevention protocols on nurses' knowledge. A literature review was conducted on delirium risk in heart failure, prevention, and education. Nurses participated in a 1-hour nursing educational intervention on delirium prevention using lecture and PowerPoint. Results demonstrated a statistically significant difference between the means of the pre- and post- assessment scores, t (19) = 5.29, p = .00004 < ∝ = 0.05. McNemar's tests showed statistically significant differences in the in the pre- and post- assessment questions numbered 1, p = 0.001 and 3, p = 0.031. Effective education, driven by the severity of outcomes and high healthcare costs, will increase nursing knowledge of delirium prevention, thereby permitting nurses to tailor delirium prevention strategies consistent with high-quality nursing care. Nurses, who are equipped to tailor individual prevention strategies, will be strong advocates for the safety, mental and physical health of heart failure patients.

Confusion and Consent: Land Tax (Kharāj) and the Construction of Judicial Authority in the Early Islamic Empire (ca. 12–183 A.H./634–800 C.E.)

This essay examines the Islamic land tax (kharāj) during the first wave of the Arab conquests (ca. 12–24/633–50) and the following century and a half. Highlighting the confused state of land tax and landholding, it argues that Sunni jurists incorporated land tax into Islamic law despite the lack of Qurʾānic injunctions and prophetic tradition. In doing so, they drew upon Qurʾānic concepts such as fay’ and ghanīma while reinterpreting a vast body of conquest narratives and traditions that helped present land tax as a bona fide Islamic practice. A major outcome of this juristic discourse of public finance was the recognition of the ruler’s right to discretionary taxation. Just as the jurists emphasized justice and equitable application of tax laws, they also enabled the government to enjoy a wide latitude in its fiscal management without legal backlash. It further allowed the jurists to speak for God and His Prophet.

Cash Management in Cameo Corporate Services Limited

The term cash management refers to the management of cash resource in such a way that generally accepted business objectives could be achieved. In this context, the objectives of a firm can be unified as bringing about consistency between maximum possible profitability and liquidity of a firm. Cash management may be defined as the ability of a management in recognizing the problems related with cash which may come across in future course of action, finding appropriate solution to curb such problems if they arise, and finally delegating these solutions to the competent authority for carrying them out The choice between liquidity and ij profitability creates a state of confusion. It is cash management that can provide solution to this dilemma.Cash management may be regarded as an art that assists in establishing equilibrium between liquidity and profitability to ensure undisturbed functioning of a firm towards attaining its li business objectives[1],[ 3],[5]

A novel neural computational model of generalized periodic discharges in acute hepatic encephalopathy.

Acute hepatic encephalopathy (AHE) due to acute liver failure is a common form of delirium, a state of confusion, impaired attention, and decreased arousal. The electroencephalogram (EEG) in AHE often exhibits a striking abnormal pattern of brain activity, which epileptiform discharges repeat in a regular repeating pattern. This pattern is known as generalized periodic discharges, or triphasic-waves (TPWs). While much is known about the neurophysiological mechanisms underlying AHE, how these mechanisms relate to TPWs is poorly understood. In order to develop hypotheses how TPWs arise, our work builds a computational model of AHE (AHE-CM), based on three modifications of the well-studied Liley model which emulate mechanisms believed central to brain dysfunction in AHE: increased neuronal excitability, impaired synaptic transmission, and enhanced postsynaptic inhibition. To relate our AHE-CM to clinical EEG data from patients with AHE, we design a model parameter optimization method based on particle filtering (PF-POM). Based on results from 7 AHE patients, we find that the proposed AHE-CM not only performs well in reproducing important aspects of the EEG, namely the periodicity of triphasic waves (TPWs), but is also helpful in suggesting mechanisms underlying variation in EEG patterns seen in AHE. In particular, our model helps explain what conditions lead to increased frequency of TPWs. In this way, our model represents a starting point for exploring the underlying mechanisms of brain dynamics in delirium by relating microscopic mechanisms to EEG patterns.

Birth of a nation‐state: A battle for boundaries or dialogue?

