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ORAL PAPER PRESENTATIONS
Saturday, November 19, 2011  •  10:15 AM – 12:15 PM

 
Session A: Cardiopulmonary Disease
  B: Delirium States and Treatment
  C: PM Medicine in Outpatient Practice Settings
  D: Physical Symptoms and Health
  E: Transplant and Immunology
  F: Psycho-Oncology and Quality of Life
  G: Webb Fellows
    [T] = Trainee Paper

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Session A:  Cardiopulmonary Disease
Moderator/Discussant:  Philip A. Bialer, MD, FAPM

[T] Effects of Anxiety on Depression Response in Hospitalized Cardiac Patients
Presenting Author:  Christopher Celano, MD
Co-Authors:  Carol Mastromauro, Emma Lenihan, James Januzzi, Bruce Rollman, Jeff Huffman

Objective: To assess the impact of anxiety on depression severity and depression response 6 months after cardiac hospitalization.

Methods: Data were analyzed from 136 depressed patients who were hospitalized on inpatient cardiac units with admission diagnoses of acute coronary syndrome, decompensated heart failure, or arrhythmia, and who enrolled in a randomized trial of collaborative care depression management. Subjects' demographic, medical, and psychiatric information at baseline was compiled, and measures of health-related quality of life, cardiac symptoms, and psychiatric symptoms, including the Hospital Anxiety and Depression Scale-Anxiety Subscale (HADS-A) for anxiety were obtained both at baseline and at 6-month follow-up. The association between baseline HADS-A score and depression response (which was defined as a reduction of ≥ 50% in the 9-item Patient Health Questionnaire [PHQ-9] score and a final PHQ-9 score < 10) at 6 months was assessed first by univariable analysis and then by multivariate logistic regression, which accounted for the effects of multiple relevant covariates (i.e., gender, admission diagnosis, study intervention group, functional status, baseline depression severity, prior depressive episodes, and depression treatment). Finally, the association between baseline HADS-A score and depression severity at 6 months (defined as the PHQ-9 score at 6 months) was assessed by linear regression, which accounted for the effects of the same covariates.

Results: Patients with higher levels of anxiety at baseline were significantly less likely to have a depression response at 6 months compared to those with lower levels of anxiety (depression response rates: 61.4% [low anxiety] vs. 43.8% [moderate anxiety] vs. 31.8% [high anxiety]; χ2 = 7.84, p = .02). On logistic regression, baseline HADS-A score was the only variable to be independently associated with lack of depression response (β = -0.12; p = .021). Baseline HADS-A score also was independently associated with greater depression severity at 6 months on linear regression (t = -2.51, p = 0.013).

Conclusion: Concomitant baseline anxiety and depression in the context of an acute cardiac event is independently associated with reduced improvement in depressive symptoms and lower rates of depression response at 6 months.

[T] Psychobiologic Effects of Family Warmth on Laboratory Stress-Induced Pulmonary Compromise in Asthmatic Children
Presenting Author:  ChiunYu Hsu
Co-Authors:  Beatrice Wood, Craig Parzynski, Jungha Lim

Purpose: Laboratory-based studies show that negative family emotional climate predicts asthma disease activity [1,2], mediated by child depression and anxiety [3,4]. This study examined whether family hostility worsened airway function during stressful family interaction, and whether family warmth buffered the effect of stressful interaction.

Method:  Families (n=310) and children with asthma, aged 7-17 (55% boys) took part in a laboratory-based family interaction study. Families were videotaped during 6 tasks: build a card house, discuss a child difficulty, discuss a sad event/loss with the child, resolve a parent-child conflict, resolve a parental conflict, and tell what they liked best about each other. Family interactions were rated according to the Iowa Family Interaction Rating Scales, a macro-level observation coding system. The Hostility code (HS) was defined as hostile, angry, critical, disapproving, and/or rejecting behavior toward another person, and warmth (WM) as expressions of liking, appreciation, praise, care, affection, concern, or support. Airway function was assessed pre and post family interaction using spirometry (FEV1).
Data analysis: Family hostility (FHS) and family warmth (FWM) was defined as the average of HS or WM across family members and tasks. Hierarchical multiple regression (HMR) controlled for confounds in assessing associations between FHS, FWM, and FEV1.

Results:  FWM predicted FEV1 scores at both baseline (B = 8.68, SE = 3.45, p < .02) and during interaction (B = 10.27, SE = 3.89, p < .01, respectively). FHS was not significant. To examine direct effects of FWM and FHS on airway function during interaction, we used HMR to examine the relationship between FHS or FWM and the amount of decrement in FEV1 from baseline to post stressful family interaction. FWM predicted less decrement in FEV1 (B = -4.25, SE = 1.73, p = .02). FHS was not significant.

Conclusion: These findings are consistent with family warmth as buffering the impact of stressful family interaction on airway function, but family hostility itself seemed to have no effect.

1. Miller GE, Chen E. Life stress and diminished expression of genes encoding glucocorticoid receptor and beta2-adrenergic receptor in children with asthma. Proc Natl Acad Sci U S A. Apr 4 2006;103(14):5496-5501.

2. Sandberg S, Jarvenpaa S, Penttinen A, Paton JY, McCann DC. Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression. Thorax. Dec 2004;59(12):1046-1051.

3. Wood BL, Lim J, Miller BD, et al. Testing the Biobehavioral Family Model in pediatric asthma: pathways of effect. Fam Process. Mar 2008;47(1):21-40.

4. Wood BL, Miller BD, Lim J, et al. Family relational factors in pediatric depression and asthma: pathways of effect. J Am Acad Child Adolesc Psychiatry. Dec 2006;45(12):1494-1502.

[T] The Effects of Insecure Attachment on Child Asthma: Depression and Autonomic Dysregulation as Possible Mechanisms
Presenting Author:  ChiunYu Hsu
Co-Authors:  Bruce Miller, Beatrice Wood

Objective: The stress of separation of infants from their mothers results in depressive symptoms and autonomic (ANS) dysregulation non-human primates [1,2] and humans [3]. Early parent loss, child maltreatment and other attachment disturbances have long-term consequences in psychobiologic development, particularly with regard to regulation of stress responses [4]. We posit that insecure attachment is destabilizing and thereby potentiates the effects of separation and loss, and that through depression and ANS dysregulation this process could affect child asthma.

Method: We studied 171 children with asthma under laboratory conditions using the film "E.T., The Extraterrestrial" to evoke emotional distress. The ET death scene was pre-selected to elicit loss-related emotions, including sadness and hopelessness. The Relatedness Questionnaire [5] indexed the child's relational security with mother, and the Child Depression Inventory indexed depressive symptoms. Asthma disease activity was assessed by NHLBI criteria. The child viewed the film alone while continuous ECG and impedance measures of heart beat were used to derive indices of sympathetic activation (pre-ejection period, PEP) and vagal activation (RSA). ANS dysregulation was indexed by a measure of vagal bias: Zrsa-Zpep. Pulmonary function was indexed by respiratory resistance (Rint).

Results: Children who were categorized as having insecure attachment with their mothers had significantly higher depressive symptoms (t=3.6, p=.001), greater vagal bias in the death scene (t=1.9, p=.06) and greater disease activity (t=2.1, p=.4). When stratified by depression score, depressed vs non-depressed children had significantly greater vagal bias in response to ET death scene (t=2.25, p=.03), and greater disease activity (t=3.2, p<.002). Finally, vagal bias was correlated with post-movie Rint (r=.39, p=.004). These findings support the proposition that insecure attachment contributes to stress vulnerability, depression and ANS dysregulation which potentiate disease activity.

1. Reite M, Kaufman IC, Pauley JD, Stynes AJ. Depression in infant monkeys: physiological correlates. Psychosom Med. Jul-Aug 1974;36(4):363-367.
2. Suomi S. Attachment in rhesus monkey. . In: Cassidy J, Shaver PR, eds. Handbook of attachment: Theory, research and clinical applications. New York: Guilford Press; 1999:p. 181-197.
3. Field T. The effects of mother's physical and emotional unavailability on emotion regulation. Monogr Soc Res Child Dev. 1994;59(2-3):208-227.
4. Cicchetti D. Stress and Development: Biological and Psychological Consequences. In: Cicchetti D, ed. Development and Psychopathology.2001.
5. Lynch M, Cicchetti D. Patterns of relatedness in maltreated and nonmaltreated children: Connections among multiple representational models. Development and Psychopathology. 1991;3(02):207-226.

Prevalence of Obstructive Sleep Apnea in Patients with Schizophrenia in a Community Dwelling Sample
Presenting Author:  Aniyizhai Annamalai
Co-Authors:  Laura Palmese, Vinod Srihari, Lydia Chwastiak, Cenk Tek

Introduction: Obstructive sleep apnea (OSA) is highly prevalent (9-24%) in the general population. It is associated with high morbidity and mortality. Non-compliance with recommended treatment, positive airway pressure (PAP) devices, is up to 50%. OSA is not well studied in schizophrenia. One study reported 19% OSA among inpatients in Japan. Atypical antipsychotic use among psychiatric patients was implicated with severity of OSA in another study. Risk factors were reported to be similar to general population in a study that reviewed patients who were referred to a sleep center for OSA. To our knowledge OSA is not studied at all among community dwelling severe mentally ill patients.

Methods: As part of an ongoing study aiming to assess sleep status of schizophrenia patients, 172 patients with DSM IV schizophrenia were interviewed and presence of diagnosis of OSA was identified. These patients were drawn from a community mental health center outpatient clinic. Patients were also assessed with established sleep related measures such as Insomnia Severity Index (ISI), Pittsburg Sleep Quality Index (PSQI), Epsworth daytime sleepiness scale, as well as quality of life enjoyment and satisfaction questionnaire (Q-LES-Q), and Clinical Global Impression (CGI) schizophrenia version, Calgary Depression Scale, and as a broad cognitive measure Digit Symbol Substitution Test (DSST). Comparisons between groups were done using chi square and t tests as appropriate. We examined the different variables as predictors of OSA using logistic regression.

Results: Rate of diagnosed OSA in this population is 23 of 172 patients (13.4%). Of these, 12 patients (52.2%) reported being prescribed PAP therapy as treatment but only 5 (41.6%) were compliant. 11 patients reported they were not prescribed or they refused PAP. Patients with OSA were significantly more obese (mean BMI 42.92 in patients with OSA and 32.3 in patients without OSA with t=6.45, p<0.0001). Body mass index (BMI) was the single significant predictor of OSA after controlling for age and gender. No single antipsychotic, nor atypical antipsychotics as a group conferred a risk factor for OSA. Other demographic or clinical ratings between groups with and without OSA were not significantly different except PSQI subscales related to daytime fatigue and nighttime breathing/snoring.

