Unmet mental health needs in patients with advanced B-cell lymphomas.

CONTEXT: Existing research on psychological distress and mental health service utilization has focused on common types of solid tumor cancers, leaving significant gaps in our understanding of patients experiencing rare forms of hematologic cancers. OBJECTIVE: To examine distress, quality of life, and mental health service utilization among patients with aggressive, refractory B-cell lymphomas. METHOD: Patients (n = 26) with B-cell lymphomas that relapsed after first- or second-line treatment completed self-report measures of distress (Hospital Anxiety and Depression Scale) and quality of life (Short-Form Health Survey, SF-12). Patients also reported whether they had utilized mental health treatment since their cancer diagnosis. RESULTS: Approximately 42% (n = 11) of patients reported elevated levels of psychological distress. Of patients with elevated distress, only one quarter (27.2%; n = 3) received mental health treatment, while more than half did not receive mental health treatment (54.5%; n = 6), and 18.1% (n = 2) did not want treatment. Patients with elevated distress reported lower mental quality of life than patients without elevated distress [F (1, 25) = 15.32, p = 0.001]. SIGNIFICANCE OF THE RESULTS: A significant proportion of patients with advanced, progressive, B-cell lymphomas may experience elevated levels of distress. Yet, few of these distressed patients receive mental health treatment. Findings highlight the need to better identify and address barriers to mental health service utilization among patients with B-cell lymphoma, including among distressed patients who decline treatment.

Development and preliminary evaluation of EMPOWER for surrogate decision-makers of critically ill patients.

OBJECTIVE: The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates' mental health and patient outcomes. METHOD: Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15-20 min modules, totaling 1.5-2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments. RESULTS: Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = -0.41), peritraumatic distress (d = -0.24), and experiential avoidance (d = -0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = -0.94), depression (d = -0.23), anxiety (d = -0.29), and experiential avoidance (d = -0.30). SIGNIFICANCE OF RESULTS: Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.

Associations between beta-blocker use and psychological distress in bereaved adults with cardiovascular conditions.

The death of a close other is a major life stressor that disrupts mental and physical health. Beta-blocker medications are indicated treatments for cardiovascular conditions that may also mitigate psychological distress in the context of stressors by reducing adrenergic activity. We sought to examine observational links between beta-blocker medication use and psychological distress during bereavement. Using publicly available data from the Midlife in the United States Refresher study, we examined associations between beta-blocker use and general distress, depressive symptoms, and anxiety symptoms (as measured by the Mood and Anxiety Symptom Questionnaire) among bereaved adults with cardiovascular conditions (n = 161) using t-tests and regression models. Beta-blocker users reported lower levels of anxiety-related general distress (b = -2.49, SE = 0.88, p = 0.005) and depression-related general distress than non-users (b = -2.39, SE = 1.14, p = 0.039) in multivariate linear regression models adjusting for demographic characteristics, mental health treatments, time since loss and comorbid health conditions. These observed links between beta-blockers and lower psychological distress in bereavement warrant further investigation in prospective and randomized studies, as beta-blockers could be a scalable intervention for mitigating distress following loss.

Timing is everything: Early do-not-resuscitate orders in the intensive care unit and patient outcomes.

