Confusional State Research Articles

Updated safety/feasibility study of concurrent tumor treating fields (TTFields) and radiation therapy for newly diagnosed glioblastoma.

e14535 Background: Tumor Treating Fields (TTFields), a non-invasive, loco-regional, anti-mitotic treatment comprises low-intensity alternating electric fields. In the phase III EF-14 study in newly diagnosed glioblastoma (ndGBM), TTFields in combination with temozolomide (TMZ) significantly improved survival compared to TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This pilot study [NCT03780569] evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) in combination with daily TMZ (75 mg/m2). In the adjuvant phase, patients received monthly TMZ (150–200 mg/m2 for 5 days) plus TTFields. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0. Results: Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and eight (80%) patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1–2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure. Conclusions: Eighty percent of patients experienced grade 1–2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed and there was no increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Based on the safety and preliminary efficacy results of this pilot study, a phase 2 randomized trial (N = 60; NCT03869242) and the Phase 3 TRIDENT trial have been initiated to further investigate the efficacy of concomitant RT/TMZ/TTFields in ndGBM. Clinical trial information: NCT03780569.

Characterization of cytokine release syndrome (CRS) and neurological events (NEs) in the phase I TRANSCEND NHL 001 trial of lisocabtagene maraleucel (liso-cel) for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).

e20046 Background: Clinical studies of liso-cel show low incidences of severe CRS and NEs. Pts with high tumor burden and inflammation are at higher risk of CRS and NEs (Borrega, Hemasphere 2019). Here, we characterize the presenting symptoms, timing, and management of CRS and NEs in pts with R/R LBCL treated with liso-cel in TRANSCEND NHL 001 (NCT02631044). A deeper understanding of CRS/NEs after liso-cel treatment may help clinicians identify and manage these toxicities. Methods: Pts with R/R LBCL and ≥2 lines of therapy received liso-cel after lymphodepletion (LD) with fludarabine and cyclophosphamide. Bridging therapy was allowed for pts with PET-positive disease before LD (Abramson, ASH 2019 #241). Investigators were educated on prospectively identifying liso-cel–related NEs and CRS, which were collected and graded per NCI CTCAE v4.03 (NEs) or 2014 Lee criteria (CRS). Timing and severity of individual CRS/NE symptoms and interventions were also collected. Results: The analysis included 269 pts (median age, 63 y): 38% had sum of perpendicular diameters ≥50 cm2 or lactate dehydrogenase ≥500 U/L, and 59% received bridging therapy. CRS and NEs had delayed onset (median, 5 and 9 d, respectively) and a low incidence of grade (Gr) ≥3 events (CRS 2%; NE 10%). CRS occurred before NEs in most pts and was Gr 1/2 at onset in all but 2 pts (Table). The most common CRS symptoms were pyrexia (40%), hypotension (20%), and tachycardia (18%). Overall, 20% of pts received tocilizumab and/or corticosteroids for CRS (10% tocilizumab only; 2% corticosteroids only; 8% both); 3% received vasopressors. The most common NE symptoms were confusional state (11%), tremor (9%), and aphasia (8%); most were low grade. A total of 17% of pts received tocilizumab and/or corticosteroids for NEs (13% corticosteroids only; < 1% tocilizumab only; 3% both); < 1% received vasopressors. Overall, 4% of pts were admitted to the ICU for CRS and/or NEs. Additional analyses on timing of intervention and type/severity of initial symptoms will be presented. Conclusions: In pts with high-risk, aggressive R/R LBCL, liso-cel treatment was associated with a low incidence of severe CRS/NEs, late onset of mostly low-grade events at presentation, and low use of tocilizumab/corticosteroids. Clinical trial information: NCT02631044 . [Table: see text]

Larsen & Toubro Infotech’s Hostile Bid for Mindtree Ltd.: Much Ado About Nothing! A Teaching Case