Discussion: Our study shows a high prevalence of OSA in patients with schizophrenia. The prevalence is likely to be underestimated since the presence of disease was based on self report. Our study indicates that the increased prevalence is associated with the endemic obesity in schizophrenia. Treatment compliance rate is poor. Early mortality is consistently reported among schizophrenia patients. In addition to evaluation and treatment of other cardiovascular and metabolic diseases that increase mortality in schizophrenia, clinicians should be aware of the increased prevalence of OSA and routinely perform appropriate diagnostic screening.

Assessment of Psychosocial Evaluation Before Left Ventricular Assist Device Implantation as a Predictor of Device-Related Complications
Presenting Author: Peter A Shapiro
Co-Authors: Nir Uriel, Natalie Gukasyan, Emily Westfal, Margaret Flannery, David Fedoronko, Yoshifumi Naka, Ulrich P Jorde, Donna M. Mancini

Purpose:  After left ventricular assist device (LVAD) implantation, device-related complications are common and associated with high morbidity and mortality. The aim of this study was to determine if pre-implantation psychosocial evaluations can predict risk of device-related complications during LVAD support.

Methods:  Psychiatric and social work evaluations were recorded prospectively in a standardized, multi-domain format for patients being considered for heart transplantation. A retrospective chart review of all patients implanted with an LVAD as a bridge to transplantation (BTT) between January 2005 and January 2010 was completed in February-March 2011. Outcomes of interest included driveline infections, bleeding, thromboembolic events, device malfunction, and deaths.

Results:  157 patients were implanted with an LVAD as BTT; of these 17 died in the post-operative hospitalization. 115 patients who had psychiatric and social work evaluations and survived to hospital discharge after the LVAD implantation were included in this analysis. Mean (SD) age was 52.8 (12.5) years, 98 (85.2%) were men, 35 (41%) had ischemic cardiomyopathy, 51 (44.4%) had hypertension, and 38 (33%) had diabetes. 82 pts (72.5%) eventually received a heart transplant within the study period. There were only five deaths and four thromboembolic events, too few to examine psychosocial evaluation as a predictor of these outcomes. Ten patients (8.7%) had device failure or serious device malfunctions. Eleven patients (9.56%) had driveline infections. Several psychosocial variables were associated with increased likelihood of driveline infections: history of problems with compliance (poor compliance 60.0%, fair 9.65%, good 5.1% p=.008), social support (poor-fair 16.3%, good 4.6% p=0.043), previous psychosocial function (poor 33.3%, fair 17.2%, good 5.1%, p=0.038), motivation for transplant or VAD therapy (poor 20.0%, fair, 15.9%, good 3.4%, p=0.036), with the presence of a personality disorder (31.2% vs 5.6%, p=0.007), and with the evaluator’s global estimate of risk for psychosocial factors to complicate management (low and low-moderate 4.9%, high-moderate and high 23.3%, p=.008). Previous history of problems with compliance was also related to higher frequency of bleeding (poor 60%, fair-good 7.92%, p=0.008). Not having a marital partner was associated with increased risk of driveline infections (p=.038) and bleeding problems (p=.009) and living alone was also associated with bleeding complications (p=.046). Current psychiatric disorder at evaluation was marginally associated with risk of device failure or serious malfunction (no disorder 3.23%, mild-severe disorder 16.3%, p =.052).

Conclusions: Pre-implantation psychosocial evaluation can predict device complications after LVAD implantation. Further research is necessary to determine if interventions to mitigate the effects of psychosocial risk factorscan improve outcomes for LVAD recipients.

 

Session B:  Delirium States and Treatment
Moderator/Discussant:  James L. Levenson, MD, FAPM

Novel Alcohol Withdrawal Treatment Methods — Beyond Benzodiazepines
Presenting Author:  Jose Maldonado

For decades it has been the general practice to use benzodiazepine agents for the prophylaxis and treatment of all phases of alcohol withdrawal. Yet, despite their undisputed usefulness of these agents they also have their difficulties. This lecture will challenge the notion of benzodiazepines as the treatment of choice for alcohol withdrawal syndromes based on ethanol's effects in the brain and neuromodulation.

Ethanol is the allosteric modulator of g-aminobutyric acid A (GABAA) receptors. Thus acutely, alcohol renders its central effects (e.g., anxiolytic, sedative, anticonvulsant, and motor coordination impairment) mainly through its agonistic effect on GABAA receptors primarily in the cerebral cortex, medial septal neurons, and hippocampal neurons. But that is not the whole story, acute alcohol use has a direct inhibitory effect on N-methyl-D-aspartate (NMDA) receptors (thus reducing excitatory glutamatergic transmission); disinhibits GABA-mediated dopaminergic-projections to the ventral tegmental area (VTA), leading to increases in extracellular dopamine (DA) in the nucleus accumbens (NA)(likely responsible for the initially pleasurable effects of alcohol and for the impulse to drink more).

Thus, the development of alcohol tolerance with chronic ethanol use is a neuroadaptive process directed at reducing the acute effects of alcohol and thereby provides homeostasis. Chronic alcohol intake leads to an adaptive suppression of GABA activity, mediated by internalization and down regulation of GABAA-BZ receptor complexes; increased synaptic glutamate (GLU) release, as well as increased NMDA and non-NMDA (e.g., a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor [AMPA], kainate receptors, and voltage-gated Ca channels) glutamatergic receptor activity; and overactivity of noradrenergic neurons in the CNS and the peripheral nervous system likely via desensitization of alpha2 receptors or lack of alpha2 agonist activity and excessive norepinephrine (NE) production as the excess extracellular DA is converted into NE via DA-b-hydroxylase.

The symptoms of alcohol withdrawal syndromes (AWS) are then associated with abnormalities in the levels of NE (i.e., symptoms of autonomic hyperactivity [tachycardia, hypertension, tremors, insomnia], DA (i.e., agitation & psychosis), and GLU (i.e., seizures). Certainly the use of benzodiazepines and other GABAergic agents (e.g., barbiturates, propofol) can lead to suppression of excess activity of all these neurotransmitters and associated receptors, but at a high cost: significant neurological (e.g., ataxia), medical (e.g., respiratory depression), and cognitive (e.g., amnesia, delirium) impairment; as well as possible development of iatrogenic benzodiazepine dependence. There is also the issue of how to manage patients requiring high doses of benzodiazepines, but not requiring further hospitalization.

This paper will review the neurobiology of alcohol dependence and neurochemical mechanisms of withdrawal and address the potential of non-benzodiazepine agents (i.e., anticonvulsants, antipsychotics and alpha-2 agonists) in the management and treatment of AWS. We will examine the available evidence for their effectiveness and compare these results to what benzodiazepines can do; highlighting advantages and pitfalls in treatment.

Outcomes of Delirious Elders Post General Anesthesia
Presenting Author:  Karin Neufeld
Co-Authors:  Jose Rios Robles, Veena Rao, Brett Wanamaker, Joshi Dhruv, Jennifer Gibson Chambers, Frederick Sieber, Dale Needham

Background:  Delirium is an important and common complication after surgery, associated with increased morbidity, mortality, and discharge to a skilled nursing facility. Postoperative delirium is common in elderly patients. Most studies examine for delirium at postoperative day 2 or later. This study evaluated the association of delirium diagnosed immediately after surgery in the post anesthesia care unit (PACU), with change in cognitive function from pre-operative baseline, cost of hospitalization, and hospital discharge location.

Methods:  Patients aged 70+ years, scheduled for surgery with general anesthetic and able to give informed consent, were enrolled. Cognitive function was evaluated using: 1) Digit Span (forward, backward), 2) Verbal Fluency (letters: s, p, and category) prior to surgery and at hospital discharge. A trained final year psychiatry resident evaluated patients in the PACU, diagnosing delirium using DSM IV criteria and a standardized neuropsychiatric exam. Patients were evaluated when Aldrete score > 8, indicating stability for discharge to home or an in-patient unit. Change in pre- versus postoperative cognitive function, length of stay and hospital charges and location of hospital disposition for patients with vs. without delirium in the PACU are presented.

Results:  Of 105 eligible consented patients, 14 were excluded (9 received no general anesthetic, 1 declined evaluation, 4 were not evaluated in the PACU). Of the remaining 91 patients, 41 (45%) were delirious in the PACU and exhibited a significantly worse mean change in category verbal fluency at the time of discharge from preoperative measures (mean +/- SD change: -2.0 + 3.3 for delirious vs 0.3 + 3.4 for non-delirious, p = .02), incurred higher mean hospital charges, ($23,300 + 14,000 vs $15,800 + 14,000, p = .02), and were 9 times less likely to return home than be discharged to acute rehabilitation or nursing home (OR=9.0, 95% CI 2.3-34.0). Although delirious patients had longer lengths of stay (4 +4 vs 3 +4 days; p = .22), and worse mean performance on digit span (forward: -0.2 +0.8 vs 0 +1.2, p =.41; backward: -0.6 +0.9 vs -0.3 +1.0, p =.34) and other verbal fluency tests ( letter ‘p': -1.1 +2.0 vs 0.4 +3.9, p =.09; letter ‘s': -0.6 +4.0 vs -0.4 +3.4, p =.88), these differences did not reach statistical significance in this small study.

Conclusions:  Among elders undergoing general anesthesia, delirium diagnosed in the PACU is associated with cognitive decline from baseline, increased hospital cost and institutionalization at hospital discharge.

Acknowledgments:

  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, SOM
  2. Johns Hopkins Predoctoral Clinical Research Training Program grant number 1TL1RR-025007 from the National Center for Research Resources
  3. The Walker Award for Research in Psychiatry, JHU SOM
  4. American Federation on Aging Research, Medical Student Training Program

Clinical Psychosomatic Experience with Physostigmine
Presenting Author:  J.J. Rasimas

Purpose:  Anticholinergic activity has been identified in many medications, including antidepressants, antipsychotics, antihistamines, and muscle relaxants. Widespread availability of these medications in all ages and demographics makes them common precipitants of delirium. Physostigmine is a rarely used antidote that reverses antimuscarinic poisoning through cholinesterase inhibition. Research was designed to investigate safety and efficacy of physostigmine in treatment of patients with suspected antimuscarinic delirium.

Methods:  Physostigmine was given by the medical toxicology service of an urban academic hospital to patients with confusion, stupor, hallucinosis, and agitation. Toxic diagnosis was not confirmed prior to physostigmine administration; patients were merely delirious, non-diaphoretic, and suspected to have access to anticholinergic agents. Antidote was given by 0.5mg/min intravenous infusion in single doses (repeated q1h prn) of 2mg in adults, 1mg in children under 50kg, and 0.5mg in toddlers. Research involved both retrospective and prospective systematic review of cases in toxicology practice. Data were gathered on comorbidities, medications, response to antidote, and adverse events.