BACKGROUND: The use of Do-Not-Resuscitate (DNR) orders has increased but many are placed late in the dying process. This study is to determine the association between the timing of DNR order placement in the intensive care unit (ICU) and nurses' perceptions of patients' distress and quality of death. METHODS: 200 ICU patients and the nurses (n = 83) who took care of them during their last week of life were enrolled from the medical ICU and cardiac care unit of New York Presbyterian Hospital/Weill Cornell Medicine in Manhattan and the surgical ICU at the Brigham and Women's Hospital in Boston. Nurses were interviewed about their perceptions of the patients' quality of death using validated measures. Patients were divided into 3 groups-no DNR, early DNR, late DNR placement during the patient's final ICU stay. Logistic regression analyses modeled perceived patient quality of life as a function of timing of DNR order placement. Patient's comorbidities, length of ICU stay, and procedures were also included in the model. RESULTS: 59 patients (29.5%) had a DNR placed within 48 hours of ICU admission (early DNR), 110 (55%) placed after 48 hours of ICU admission (late DNR), and 31 (15.5%) had no DNR order placed. Compared to patients without DNR orders, those with an early but not late DNR order placement had significantly fewer non-beneficial procedures and lower odds of being rated by nurses as not being at peace (Adjusted Odds Ratio namely AOR = 0.30; [CI = 0.09-0.94]), and experiencing worst possible death (AOR = 0.31; [CI = 0.1-0.94]) before controlling for procedures; and consistent significance in severe suffering (AOR = 0.34; [CI = 0.12-0.96]), and experiencing a severe loss of dignity (AOR = 0.33; [CI = 0.12-0.94]), controlling for non-beneficial procedures. CONCLUSIONS: Placement of DNR orders within the first 48 hours of the terminal ICU admission was associated with fewer non-beneficial procedures and less perceived suffering and loss of dignity, lower odds of being not at peace and of having the worst possible death.

Illness Understanding and Advance Care Planning in Patients with Advanced Lymphoma.

Background: The prognosis of an aggressive lymphoma can change dramatically following failure of first-line treatment. This sudden shift is challenging for the promotion of illness understanding and advance care planning (ACP). Yet, little is known about illness understanding and ACP in patients with aggressive lymphomas. Objective: To examine illness understanding, rates of engagement in ACP, and reasons for lack of ACP engagement in patients with advanced B cell lymphomas. Design: Cross-sectional observational study. Setting/Subjects: Patients (n = 27) with aggressive B cell lymphomas that relapsed after first- or second-line treatment treated at a single urban academic medical center. Measurements: Participants were administered structured surveys by trained staff to obtain self-report measures of illness understanding (i.e., aggressiveness, terminality, curability) and ACP (i.e., discussions of care preferences, completion of advance directives). Results: The majority of patients reported discussing curability (92.6%), prognosis (77.8%), and treatment goals (88.9%) with their medical team. Yet, less than one-third of patients reported being terminally ill (29.6%) and having incurable disease (22.2%). Most patients had a health care proxy (81.5%) and had decided about do-not-resuscitate status (63%), but the majority had not completed a living will (65.4%) or discussed their care preferences with others (55.6%). Conclusions: The accuracy of lymphoma patients' illness understanding following first-line treatment is difficult to determine due to the potential for cure following transplant. However, this study suggests that a large proportion of patients with advanced B cell lymphomas may underestimate the severity of their illness, despite discussing illness severity with their medical team. Providing patients with information on prognosis, and the ACP process may increase engagement in ACP.

Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience (EMPOWER) among Surrogate Decision-Makers of ICU Patients: study protocol for a randomized controlled trial.

BACKGROUND: Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers, especially their surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients' quality of life and death and dying as well as surrogates' mental health. METHODS: Clinician stakeholder and surrogate participant feedback (n = 15), as well as results from an open trial (n = 10), will be used to refine the intervention, which will then be evaluated through a multisite randomized controlled trial (RCT) (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of post-traumatic stress disorder, prolonged grief disorder, and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at 1 and 3 months from post-intervention assessment. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment. Participant exit interviews will be conducted at the 3-month assessment time point and will be analyzed using qualitative thematic data analysis methods. DISCUSSION: The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03276559 . Retrospectively registered on 8 September 2017.

Suicidal Ideation in Bereavement: A Systematic Review.

