Symptom-triggered therapy for assessment and management of alcohol withdrawal syndrome in the emergency department short-stay clinical decision unit.

INTRODUCTION: We previously reported that benzodiazepine detoxification for alcohol withdrawal using symptom-triggered therapy (STT) with oral diazepam reduced length of stay (LOS) and cumulative benzodiazepine dose by comparison with standard fixed-dose regimen. In this study, we aim to describe the feasibility of STT in an emergency department (ED) short-stay clinical decision unit (CDU) setting. METHODS: In this retrospective cohort study, we describe our experience with STT over a full calendar year (2014) in the CDU. A retrospective chart review was conducted and data collection included demographics, clinical details, total cumulative dose of diazepam, receipt of parenteral thiamine, LOS and disposition. RESULTS: 5% (n=174) of 3222 admissions to CDU required STT. Collapse or seizure (41%, n=71) and alcohol withdrawal (21%, n=37) were the most common reasons recorded for admission to CDU in those who required STT. Median Alcohol Use Disorders Identification Test score was 25 and 112 patients (64%) had at least one Clinical Institute Withdrawal Assessment for Alcohol revised measurement ≥10, triggering a dose of diazepam (20 mg). The median cumulative oral diazepam dose was 20 mg while 24 (15%) patients received a cumulative dose of 100 mg or more. Median time for STT was 12 hours (IQR=12, R=1-48). 3% (n=5) of patients required further general hospital admission and median LOS in CDU, was 22 hours (IQR=20, R=1-168). CONCLUSION: STT is potentially feasible as a rapid and effective approach to managing alcohol withdrawal syndrome in the ED/CDU short-stay inpatient setting where patient LOS is generally less than 24 hours.

Steroid-induced mental disorders in cancer patients: a systematic review.

Corticosteroids are a central part of many cancer treatment regimens. Neuropsychiatric toxicity has complicated their use, including an association with a spectrum of symptoms, from insomnia, cognitive impairment and mood symptoms, to severe mental disorders, including mania, psychosis and severe depression. Although steroid-induced mental disorders were first reported in medicine more than 60 years ago, there is a dearth of evidence available to date on optimal treatment and prevention to guide cancer clinicians. We completed a systematic review of the current evidence for therapeutic and prophylactic interventions of steroid-induced mental disorders in cancer. We searched Medline, Embase and PsycINFO and selected studies related to steroid-induced mental disorder. The studies found were limited to case series and case reports only.

Urethral stricture secondary to self-instrumentation due to delusional parasitosis: a case report.

INTRODUCTION: Delusional parasitosis is a rare psychiatric disorder which often presents with dermatological problems. Delusional parasitosis, which involves urethral self-instrumentation and foreign body insertion, is exceptionally rare. This is the first case report to date that provides a detailed presentation of the urological manifestation of delusional parasitosis with complications associated with repeated self-instrumentation and foreign body insertion, resulting in stricture formation and requiring perineal urethrostomy. CASE PRESENTATION: A 45-year-old Irish man was electively admitted for perineal urethrostomy with chronic symptoms of dysuria, haematuria, urethral discharge, and intermittent urinary retention. He reported a 4-year history of intermittent pain, pin-prick biting sensations, and burrowing sensations, and held the belief that his urethra was infested with ticks. He also reported a 2-year history of daily self-instrumentation, mainly injecting an antiseptic using a syringe in an attempt to eliminate the ticks. He was found to have urethral strictures secondary to repeated self-instrumentation. A foreign body was found in his urethra and was removed via cystoscopy. On psychiatric assessment, he displayed a fixed delusion of tick infestation and threatened to surgically remove the tick himself if no intervention was performed. The surgery was postponed due his mental state and he was started on risperidone; he was later transferred to an acute in-patient psychiatric unit. Following a 3-week admission, he reported improvement in his thoughts and distress. CONCLUSIONS: Delusional parasitosis is a rare psychiatric disorder. Self-inflicted urethral foreign bodies in males are rare and have high comorbidity with psychiatric disorders; hence, these patients have a low threshold for referral for psychiatric assessment. The mainstay treatment for delusional parasitosis is second-generation antipsychotic drugs.