This article tries to understand and analyse the recent acquisition of Mindtree Ltd. by the corporate conglomerate giant Larsen & Toubro (L&T). L&T Infotech (LTI), which looks after the information technology (IT) business of the L&T group made a hostile bid for Mindtree Ltd., one of India’s leading and fastest growing infotech companies in March 2019. The case goes on to analyse the deal and delves into the reasons for the deal turning hostile. The objective of the case study is to understand the concept of hostile takeovers and the business environment that augur acquisitions. The second part of the article tries to focus on anti-takeover tactics, which the company adopts to avoid the takeover attempt. Here, Mindtree’s decision of share buyback, immediately after L&T’s bid, has been examined. Two perspectives have been studied here—one from the point of view of the promoters of Mindtree, and the other from the point of view of investors. There have been certain very interesting and jocular exchanges of words between the promoters of Mindtree and LTI1 during the whole phase of takeover, which put the focus on the human element in acquisitions. The business environment and industry analysis have been conducted to understand the nature and circumstances of the deal. Legalities of the acquisition and dominant player misuse have also been examined. LTI’s take on the acquisition was very clear. For them, it was a pure business deal. They were on the path for fast growth, which Mindtree would help them achieve. Certain sectors such as Retail, Consumer Packaged goods, Media and Technology are underachieved for LTI where Mindtree has a formidable presence. Mindtree would help LTI explore geographies in Europe that so far were unexplored. However, for the promoters of Mindtree, this bid for takeover became an emotional issue. It all started when one of the non-executive directors of Mindtree itself—V. G. Siddharth—came up to LTI and offered his shareholding of 21 per cent in Mindtree. LTI grabbed this offer and went on to announce that it would acquire a total of about 60 per cent in the company, which made the other promoters very uncomfortable. There was a lot of resistance from some of the Mindtree promoters, and certain hasty announcements and statements in the media were also made. This interesting interlude between the two companies brought a lot of attention to the acquisition and left the investors in a state of confusion. The main objective of the case will be to analyse and teach the different corporate actions which took place and the strategic decisions that were taken during the entire interaction between the two companies. This case would address teaching objectives for the topics such as hostile takeovers; share buybacks as a new approach to anti-takeover defence; political, legal and industrial analysis relevant to corporate restructuring decisions; and Hubris and Managerialism. A separate teaching perspective on Corporate Business Communication has also been explored.

Performa Punch: Subverting the Female Aggressor Trope

Performa Punch: Subverting the Female Aggressor Trope

SUN-498 A Case of Thyroid Storm with Systemic Thromboembolism

BackgroundThyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Whilst a thyroid storm is known to be a hypercoagulable state, it remains unclear if routine anticoagulation should be initiated, especially in the absence of atrial fibrillation.Case presentationA 22-year-old seaman presented to Accident and Emergency Department with a history of severe generalized abdominal pain and vomiting for 9 days. He was previously well with no significant past medical history. On examination, he appeared very anxious and agitated. He had sinus tachycardia (170 beats/min), was normotensive (Blood pressure 116/90 mmHg). He had exophthalmos, lid lag, a diffusely enlarged goiter with bruit and fine tremors on outstretched hands. There was generalized abdominal tenderness with guarding and sluggish bowel sounds. Electrocardiogram confirmed sinus tachycardia. Laboratory results showed primary hyperthyroidism [Free T4 66.2 (0.8–14.4 pmol/L), TSH <0.010 (0.65–3.70 MU/L)]. TSH Receptor Antibody was elevated at 6.23 IU/L (<1.76 IU/L), consistent with Grave’s Disease. He had acute renal impairment [urea 10.8 (2.7–6.9 mmol/l), creatinine 221 (54–101 umol/l)]. Burch & Wartofsky score was 60. Treatment with rectal propylthiouracil (PTU), i.v sodium iodide and i.v hydrocortisone were initiated.An initial CT Abdomen on Day 1 of admission demonstrated a long segment of jejunitis and marked distension of the duodenum, stomach and oesophagus. 4 days later, fT3 and fT4 levels had improved as did tachycardia and his confusion state, yet he remained febrile. Blood and urine cultures did not reveal any causative organisms. A contrast-enhanced CT revealed extensive thromboses of the portal, superior mesenteric, right external iliac, common femoral veins with left lower lobe pulmonary embolism. Thrombophilia screen was normal. He was given low-molecular-weight heparin and required total parenteral nutrition in view of prolonged bowel ileus from mesenteric ischaemia. Rectal PTU was continued to treat thyrotoxicosis. He made sufficient progress with improvement of the bowel ileus with s.c enoxaparin and was discharged 6 weeks later on oral carbimazole (on discharge: fT4 10pmol/L, TSH<0.010). However, due to extensive thromboses within the mesenteric venous system and consequent ischaemic jejunitis, he required a jejunectomy eventually 2 weeks later. Radioiodine ablation was subsequently given and he is currently hypothyroid requiring thyroxine replacement.ConclusionExtensive systemic thromboembolism may occur in the setting of a thyroid storm. Routine prophylactic anticoagulation should be considered, even in the absence of atrial fibrillation.

