A Study of the Psychometric Properties of the "Stanford Proxy Test for Delirium" (S-PTD): A New Screening Tool for the Detection of Delirium.

BACKGROUND: Delirium is a prevalent neuropsychiatric disorder associated with increased morbidity and mortality. Half the cases remain misdiagnosed. OBJECTIVE: Assess the effectiveness of the Stanford Proxy Test for Delirium (S-PTD) in detecting delirium in an inpatient setting. METHODS: This is a comparison study. Daily assessment with S-PTD, by the patient's nurse, and a neuropsychiatric assessment by a psychiatrist. Assessments were blinded. Inclusion criteria included 18 years or older. Exclusion criteria included patient's or surrogate's unwillingness to participate, inability to consent if a surrogate was not available, and inability to communicate in English or Spanish. A total of 309 patients were approached: 27 declined participation, 4 were excluded, and 278 subjects were followed up throughout their hospital stay. In the end, 78 were excluded for lack of neuropsychiatric assessment, S-PTD, or both. One was excluded for lack of demographic data. The sensitivity and specificity of the S-PTD in detecting delirium when compared with a neuropsychiatric assessment. RESULTS: Participants were on average 60.8 years old and 54.3% were male. Patients who developed delirium were, on average, older (15.12 y, confidence interval: 8.94-21.32). A total of 199 patients were analyzed; 43 patients (21.6%) met criteria for delirium. S-PTD detected 67 days with delirium (16.5%) of 405 hospital days, while neuropsychiatric evaluation identified 83 (20.5%). S-PTD had a sensitivity of 80.72% and a specificity of 90.37%. CONCLUSION: S-PTD is an effective, comprehensive, and simple screening tool for delirium, which is robust despite fluctuating symptoms and lack of cooperation. The use of S-PTD may enhance early diagnosis of delirium.

Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality.

BACKGROUND: Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized. METHODS: The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, and one-year mortality. RESULTS: Thirty-six percent of patients developed early-onset, and 44% developed ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first postoperative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (P=.001), ICU LOS (P<.001), and hospital LOS (P=.005). Ever-onset delirium was associated with longer ICU (P<.001) and hospital LOS (P<.001). After adjusting for clinical variables, delirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55). CONCLUSIONS: Delirium is common after lung transplant surgery and associated with increased hospital resources.

Frontal Lobe Epilepsy: A Primer for Psychiatrists and a Systematic Review of Psychiatric Manifestations.

BACKGROUND: Frontal lobe epilepsy (FLE) can masquerade as a primary psychiatric condition, be misdiagnosed in-lieu of a true psychiatric disorder, or may be comorbid with psychiatric illness. OBJECTIVES: To (1) qualitatively review psychiatric manifestations of FLE and (2) to systematically review the cases/case series of psychiatric manifestations of FLE presented in the literature to date. METHODS: A systematic review of the literature was performed following the PRISMA guidelines and using PubMed/Medline, PsychInfo, and Cochrane database of systematic reviews to identify cases and case series of psychiatric manifestations of FLE. RESULTS: A total of 35 separate articles were identified. Further, 17 patients primarily presented with psychosis, 33 with affective symptoms, and 16 with personality changes. Also, 62% of cases were males and 38% were females. Ages ranged from 2-83 years with the average age of 32.7. Prior psychiatric history was reported in 27.3% of cases. Causes of seizure were known in 53%, with the most common causes being dysplasia and tumor. Only 6 cases (<10%) did not have electroencephalographic correlations. Psychiatric manifestations were primarily ictal in 74.3% of the cases. Associated manifestations included motor (63.6%), cognitive (34.8%), and medical (9.0%) findings. Surgery was required in 31.8% of the cases, whereas others were treated with medications alone. All, but 3, patients were seizure free and saw an improvement in symptoms with treatment. CONCLUSIONS: Given the complexity and multifunctionality of the frontal lobes, FLE can present with complex, psychiatric manifestations, with associated motor, cognitive, and medical changes; thus, psychiatrists should keep FLE on the differential diagnosis of complex neuropsychiatric cases.

The Stanford Integrated Psychosocial Assessment for Transplantation: A Prospective Study of Medical and Psychosocial Outcomes.