Results:  Retrospective review from June 2003 to June 2009 revealed that the toxicology service cared for 5063 adult, pediatric, and geriatric patients; 868 received physostigmine with an overall positive response rate of 81.3%. Therapeutic benefits included calming of agitation and clearing of cognition that allowed partnership in care and reduced the need for aggressive interventions such as physical restraint, sedation, intubation, and urinary catheterization. The rate of seizures was under 1%, and only one patient developed an asymptomatic arrhythmia. The response rate in patients with TCA toxicity was 94%, and none experienced arrhythmias or seizures from physostigmine. Comorbid heart disease, lung disease, seizure disorder, or sedative abuse did not increase risk of adverse events.

Prospective study from July 2009 to July 2010 involved 1026 cases, 329 of whom received physostigmine. 74% had a positive response. Fewer than 10% experienced adverse effects, the most common being diaphoresis, nausea, and vomiting. There were no morbid cardiac arrhythmias. 62 of 63 patients with TCA toxicity responded to physostigmine without seizures or arrhythmias. 44% of patients were eventually assigned more than one toxicologic diagnosis. Heart disease, lung disease, or sedative abuse did not increase adverse events. One of two patients who seized after physostigmine treatment had epilepsy with inadequate serum levels of anticonvulsants. The prospective study better accounts for minor side effects of giving physostigmine; both phases are limited by lack of control groups and recorder bias.

Conclusions:  On the basis of these results, physostigmine is a safe and effective antidote when administered to patients presenting with antimuscarinic toxicity. As the study involved treating patients without confirmed diagnoses, and many ingested multiple substances, physostigmine may be viewed as useful both diagnostically and therapeutically in patients with delirium of unknown etiology.

Clinical Psychosomatic Experience with Flumazenil
Presenting Author:  J.J. Rasimas

Purpose:  Sedative and hypnotic agents are widely used and misused. Patients present with CNS impairment after purposeful and accidental overdoses of these drugs. Administration of benzodiazepines and related hypnotics in the hospital can lead to both acute and chronic iatrogenic complications. Although not often employed, flumazenil is an imidazobenzodiazepine reversal agent that restores wakefulness and cognition in sedative-toxic patients. Research was designed to investigate safety and efficacy of flumazenil in treatment of patients with suspected sedative toxicity.

Methods:  Flumazenil was given by the medical toxicology service of an urban academic hospital to patients with lethargy and coma. Toxic diagnosis was not confirmed prior to antidote administration; patients were merely suspected to have access to sedating agents and displayed impaired consciousness, normal or diminished reflexes, and non-elevated autonomic indices. Antidote was given in single doses of 0.5mg over 30 seconds via intravenous infusion and repeated q1h prn. Research involved both retrospective and prospective systematic review of cases in toxicology practice. Data were gathered on comorbidities, medications, response to antidote, and adverse events.

Results:  Retrospective review from June 2003 to June 2009 revealed that the toxicology service cared for 5063 adult, pediatric, and geriatric patients; 519 received flumazenil with an overall positive response rate of 81.7%. Therapeutic benefits included restoration of adequate ventilation, prevention of aspiration, and ccognitive clearing that allowed partnership in care and reduced the need for aggressive interventions such as intubation and urinary catheterization. Intubated patients were promptly extubated and maintained without needing ventilatory support. There were no documented seizures, arrhythmias, or other major side effects. Comorbid heart disease, lung disease, epilepsy, alcohol abuse, and sedative abuse were all common in flumazenil-treated patients.

Prospective study from July 2009 to July 2010 involved 1026 cases, 212 of whom received flumazenil. 80% had a positive response. Fewer than 6% experienced adverse effects, the most common being self-limited anxiety. There were no seizures or arrhythmias. Heart disease, lung disease, alcohol abuse, or seizure disorder did not increase adverse events. Anxiety upon arousal was more common in patients chronically taking and/or abusing benzodiazepines. Patients near the end of treatment for sedative and alcohol withdrawal were successfully treated with flumazenil to reverse oversedation and allow patients to participate in care. The prospective study better accounts for minor side effects of giving flumazenil; both phases are limited by lack of control groups and recorder bias.

Conclusions:  On the basis of these results, flumazenil is a safe and effective antidote when administered to patients presenting with signs of sedative toxicity. As the study involved treating patients without confirmed diagnoses and many ingested multiple substances, flumazenil may be viewed as useful both diagnostically and therapeutically in patients with flaccid coma or sedate delirium of unknown etiology.

[T] Identification of Individual Risk Profiles for Post-Operative Delirium After Joint Replacement Surgery
Presenting Author:  Felipe Jain
Co-Authors:  John Brooks, Kenneth Larsen, Susan Kelly, Robert Bode, Gerard Sweeney, Theodore Stern

Background:  Delirium occurs in nearly half of older patients after joint replacement surgery. However, risk profiles for developing delirium have not been established.

Objective:  We sought to identify risk profiles for delirium in patients following joint replacement surgery.

Method:  Based on data from a randomized, double-blind, placebo-controlled trial of olanzapine (10 mg) as delirium prophylaxis in 400 patients (67-81 years old) undergoing hip or knee replacement surgery, we performed a signal detection analysis to develop risk profiles for post-surgical delirium (using baseline patient characteristics, iatrogenic factors, and physiological response parameters).

Results:  Olanzapine reduced the incidence of delirium by 63% relative to placebo. Among patients receiving placebo, those with an ASA class = 3 and age ≥ 74 years had a 64% risk of delirium. Those with ASA class < 3 still had a 67% risk of delirium if post-operative oxygen saturation was < 95%. Patients who received olanzapine had an 83% risk of developing delirium if they received ≥ 42.5mg equivalents of intra-operative morphine, were ≥ 74 years old, and had a mean arterial pressure (MAP) < 90 mm Hg at the pre-surgical screening visit. Patients with the lowest risk (6%) of developing delirium received olanzapine, had a hematocrit ≥ 28%, and a pre-surgical MAP ≥ 90.

Conclusion:  Although use of prophylactic olanzapine reduced the incidence of delirium, subsets of patients remained likely to develop delirium. The risk of developing delirium may be reduced through prophylactic dispensation of olanzapine, maintaining optimal perfusion and oxygenation, and limiting intra-operative opioids.

 

Session C:  PM Medicine in Outpatient Practice Settings
Moderator/Discussant:  Linda L.M. Worley, MD

Pharmacogenomic Testing and Outcome among Depressed Patients in a Tertiary Care Outpatient Psychiatric Consultation Practice
Presenting Author:  James Rundell
Co-Authors:  Maria Harmandayan, Jeffrey Staab

Background and Aims:  The authors tested the hypothesis that pharmacogenomic genotype knowledge is associated with better clinical and cost outcomes in depressed patients, after controlling for other factors that might differentiate tested and untested patients.

Methods:  Medical records of 251 patients seen in the Mayo Clinic Rochester outpatient psychiatric practice who had Patient Health Questionnaire-9 (PHQ-9) scores before and after consultation were reviewed. Comparisons of differences in pre-consultation and post-consultation PHQ-9 slopes between tested and non-tested patients, and between genotype categories of tested patients, were evaluated along with healthcare cost and utilization comparisons between tested and untested patients, using Kruskal-Wallis tests, Wilcoxon rank sum tests, and group mean comparisons, controlling for significant demographic and clinical differences.

Results:  Tested patients had significantly higher depression diagnosis frequency, baseline PHQ-9 scores, family history of depression, psychiatric hospitalization history, and numbers of antidepressant, mood stabilizer, and antipsychotic medication trials. After controlling for these differences, there was no difference between tested and non-tested patients in slopes of post-index PHQ-9 score changes. For a subgroup (n=46) with > 2 pre- and post-index PHQ-9 scores, the mean difference between pre-index and post-index slopes for tested patients was -0.08 (median -0.01; range -1.20 to 0.15) compared with 0.13 (median 0.02; range -0.18 to 2.16) for non-tested patients (p=0.03). The significant difference between tested and non-tested patients remained after adjusting for diagnosis of depression (p=0.03), family history of mood disorders (p=0.046), and numbers of prior antidepressant, mood stabilizer, and antipsychotic trials (p=0.04), but not after adjusting for baseline PHQ-9 score (p=0.28), psychiatric hospitalization history (p=0.49), or after adjusting for all of the features listed above (p=0.88). Among genotype categories, mean differences between pre-consultation and post-consultation slopes was significantly better for poor CYP2D6 metabolizers than intermediate or extensive metabolizers (p=.04). A subset of local tested and consultant-matched non-tested case controls (n=19), who had 8 years of longitudinal care within the health system, had similar overall mean healthcare costs before and after testing; however, tested patients on average had significantly fewer time-adjusted post-index psychiatric admissions (0.8 v 3.8, p=0.04) and fewer time-adjusted psychiatric consultations and comprehensive mental health specialty evaluations (4.2 v 9.9, p=0.03).

Conclusion:  Prospective study is indicated as to whether and how pharmacogenomic testing in a psychiatric consultation practice may improve clinical and cost outcomes.

Factors Associated with Depression Remission and Response in an Outpatient Psychosomatic Medicine Practice
Presenting Author:  James Rundell

Background and Aims:  The author explored the depression remission and response rates in an outpatient psychosomatic medicine practice and assessed for which factors were significantly associated with remission or response.

Methods:  Medical records of 251 patients seen in the Mayo Clinic Rochester outpatient psychiatric practice who had Patient Health Questionnaire-9 (PHQ-9) scores before and after consultation were reviewed. Comparisons of differences in pre-consultation and post-consultation PHQ-9 scores were evaluated to identify patients with remission (PHQ-9 score < 5) and response (PHQ-9 score decreased by > 50%). Demographic and clinical factors were studied that might be associated with remission or response, using Kruskal-Wallis and Wilcoxon rank sum tests, then by using logistic regression to account for multiple significant group differences.

Results:  Univariate comparisons of significant differences and statistical trends between remission (N=24) and non-remission (N=88) patients revealed differences in average number of antidepressant trials (2.8 v 3.9, ChiSq 3.615, p=0.057), current abuse (0.0% v 8.0%, ChiSq 3.371, p=0.066), reported good friend (87.5% v 56.8%, ChiSq 11.162, p=0.0008) and family (83.3% v 39.2%, ChiSq 3.222, p=0.073) social support, and depressive disorder diagnosis (58.3% v 89.8%, ChiSq 4.590, p=0.032). Comparisons between patients with response (N=29) and non-response (N=83) revealed differences in average number of antidepressant (2.9 v 3.9, ChiSq 4.299, p=0.038) and antipsychotic (0.2 v 0.6, ChiSq 11.180, p=0.0008) medication trials, being unmarried (41.4% v 53.0%, ChiSq 8.274, p=0.004), reporting good friend (83.3% v 69.2%, ChiSq 3.222, p=0.073) and family (86.2% v 67.5%, ChiSq 8.538, p=0.004) support, and depressive disorder diagnosis (58.1% v 71.1%, ChiSq 4.590, p=0.032). Separate analysis of depressive disorders, anxiety disorders, and somatoform disorders subgroups yielded similar associations. After controlling for other factors, reported good friend support did not remain significant for the remission/non-remission comparison but did remain significantly different for the response/non-response comparison (ChiSq 20.5329, p=0.0004). Similarly, number of past antidepressant trials did not remain significant for the remission/response comparison but did remain significantly different for the response/non-response comparison (ChiSq 8.8589, p=0.031).