The Neuropsychiatric Iceberg Under Withdrawal Syndrome.

We have read with a great interest the article “Validation of the Withdrawal Assessment Tool-1 in Adult Intensive Care Patients,”1 by Capilnean and colleagues. The study emphasizes the importance of a validated tool to detect opioid withdrawal syndrome in adult intensive care units (ICUs), and yet we wonder if one possible explanation for the low accuracy of the Withdrawal Assessment Tool (WAT-1) in their study was that they included all patients with brain injury and a score of 9 or greater on the Glasgow Coma Scale (GCS) if the patient’s intracranial pressure was not increased. Although the number of patients in the study with nervous system disorders as the cause of admission to the ICU was low, we note that such patients made up nearly 15% of the patients in the study who had iatrogenic withdrawal syndrome.Although we suspect that using such broad inclusion criteria is a logical and reasonable way to improve the generalizability of such a small prospective study, this approach may have decreased the accuracy of the WAT-1 in their cohort. For instance, consider a patient with traumatic brain injury being evaluated in the ICU who has a right-sided patchy subarachnoid hemorrhage with a GCS score of 12. Such a patient’s WAT-1 score of 3 or greater could be due to probable autonomic dysfunction,2 increased tonus,3 and acute confusional state,4,5 all of which could be attributed to the organic involvement of subarachnoid hemorrhage. In this situation, if one uses the criteria in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition), unlike WAT-1, such patients would not be placed in the “withdrawal-positive” group because of the presence of another medical condition that better explains the symptoms.In an ongoing cohort study being conducted in our tertiary care university hospital, we have so far found the accuracy of WAT-1 to be nearly 85% in our preliminary analysis using more rigid criteria that excluded all patients with other neurologic and/or psychiatric disorders. We think an algorithm that separates patients with organic cerebral involvement from those without will shed much more light on this ambiguous issue of “opioid withdrawal syndrome.”

Functional Resting-State Connectivity Changes After Post-Operative Delirium in the Elderly

Post-operative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This study aims to examine changes of specific resting-state neuronal networks across different time points (before and 3 months after surgery) in delirious patients compared to no-POD patients.

Nighttime restlessness in elderly patients: differential diagnosis and treatment - Differential diagnosis and therapy

Elderly individuals, particularly those with cognitive impairment, are oftentimes restless during the night, and this increases the distress of relatives, professional carers and themselves. A number of conditions other than dementia need to be considered from nyctophobia and insomnophobia, to pain, specific motor disorders during sleep, parasomnias as REM-sleep behaviour disorder, dipping, hypoglycemia, withdrawal or excessive tea, coffee and alcohol consumption. A clear-cut differential diagnosis between dementia and delirium is not always possible, as dementia is the major risk factor for confusional states decreasing the vulnerability by anticholinergic medication and any other disruptive factor, biological or psychological. Treatment of nocturnal agitation usually requires (1) reassurance and re-orientation; (2a) the discontinuation of anticholinergic substances; (2b) symptomatic psychotropic intervention; and (3) causal treatment of underlying problems. Benzodiazepines should only be used at the lowest necessary dosage for the shortest possible time, particularly in individuals who are already benzodiazepine-dependent. Quetiapine or mirtazapine at low dosages can be employed in patients with psychotic or depressive symptoms. Melatonin and its derivatives hold promise for chronic circadian rhythm disorders. There is no "one fits all" recipe for this notorious problem and each case needs to be examined individually.