BACKGROUND: Psychosocial factors may significantly affect post-transplant outcomes. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) was developed as an assessment tool to enhance the pre-transplant psychosocial evaluation. METHODS: We identified heart, lung, liver, or kidney transplant recipients assessed with the SIPAT pre-transplantation and transplanted between June 1, 2008, and July 31, 2011, at our institution. We analyzed prospectively accumulated psychosocial and medical outcomes at 1 year of follow-up. RESULTS: 217 patients were identified and included in the analysis. The primary outcomes of organ failure and mortality occurred in 12 and 21 patients, respectively, and were not significantly associated with the pre-transplant SIPAT scores. On the other hand, SIPAT scores were significantly correlated with the probability of poor medical and psychosocial outcomes (secondary outcomes). In fact, higher SIPAT scores predicted higher rates of rejection episodes (Spearman ρ = 0.15, 95% 95% confidence interval [CI] = 0.02-0.28, p = .023), medical hospitalizations (ρ = 0.29, 95% CI = 0.16-0.41, p < .001), infection rates (p = .020), psychiatric decompensation (p = .005), and support system failure (area under the curve = 0.70, 95% CI = 0.60-0.79, p < .001). The relationship with nonadherence suggested a trend, but no statistical significance was observed (area under the curve = 0.60, 95% CI = 0.50-0.71, p = .058). CONCLUSIONS: Study outcomes suggest that SIPAT is a promising pre-transplantation assessment tool that helps identify candidate's areas of psychosocial vulnerability and whose scores are associated with both psychosocial and medical outcomes after transplantation.

Adjunctive Valproic Acid in Management-Refractory Hyperactive Delirium: A Case Series and Rationale.

Patients with delirium may fail to respond to standard therapies. Sixteen patients with management-refractory hyperactive delirium responded to adjunctive valproic acid, with complete resolution of hyperactive delirium in 13 cases. A rationale for using valproic acid in such circumstances is discussed.

Valproic Acid for Treatment of Hyperactive or Mixed Delirium: Rationale and Literature Review.

BACKGROUND: Delirium is the most often encountered psychiatric diagnosis in the general hospital, with an incidence of up to 82% in the intensive care unit setting and with significant detrimental effects on patients' morbidity and mortality. Antipsychotics are often considered the first-line pharmacological treatment of delirium, but their use may be limited by lack of efficacy, existing contraindications (e.g., prolonged QTc intervals), or resulting side effects (e.g., akathisia). Valproic acid (VPA) is a potential alternative or adjunct treatment. It has multiple mechanisms of action, including effects on neurotransmitter modulation, neuroinflammation, oxidative stress, and transcription, all of which are implicated in the pathophysiology of delirium. Yet, data on the use of this agent in delirium are limited. OBJECTIVE/METHODS: In this article, we discuss postulated mechanisms of VPA action that provide a theoretical basis for its use in the treatment of hyperactive and mixed type delirium, based on the known and theorized pathophysiology of delirium. We also discuss potential side effects and considerations with use of VPA. CONCLUSIONS: VPA has multiple modulatory effects on neurotransmitter systems, inflammation, oxidative stress, and transcriptional changes implicated in pathophysiology of delirium. When carefully chosen, VPA can be an effective and well-tolerated treatment option for the management of hyperactive and mixed type delirium. Randomized controlled trials are needed to establish tolerability and efficacy of VPA for treatment of delirium.

Prospective Validation Study of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) in Medically Ill Inpatients: A New Scale for the Prediction of Complicated Alcohol Withdrawal Syndrome.

AIMS: The prevalence of alcohol use disorders (AUDs) among hospitalized medically ill patients exceeds 40%. Most AUD patients experience uncomplicated alcohol withdrawal syndrome (AWS), requiring only supportive medical intervention, while complicated AWS occurs in up to 20% of cases (i.e. seizures, delirium tremens). We aimed to prospectively test and validate the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), a new tool to identify patients at risk for developing complicated AWS, in medically ill hospitalized patients. METHODS: We prospectively considered all subjects hospitalized to selected general medicine and surgery units over a 12-month period. Participants were assessed independently and blindly on a daily basis with PAWSS, Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) and clinical monitoring throughout their admission to determine the presence and severity of AWS. RESULTS: Four hundred and three patients were enrolled in the study. Patients were grouped by PAWSS score: Group A (PAWSS < 4; considered at low risk for complicated AWS); Group B (PAWSS ≥ 4; considered at high risk for complicated AWS). The results of this study suggest that, using a PAWSS cutoff of 4, the tool's sensitivity for identifying complicated AWS is 93.1% (95%CI[77.2, 99.2%]), specificity is 99.5% (95%CI[98.1, 99.9%]), positive predictive value is 93.1% and negative predictive value is 99.5%; and has excellent inter-rater reliability with Lin's concordance coefficient of 0.963 (95% CI [0.936, 0.979]). CONCLUSION: PAWSS has excellent psychometric characteristics and predictive value among medically ill hospitalized patients, helping clinicians identify those at risk for complicated AWS and allowing for prevention and timely treatment of complicated AWS.

Myoclonus, Uremia, and Delirium in a Liver Transplant Recipient: A Case Report and Literature Review.