Conclusion: Though underpowered to adequately assess all potential contributors, retrospective examination of factors associated with depression treatment remission and response in this outpatient psychosomatic medicine practice emphasizes the relevance of number of past antidepressant medication trials and perception of social support as markers of prognosis and outcome.

Depression Increases Risk of Dementia in Patients with Type 2 Diabetes
Presenting Author:  Wayne Katon
Co-Authors:  Courtney R. Lyles, Melissa M. Parker, Andrew J. Karter, Elbert S. Huang, Rachel A. Whitmer

Background:  Depression affects approximately 20% of adults with type 2 diabetes. Although depression is a risk factor for dementia in the general population, its association with dementia among patients with diabetes has not been well studied.

Methods:  This prospective cohort study included 19,239 patients with type 2 diabetes enrolled in a large, integrated managed care setting. The Patient Health Questionnaire-8 (PHQ-8), ICD-9 diagnoses of depression, and/or antidepressant prescriptions in the 12 months prior to baseline were used to identify prevalent cases of depression. Clinically recognized dementia was captured among subjects with no prior ICD-9 diagnoses of dementia. To exclude the possibility that depression was a prodrome of dementia, dementia diagnoses were only based on ICD-9 diagnoses identified in years 3 to 5 post-baseline. The risk of dementia for patients with both depression and diabetes relative to patients with diabetes alone was estimated using Cox proportional hazard regression models that adjusted for sociodemographic and clinical factors, health risk behaviors, and health care utilization.

Results:  19.6% of patients met criteria for depression at baseline. During the 3- to 5-year period, 80 (2.12%) of 3,766 patients with comorbid depression and diabetes (incidence rate of 5.5 per 1,000 person years) versus 158 (1.02%) of 15,473 patients with diabetes alone (incidence rate of 2.6 per 1000 person-years) had one or more ICD-9 diagnoses of dementia. Patients with comorbid depression had a 100% increased risk of dementia during the 3 to 5 years post-baseline period (fully adjusted hazard ratio 2.02, 95% CI 1.73, 2.35). Effect estimates were robust across model specifications and multiple sensitivity analyses.

Conclusion:  Depression in patients with diabetes was associated with a substantively increased risk for development of dementia compared to those with diabetes alone. This study of over 19,000 patients confirms the findings of one previous study that our group completed with 4,000 patients with diabetes. Depression is a risk factor for dementia in this population that is particularly vulnerable to cognitive impairment.

Structure of Health Anxiety, State Anxiety, Depression, Physical Symptoms, and Disability in a Tertiary Psychosomatic Medicine Population
Presenting Author:  Jeffrey Staab
Co-Authors:  Richard Seime, Rebecca Mueller-Gursky, David Hall, Michele Rosenblad, Gary Campbell, Jill Snuggerud, James Rundell

Purpose:  Health anxiety is a construct that describes a pattern of thoughts and behaviors including heightened awareness of bodily sensations, excessive worry about causes and consequences of physical symptoms, catastrophic fears about sickness, and difficulty being reassured about health status. Health anxiety is a broader, more dimensional construct than the categorical diagnosis of hypochondriasis in the DSM-III/IV. It exists in the presence or absence of active medical disease and appears to underlie a wide range of somatic symptom presentations from physical complaints that defy medical explanation to functional impairment in excess of known medical illness. Most data supporting the concept of health anxiety were derived from studies of normal individuals, primary care patients, and patients with primary DSM-III/IV anxiety disorders or hypochondriasis. Its validity and utility for psychosomatic medicine in tertiary care settings is not well established. The purpose of this study was to test the hypothesis that health anxiety captures an illness dimension not explained by state anxiety, depression, or somatic symptom burden in tertiary care psychosomatic medicine outpatients.

Methods:  This study was a retrospective analysis of self-reports from 252 consecutive patients referred to an outpatient psychosomatic medicine practice at a tertiary medical institution from February to April 2011. All patients completed the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), short form Health Anxiety Inventory (SHAI), and Sheehan Disability Scale (SDS), plus a standardized review of symptoms (ROS) checklist containing 63 items. Exploratory factor analyses were performed on item responses from the four validated questionnaires and a variable representing the number of positive ROS items for each subject. Solutions were developed using the PHQ-9, GAD-7, and SHAI with and without the SDS and ROS.

Results:  Mean subject age was 46±15 years (range 18-88), with a 2:1 female preponderance. A wide variety of psychosomatic problems and full range of self-report scores were represented in the subject population. Scree plots suggested 2-4 factor solutions. In two factor solutions, the SHAI separated completely from other measures. In three factor solutions, the SHAI plus PHQ-9/GAD-7 affective symptoms formed one factor, ROS plus PHQ-9/GAD-7 vegetative symptoms formed a second factor, and the SDS formed the third factor. The most elegant solution was a four factor model comprised of: (1) SHAI serious illness worry plus PHQ-9/GAD-7 affective symptoms, (2) ROS somatic symptom burden plus PHQ-9/GAD-7 vegetative symptoms, (3) SDS disability, and (4) SHAI bodily sensations. These accounted for 30% of unique variance.

Conclusion:  Two health anxiety factors were identified, serious illness worry (with anxious and depressive affect) and body vigilance. They coexisted with two other factors, disability and somatic/vegetative symptoms. Taken together, these four factors may represent a general structure of tertiary care psychosomatic illness with health anxiety as a core component.

Screening for Suicidal Ideation in VA Ambulatory Settings
Presenting Author:  Steven Dobscha
Co-Authors:  Kathryn Corson, Drew Helmer, Matthew Bair, Lauren Denneson, Linda Ganzini

Background:  Suicide is devastating to families and communities. Approximately 6,000 Veterans complete suicide each year. Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans often have multiple risk factors for suicide. As part of its overall suicide prevention strategy, in 2008 the Veterans Affairs (VA) healthcare system began systematic screening for suicidal ideation (SI). While much research has been done to understand completed suicide and suicide attempts, relatively less is known about SI.

Objective:  To identify rates of positive depression and SI screens among OEF/OIF veterans treated in VA ambulatory care settings, and to examine correlates of positive SI screens among those screened in primary care and mental health settings.

Methods:  We used VA administrative databases to identify 8,912 OEF/OIF veterans who were screened for depression in ambulatory settings of three large, urban VA Medical Centers in different geographic regions between April 2008 and September 2009. Depression screening was conducted using the Patient Health Questionnaire (PHQ)-2 or the PHQ-9. SI screening tools, specific screening processes, and SI screen-scoring algorithms varied across the three sites. Manual medical record review was used to obtain or confirm screening dates and screen results. Chi-square and t-tests were used to compare groups in site-stratified analyses.

Results:  Of the 8,912 OEF/OIF veterans screened for depression, rates of positive depression screens ranged from 15% to 25% across the three sites. Of the 1,662 veterans screened in primary care or ambulatory mental health settings who had positive depression screens, 75% to 85% were subsequently screened for SI within 30 days of positive depression screens. Within this group, the prevalence of positive SI screens ranged from 33% to 38%. At one site, veterans with positive SI screens were more likely to have been screened for depression in mental health, as compared to primary care settings (35% vs. 22%; χ2=11.8, p=.001). At another site, nonwhites were more likely than whites to screen positive for SI (χ2=9.8. p=.02) and veterans between the ages of 25 and 34 were more likely to screen positive for SI than patients younger than 25 or older than 34 (χ2=13.6 and p=001). Otherwise, we detected no significant differences by location of screening, sex, or newness to VA care when comparing veterans with positive SI screens to veterans with negative SI screens.

Conclusions:  Suicidal ideation is common among OEF/OIF veterans with depressive symptoms who receive care in VA ambulatory settings. We did not detect demographic differences to distinguish veterans who endorse SI during clinic screening from those who do not endorse SI.

 

Session D:  Physical Symptoms and Health
Moderator/Discussant:  Philip R. Muskin, MD, FAPM

Depression in Survivors of Severe Sepsis
Presenting Author:  Dimitry Davydow
Co-Authors:  Catherine Hough, Kenneth Langa, Theodore Iwashyna

Background:  Little is known about the mental health outcomes of severe sepsis, the most common non-cardiac cause of critical illness. This study uses prospectively collected assessments of depression before and after incident severe sepsis to examine if severe sepsis is associated with an increased risk of substantial symptoms of depression. We also assess which patient and clinical characteristics are associated with an increased risk of post-sepsis depression.

Methods: Interviews were conducted with a prospective cohort of 516 patients with 623 hospitalizations for severe sepsis as part of the Health and Retirement Study, a nationally representative survey of U.S. adults (1998-2006). Included in the analysis were 439 patients who survived 471 hospitalizations for severe sepsis and completed at least one follow-up interview that included a standardized depression measure. Severe sepsis was identified using Medicare claims. Depressive symptoms were assessed with an 8-item version of the Center for Epidemiologic Studies Depression Scale. We used a cutoff score of 4 or higher on the 8-item CES-D to define clinically significant depressive symptoms. To test the hypothesis that severe sepsis is associated with an increased risk of clinically significant depressive symptoms, we used fixed effects Poisson regression models which use the longitudinal nature of the data to control for all stable patient characteristics. To examine patient characteristics and clinical factors associated with an increased risk of post-sepsis clinically significant depressive symptoms, we used Poisson regression models with robust error variances.

Results: The point prevalence of clinically significant depressive symptoms was 28% at a median of 1.2 years before sepsis, and remained 28% at a median of 0.9 years after sepsis. Neither incident severe sepsis [Relative Risk (RR) 1.00, 95%Confidence Interval (95%CI) (0.73, 1.34)] nor any single clinical characteristic of the severe sepsis-related hospitalization (i.e., organ dysfunction score, admission to an intensive care unit, hospital length of stay, as well as requirements for major surgery, mechanical ventilation, or dialysis) were significantly associated with subsequent clinically significant depressive symptoms. After adjusting for baseline characteristics (i.e., age, sex, race, education, marital/partner status, medical comorbidity) and health-risk behaviors (i.e., alcohol use, smoking), clinical characteristics, and post-sepsis cognitive and functional impairment (i.e., impairments in activities of daily living (ADLs) and instrumental ADLs), pre-sepsis clinically significant depressive symptoms [RR 2.20, 95%CI (1.66, 2.90)] and worse post-sepsis functional impairment [RR 1.08 per new limitation, 95%CI (1.03, 1.13)] were independently associated with a greater risk of post-sepsis clinically significant depressive symptoms.