The association of delirium severity with patient and health system outcomes in hospitalised patients: a systematic review.

Backgrounddelirium is an acute state of confusion that affects >20% of hospitalised patients. Recent literature indicates that more severe delirium may lead to worse patient outcomes and health system outcomes, such as increased mortality, cognitive impairment and length of stay (LOS).Methodsusing systematic review methodology, we summarised associations between delirium severity and patient or health system outcomes in hospitalised adults. We searched MEDLINE, EMBASE, PsycINFO, CINAHL and Scopus databases with no restrictions, from inception to 25 October 2018. We included original observational research conducted in hospitalised adults that reported on associations between delirium severity and patient or health system outcomes. Quality of included articles was assessed using the Newcastle–Ottawa Scale. The level of evidence was quantified based on the consistency of findings and quality of studies reporting on each outcome.Resultswe included 20 articles evaluating associations that reported: mortality (n = 11), cognitive ability (n = 3), functional ability (n = 3), patient distress (n = 1), quality of life (n = 1), hospital LOS (n = 4), intensive care unit (ICU) LOS (n = 2) and discharge home (n = 2). There was strong-level evidence that delirium severity was associated with increased ICU LOS and a lower proportion of patients discharged home. There was inconclusive evidence for associations between delirium severity and mortality, hospital LOS, functional ability, cognitive ability, patient distress and quality of life.Conclusiondelirium severity is associated with increased ICU LOS and a lower proportion of patients discharged home. Delirium severity may be a useful adjunct to existing delirium screening to determine the burden to health care system resources.

Concurrent Tumor Treating Fields (TTFields) and Radiation Therapy for Newly Diagnosed Glioblastoma: A Prospective Safety and Feasibility Study.

Background: TTFields are a loco-regional, anti-mitotic treatment comprising low-intensity alternating electric fields. In the EF-14 study of newly diagnosed glioblastoma (ndGBM), TTFields in combination with temozolomide (TMZ) significantly improved survival vs. TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This study prospectively evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients.Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) combined with daily TMZ (75 mg/m2). In the adjuvant phase, patients received monthly TMZ (150–200 mg/m2 for 5 days) plus TTFields. Patients were followed for 24 months or until second disease progression. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0.Results: Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and 80% patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1–2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure.Conclusions: Eighty percent of patients experienced grade 1–2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed without an increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Preliminary efficacy results are promising and warrant further investigation of concurrent TTFields/RT/TMZ treatment in ndGBM patients.

Perceptions of Racial Progress and Mistreatment Today

In 1967, President Lyndon B. Johnson established the National Advisory Commission on Civil Disorders to examine why race relations in the United States were in such a state of confusion that it had resulted in civil disturbances. By 1968, the trajectory of race relations and racial disparities, with regard to the quality of life and standards of living, were such that the commission wrote, “Our nation is moving toward two societies, one Black, one White, separate and unequal.” Since the start of the twenty-first century, economic recessions, natural disasters, and civil unrest have exposed the continuation of pervasive differences in the perceptions of racial progress between Blacks and Whites. This article aims to examine perceptions of racial progress and the continuation of unfair racial treatment within the context of the commission’s “two nations” thesis. The findings of this article suggest that Blacks remain considerably more pessimistic than Whites about the state of racial affairs in the US today. How do we explain this conundrum in light of the passage of the civil rights legislation of the 1960s? We begin with the premise that race is still a problem in today’s society, but it is a problem in ways that are very different from when the Kerner Commission report was released.