BACKGROUND: Consultation-liaison (CL) psychiatrists are frequently asked to consult on various abnormal movements (1). CL psychiatrists can be instrumental in aiding the primary teams to identify and manage these movement disorders. In this manuscript, we provide an illustrative case of a patient presenting with myoclonus and offer a review on this important topic. Myoclonus accompanied by delirium represents a rare post-transplant complication and can be associated with heightened morbidity and mortality. The incidence of this complication in solid organ transplant recipients is scarcely documented, and its pathophysiology remains inadequately understood. Potential etiologies in the intensive care unit are numerous and likely multifactorial. The literature lacks detailed descriptions of the correlation and association between myoclonus and uremia. Management of this condition requires a multimodal approach, focusing on resolving underlying metabolic disturbances and providing symptomatic treatment. OBJECTIVE: This manuscript describes the clinical presentation of myoclonus in a liver transplant recipient accompanied by delirium and precipitated by uremia. We aim to highlight the diagnostic and therapeutic complexities, help providers distinguish myoclonus from other movement disorders, and aid appropriate management. METHODS AND RESULTS: We present a case of acute myoclonus in an elderly female liver transplant recipient precipitated by uremia and improved after continuous renal replacement treatment. In addition, we conducted a systematic review utilizing EMBASSE and PubMed of reported cases of myoclonus, delirium, and/or encephalopathy accompanied by uremia. We included 12 manuscripts in our review and discussed their findings. CONCLUSIONS: CL psychiatrists are frequently consulted for a range of movement disorders in the intensive care unit, including myoclonus. Accurate diagnosis and identification of contributing etiologies are critical in these cases. Management typically involves addressing the underlying disorder, such as using dialysis for uremia, alongside symptomatic treatment with benzodiazepines to mitigate the frequency and amplitude of myoclonus. This approach helps to alleviate both the physical burden and psychological distress associated with the condition. This case underscores the pivotal role of the CL psychiatrist within a complex multidisciplinary team, contributing to diagnostic precision and optimization of management strategies for movement disorders.

Dyspnea and Dyspnea-Associated Anxiety in the ICU Patient Population: A Narrative Review for CL Psychiatrists.

BACKGROUND: Consultation-liaison psychiatrists frequently address dyspnea in intensive care unit (ICU) patients. Dyspnea is common in this patient population, but is frequently misunderstood and underappreciated in noncommunicative ICU patients. OBJECTIVE: This paper provides an updated review on dyspnea specifically in the ICU population, including its pathophysiology and management, pharmacological and nonpharmacological, aimed at consultation-liaison psychiatrists consulting in ICU. METHODS: A literature review was conducted with PubMed, querying published articles for topics associated with dyspnea and dyspnea-associated anxiety in ICU patient populations. When literature in ICU populations was limited, information was deduced from dyspnea and anxiety management from non-ICU populations. Articles discussing the definition of dyspnea, mechanistic pathways, screening tools, and pharmacologic and nonpharmacologic management were included. RESULTS: A reference guide was created to help consultation-liaison psychiatrists and intensivists in the screening and treatment of dyspnea and dyspnea-associated anxiety in critically ill patients. CONCLUSIONS: Dyspnea is frequently associated with anxiety, prolonged days on mechanical ventilation, and worse quality of life after discharge. It can also increase the risk of posttraumatic stress disorder post-ICU discharge. However, it is not routinely screened for, identified, or addressed in the ICU. This manuscript provides an updated review on dyspnea and dyspnea-associated anxietyin the ICU population, including its pathophysiology and management, and offers a useful reference for consultation-liaison psychiatrists to provide treatment recommendations.

Delayed-Onset Psychosis Secondary to Tacrolimus Neurotoxicity After Lung Transplant: A Case Report and Systematic Review.

BACKGROUND: Tacrolimus is the most common immunosuppressant used after transplant, yet it can result in moderate-to-severe neurotoxicity in up to 32% of patients. Signs of neurotoxicity can vary from mild (tremor or headache) to severe (posterior reversible encephalopathy syndrome or psychosis. Prompt recognition and management is needed to lead to symptom resolution. OBJECTIVE: The objective of this study is to describe the clinical presentation of tacrolimus-induced psychosis, a type of tacrolimus-inducted neurotoxicity, and distinguish it from other central nervous system disturbances, including delirium. METHODS AND RESULTS: We present a case of delayed onset tacrolimus-induced psychosis with focus on unique clinical features and management strategies. We conducted a systematic review of cases of tacrolimus-induced psychosis using the PubMed database and included 15 manuscripts in our review. CONCLUSIONS: Tacrolimus-induced psychosis is a unique presentation of tacrolimus-related neurotoxicity and can present without the cardinal symptoms of delirium. The data on isolated psychotic symptoms are limited with current literature focusing on more common presentations of tacrolimus-induced neurotoxicity, such as delirium and tremor. Development of psychosis can occur later in the treatment course and at normal tacrolimus serum levels. It can improve with antipsychotic therapies, but primary management should include cross-titration to an alternate immunosuppressant regimen.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT): a new tool for the psychosocial evaluation of pre-transplant candidates.