Anti-NMDA receptor encephalitis: a cause of acute psychosis and catatonia.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a newly described form of encephalitis associated with prominent psychiatric symptoms at onset. Recognition of the symptom complex is the key to diagnosis. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from initial psychiatric symptoms to memory disturbance, seizures, dyskinesia, and catatonia. Psychiatric manifestations include anxiety, mania, social withdrawal, and psychosis (i.e., delusions, hallucinations, disorganized behavior). The disorder is more common in females (80%), in approximately half of whom it is associated with an underlying ovarian teratoma. Treatment involves immunosuppression, with steroids and intravenous immunoglobulin considered first line. The disorder is particularly relevant to psychiatrists, because most patients are initially seen by psychiatric services. Psychiatrists should consider anti-NMDAR encephalitis in patients presenting with psychosis as well as dyskinesia, seizures, and/or catatonia, especially if there is no history of a psychiatric disorder. We present the case of a 37-year-old woman who demonstrated many of the key clinical features of this potentially treatable disorder.

Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

Sensitivity and specificity of the Distress Thermometer and a two-item depression screen (Patient Health Questionnaire-2) with a 'help' question for psychological distress and psychiatric morbidity in patients with advanced cancer.

OBJECTIVES: Brief screening tools may help clinicians in busy settings detect patients who are experiencing severe psychological distress. This study examined the performance of the Distress Thermometer (DT) and a two-item depression screen [the Patient Health Questionnaire-2 (PHQ-2)] with a 'help' question in screening for distress and psychiatric morbidity among patients with advanced cancer. METHODS: Two hundred and five patients with advanced cancer completed the DT, the PHQ-2 and 'help' question and the Hospital Anxiety and Depression Scale and were interviewed using the Structured Clinical Interview for DSM-IV (SCID). The performance of the screening tools was examined against the Hospital Anxiety and Depression Scale and the SCID. RESULTS: Overall, discrimination levels were comparable for the DT [area under the curve (AUC) 0.80-0.81] and the PHQ-2 (AUC 0.73-0.85). The DT performed best in detecting cases of distress and mood, anxiety or adjustment disorders (sensitivity 100%), but it had poor specificity (49-60%). The best performance in terms of combined sensitivity and specificity was the PHQ depression item versus the SCID (sensitivity 88%, specificity 73%). The inclusion of the 'help' question with the PHQ-2 resulted in high levels of specificity (≥89%), but there was a significant drop in sensitivity (≤54%). CONCLUSION: Ultra-brief screening tools offer an efficient means of identifying patients with advanced cancer with severe distress or psychiatric morbidity but are less effective at identifying non-distressed individuals. Used in conjunction with a 'help' question, these tools can help clinicians identify patients who are both distressed and likely to accept professional support.

Marked elevations in pro-inflammatory polyunsaturated fatty acid metabolites in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists. Although the pathophysiology remains unclear, accumulating evidence points to the presence of low-level immune activation both in the gut and systemically. Circulating polyunsaturated fatty acids (PUFA) have recently attracted attention as being altered in a variety of disease states. Arachidonic acid (AA), in particular, has been implicated in the development of a pro-inflammatory profile in a number of immune-related disorders. AA is the precursor of a number of important immunomodulatory eicosanoids, including prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)). We investigated the hypothesis that elevated plasma AA concentrations in plasma contribute to the proposed pro-inflammatory profile in IBS. Plasma AA and related PUFA were quantified by gas chromatography analysis in IBS patients and controls. Both PGE(2) and LTB(4) were measured in serum using commercially available ELISA assays. AA concentrations were elevated in our patient cohort compared with healthy controls. Moreover, we demonstrated that this disturbance in plasma AA concentrations leads to downstream elevations in eicosanoids. Together, our data identifies a novel proinflammatory mechanism in irritable bowel syndrome and also suggests that elevated arachidonic acid levels in plasma may serve as putative biological markers in this condition.

Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that affects 10-15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26). METHODS: Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay. RESULTS: Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio. CONCLUSION: These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.

Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity.

Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.

Clinical characteristics and outcome of patients diagnosed with psychogenic nonepileptic seizures: a 5-year review.

OBJECTIVE: The goal of this article was to describe the clinical characteristics and outcomes of patients diagnosed with psychogenic nonepileptic seizures (PNES). METHODS: We conducted a retrospective review of patients diagnosed with PNES in a 5-year period. RESULTS: Fifty patients with PNES were identified, giving an estimated incidence of 0.91/100,000 per annum. Thirty-eight were included for review, 15 of whom were male (39%). Eighteen patients had been diagnosed with epilepsy as well as PNES (47%). We demonstrated a gender difference in our patients, with males having higher seizure frequencies, more antiepileptic drug use, and a longer interval before diagnosis of PNES. Females were diagnosed with other conversion disorders more often than males. Impaired social function was observed in PNES, as was resistance to psychological interventions with a subsequent poor response to treatments. CONCLUSIONS: PNES remains a difficult condition to treat, and may affect males in proportions higher than those described in previous studies.

Late multidisciplinary rehabilitation in young people after stroke.

PURPOSE: Stroke has a major impact on physical and cognitive ability, and quality of life. This study aims to examine the effect of multidisciplinary rehabilitation on outcome in an Irish young stroke population. METHODS: Fifty consecutive patients younger than 65 were prospectively recruited to this observational study. Physical and cognitive ability, and quality of life were measured on admission and discharge. RESULTS: All patients were transferred to the rehabilitation unit from the acute hospital where they had received their initial management. Median length of time from stroke onset to transfer was 112 days. After a median of 70 days, 43 patients were discharged home. Patients made significant gains in physical (Barthel index 12 to 18) and cognitive ability (mini-mental state examination 22 to 25). Quality of life improved in all eight domains of the 36-items Short Form with four domains returning to level seen in the general population. CONCLUSIONS: This study documents the improvements in physical and cognitive abilities, and quality of life in a sample of patients in rehabilitation. A comprehensive rehabilitation programme that includes acute and late multidisciplinary phases can improve the outcome of patients following stroke.

Factors associated with burden of primary headache in a specialty clinic.

OBJECTIVE: To examine factors associated with social, occupational, and psychological burden of common primary headache (migraine and tension-type headache). BACKGROUND: The personal and social burden of primary headache is high. Health, occupational, social, and psychological factors contributing to burden in people with disabling headache have not been fully unravelled. METHODS: One hundred eighty consecutive patients with either migraine or tension-type headache attending a specialty headache outpatient clinic for the first time were evaluated over a 9-month period. Headache subtype was operationally defined according to International Headache Society criteria. Headache frequency, duration, and severity were recorded. Occupational and social disability were quantified using the Migraine Disability Assessment questionnaire. Psychological burden was quantified using the 28-item General Health Questionnaire, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Premorbid vulnerability to life stress was quantified using the neuroticism subscale of the Eysenck Personality Inventory. RESULTS: Patients with frequent (chronic) headache scored higher on the Migraine Disability Assessment questionnaire and had higher Beck Depression Inventory and General Health Questionnaire depression scores than those with less frequent (episodic) headache. Frequency of headache, but not pain severity, duration, or diagnosis, predicted both Migraine Disability Assessment total disability and General Health Questionnaire/Beck Depression Inventory depression. Neuroticism was predictive of depression but not disability. Patients with chronic migraine had the highest depression and disability scores. CONCLUSION: The number of days per month with headache is a key determinant of headache-related burden in those attending specialty clinics. Frequent (chronic) headache is associated with significantly higher psychopathology scores and general social impairment, but the direction of this relationship is not clear. Those with migraine and chronicity are the most impaired.