COVID-19 Crisis: Early Observations on a Pandemic's Psychiatric Problems

We have recently observed several clusters of psychiatric symptoms in the context of COVID-19: (1) increased anxiety in psychiatric in- and outpatients with different diagnoses; (2) more cases of domestic violence often associated with increased drug- or alcohol-consumption in offenders and victims; (3) a nihilistic "apocalyptic" syndrome of elderly patients cut-off from their families; (4) visual and acoustic hallucinoses due to pneumonia and sepsis-related confusional states. Cases of chloroquine-related toxicity have been reported elsewhere, but have not been observed in our hospital so far. Mental issues related to COVID-19 reported from China and practical recommendations are briefly summarized. Many patients with serious mental disorders will suffer world-wide due to a reallocation of medical, social and financial ressources.

Ready for a long fight against the COVID-19 outbreak: an innovative model of tiered primary health care in Taiwan.

<h3>Background</h3> A 78-year-old woman was admitted to hospital with a hip fracture. Medical history included: hypertension, type 2 diabetes, atrial fibrillation, Graves’ disease and dyspepsia. Domiciliary medications included: omeprazole 20 mg/24 hours, tiamazole 10 mg/24 hours, apixaban 5 mg/12 hours, metoprolol 15 mg/12 hours, enalapril 20 mg/24 hours, atorvastatin 40 mg/24 hours and alprazolam 0.5 mg/24 hours. <h3>Purpose</h3> To report a case of acute confusional state (ACS). <h3>Material and methods</h3> Medication reconciliation, electronic medical records review and clinical patient interview. <h3>Results</h3> <b>Medication reconciliation was performed</b> The pharmacist verified patient adherence to the treatment, compiled a complete and accurate list of the patient’s home medications and identified discrepancies in the drug regimens. Alprazolam is a potentially inappropriate drug in the elderly (PRISCUM 2010 criteria). The pharmacist recommended gradual tapering of the dose but it was abruptly discontinued. Omeprazole duplicity was detected. The patient required a hip replacement. The pharmacist advised stopping apixaban 36 hours before surgery. On day 1, the patient suffered from acute and neuropathic pain and was prescribed amitriptyline 25 mg/24 hours, tramadol 100 mg/8 hours, ketorolac 30 mg/8 hours and pethidine as rescue analgesic. The pharmacist proposed ketorolac dose reduction (which was accepted), amitriptyline starting dose of 10 mg at bedtime and an alternative opioid to pethidine (not recommended in elderly population) but these two suggestions were not accepted by the physician. At night, the patient experienced fever (39°C) and chills. Blood pressure was 120/90 mm Hg, and heart rate was 110 beats/min. Chest radiography revealed a community acquired pneumonia and levofloxacin 500 mg/24 hours was started. On day 2, she developed severe agitation, fluctuating levels of consciousness and visual hallucinations (the presence of a cat in her room). She was diagnosed as suffering from ACS and prescribed haloperidol 5 mg. The pharmacist suggested discontinuation of anticholinergic drugs (amitriptyline and pethidine) and low dose benzodiazepine re-introduction along with non-pharmacological measures, with a favourable evolution for the patient <h3>Conclusion</h3> ACS could have been prevented, avoiding factors known to cause or aggravate it—for example, anticholinergic drugs, withdrawal states (benzodiazepine), dehydration, immobilisation and sleep disturbances. The pharmacist contributed to the integral patient care providing continuity in individualised pharmacotherapeutic care. Interventions included correcting/clarifying orders, providing drug information, suggesting alternative therapies and dose adjustments, checking discrepancies and improvement in ACS manifestations <h3>References and/or acknowledgements</h3> Towards better patient care: drugs to avoid in 2015. <i>Prescrire Int</i> 2015;<b>24</b>:78.1–6. No conflict of interest

Between bragging and reality: Italy’s confusing place in a changing world order

ABSTRACTIn theory, in 2019 Italian politics experienced a sharp discontinuity. In September, a new government of the Democratic Party and the Five Star Movement (M5S) replaced a populist coalition of the M5S and the League. The new government aimed to abandon the ‘sovereignist’ turn that had driven Italy towards Russia and China and away from its traditional allies, the EU and the US. This article argues that, unlike the contrasting rhetoric of the two governments, Italy’s position on the world stage did not change very much. Under both governments, Italy was fully committed to staying in the EU and the Eurozone. For example, fiscal policy remained compliant with the rules of the monetary union. Both governments also maintained a flexible stance with respect to the rest of the world, in response to the confused and fast-changing state of global politics. In 2019, Italy progressively lost political influence on the world stage. In spite of the rhetorical differences, both governments contributed to the country’s international decline.