Background: Bereavement is associated with impaired mental health, increases in adverse health behaviors, and heightened risk of suicidal ideation, attempts, and death by suicide. The purpose of this literature review was to explore associations between cause of death and suicidal thoughts among bereaved individuals. Our aim was to compare incidence of suicidal ideation by cause of death and identify gaps in this literature to guide future research and clinical intervention. Methods: PRISMA-P guidelines were used to structure an electronic literature search in the PsycINFO, MEDLINE, and Web of Science databases. The search focused on English language studies that were published before February 2019 and sought to compare rates of suicidal ideation among bereaved people who lost a loved one to suicide, accidental overdose, cancer, dementia, cardiovascular disease, and HIV/AIDs. Results: Ten articles were identified with suicide as cause of death, zero articles for accidental overdose, zero articles for cardiovascular disease, eight articles for cancer, one article for dementia, and one article for HIV/AIDs. Given the limited number of articles generated by our search, a formal meta-analysis was not appropriate. However, a comparison of results did suggest that suicide bereavement was associated with the highest rates of suicide ideation (14.1% to 49%). Stigma, isolation, avoidance behaviors, and psychological distress were associated with suicidal thoughts among bereaved individuals, regardless of the deceased's cause of death. Conclusions: Findings of this literature search revealed significant gaps in the literature, especially regarding thoughts of suicide in bereaved survivors of accidental overdose and cardiovascular disease. Results suggest that multiple causes of death are associated with suicidal ideation in bereavement, but that suicide bereavement may be the cause of death associated with the highest risk of suicidal ideation. More research is needed to understand the ways in which cause of death influences prevalence, risk, and protective factors associated with suicidal thoughts among bereaved individuals.

Underdetection and Undertreatment of Dyspnea in Critically Ill Patients.

Rationale: Dyspnea is a common and distressing physical symptom among patients in the ICU and may be underdetected and undertreated. Objectives: To determine the frequency of dyspnea relative to pain, the accuracy of nurses and personal caregiver dyspnea ratings relative to patient-reported dyspnea, and the relationship between nurse-detected dyspnea and treatment. Methods: This was an observational study of patients (n = 138) hospitalized in a medical ICU (MICU). Nurses and patients' personal caregivers at the bedside reported on their perception of patients' symptoms. Measurements and Main Results: Dyspnea was assessed by patients, caregivers, and nurses with a numerical rating scale. Across all three raters, the frequency of moderate to severe dyspnea was similar or greater than that of pain (P < 0.05 for caregiver and nurse ratings). Personal caregivers' ratings of dyspnea had substantial agreement with patient ratings (κ = 0.65, P < 0.001), but nurses' ratings were not significantly related to patient ratings (κ = 0.19, P = 0.39). Nurse detection of moderate to severe pain was significantly associated with opioid treatment (odds ratio, 2.70; 95% confidence interval, 1.10-6.60; P = 0.03); however, nurse detection of moderate to severe dyspnea was not significantly associated with any assessed treatment. Conclusions: Dyspnea was reported at least as frequently as pain among the sampled MICU patients. Personal caregivers had good agreement with patient reports of moderate to severe dyspnea. However, even when detected by nurses, dyspnea appeared to be undertreated. These findings suggest the need for improved detection and treatment of dyspnea in the MICU.

Dying Patient and Family Contributions to Nurse Distress in the ICU.

RATIONALE: Caring for patients at the end of life is emotionally taxing and may contribute to burnout. Nevertheless, little is known about the factors associated with emotional distress in intensive care unit (ICU) nurses. OBJECTIVES: To identify patient and family factors associated with nurses' emotional distress in caring for dying patients in the ICU. METHODS: One hundred nurses who cared for 200 deceased ICU patients at two large academic medical centers in the Northeast United States were interviewed about patients' psychological and physical symptoms, their reactions to those patient experiences (e.g., emotional distress), and perceived factors contributing to their emotional distress. Logistic regression analyses modeled nurses' emotional distress as a function of patient symptoms and care. RESULTS: Patients' overall quality of death (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.31-7.25), suffering (OR, 2.34; CI, 1.03-5.29), and loss of dignity (OR, 2.95; CI, 1.19-7.29) were significantly associated with nurse emotional distress. Some 40.5% (79 of 195) of nurses identified families' fears of patient death, and 34.4% (67 of 195) identified families' unrealistic expectations as contributing to their own emotional distress. CONCLUSIONS: Patients' emotional distress, physical distress, and perceived quality of death are associated with nurse emotional distress. Unrealistic family expectations for the patient may be a source of nurse emotional distress. Improving patients' quality of death, including enhancing their dignity, reducing their suffering, and promoting acceptance of an impending death among family members may improve the emotional health of nurses.

Beyond Pain: Nurses' Assessment of Patient Suffering, Dignity, and Dying in the Intensive Care Unit.