Platelet surface glycoprotein expression in post-stroke depression: a preliminary study.

Depression is a significant risk factor for and consequence of both cardiovascular disease and stroke. The pathophysiological processes underlying this association are poorly understood. This study utilised a technique for measurement of whole blood platelet surface glycoproteins involved in early adhesion and aggregation in sample populations of patients with depression and stroke, and healthy controls. We analysed the platelet surface glycoproteins GPIb and GPIIbIIIa using flow cytometry in eight depressed subjects (Hamilton depression score >17), 14 post-stroke subjects (seven depressed and seven non-depressed), and in eight healthy control subjects. The number of GPIb receptors was significantly increased in subjects with depression and in post-stroke subjects compared to control subjects. The number of GPIb receptors from post-stroke subjects was not significantly different from that of depressed subjects. There were no differences between any groups in measures of GPIIbIIIa receptor numbers. No additive effect of co-morbid depression on the surface expression level of either marker could be detected in the post-stroke subjects. Platelet dysfunction may be involved in the pathophysiological process underlying the association between depression and cerebrovascular disease.

Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone.

Despite the importance of the 5HT1A receptor in regulating central serotonergic tone, there is a dearth of research examining its role in migraine. In this study, we examined the hypothesis that there would be altered neuroendocrine responses to a 5HT1A agonist challenge in different migraine subtypes. Prolactin (PRL) responses to the 5HT1A receptor agonist drug buspirone were compared in 30 female subjects with migraine (ten migraine with aura, MA; ten migraine without aura, MO and ten chronic/transformed migraine, CM), and ten healthy controls matched for age, gender and menstrual status. None of the subjects were taking psychotropic medication or migraine prophylactic treatment and those with formal psychiatric disorder were excluded. Endocrine responses were determined by measuring differences between baseline PRL and maximum increases post-buspirone (deltaPRL). There was no difference in baseline PRL between groups. MA subjects did not differ in their PRL responses to buspirone compared to healthy controls. The MO group had a four-fold increase in mean deltaPRL responses compared to healthy controls. Mean deltaPRL was also increased in the CM group compared to controls, but the difference was less exaggerated. This study indicates that there is supersensitive central amine receptor function in MO and CM, but not in MA. These findings support the hypothesis that central 5HT function differs among the migraine subtypes. The results also suggest that migrainous 'transformation' may be associated with adaptive changes in central 5HT receptor sensitivity. The relative contribution of 'state' and 'trait' receptor function to these findings as well as the possible role of dopamine receptors is discussed.

Acute effects of low-dose interferon-alpha on serum cortisol and plasma interleukin-6.

Major depression is associated with both hypothalamic-pituitary-adrenal (HPA) axis overactivity and immune system activation. Depression is a common occurrence following interferon (IFN)-a treatment. While IFN-alpha is known to stimulate the HPA axis, little is known about the effects of exogenous IFN-a in humans on the proinflammatory cytokine interleukin (IL)-6, a marker of immune system activation. This study examined the acute effects of IFN-alpha on cortisol and IL-6 release, and the time course of any changes in these variables. Serum cortisol and plasma IL-6 were assessed in healthy volunteers over an 8-h period following 3 million units subcutaneous IFN-alpha or placebo using a double-blind, placebo-controlled crossover design. IFN-alpha resulted in a significant increase in both cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential effect of the rise in these variables over time. We conclude that IFN-alpha acutely stimulates both the HPA axis and proinflammatory cytokine release. The hypothesis that the effect of IFN-alpha on the HPA axis is indirect and mediated by IL-6 was not supported by this study. Our findings are nonetheless of relevance to the aetiology of depression following IFN-alpha.