DOMESTIC VIOLENCE IN GEORGE BERNARD SHAW’S CANDIDA

The aim of the paper alleges on domestic violence in George Bernard Shaw’s Candida. Domestic violence is the focal concept in literature. It concerns about violence, especially those who are having problems inside the family. The issue of domestic violence abbreviates on the problems inside the family. George Bernard Shaw is the vitalized writer. His famous work Candida is about the couple James Morell and Candida. James is a Christian socialist clergyman, and Candida is very young and housewife. When the character Eugene Marchbanks enters into their home, and their family is in the state of confusion. So, this paper abbreviates the character Eugene Marchbanks under the issue of domestic violence. The famous domestic violence theorists are Nicole Westmarland, John Hamel, Tonia Nicholls, Elizabeth Kandel Englander, Amartya Sen and Martin Bidder. Countable articles are published under the title of domestic violence and analyze domestic violence theorist’s theory by various authors. The issue of domestic violence in Candida is analyzed by using the theories related to violence. The incidents are discussed and compared with other studies. Finally, the concept of domestic violence contributes to the work of Bernard Shaw through the character of Eugene Marchbanks because of his activity in the family of Morell. Eugene creates many problems in Morell’s family.

Iatrogenic delirium on symptom-triggered alcohol withdrawal protocol.

The purpose of this paper is to illustrate delirium as a possible consequence of the application of symptom-triggered therapy for alcohol withdrawal and to explore alternative treatment modalities. In the management of alcohol withdrawal syndrome, symptom-triggered therapy directs nursing staff to regularly assess patients using standardized instruments, such as the Clinical Institute for Withdrawal Assessment of Alcohol, Revised (CIWA-Ar), and administer benzodiazepines at symptom severity thresholds. Symptom-triggered therapy has been shown to lower total benzodiazepine dosage and treatment duration relative to fixed dosage tapers (Daeppen et al., 2002). However, CIWA-Ar has important limitations. Because of its reliance on patient reporting, it is inappropriate for nonverbal patients, non-English speakers (in the absence of readily available translators) and patients in confusional states including delirium and psychosis. Importantly, it also relies on the appropriate selection of patients and considering alternate etiologies for signs and symptoms also associated with alcohol withdrawal. The authors report a case of a 47-year-old male admitted for cardiac arrest because of benzodiazepine and alcohol overdose who developed worsening delirium on CIWA-Ar protocol. While symptom-triggered therapy through instruments such as the CIWA-Ar protocol has shown to lower total benzodiazepine dosage and treatment duration in patients in alcohol withdrawal, over-reliance on such tools may also lead providers to overlook other causes of delirium. This case illustrates the necessity for providers to consider using other available assessment and treatment options including objective alcohol withdrawal scales, fixed benzodiazepine dosage tapers and even antiepileptic medications in select patients.

Mother Tongue in the Development of Early Educational Potentials of Igbo Bilingual Children

There are different ways of ensuring the development of educational potentials in a child. One of such ways is the use of Mother Tongue, although some scholars have argued against this hinging their arguments on certain assumptions. However, this paper seeks to ascertain and advocate that the use of MT enhances the development of early educational potentials in a child. Igbo bilingual children have been trapped in a web of the civilization and dynamism of the nation to the extent of total confusion and loss of self-identity, a situation which has given this research its impetus. What used to bring pride and joy to some Igbo parents, who had insisted that their children must speak and interact in English language and must attend early child care and primary schools where it is used as the sole means of instruction, has today become a general problem inhibiting the development of the early educational potentials of Igbo bilingual children. This situation is equally worsened by the ineffectiveness of the National Policy on Education (1997) which had stipulated that the MT should be used as the medium of instruction in the first two years of primary school education thereby encouraging the attainment of basic literacy in Mother Tongue. The population of this study was closely monitored in a controlled environment using questionnaire, interview, and observation and it was discovered that MT was a greater facilitator (though not at appreciable level of development) than L2 which rather causes interference and state of confusion in the learners.