AbstractIn this article, I propose extending group and family psychoanalytic theories to understand the unconscious dynamics that may underlie a nation‐state's constitution and the conflict that manifests during the process of establishment. I reflect on Lebanon's history, its birth, its development, and its crises during its process of “becoming.” An independent nation‐state requires clear borders or a body envelope to build itself; otherwise, its psychic envelope will fail to contain and transform primitive transgenerational persecutory and annihilating anxieties of its nation‐group and its citizens. I also analyze whether Lebanon's difficulty in delineating its borders has left it in a state of confusion with its two Siamese neighbors and characterize its group psychic apparatus as a pregenital, narcissistic, “incestual” mode of family functioning. I then reflect on whether Lebanese citizens are metaphorically part objects, who enact, through their fraternal pacts, the unconscious fratricidal fantasies of the archaic fraternal complex. Through these psychoanalytic reflections, I hope to contribute to the national and international dialogues and facilitate sibling countries to better mourn their original symbiotic state, thus allowing the Lebanese, as a result, to build their own nation‐state.

Chemokine CCL7 regulates spinal phosphorylation of GluA1-containing AMPA receptor via interleukin-18 in remifentanil-induced hyperalgesia in rats

BackgroundRemifentanil-induced hyperalgesia (RIH) may be a potential component for acute confusional state and chronic pain after surgery, but specific mechanism remains elusive. Chemokines and inflammatory mediators associated neuroinflammation is involved in central nociceptive sensitization. The contribution of AMPA receptor to excitatory synaptic transmission in pathologic pain has been indicated. This study investigated whether chemokine CCL7 modulated spinal phosphorylation of AMPA receptor via interleukin (IL)-18 in a rat model of RIH. MethodsMechanical allodynia and thermal hyperalgesia after remifentanil infusion were verified by assessment of paw withdrawal threshold and paw withdrawal latency, respectively. A neutralizing antibody against CCL7, IL-18 antagonist and recombinant CCL7 were employed to identify the mechanisms. Levels of CCL7 and its receptors, expressions of IL-18 and its receptor IL-18R, and the phosphorylation of GluA1 in the spinal cord dorsal horn were evaluated. ResultsWe reported that acute exposure to remifentanil caused and maintained behavioral RIH with up-regulation of expression in CCL7/CCR2 and IL-18/IL-18R and the phosphorylation of GluA1 in the dorsal horn. Spinal inhibition of CCL7/CCR2 impaired RIH, spinal expression of IL-18/IL-18R and the phosphorylation of GluA1. Central blockage of IL-18/IL-18R reduced spinal phosphorylation of GluA1 and behavioral RIH. Also, intrathecal injection of exogenous CCL7 facilitated acute pain behaviors and spinal phosphorylation of GluA1 in naïve mice, which was suppressed by co-administration of IL-18 antagonist. ConclusionOur current findings demonstrate that spinal CCL7/CCR2 modulation of GluA1-containing AMPA receptor activation via IL-18 and IL-18R over-expression is an important pathogenesis of remifentanil-induced hyperalgesia in rats.

Fear and disgust: case report of two uncommon emotional disturbances evoked by visual disperceptions after a right temporal-insular stroke

BackgroundEmotional processes and responses are underestimated in stroke patients because the massive clinical picture of large hemispheric strokes often hides these symptoms. We report on a patient with peculiar unpleasant emotional responses after temporal stroke.Case presentationWe describe a 62-years old man with significant unpleasant emotional responses that occurred after an acute episode of confusional state, disorientation, agitation, vertigo, postural instability, vomiting, and photophobia. Since then, he complained that vision of pictures containing curved/multicolored lines or tangles was associated with an uncomfortable feeling of fear and disgust, lasting few minutes, so that he avoided looking at them. Notably, he also showed an abnormal facial expression of disgust and fear, together with neurovegetative reaction and horripilation, at the presentation of pictures of objects or animals containing curved, multicolored, or tangled lines. A post-acute infarction of the right temporal-insular region, together with mild periventricular white matter changes, were evident at the brain magnetic resonance imaging.ConclusionsThe anterior insula is crucial in transforming unpleasant sensory input into visceromotor reactions and the accompanying feeling of disgust. It is also known that temporal pole modulates visceral emotional functions in response to emotionally evocative perceptual stimuli. In the present case, the ischemic lesion of anterior part of the insula and temporal pole may have caused a decoupling of emotional and visceral response to complex visual stimuli. Further reports will provide a significant contribution to the taxonomy of these complex and relatively uncommon non-motor post-stroke symptoms that negatively affect quality of life.