Showing papers by "David Spiegel published in 2011"

Decrease in Depression Symptoms Is Associated With Longer Survival in Patients With Metastatic Breast Cancer: A Secondary Analysis

Abstract: Purpose Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival. Methods In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies–Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival.

Classification of trauma and stressor-related disorders in DSM-5.

Abstract: This review examines the question of whether there should be a cluster of disorders, including the adjustment disorders (ADs), acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and the dissociative disorders (DDs), in a section devoted to abnormal responses to stress and trauma in the DSM-5. Environmental risk factors, including the individual's developmental experience, would thus become a major diagnostic consideration. The relationship of these disorders to one another is examined and also their relationship to other anxiety disorders to determine whether they are better grouped with anxiety disorders or a new specific grouping of trauma and stressor-related disorders. First how stress responses have been classified since DSM-III is reviewed. The major focus is on PTSD because it has received the most attention, regarding its proper placement among the psychiatric diagnoses. It is discussed whether PTSD should be considered an anxiety disorder, a stress-induced fear circuitry disorder, an internalizing disorder, or a trauma and stressor-related disorder. Then, ASD, AD, and DD are considered from a similar perspective. Evidence is examined pro and con, and a conclsion is offered recommending inclusion of this cluster of disorders in a section entitled "Trauma and Stressor-Related Disorders." The recommendation to shift ASD and PTSD out of the anxiety disorders section reflects increased recognition of trauma as a precipitant, emphasizing common etiology over common phenomenology. Similar considerations are addressed with regard to AD and DD.

A review of acute stress disorder in DSM-5.

Abstract: Acute stress disorder (ASD) was introduced into DSM-IV to describe acute stress reactions (ASRs) that occur in the initial month after exposure to a traumatic event and before the possibility of diagnosing posttraumatic stress disorder (PTSD), and to identify trauma survivors in the acute phase who are high risk for PTSD. This review considers ASD in relation to other diagnostic approaches to acute stress responses, critiques the evidence of the predictive power of ASD, and discusses ASD in relation to Adjustment Disorder. The evidence suggests that ASD does not adequately identify most people who develop PTSD. This review presents a number of options and preliminary considerations to be considered for DSM-5. It is proposed that ASD be limited to describing severe ASRs (that are not necessarily precursors of PTSD). The evidence suggests that the current emphasis on dissociation may be overly restrictive and does not recognize the heterogeneity of early posttraumatic stress responses. It is proposed that ASD may be better conceptualized as the severity of acute stress responses that does not require specific clusters to be present.

Mind Matters in Cancer Survival

Abstract: The field of psycho-oncology is hung up on the hyphen in its name. How do we understand the link between mind and body? Is that hyphen merely an arrow to the left, indicating that cancer in the body affects the mind? Can it be an arrow to the right as well, mind affecting the course of cancer? We know that social support affects survival, 1 including that with cancer.2 Also, people tend to die after rather than before their birthdays and major holidays.3,4 Depression worsens survival outcome with cancer.5,6 Yet we have been understandably delicate about mind-body influence, not wanting to claim too much, or to provide unwitting support for overstated claims that wishing away cancer or picturing white blood cells killing cancer cells would actually do it. That arrow to the right is a connection, not a superhighway. Yet in our desire to be respected members of the oncology community we have often minimized a natural ally in the battle against cancer – the patient’s physiological stress coping mechanisms. Even at the end of life, helping patients face death, make informed decisions about level of care, and controlling pain and distress is not only humane but appears to be medically more effective than simply carrying on with intensive anti-cancer treatment alone.7 A recent randomized clinical trial of palliative care for non-small cell lung cancer patients8 makes that case strongly. The authors reported a clear but apparently paradoxical finding: “Despite receiving less aggressive end-of-life care, patients in the palliative care group had significantly longer survival than those in the standard care group (median survival, 11.65 vs. 8.9 months; P=0.02)” (p. 738). Those randomized to palliative care became less depressed as well. The palliative care condition consisted of an average of 4 visits that focused on choices about resuscitation preferences, pain control, and quality of life. The study suggests that at the end of life the most aggressive treatments may not be the most effective, not only psychologically, but also medically. How could living better at the end of life lead to living longer? When we began to investigate the effects of support groups for people with cancer in the 1970’s, we and others were concerned that watching others die of the same disease would demoralize patients, and might even hasten their death. We evaluated mood and discussion content minute-by-minute to determine whether bad news about other group members was despressogenic. We found that these women with advanced breast cancer talked more seriously about death and dying, but showed no signs of depression or panic.9 Indeed our initial studies, confirmed by many others, indicated that we reduced distress and pain.10,11 But now the results are showing something more profound than reduced distress and pain or feeling better, they are showing that facing death better helps people to live longer with cancer. We reported in 1989 the results of a clinical trial demonstrating that women with metastatic breast cancer randomized to a year of weekly group therapy lived 18 months longer than control patients, and that the difference was not due to differences in initial disease severity or subsequent chemo- and radiotherapy. The result of this 10 year study, cited at last count on Google Scholar 2,222 times, was first greeted with great excitement and later skepticism. Now 21 years later, the findings are being confirmed. A decade later we conducted an IRB-approved replication study that showed no overall effect of a similar group therapy on breast cancer survival, but a significant interaction with tumor type, such that those with estrogen receptor negative cancers who were randomized to group therapy lived significantly longer than did ER negative patients receiving standard care alone.12 While this is a clear disconfirmation of the hypothesis that facing death together could improve survival, major advances in hormonal and chemotherapies had improved overall survival for women with metastatic breast cancer in the interim.13 However, women with ER negative tumors were largely excluded from the benefit of hormonal treatments, which could account for the difference in findings.13 Further support for this explanation comes from the fact that overall survival of our cohorts of women with metastatic breast cancer has improved over the decades (See Figure 1). Figure 1 Comparison of Survival across 3 Spiegel Metastatic Breast Cancer Studies More recently, a randomized trial of psychoeducational groups for women with primary breast cancer found both significantly reduced rates of relapse and longer survival. 14,15 In addition to this, our original study16, and the recent palliative care study referred to above,8 three other published randomized psychotherapy trials17–20 and one matched cohort trial21 have reported that psychosocial treatment for patients with a variety of cancers enhanced both psychological and survival outcome (See Table 1). However, six other published studies, 22–27 four involving breast cancer patients,24–27 found no survival benefit for those treated with psychotherapy. (See Table 2) Three of these six studies reported no emotional benefit from the interventions,23–25 making enhanced survival unlikely. In another major multicenter replication trial,26 Supportive-Expressive Group Psychotherapy did significantly reduce depression, but did not improve survival. However, the odd thing about this study is that the women randomized to treatment were more depressed to begin with, making their medical prognosis worse at baseline.6 Furthermore, the outcome of all of these studies is not random: no studies show that gathering cancer patients together in groups and directing their attention to emotional expression and mortality shortens survival.28 Table 1 Randomized Trials Showing Survival Benefit from Psychotherapy Table 2 Randomized Trials Showing No Survival Benefit of Psychotherapy The most provocative but also discordant results have occurred in studies of women with breast cancer, where treatment for ER positive and also human epidermal growth factor receptor 2-positive (HER2+) tumors has improved substantially. Among cancers with poorer medical prognosis, such as ER negative breast cancer, malignant melanoma, non-small cell lung cancer, leukemia, and gastrointestinal cancers, intensive emotional support seems to extend survival. Patients who benefit from a targeted and highly effective chemotherapeutic approach obtain less apparent survival benefit from emotional support than do those with less effective biomedical interventions. Thus, especially in the palliative settling in which aggressive anti-tumor treatments are less efficacious, supportive approaches become more useful. One would think that psychosocial support would have the least biomedical effect in more advanced cancers, and yet our original observation involved women with metastatic breast cancer. By the time someone dies with cancer, they usually have a kilogram of tumor in their body. Yet this may be when the body’s resources for coping with physiological as well as psychological stress matter the most.