THE RELATIONSHIP BETWEEN TOLERANCE OF AMBIGUITY AND CREATIVITY IN ARCHITECTURAL DESIGN STUDIO

Creativity is a cognitive ability that enables individuals to come up with both original and functional ideas and products. As architectural design requires producing aesthetic and practically useful solutions, it is a primary concern to enhance creativity in design disciplines. Many theorists argued that design is a non-linear process and many components of design problems are not clear at the beginning. At the start of the process, designers are always working at the periphery of a solution space where there is less coherence and more ambiguity. Thus, they must deal with a lot of ambiguity in every design situation. These states of uncertainty and confusion can be annoying for architecture students. On the other hand, tolerance of ambiguity is a personality trait that has been linked to creative thinking. Therefore, this paper attempts to investigate the correlation between tolerance of ambiguity of architectural students and their creativity via a qualitative study. The researchers implemented a mixed-method approach and recruited 18 architecture students. The results from this study revealed that there is a significant correlation between students’ creative thinking abilities and their tolerance for ambiguity. Our results also indicated that there is no statistically significant correlation between students’ tolerance of ambiguity and their design creativity.

ACUTE CONFUSIONAL STATES IN OLDER ADULTS WITH MAJOR NEUROCOGNITIVE DISORDER AND BACTERIURIA: IS ANTIBIOTIC TREATMENT WARRANTED?

Introduction Uncomplicated urinary tract infection (UTI)/acute simple cystitis (ASC) is defined as an infection confined to the bladder/lower urinary tract with the absence of signs and symptoms that would suggest an upper tract or systemic infection (such as fever, chills, rigors, significant fatigue or malaise beyond baseline, flank pain, costovertebral angle tenderness, pelvic or perineal pain in men). Presence of systemic symptoms suggests a complicated UTI. Symptoms of ASC include dysuria, urinary frequency or urgency, and/or suprapubic pain. The term asymptomatic bacteriuria refers to isolation of bacteria in an appropriately collected urine specimen from an individual without symptoms of UTI. Asymptomatic bacteriuria generally is not treated unless the patient is pregnant, undergoing urological procedure or has a history of recent renal transplant. However, it is recommended that ASC be treated empirically with antibiotics. Minimum criteria for the initiation of antibiotics for urinary tract infection in long-term care residents without indwelling catheter include acute dysuria or fever and at least one of the following: new or worsening urgency, frequency, suprapubic pain, gross hematuria, CVA tenderness, urinary incontinence. Acute change in mental status is not considered as a criterion to diagnose and treat UTI. However, it is known that infection in older patients may be associated with nonspecific symptoms such as increased confusion, falling, and anorexia besides other classic symptoms of infection. Diagnosis of ASC is based solely on the subjective complaints of patients. Cognitive impairment with reduced capacity to specifically communicate symptoms makes it challenging to rule out the diagnosis of ASC in older patients with major neurocognitive disorder (MNCD). Such patients may communicate the pain and discomfort from ASC by having increased confusion and behavioral disturbances. Under these circumstances, is bacteriuria a clinically significant condition that warrants antibiotic therapy? Guidelines to relate urinalysis findings to the diagnosis of ASC in older adults with MNCD with behavioral disturbance are not currently available. Establishing the diagnosis in older patients is further complicated due to the higher prevalence in this group, of asymptomatic bacteriuria and chronic urinary symptoms (such as chronic urinary nocturia, incontinence, and general sense of lack of well-being). The Infectious Diseases Society of American (IDSA) Guidelines of 2019 recommend against antibiotic “trials” as these may cause drug toxicity, drug-drug interactions, and antimicrobial resistance. Recommendation is not to routinely test urine in elderly or debilitated patients with nonspecific changes in mental or functional status in the absence of focal urinary tract symptoms, and instead hydrate, carefully observe, and assess other potential contributing factors.However, as a part of work-up for delirium/acute change in mental status ruling out UTI with UA is still standard practice despite the recommendation not to do so in the absence of specific genitourinary symptoms. This is possibly due to the failure of current guidelines to convince clinicians of its adequacy to rule out possibility of UTI in cognitively impaired patients. This diagnostic challenge often leads to dilemma in the treatment approach of these patients. Methods Case series, systematic literature review Results Case identification: Six cases of elderly patients with MNCD who presented to the emergency department with acute change in mental status and behavioral disturbance were identified. Initial work-up included abnormal urinanalysis results. In the absence of patients reporting genitourinary symptoms, a diagnosis of UTI was not considered and they were admitted to a geriatric psychiatric unit for evaluation and behavioral management.. Variation in the treatment approach for each case was evaluated which included either considering the mental status change to be a result of UTI and treating with antibiotics or managing them with psychotherapeutic interventions and psychotropic medications for behavioral stabilization if safety and well-being were concerns. Discrepancies were noted in the recommendations made by the consulting internist and geriatric psychiatrist regarding whether or not antibiotic therapy vs. psychotropic medication treatment was most appropriate for older adults with MNCD and acute confusional states who had bacteriuria >100,000?CFU/?ml. While internists were concerned about adding load of antibiotic resistance to the community, psychiatrists were worried about the adverse effects of antipsychotics including thromboembolic events and sudden deaths in elderly patients. Conclusions The cases described here illustrate the need for concrete specialized diagnostic criteria for early and accurate identification of uncomplicated UTI/ ACS in elderly population with MNCD along with an appropriate management protocol. This research was funded by: Not applicable