Conclusions: The prevalence of substantial symptoms of depression is quite high among severe sepsis survivors - both before and after their hospitalization. Efforts to identify severe sepsis survivors at increased risk for major depression and beginning functional rehabilitation prior to hospital discharge may improve outcomes.

Are Bodily Distress Syndrome (BDS) / Physical Symptom Disorder and Health Anxiety (HA) Different Disorders?
Presenting Author:  Per Fink

Background:  Misinterpretations of bodily sensations and other psychological-behavioral characteristics are hypothesized to be the reason why some patients present with somatic symptoms not attributable to any known medical condition. Because of this hypothesis, it has been suggested that health anxiety (HA), previously called hypochondrias, which is only defined by psychological-behavioral characteristics, may be the same phenomenon as patients presenting with somatic symptoms, i.e., bodily distress syndrome (BDS).
The "point of rarity" or comorbidity between BDS and HA is poorly studied.

Method:  701 consecutive primary care patients were assessed by a research interview (the Schedules for Clinical Assessment in Neuropsychiatry, SCAN) to establish diagnoses of BDS, HA, and other mental disorders. For the analyses, the patients were grouped into 1) patients with BDS only, 2) patients with BDS and HA, 3) patients with BDS and psychological symptoms but not HA, 4) patients with psychological symptoms only, and finally 5) patients with HA only. The patients were followed up for two years as to self-rated health and health care costs.

Results:  35.1% of the patients with BDS single-organ type did not complain of any psychological symptoms or HA, whereas this was the case in only 2.8 % of the patients with BDS multi-organ type. Conversely, 25 (30.7%) of the 81 patients with HA did not have BDS, and 23 (28.4%) of the HA patients did not have any significant somatic symptom complaints.

Patients with BDS and no psychological symptoms or a HA diagnosis only had slightly better outcome during follow-up than patients with comorbid psychological symptoms or a HA diagnosis. Patients with HA only or psychological symptoms only seemed to have slightly better outcome than patients with BDS. Three out of 25 patients with HA only had comorbid anxiety disorder and one had a major depressive episode. The highest comorbidity was found in the group of patients with BDS, particularly in patients who also had HA.

Conclusion:  The study supports that BDS and HA are two distinct phenomena, and therefore different treatment approaches may be needed.

The UK Medical Research Council PACE Trial of Treatments for Chronic Fatigue Syndrome
Presenting Author:  Michael Sharpe
Co-Authors:  Peter White, Trudie Chalder

Purpose:  Chronic Fatigue Syndrome (CFS) describes a condition characterised by chronic fatigue and disability unexplained by a known medical condition. A large number of treatments, both drug and non-drug, have been suggested, although the best available evidence favors non-drug treatments, such as cognitive behaviour therapy (CBT) and graded exercise therapy (GET). These treatments remain controversial; patient advocacy groups claim that they are harmful and favor a non-rehabilitative treatment that aims to achieve adaptation to disability rather than change, called adaptive pacing therapy (APT), which has been widely advocated but not previously formally tested. There is, therefore, a need for a definitive trial to compare the effectiveness and safety of therapies based on behavioural change (CBT and GET) and on adaption to disability (APT) with simple specialist medical care alone (SMC).

Aim:  This UK-wide trial aimed to compare the effectiveness of four different non-drug treatments for patients with CFS on fatigue and physical function at 12 months. The treatments were (a) SMC alone, (b) SMC plus APT, (c) SMC plus GET, (d) SMC plus CBT.

Method:  641 patients with CFS (defined by Oxford criteria) were recruited from consecutive outpatient referrals to CFS clinics in six UK centres. They were randomly allocated to the four treatment groups. The primary outcomes were self-rated fatigue (Chalder fatigue scale) and self-rated physical function (SF-36 physical function scale) at 12 months.

Results:  An intention to treat analysis was performed. There was little missing outcome data. Treatment with CBT and GET resulted in less fatigue (p=0.003 and 0.006 respectively) and better physical function than with APT (p<0.001 for both). Analysis of sub-groups meeting International criteria for CFS (n=427) and London criteria for myalgic encephalomyelitis (ME) (n=329) yielded similar results. Secondary outcomes were consistent with primary outcomes. The percentages (numbers) of participants rating themselves as "much" or "very much" better in overall health at 52 weeks were 41% (61/147) for CBT, 41% (62/152) for GET, 31% (47/153) for APT and 25% (38/152) for SMC. Serious adverse outcomes were uncommon for all treatments.

Discussion:  PACE is the largest trial of treatments for CFS ever conducted. The findings have both theoretical importance, in suggesting some reversibility of CFS and practical importance, in suggesting that CBT and GET but not APT are useful treatments for CFS however defined. The presentation will include unpublished information on trial procedures and reactions to its publication.

Funding: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, UK Department for Work and Pensions. Trial registration ISRCTN54285094

Prevalence of General Physical Symptoms in the United States and Their Association with Race/Ethnicity and Acculturation
Presenting Author:  Amy Bauer
Co-Authors:  Chih-Nan Chen, Margarita Alegría

Purpose:  Although physical symptoms are a leading reason for primary care visits and strongly associated with disability and psychopathology, there is a lack of data from national samples on the prevalence of physical symptoms among major racial/ethnic groups in the United States. Furthermore, although many believe that physical symptoms are especially common among racial/ethnic minorities, the data suggesting associations between race/ethnicity, acculturation, and physical symptoms is inconsistent. This study sought to determine the prevalence of physical symptoms among white, Latino, and Asian Americans in the United States, and to examine the association of symptoms with race/ethnicity and acculturation.

Methods:  Data were analyzed from the National Latino and Asian American Study, part of the NIMH Collaborative Psychiatric Epidemiology Studies. Participants were a nationally-representative sample of non-institutionalized adults. The final sample included 2554 Latino Americans (Mexican, Puerto Rican, Cuban, and "other"), 2095 Asian Americans (Chinese, Vietnamese, Filipino, and "other") and 215 non-Latino whites who were interviewed in one of the following languages: English, Spanish, Mandarin, Vietnamese, or Tagalog. We computed the age- and gender-adjusted prevalence of fourteen physical symptoms and compared the prevalence rates among white, Latino, and Asian Americans. Multivariate logistic regression analyses estimated the effect of acculturation (determined by proxy indicators: English proficiency, nativity, generational status, and proportion of lifetime in the United States) on the number of physical symptoms among Latino and Asian Americans after adjusting for additional sociodemographic and clinical variables.

Results:  Whites and Latinos did not differ significantly in the total number of physical symptoms (1.00 versus 0.95) or the rate of reporting 3 or more symptoms (15.4% versus 13.0%). In contrast, compared to whites, Asians reported significantly fewer symptoms (0.60, p < 0.01) and were significantly less likely to have 3 or more symptoms (7.7%, p < 0.05). Of fourteen individual symptoms, twelve were equally common among Latinos and whites and two (shortness of breath and palpitations) were significantly more common among Latinos. In contrast, five individual symptoms (back pain, stomach pain, diarrhea/constipation, menstrual pain, and gastrointestinal distress) were significantly less common among Asians than whites. In multivariate logistic regression models, English proficiency was unrelated to symptoms, whereas lower acculturation was associated with fewer physical symptoms among both Latino and Asian Americans.

Conclusions:  The prevalence of physical symptoms differs across racial/ethnic groups, with Asian Americans reporting fewer symptoms than whites. Consistent with a ‘healthy immigrant' effect, increased acculturation was strongly associated with greater symptom burden among both Latino and Asian Americans.

References

  1. Kroenke & Price. Arch Intern Med 1993; 153:2474-2480
  2. Simon et al. N Engl J Med 1999; 341:1329-1335
  3. Kirmayer & Young. Psychosom Med 1998; 60:420-430
  4. Alegría et al. Int J Methods Psychiatr Res 2004; 13:208-20
  5. Kirmayer & Sartorius. Psychosom Med 2007; 69:832-840

Modifiable Risk Factors and Treatment Preferences for Depression after Spinal Cord Injury: Opportunities for Treatment
Presenting Author:  Jesse Fann
Co-Authors:  Charles Bombardier, Denise Tate, J. Scott Richards, Catherine Wilson, Ann Marie Warren, Allen Heinemann, Daniel Graves

Purpose: To identify promising depression treatment approaches for people with spinal cord injury (SCI) by examining: (1) the relationship between depression severity and theoretical depression risk factors (Physical Activity, Environmental Reward, and Self-Efficacy) and (2) depression treatment preferences.

Methods: Cross-sectional surveys were conducted in persons with SCI in: (Study 1) outpatient and community settings in Seattle WA, Birmingham AL, Ann Arbor MI, Dallas TX, Chicago IL, and (Study 2) rehabilitation inpatient services in Seattle WA, Ann Arbor MI, Houston TX. Outcome measures were: Patient Health Questionnaire-9 depression scale (PHQ-9), International Physical Activity Questionnaire (IPAQ), Environment Rewards Observation Scale (EROS), Modified Lorig Chronic Disease Self-Management Scale (CDSMS), and Depression Treatment Preference Survey

Results: (Study 1) 236 participants were 77% male and 65% Caucasian and 58% were >40 years old and 51% were >10 years post-injury. After controlling for other predictors of depression (not completing high school, unemployed, completeness of injury, and fewer years post-SCI; R2=.128), lower EROS (change in R2=.371, p<.001) and lower CDSMS (change in R2=.260, p<.001) were independent predictors of higher PHQ-9 scores. (Study 2) Among 181 inpatients (48 had PHQ-9>10 indicating moderate depression), a physical exercise program was the most preferred treatment option (78% somewhat or very likely to try), followed by antidepressants through a primary care provider (64%) and individual counseling in a medical or rehabilitation clinic (62%), if they became depressed. More depressed individuals were likely to state a willingness to try antidepressants and counseling for depression compared with non-depressed individuals.

Conclusions: Lower levels of environmental reward and self-efficacy were strong independent predictors of depression severity in persons with SCI. Physical exercise and antidepressants and counseling in a medical or rehabilitation setting were generally acceptable treatment options. The results of these two studies suggest that antidepressants and counseling, such as Behavior Activation aimed at improving access to pleasant rewarding activities, may be promising interventions for depression in this population, particularly if they are integrated into a person's medical care.