CONTEXT: Deaths in the intensive care unit (ICU) are increasingly common in the U.S., yet little is known about patients' experiences at the end of life in the ICU. OBJECTIVES: The objective of this study was to determine nurse assessment of symptoms experienced, and care received by ICU patients in their final week, and their associations with nurse-perceived suffering and dignity. METHODS: From September 2015 to March 2017, nurses who cared for 200 ICU patients who died were interviewed about physical and psychosocial dimensions of patients' experiences. Medical chart abstraction was used to document baseline patient characteristics and care. RESULTS: The patient sample was 61% males, 70.2% whites, and on average 66.9 (SD 15.1) years old. Nurses reported that 40.9% of patients suffered severely and 33.1% experienced severe loss of dignity. The most common symptoms perceived to contribute to suffering and loss of dignity included trouble breathing (44.0%), edema (41.9%), and loss of control of limbs (36.1%). Most (n = 9) remained significantly (P < 0.05) associated with suffering, after adjusting for physical pain, including fever/chills, fatigue, and edema. Most patients received vasopressors and mechanical ventilation. Renal replacement therapy was significantly (<0.05) associated with severe suffering (adjusted odds ratio [AOR] 2.53) and loss of dignity (AOR 3.15). Use of feeding tube was associated with severe loss of dignity (AOR 3.12). CONCLUSION: Dying ICU patients are perceived by nurses to experience extreme indignities and suffer beyond physical pain. Attention to symptoms such as dyspnea and edema may improve the quality of death in the ICU.

Socio-economic factors affect the outcome of soft tissue sarcoma: an analysis of SEER data.

BACKGROUND: This study analyzed whether socio-economic factors affect the cause specific survival of soft tissue sarcoma (STS). METHODS: Surveillance, Epidemiology and End Results (SEER) soft tissue sarcoma (STS) data were used to identify potential socio-economic disparities in outcome. Time to cause specific death was computed with Kaplan-Meier analysis. Kolmogorov-Smirnov tests and Cox proportional hazard analysis were used for univariate and multivariate tests, respectively. The areas under the receiver operating curve were computed for predictors for comparison. RESULTS: There were 42,016 patients diagnosed STS from 1973 to 2009. The mean follow up time (S.D.) was 66.6 (81.3) months. Stage, site, grade were significant predictors by univariate tests. Race and rural-urban residence were also important predictors of outcome. These five factors were all statistically significant with Cox analysis. Rural and African-American patients had a 3-4% disadvantage in cause specific survival. CONCLUSIONS: Socio-economic factors influence cause specific survival of soft tissue sarcoma. Ensuring access to cancer care may eliminate the outcome disparities.

Association between urinary cadmium and all cause, all cancer and prostate cancer specific mortalities for men: an analysis of national health and nutrition examination survey (NHANES III) data.

AIM: This study employed public use National Health and Nutrition Examination Survey (NHANES III) data to investigate the association between urinary cadmium (UDPSI) and all cause, all cancer and prostate cancer mortalities in men. PATIENTS AND METHODS: NHANES III household adult, laboratory and mortality data were merged. The sampling weight used was WTPFEX6, with SDPPSU6 applied for the probability sampling unit and SDPSTRA6 to designate the strata for the survey analysis. RESULTS: For prostate cancer death, the significant univariates were UDPSI, age, weight, and drinking. Under multivariate logistic regression, the significant covariates were age and weight. For all cause mortality in men, the significant covariates were UDPSI, age, and poverty income ratio. For all cancer mortality in men, the significant covariates were UDPSI, age, black and Mexican race. CONCLUSIONS: UDPSI was a predictor of all cause and all cancer mortalities in men as well as prostate cancer mortality.

Antiviral prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection.

Chronic hepatitis B virus (HBV) carriers are at considerable risk of reactivation of HBV infection when undergoing chemotherapy or immunosuppressive therapy. Complications of HBV reactivation, including asymptomatic elevation of HBV DNA levels, acute hepatitis, acute liver failure, and delays or dose reductions in chemotherapy, are avoidable with appropriate prophylactic oral antiviral therapy. This article reviews evidence for and presents a grade A recommendation supporting primary prophylaxis among HBV carriers with lamivudine. The dose and duration of prophylaxis, risk of lamivudine resistance, and future directions of prophylactic therapy for HBV reactivation during chemotherapy are discussed. Recommendations are suggested based on expert opinion for prophylaxis with the combination of lamivudine plus adefovir or with entecavir as alternative antiviral strategies that substantially reduce or avoid the risk of HBV antiviral drug resistance.