BACKGROUND: While medical criteria have been well established for each end-organ system, psychosocial listing criteria are less standardized. To address this limitation, we developed and tested a new assessment tool: the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT). METHODS: The SIPAT was developed from a comprehensive review of the literature on the psychosocial factors that impact transplant outcomes. Five examiners blindly applied the SIPAT to 102 randomly selected transplant cases, including liver, heart, and lung patients. After all subject's files had been rated by the examiners, the respective transplant teams provided the research team with the patient's outcome data. RESULTS: Univariate logistic regression models were fit in order to predict the transplant psychosocial outcome (positive or negative) using each rater's SIPAT scores. These results show that SIPAT scores are highly predictive of the transplant psychosocial outcome (P < 0.0001). The instrument has excellent inter-rater reliability (Pearson's correlation coefficient = 0.853), even among novice raters. CONCLUSIONS: The SIPAT is a comprehensive screening tool to assist in the psychosocial assessment of organ transplant candidates. Its strengths includes the standardization of the evaluation process and its ability to identify subjects who are at risk for negative outcomes after the transplant, in order to allow for the development of interventions directed at improving the patient's candidacy. Our goal is that the SIPAT, in addition to a set of agreed upon minimal psychosocial listing criteria, would be used in combination with organ-specific medical listing criteria in order to establish standardized criteria for the selection of transplant recipients.

The impact of depression in heart disease.

Depression and heart disease affect millions of people worldwide. Studies have shown that depression is a significant risk factor for new heart disease and that it increases morbidity and mortality in established heart disease. Many hypothesized and studied mechanisms have linked depression and heart disease, including serotonergic pathway and platelet dysfunction, inflammation, autonomic nervous system and hypothalamic-pituitary-adrenal axis imbalance, and psychosocial factors. Although the treatment of depression in cardiac patients has been shown to be safe and modestly efficacious, it has yet to translate into reduced cardiovascular morbidity and mortality. Understanding the impact and mechanisms behind the association of depression and heart disease may allow for the development of treatments aimed at altering the devastating consequences caused by these comorbid illnesses.

Psychiatric Aspects of Lung Disease in Critical Care.

Respiratory conditions are some of the most common indications for admission to critical care units. Psychiatric disorders and symptoms are highly comorbid with lung disease. They can occur as a risk factor to lung disease, as a co-occurring condition, as a consequence of a pulmonary condition, or as a treatment side effect either from medications or assistive devices. Patients can experience a myriad of mood, anxiety, and cognitive disorder symptoms and conditions in critical care units. Intensivists and psychiatrists must be aware of the interplay between pulmonary and psychiatric symptoms as well as medication effects and interactions.

Psychiatric Aspects of Organ Transplantation in Critical Care: An Update.

Transplant patients face challenging medical journeys, with many detours to the intensive care unit. Before and after transplantation, they have significant psychological and cognitive comorbidities, which decrease their quality of life and potentially compromise their medical outcomes. Critical care staff are essential in these journeys. Being cognizant of relevant psychosocial and mental health aspects of transplant patients' experiences can help critical care personnel take comprehensive care of these patients. This knowledge can empower them to understand their patients' psychological journeys, recognize patients' mental health needs, provide initial interventions, and recognize need for expert consultations.

Effect of anoxia/reperfusion on the reversible active/de-active transition of NADH-ubiquinone oxidoreductase (complex I) in rat heart.

The multi-subunit mammalian NADH-ubiquinone oxidoreductase (complex I) is part of the mitochondrial electron transport chain and physiologically serves to reduce ubiquinone with NADH as the electron donor. The three-dimensional structure of this enzyme complex remains to be elucidated and also little is known about the physiological regulation of complex I. The enzyme complex in vitro is known to exist as a mixture of active (A) and de-active (D) forms [Biochim. Biophys. Acta 1364 (1998) 169]. Studies are reported here examining the effect of anoxia and reperfusion on the A/D-equilibrium of complex I in rat hearts ex vivo. Complex I from the freshly isolated rat heart or after prolonged (1 h) normoxic perfusion exists in almost fully active form (87+/-2%). Either 30 min of nitrogen perfusion or global ischemia decreases the portion of active form of complex I to 40+/-2%. Upon re-oxygenation of cardiac tissue, complex I is converted back predominantly to the active form (80-85%). Abrupt alternation of anoxic and normoxic perfusion allows cycling between the two states of the enzyme. The possible role in the physiological regulation of complex I activity is discussed.