 

Session E:  Transplant and Immunology
Moderator/Discussant:  Catherine C. Crone, MD, FAPM

Ethics and Psychological Profiles of Altruistic Kidney Donors
Presenting Author: Alison Heru
Co-Authors: Judith Mayne, Cheryl Chessick, Michael Allen

There are 87,903 patients nationwide waiting to receive a kidney (www.hhs.gov, accessed 2/23/11). In 2010, 15,429 kidney transplants were completed nationwide, with 184 anonymous donations. In 2009, at the University of Colorado Hospital, Denver, there were 6 altruistic donations, one in 2005, one in 2006, one in 2008, 3 in 2010.

This presentation reviews the psychiatric assessment of 12 altruistic potential donors at the University of Colorado, Denver, during 2010. In addition, the presentation discusses the role of the psychiatrist on the transplant team, in the ethical decision-making process regarding altruistic donors.

The donor profile has changed over the past decade with more anonymous, Good Samaritan donors. Socially, the importance of Internet sites such as matchingdonors.com and other media support for altruistic donation is increasing. Professionally, the American Society of Transplant Surgeons (ASTS) state that "maintaining altruism as the central incentive to donation has averted the donation of organs from becoming a commodified exchange which could be exploitive in nature, and could bring an unacceptable commerce to the value of human life."

The ethical issues for the psychiatrist and the transplant team consist of two opposing positions: the need to protect potential patients from harm, and the need to respect individual autonomy. The position of the ASTS is that competent adults can choose to act altruistically by offering to donate a solid organ unconditionally, and should be allowed to donate if they understand the risks and benefits and can provide voluntarily consent.

The role of the psychiatric evaluation is to exclude major psychopathology that precludes good decision-making and ensure that the donor's motives are understandable. Several questions arise, however: How should we assess and make determination of serious characterological difficulties? Should the healthcare system prioritize altruistic donors' health care needs over other patients? Currently, if kidney donors need a new kidney, they are put to the top of the transplant list. However, in 2009, 17% of altruistic donors had no health insurance. There are several suggested recommendations: the use of an institutional screening tool for all altruistic donors, a waiting time before surgery is scheduled to allow the donor adequate time to reconsider, a minimum age requirement that would exclude those under 21 years of age from being considered, and a protocol for managing any psychiatric recommendations post donation.

References:

  1. Seelig BJ, Rosof LS: Normal and pathological altruism. J Am Psychoanal Assoc 2006; 49:933-59
  2. Morrissey PE, Dube C, Gohh R, Yango A, Gautam A, Monaco AP. Good samaritan kidney donation. Transplantation 2005 (Nov27); 80(10):1369-73
  3. Dew MA, Jacobs CL, Jowsey SG, Hanto R, Miller C, Delmonico FL. Guidelines for the Psychosocial Evaluation of Living Unrelated Kidney Donors in the United States. American Journal of Transplantation 2007; 7:1047-1054

Pre-Transplant Psychosocial Factors Predict T Cell Recovery following Hematopoietic Stem Cell Transplantation
Presenting Author:  Jennifer Knight
Co-Authors:  Jan Moynihan, Susan Messing, Bryan Hunter, Li-Shan Huang, Rosie Obi, D'Arcy Gaisser, Jane Liesveld, Olle Jane Sahler

Purpose:  Immune reconstitution is a critical step in the recovery of hematopoietic stem cell transplant (HSCT) patients and may be affected by psychosocial variables. Stress and other psychosocial factors are known to influence T cell numbers; however, this relationship has not been examined in HSCT recipients. The purpose of this study was to examine the effects of pre-transplant psychosocial factors on post-transplant T cell subsets, including CD3+, CD4+, and CD8+ T cells, as well as the CD4+/CD8+ ratio.

Methods:  65 adults undergoing HSCT for any reason participated in this study. Pre-transplant coping styles and perceived social support were measured using the Brief COPE and the Schaefer Perceived Social Support Scale, respectively. The absolute number of CD3+, CD4+, and CD8+ T cells, as well as the CD4+/CD8+ ratio, were assessed an average of 48 days post-transplant (range 0-100). Correlation coefficients were calculated for psychosocial factors and each T cell subtype and CD4+/CD8+ ratio.

Results:  Emotional support, evaluated as a subscale in both the coping and perceived social support questionnaires, was significantly associated with lower absolute values of CD8+ T cells (p<.05). Religious coping was also associated with fewer CD8+ cells (p<.05), while behavioral disengagement was associated with significantly higher absolute values of CD8+ cells (p<.05). Emotional support as evaluated in the social support subscale as well as optimism were significantly associated with higher CD4+/CD8+ ratios (p<.05), whereas behavioral disengagement used as a coping method was significantly associated with a lower CD4+/CD8+ ratio (p<.01).

Conclusions:  Perceived emotional social support predicted lower numbers of CD8+ cells and a higher CD4+/CD8+ ratio in HSCT recipients, whereas behavioral disengagement predicted higher numbers of CD8+ cells and a lower CD4+/CD8+ ratio. Our findings indicate that positive psychosocial factors predict lower numbers of CD8+ cells, which others have shown to be associated with a decreased risk for graft-versus-host-disease, the major complication after allogeneic HSCT. We also demonstrate that negative psychosocial factors predict a lower CD4+/CD8+ ratio, which has been shown to be a poor prognostic index in other populations. Further research is needed to identify whether interventions aimed at impacting these psychosocial factors may result in improved immune reconstitution and clinical outcomes in HSCT recipients.

Psychosocial Predictors of Non-Adherence in Autoimmune Hepatitis
Presenting Author:  Sanjeev Sockalingam
Co-Authors:  Diana Blank, Nour Abdelhamid, Susan Abbey, Gideon Hirschfield

Background:  Autoimmune hepatitis accounts for 6% of liver transplantations in the United States and approximately 40% of patients with untreated severe AIH die within 6 months. Therefore, AIH treatment is paramount to reducing mortality in this patient group and reinforces the need for adherence to immunosuppressant medication regimens. We attempted to determine the level of psychological distress and AIH disease severity in AIH patients with reduced adherence to immunosuppressant therapy. We also aimed to determine if psychosocial factors predicted adherence to immunotherapy in AIH patients.

Methods:  Fifty-two AIH patients were recruited from the Toronto Western Hospital Liver Centre for this cross-sectional study examining patients’ self-reported adherence to AIH immunosuppressant therapy. Patient-reported adherence was measured using a visual analogue scale for adherence. Depression and anxiety were measured using the Patient Health Questionnaire-9 (PHQ9) and Generalized Anxiety Disorder-7 (GAD7) questionnaires. Attachment style was measured using the Experiences for Close Relationships-16 (ECR-16) to determine the influence of relationship style, specifically attachment avoidance (ECR-avoidance) and attachment anxiety (ECR-anxiety) on treatment adherence.

Results:  The mean age of patients in this study was 47.2 years, 67% were female and 54% had liver cirrhosis confirmed by ultrasound. Approximately 60% were taking steroid therapy and 89% were taking an immunosuppressant agent. 15.4% and 11.5% of patients screened positive for depression (PHQ9) and anxiety (GAD7), respectively. Patients treated with steroids did not demonstrative significantly different scores on the PHQ9 and GAD7. Patients with reduced adherence (≤80%) had significantly higher IgG, ALT and AST (p<0.01) and significantly higher depressive and anxious symptoms (p<0.01). PHQ9, GAD7, ECR-avoidance and ECR-anxiety scores did not predict adherence to immunosuppressant medications.

Conclusions:  We observed high rates of depression and anxiety on self-report measures in our sample of AIH patients. AIH patients with reduced immunosuppressant medication adherence demonstrated significantly higher depressive and anxiety symptoms and poorer liver disease indices. However, anxiety, depression and attachment style did not predict immunosuppressant adherence in our study and warrant further investigation in future studies.

[T] Inflammation and Anxiety: A Meta-Analysis
Presenting Author:  Pamela Mirsky
Co-Author:  Nicholas Breitborde

Purpose:  The objective of this study is to assess the relationship between inflammation and anxiety.

Methods:  A systematic review of the literature through the PubMed and PsycInfo electronic databases was conducted to identify all human, English language studies reporting the relationship between C-reactive protein (CRP), interleukin (IL)-6, IL-1β and/or tumor necrosis factor (TNF)-α and anxiety completed prior to January 2011. For each study, we calculated the effect size (r) of the relationship between anxiety and each inflammatory marker. Prior to completing the analyses, all values of r were transformed to z-scores so as to reduce departures from normality in the distribution of the effect sizes [1]. A random-effects meta-analytic model was utilized to account for possible heterogeneity in the effect sizes across studies [2]. After the completion of the meta-analyses, we calculated Rosenthal’s file drawer statistic to determine the robustness of each effect. This statistic provides an estimate of how many new or unpublished studies with null results would be required to reduce the effect size to just barely no longer statistically significant (i.e., p = 0.05).

Results:  A statistically significant positive association between anxiety and inflammation was found across studies (z = 3.64; p < 0.01). This association varied by inflammatory marker, with IL-6 being the only marker that was independently associated with anxiety (z = 4.16; p < 0.01). The association between anxiety and inflammation also varied by the source of the inflammatory marker (e.g., blood, saliva, etc.) and by the illness status of the subjects. More specifically, an association between anxiety and inflammation was only evident in studies that extracted inflammatory markers from blood, and only in studies that examined individuals with a diagnosed illness.

Conclusions:  There is a relationship between inflammation and anxiety, such that higher levels of inflammation are correlated with higher levels of anxiety. However, this relationship appears to vary by (1) which inflammatory marker is measured; (2) how this inflammatory marker is measured; and (3) the illness status of the subjects. Clarifying the specific nature of the relationship between anxiety and inflammation could have wide-ranging clinical implications. More specifically, this may help us move towards a model where medical and psychiatric symptoms are not viewed as separate entities. Patients will benefit from our knowledge of how their inflammatory disorders may affect their mental health, and vice versa.

References:

  1. Rosenthal, R. Meta-analytic procedures for social research. Newbury Park, NJ: Sage, 1991
  2. National Research Council. Combining information: Statistical issues and opportunities for research. Washington, DC: National Academy Press, 1992

An Intervention to Prevent Psychiatric Morbidity and Poor Psychosocial Outcomes in Living Organ Donors: Initial Evaluation of Feasibility and Effectiveness
Presenting Author:  Mary Amanda Dew
Co-Authors:  Andrea F. DiMartini, Annette J. DeVito Dabbs, Allan M. Zuckoff, Galen E. Switzer, Henkie P. Tan

Purpose:  Living organ donation is a mainstay of transplantation in the United States. Donors provide an incomparable gift, and the protection of living donors' well-being is among the foremost priorities in transplantation. Nevertheless, the risk of poor psychiatric and other psychosocial outcomes in the first several years post-donation remains high: up to 54% of donors report clinically significant psychiatric symptomatology, poor perceived physical well-being, and strained spousal or other family relationships. No preventive interventions have been mounted or tested for their ability to avert poor psychosocial outcomes in living donors. We sought to develop and examine the feasibility and effectiveness of a new intervention for this purpose. The new intervention utilizes motivational interviewing (MI) to address lingering concerns and any remaining ambivalence that individuals may have about proceeding with living donation.