Short- and long-term outcomes of standardized EMR of nonpolypoid (flat and depressed) colorectal lesions > or = 1 cm (with video).

BACKGROUND: Nonpolypoid (flat and depressed) colorectal lesions are increasingly recognized. Their endoscopic removal requires specialized EMR techniques, which are more complex to perform. Outcomes data on EMR of nonpolypoid neoplasms in the United States is needed. OBJECTIVE: To determine the safety and efficacy of EMR in the resection of nonpolypoid colorectal neoplasms > or = 1 cm. DESIGN: Retrospective analysis. SETTING: Veterans Affairs Palo Alto Health Care System. PATIENTS: Over a 5-year period, patients who underwent EMR for nonpolypoid colorectal lesions > or = 1 cm. INTERVENTION: A standardized approach that included lesion assessment, classification, inject-and-cut EMR technique, reassessment, and treatment of residual tissue. MAIN OUTCOME MEASUREMENTS: Complete resection, bleeding, perforation, development of advanced cancer, and death. RESULTS: A total of 100 patients (125 lesions: 117 flat and 8 depressed) met inclusion criteria. Mean size was 16.7 +/- 7 mm (range, 10-50 mm). Histology included 5 submucosal invasive cancers, 5 carcinomas in situ, and 91 adenomas. Thirty-eight patients (48 lesions) did not receive surveillance colonoscopy: 8 had surgery, 16 had hyperplastic pathology, and 14 did not undergo repeat examination. Surveillance colonoscopy was performed on 62 patients (77 lesions). Complete resection was achieved in 100% of these patients after 1 to 3 surveillance colonoscopies. All patients received follow-up (mean [standard deviation] = 4.5 +/- 1.4 years); none developed colorectal cancer or metastasis. LIMITATIONS: Single endoscopist, retrospective study. CONCLUSIONS: A standardized EMR (inject-and-cut) technique is a safe and curative treatment option in nonpolypoid colorectal neoplasms (> or = 1 cm) in the United States.

Efficacy and safety of CyberKnife radiosurgery for acromegaly.

OBJECTIVE: Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly. DESIGN: A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital. PATIENTS: Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK). MEASUREMENTS: Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed. RESULTS: After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism. CONCLUSIONS: CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly.

Isolated Langerhans cell histiocytosis in an adult with central diabetes insipidus: case report and review of literature.

OBJECTIVE: To report a case of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) in a patient with two distinct neuroendocrine tumors and to highlight the difficulties of establishing the differential diagnosis of EAS. METHODS: We describe the clinical presentation of the current case, discuss its management, and report the results of molecular studies undertaken to determine whether the two tumors had a common origin. RESULTS: A 52-year-old woman presented with obvious features of Cushing's syndrome. Findings on hormonal evaluation were consistent with EAS. Pituitary magnetic resonance imaging revealed normal findings. Computed tomographic imaging disclosed two masses, one in the lung and one in the pancreas. Somatostatin receptor scintigraphy showed uptake only in the pancreatic mass, which was surgically removed. It was a well-differentiated neuroendocrine tumor, with negative immunostaining for ACTH. Hypercortisolemia did not resolve after removal of the pancreatic tumor. The lung mass was subsequently excised, and pathology examination showed a carcinoid tumor with immunostaining for ACTH. Thereafter, plasma ACTH became immeasurable. The two tumors had similar patterns of X-chromosome inactivation; thus, whether they arose independently could be neither confirmed nor excluded. CONCLUSION: This case demonstrates that, in the presence of more than one neuroendocrine tumor, somatostatin receptor scintigraphy may misguide the decision regarding the appropriate surgical course in patients with EAS, and it highlights the need for accurate studies to determine the source of ACTH in patients with EAS.