SAT-104 A rare drug toxicity as an unexpected finding on kidney biopsy

Renal biopsy in cases of unexplained renal failure can occasionally show findings which may not be directly relevant to the clinical scenario, but which nonetheless has a bearing on the long term follow up and management, in the form of addition of a therapeutic regimen, or preventing further exposure to an offending drug. A 35 year old Emirati gentleman was admitted to the hospital on 25th of April 2019 with complaints of left flank pain, dysuria, increased urination, headache and mildly confused state. Past history was significant for bipolar affective disorder for which he was on therapy from a different hospital with Risperidone, Clonazepam and Procyclidine. There was no history of renal disease. Clinical examination revealed an individual who was disoriented in time and place, and hypertension, with rest of the examination findings being unremarkable. Investigations revealed anemia, bland urine sediments, azotemia, hyponatremia, low serum and urine osmolality and normal sized kidneys on ultrasound with mild increase in cortical echogenicity. He was diagnosed with hyponatremia and unexplained renal failure. The serum sodium was corrected with 3% saline and water restriction, and a renal biopsy was performed The biopsy returned a picture of mild mesangial expansion (Image 1), foci of acute kidney injury, chronic interstitial nephritis and microcystic dilatation of the tubules ( Image 2), one of the lesions seen in chronic lithium toxicity. On further enquiry with the patient, a remote history of Lithium consumption was obtained but the duration was unknown. It was stopped completely 3 years ago. During clinic follow up, urine output and Sodium was maintained normal with fluid restriction alone. The renal functions showed an improvement from the time of admission, and since has remained stable.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Lithium nephrotoxicity spans a spectrum, from concentration defects to nephrogenic diabetes insipidus, chronic interstitial nephritis and rare glomerular involvement. Duration of treatment and cumulative dose are the determinants of renal toxicity. Careful monitoring and early withdrawal are the key to limiting damage, as a creatinine more than 2.5mg/dl at biopsy is a risk for progression to ESRD. In those with early signs of toxicity, but in whom Lithium would be necessary, a concurrent use of Amiloride could limit the damage.