Methods:  Two phases of work are being undertaken. In Phase I, we refined the intervention for prospective living donors, manualized it, and trained interventionists to reliably administer it. In Phase II, a randomized controlled trial (RCT) is underway in which living kidney and liver donors are randomized to (a) receive the individual, 2-session telephone-based MI intervention (+ usual care), (b) participate in a comparison telephone-based attention control (in which they receive information about healthy lifestyle habits) + usual care, or (c) receive usual care only. The intervention and comparison condition are administered before donation, with study outcomes (psychiatric symptoms, somatic complaints, interpersonal relationships within the family, overall health-related quality of life) assessed at 6 weeks, 3 months, and 6 months post-donation. Assessors are blinded as to which condition study participants are in.

Results:  Phase I initially enrolled 8 donors, and established that (a) donors were willing to complete the telephone sessions, (b) they were satisfied with the content and usefulness of the sessions, and (c) they were able to complete study-based assessments both before and after donation. An additional 14 donors were then enrolled so that interventionists could be trained to reliability in administering the intervention. To date, 66 individuals have been enrolled and randomized in the RCT (target sample size = 150). The refusal rate has been low (12%), and there has been no attrition post-donation. Study participants report high levels of perceived satisfaction with the intervention. Initial RCT findings will be summarized in Fall 2011.

Conclusions:  A novel intervention designed to prevent poor psychiatric and psychosocial outcomes in living organ donors appears promising in terms of initial feasibility and donor willingness and interest in participating. The results of the RCT will provide important data for the further design of strategies to prevent poor psychiatric and psychosocial outcomes after living organ donation.

 

Session F:  Psycho-Oncology and Quality of Life
Moderator/Discussant:  Linda K. Ganzini, MD, FAPM

Rapid Treatments for Depression and Anxiety in Patients Receiving Hospice Care
Presenting Author:  Scott Irwin

Depression is prevalent and under-treated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine and methylphenidate may provide viable alternatives for the rapid treatment of depression in this population.

Data will be presented from a retrospective chart review of 80 patients receiving inpatient hospice care who were diagnosed with a depressive disorder. Those treated with methylphenidate exhibited a significantly better therapeutic effect than other treatments (2.33±0.23 vs. 3.06±0.3; U=87, p<0.05), but significantly more side effects, though all groups were in the “do not interfere with functioning” range on the CGI (1.72±0.23 vs. 1.13±0.13; U=197 p<0.05). A similar investigation of ketamine use for depression in hospice patients is underway, and data from it will be presented as well.

Pilot data from an open label clinical trial of oral ketamine for depression, which showed an average 41% drop in Hamilton Rating Scale Depression Scores at 60 minutes after initial dosing (n = 3) which continued to improve over two weeks, will also be presented. In another trial of methylphenidate for the rapid treatment of depression, it demonstrated a 53% drop in Hospital Anxiety and Depression Scale Scores one day after initial dosing (n = 2) which continued to improve over one week. Ketamine appears to provide rapid and sustained relief of depressive symptoms with minimal adverse effects as measured by several standardized assessment tools. In addition, ketamine also provided an average 76% drop in Anxiety Scores by 120 minutes after initial dosing (n = 2). The single patient receiving methylphenidate had to have it tapered after 14 days due to emerging anxiety symptoms.

Further investigation with randomized, controlled clinical trials is necessary to firmly establish the effectiveness of oral ketamine and methylphenidate for the treatment of depression and anxiety in patients receiving hospice care. Both may be promising safe, effective, and cost-effective treatment for depression in this population, and ketamine might prove useful for anxiety as well.

A Comparison of Self-Reported Cognitive Difficulties in a National Sample of Long-Term Cancer Survivors and Cancer-Naïve Controls
Presenting Author:  Ilana Braun
Co-Authors:  Sowmya Rao, William Pirl

Introduction:  A growing body of evidence suggests that cancer survivors experience greater cognitive dysfunction than individuals without cancer. This study tests that notion by comparing self-reported cognitive difficulties among long-term cancer survivors and cancer naïve controls in a probability sample of community-dwelling United States residents.

Methods:  National Comorbidity Survey-Replication (NCS-R) researchers conducted face-to-face interviews in a national sample of 9,282 people, of whom 5,692 were assessed for a history of cancer. The NCS-R contains two cognitive symptom screens, a question investigating the number of days per month symptoms persist; and five items drawn from Domain 1 (Cognition) of the World Health Organization Disability Assessment Schedule 2.0. The authors of the current study identified long-term survivors of adult cancers in the NCS-R as individuals who were at least 18 years old at time of diagnosis; greater than five years following diagnosis; and with their cancer reportedly in remission or cured. Odds ratios and 95% confidence intervals were obtained from multivariable logistic regression models that were fit to evaluate the relationship between cancer status (long-term survivor versus cancer-naïve control) and cognitive symptoms.

Results:  Of NCS-R participants, 225 met criteria for long-term cancer survivor and 4,096 for cancer-naïve control. Long-term cancer survivors screened positive for cognitive symptoms at a rate of 19.5% for the first screen and 16.0% for the second; cancer-naïve controls at a rate of 20.0% for the first screen and 16.4% for the second. Adjusting for demographics and psychiatric variables, long-term cancer survivors did not carry increased odds of experiencing cognitive symptoms [(OR) 1.02 (95% CI, .61 to 1.70); (OR) .97 (95% CI, .59 to 1.61)].

Conclusions:  Self-reported cognitive symptoms are common among cancer survivors and members of the general population; surprisingly, long-term cancer survivors do not report cognitive symptoms at greater frequency.

[T] Assessment of Decision-Making Capacity in Terminally Ill Patients
Presenting Author:  Elissa Kolva
Co-Authors:  Barry Rosenfeld, Hayley Pessin, Robert Brescia

Purpose:  Terminally ill patients must make treatment-decisions with important legal and ethical consequences even after their disease has progressed beyond the possibility for cure. Yet, there is no consensus as to how decision-making capacity should be evaluated and how much capacity is required for competent decision-making. A recent study found general impairments in capacity to provide informed consent in terminally ill patients (Sorger et al., 2007). However, little research has specifically addressed the capacity to make end-of-life treatment decisions, which is especially need given that this population is at increased risk for cognitive impairment.

Method:  24 terminally ill patients admitted to an inpatient, palliative care hospital for end-of-life care were administered the MacArthur Competence Assessment Tool, Treatment version (MacCAT-T), a structured measure of competency. Patients were read one of two vignettes designed to assess decision-making abilities about end-of-life issues (i.e., artificial nutrition and hydration or dialysis). The MacCAT-T includes 4 hierarchical subscales, Choice, Understanding, Appreciation, and Reasoning. Pass/fail scores for the MacCAT-T subscales were calculated as per Schillerstrom (2008). Participants also completed measures of general cognitive functioning (MMSE), anxiety, and depression (HADS).

Results:  Participants were predominantly Caucasian (83%) and well-educated (70% had at least some college) with a mean age of 69.3 (SD=13.2). In general participants were found to be "cognitively intact", 80% exceeded the cut-off score associated with grossly intact cognitive functioning (MMSE ≥ 23; Kim et al., 2002). However, the majority of participants (58%) were impaired on the Understanding subscale, which requires patients to paraphrase content provided in the vignette. Only 8% were impaired on the Reasoning and Choice subscales and none were impaired on the Appreciation subscale. Cognitive functioning was significantly correlated with performance on the Understanding subscale (r = .61), but not with any of the other subscales. Anxiety and depression, as well as relevant demographic factors (i.e., age, education) were not significantly associated with performance on the MacCAT subscales.

Conclusions:  The majority of participants had some level of decision-making impairment, primarily related to ability to understand information relevant to a treatment decision while other more complex cognitive functioning appeared to remain intact. This contradicts the general assumption in the literature that Understanding involves less rigorous cognitive processes than Appreciation and Reasoning. Patients appear to retain the ability to think rationally about treatment-related information, but have difficulty articulating newly presented information. Clinicians might employ strategies such as providing information in multiple forms of presenting information in smaller chunks to improve understanding. Furthermore, traditional capacity assessment methods of relying on gross measures of cognitive function appear be inadequate and insensitive for detecting impairment in capacity. The MacCAT-T is a relevant and feasible measure for studying end-of-life decision-making and should be incorporated into clinical assessments of capacity.

Associations between Patient Cognitive Status and Caregiver Psychiatric Disorders in Terminally Ill Cancer Patients
Presenting Author:  Fremonta Meyer
Co-Authors:  Xin Gao, Holly Prigerson

Purpose:  Cognitive disorders, primarily delirium, are prevalent in advanced cancer patients and can render patients unable to communicate their treatment wishes. Caregivers who serve as health care proxies often assume decision-making responsibility at a time of mounting distress at the end of life (EOL). Recently submitted results from our group indicate that cognitively impaired patients and their caregivers not only exhibit poor agreement at baseline regarding preferences for life-extending versus palliative therapies, but that caregivers' preferences may actually dictate the intensity of medical care that cognitively impaired patients receive at EOL. Because increased decisional responsibility may constitute an added stressor for caregivers, we hypothesized that caregivers of cognitively impaired patients would exhibit higher rates of pre- and post-loss major depressive disorder and anxiety disorders as compared to caregivers of cognitively intact patients.

Methods:  Study participants were recruited as part of the Coping with Cancer study, a prospective, longitudinal, multi-institutional cohort study of terminally ill cancer patients and their informal (unpaid) caregivers funded by NCI/NIMH. This report characterizes the caregivers of 234 patients who completed the Short Portable Mental Status Questionnaire (SPMSQ). At a median of 3.6 months prior to death, patients completed the 10-item SPMSQ previously validated as a screening tool for delirium and dementia in elderly patients. Mild cognitive impairment was defined as greater than 3 errors on SPMSQ. Caregivers simultaneously completed the Structured Clinical Interview for DSM-IV (SCID), followed by repeat SCID at a median of 6.5 months after the patient's death.

Results:  Caregivers of cognitively impaired patients were more likely to be Hispanic (p<0.0001), have less formal education (p<0.0001), have larger household sizes (p=0.001), report more functional disability (p=0.01), and experience pre-loss grief (p=0.01). There were no associations between patient cognitive status and caregiver marital status, gender, or relationship to patient (spouse vs. child vs. other). In comparison to caregivers of cognitively intact patients, caregivers of cognitively impaired patients were more likely to have MDD at baseline (OR 3.247 [1.063-9.917]; p=0.0387) and PTSD after their loved one's death (OR 3.060 [1.224, 7.651]; p=0.0168). There were no significant differences in rates of baseline PTSD (OR 0.928 [0.258, 3.338]; p=0.9086) or post-loss MDD (OR 1.626 [0.749, 3.531]; p=0.2193). There were no significant differences in rates of GAD or panic disorder at either time-point.

Conclusion:  Caregivers of cognitively impaired advanced cancer patients may be particularly vulnerable to depression and post-traumatic stress disorder. Further analysis of the data set will be conducted in order to adjust for sociodemographic variables and other covariates including baseline (caregiver pre-loss) psychiatric status.

Associations of Cognitive Function, Cerebral Metabolism and Perfusion, and Quality of Life with Metabolic Aspects in Aged Patients with Metabolic Syndrome: Preliminary Results
Presenting Author:  Vanessa A. Citero
Co-Authors:  Alessandro F. Jacinto, Nadia Shigaeff, Gabriela Chiochetta, Maysa S. Cendoroglo, Roberto D. Miranda, Edson Amaro, Jr., Miriam R. Ikeda, Maryana C. Alegro, Fabio G.M. Franco

Background:  Metabolic Syndrome (MS) has been related to cognitive impairment, low quality of life, and cerebral hypoperfusion in the elderly. Some researchers linked this low vascular perfusion as a contributive cause for Alzheimer's Disease which occurs simultaneously with the process of neurodegeneration (vascular hypothesis).

Purpose:  To associate cognitive function, pre-frontal cerebral perfusion, and quality of life with metabolic aspects in aged patients with metabolic syndrome. It was hypothesized that aged patients with well-controlled MS present cognitive impairment associated to cerebral hypoperfusion, and quality-of-life impairment associated to cognitive deficits.

Methods This is a preliminary report of a one-year longitudinal case-control study that has been developed with 80 aged patients (≥65 years-old). This communication was developed with 13 patients with MS who completed the entry survey (cross-sectional study). They were assessed using the Global Geriatric Evaluation, a neuropsychological battery, the WHOQOL Brief and OLD, the BOLD functional magnetic resonance imaging (fMRI) and an Arterial Spin Labeling Perfusion magnetic resonance imaging (ASL). The Spearman correlation test was applied, and statistical significance was p≤0.05.

Results:  92% of patients were female, median age of 72 years, 82% with low scholarship (up to 4 years), Mini Mental Status Examination mean score of 26, Geriatric Depression Scale mean score of 3, and no one present any neurodegenerative disease. They had means of medium arterial pressure=117mmHg, abdominal circunference=104cm, glicemic level=118mg/dl, HDL-colestherol level=49mg%, and triglycerides level=129mg/dl. Abdominal circunference was correlated to clock drawing test (r=0.62), and to Rey Auditory Verbal Learning Test (total list A, r=-0.77). Medium arterial pressure was correlated only to Digits (r=-0.81). Glicemic level was correlated to physical domain of QoL (r=-0.57), to Rey Auditory Verbal Learning Test (recognition of list B, r=-0.89). HDL-colestherol level was correlated to physical domain of QoL (r=-0.59), to social participation domain of QoL (r=0.55). Tryglicerides level was correlated to social relationships domain of QoL (r=-0.66), to Rey Auditory Verbal Learning Test (recognition of list B, r=-0.58). Glicemic level, abdominal circunference and triglycerides were correlated to right and left temporal and parietal gyrus thickness and volume, and to right entorhinal cortex volume. The difference between incongruents and congruents answers in STROOP test showed reduction of metabolism in frontal cortex related to high glicemic levels.The final data with ASL results will be presented at the meeting.

Conclusions:  This preliminary and exploratory study shows that aged patients with well-controlled MS may present mild cognitive impairment (episodic and operational memory, attention, and executive function). Higher trygliceride levels were associated to lower thickness and volume in temporal cortex, and higher glicemic levels were related to lower thickness in temporal and entorhinal cortex, which were congruent with cognitive impairment findings. These patients also presented lower quality of life in physical domain, probably interfering to social aspects.

 

Session G:  Webb Fellows
Moderator/Discussant:  John L. Shuster, Jr., MD, FAPM

Scott Beach
Scott Beach, MD
Laura Kent
Laura Kent, MD
Marlynn Wei
Marlynn Wei, MD, JD
Lex Denysenko
Lex Denysenko, MD

Assessment of Autonomic Dysfunction in Patients with Heart Failure
Presenting Author:  Scott R. Beach
Site Mentors:  Donna Chen, University of Virginia; Jeff Huffman, Massachusetts General Hospital

Background:  Depression in patients with heart failure (HF) has been associated with mortality, independent of other risk factors. The mechanism by which depression impacts medical outcomes remains unclear, but depression has been associated with dysfunction of the autonomic nervous system (ANS) in other populations. ANS function may be a key mediator in the established links between depression and cardiac mortality in patients with HF. It is therefore important to determine (a) whether there are feasible methods to measure ANS function in patients with HF and (b) whether ANS dysfunction is in fact greater in depressed as opposed to non-depressed HF patients. It appears possible to assess ANS function safely and non-invasively using two separate devices to measure parameters including galvanic skin response (GSR), heart rate variability (HRV), and sleep.

Methods:  We will enroll 20 patients with HF and depression in addition to 20 matched controls who have been diagnosed with HF but do not have depression. Subjects will wear two devices, the Affectiva Q Sensor and the Innerscope Biometric Belt, for 24 hours on hospital day #3. During this time, a 24-hour urine collection will also be performed to measure urine catecholamines. At the time of discharge, subjects will take the devices home, and wear them again for 24 hours on day #3 after discharge.

Results:  We hypothesize that at least 60% of eligible patients (both depressed patients and non-depressed matched controls) will enroll, and over 70% of enrolled subjects will complete all measurements both in the hospital and following discharge. We further hypothesize that during hospitalization and following discharge, depressed HF patients will have greater sympathetic nervous system arousal, as measured by the above parameters, than control subjects matched in multiple domains. We believe that subjects with elevated GSR will also demonstrate worse sleep, decreased HRV, and increased urine catecholamines.

Addressing the Empty Bed:  Stress, Depression and Unexpected Deaths during Medicine Residency in the MICU
Presenting Author:  Laura Kent
Co-Authors:  David Chong, Peter Shapiro

Goal:  To better understand medicine residents’ internal experience of residency and their reactions to the occurrence of unexpected patient deaths.

Objective:  To determine what psychological factors are most prominently in play during difficult months of residency in which housestaff may experience the unexpected deaths of patients.  In addition, to measure the extent of those psychological factors and the effect of unexpected patient deaths on medicine residents.

Methods:  A psychiatrist met twice monthly for one year (July 2010–June 2011) with medicine residents (both PGY1s and PGY2s) in a group setting (total n = 80).  There were approximately 8 members in each group.  The group was an opportunity for free expression about clinical issues, with several guided questions to each group:  most challenging aspects of residency, experiences with unexpected deaths.  A better understanding of psychological factors affecting residents was garnered from these groups.  This information was used to design a voluntary, anonymous survey.  The survey used the PTSD Checklist Civilian Version and the PHQ2 to screen for symptoms of PTSD and depression, respectively.  This survey was given to subsequent groups of residents rotating through the MICU at the beginning and end of their rotation, starting in July 2011.

Results:  Qualitative data from the group meetings over one year suggested that residents might have symptoms of PTSD and depression. In particular, themes of feeling traumatized, helpless, and without adequate validation and support were notable.  In July-October 2011, 8 PGY1 residents and 4 PGY2 residents completed the survey.  PTSD scores increased for both PGY1s and PGY2s from the beginning to the end of the MICU rotation.  The symptom with the highest response was, “Feeling as if your future will somehow be cut short.”  The mean response for this symptom on a scale of 1-5 was 1.94.  PTSD symptoms were more prominent than depression symptoms. All but one of the housestaff experienced an unexpected death.  All but two housestaff reported a positive experience surrounding a patient’s death.  There was no relationship between having experienced an unexpected death or the number of unexpected deaths experienced, with  the PTSD score or the depression score.

Conclusion:  Medicine residents have more symptoms of PTSD than of depression during their MICU rotation.  Symptoms of PTSD increase during the month.  Most residents experience the unexpected death of a patient at some point during the month.  More research is needed to better understand the mechanism of increased PTSD symptoms and to determine appropriate mitigating interventions.

Psychiatric Evaluation of Prisoners in the General Hospital
Presenting Author: Marlynn H. Wei

Psychiatric evaluations of individuals involved in legal proceedings (e.g., those who are prisoners, under arrest, awaiting arraignment or sentencing, or who have been arraigned) who have been referred to general hospitals require special attention to the interface of law enforcement and clinical practice. The mental health needs of such individuals and their psychiatric evaluations (and how they can be viewed in the context of the criminal process) will be reviewed.  An understanding of basic criminal procedure, available resources at prisons and jails, and risks while in custody can help psychiatrists provide safe and thorough clinical assessments and appropriate dispositions. Challenging cases (e.g., those who refuse to participate in the interview, who make conditional suicide threats, and who seek secondary gain) will also be discussed.

Alpha-Lipoic Acid as an Augmentation Treatment for Patients with Depression, A Pilot Study
Presenting Author: Lex Denysenko

Background:  Depression and obesity are correlated disorders associated with high medical morbidity. Alpha-lipoic acid (ALA) is produced in the human body and is a cofactor for mitochondrial respiratory enzymes. It regulates glucose metabolism, decreases appetite, causes weight loss, and has been shown to have possible neuroprotective effects. Although limited data suggests that ALA may subjectively improve energy, it has not been investigated as a possible augmentation agent for patients with depression.

Objective:  To determine if ALA improves depression symptoms and weight loss in patients currently in treatment for depression.

Methods:  Adult patients age 18-75 currently in treatment for unipolar or bipolar depression but still with depressive symptoms who consent to the study will participate in a 6 week, open-label pilot trial of oral ALA 600mg twice daily in addition to their usual treatment. Subjects will be measured for effect in their depressive symptoms and quality of life using the Hospital Anxiety and Depression Scale, the Montgomery-Asberg Depression Rating Scale, and the Short Form-36 Health Survey at the beginning, midpoint, and end of the study period. In addition, subjects will have their weight monitored throughout the study.

Results:  Descriptive statistics will be used to analyze the results to determine if subjects had any improvement in depressive symptoms, quality of life, and weight over the course of the trial.

Conclusion:  ALA may be a potentially useful adjunctive therapy for the treatment of depression, and may have the additional benefit of weight loss in the depressive patient population.


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