A comparison of trauma-focused and present-focused group therapy for survivors of childhood sexual abuse: A randomized controlled trial.

Abstract: This randomized controlled trial compared trauma-focused group psychotherapy (TFGT) with presentfocused group psychotherapy (PFGT) and a waitlist condition for 166 survivors of childhood sexual abuse who were at risk for HIV infection. Primary outcomes included risk for HIV infection (based on sexual revictimization, drug and alcohol use, and risky sex) and posttraumatic stress disorder (PTSD) symptoms. It was hypothesized that TFGT would be superior to the PFGT and waitlist conditions and that receiving either treatment (combining both TFGT and PFGT) would be superior to no treatment (waitlist condition). Intention-to-treat analyses for HIV risk found that all conditions reduced risk; however, there was no effect for condition on HIV risk. Intention-to-treat analyses for PTSD symptoms found a reduction for all conditions. There was no advantage for either TFGT or PFGT in reducing PTSD symptoms; however, there was an effect for treatment compared with the waitlist condition. On secondary outcomes, there was a greater reduction in anger for TFGT compared with PFGT, and when comparing treatment with the waitlist condition, there was a greater reduction in hyperarousal, reexperiencing, anger, and impaired self-reference for the treatment condition. Adequate dose analyses generally confirmed the intention-to-treat findings and additionally found that treatment led to reductions in depression, dissociation, and sexual concerns.

Quantifying surgical and anesthetic availability at primary health facilities in Mongolia.

Abstract: Significant barriers limit the safe and timely provision of surgical and anaesthetic care in low- and middle-income countries. Nearly one-half of Mongolia’s population resides in rural areas where the austere geography makes travel for adequate surgical care very difficult. Our goal was to characterize the availability of surgical and anaesthetic services, in terms of infrastructure capability, physical resources (supplies and equipment), and human resources for health at primary level health facilities in Mongolia. A situational analysis of the capacity to deliver emergency and essential surgical care (EESC) was performed in a nonrandom sample of 44 primary health facilities throughout Mongolia. Significant shortfalls were noted in the capacity to deliver surgical and anesthetic services. Deficiencies in infrastructure and supplies were common, and there were no trained surgeons or anaesthesiologists at any of the health facilities sampled. Most procedures were performed by general doctors and paraprofessionals, and occasionally visiting surgeons from higher levels of the health system. While basic interventions such as suturing or abscess drainage were commonly performed, the availability of many essential interventions was absent at a significant number of facilities. This situational analysis of the availability of essential surgical and anesthetic services identified significant deficiencies in infrastructure, supplies, and equipment, as well as a lack of human resources at the primary referral level facilities in Mongolia. Given the significant travel distances to secondary level facilities for the majority of the rural population, there is an urgent need to strengthen the delivery of essential surgical and anaesthetic services at the primary referral level (soum and intersoum). This will require a multidisciplinary, multi-sectoral effort aimed to improve infrastructure, procure and maintain essential equipment and supplies, and train appropriate health professionals.

Magnesium in chronic kidney disease: unanswered questions.

Abstract: Background: Magnesium ion is critical for life and is integrally involved in cellular function and a key component of normal bone mineral. In health, the kidneys, gastrointestinal tract and bone are responsible for maintaining serum magnesium concentrations in the normal range and magnesium balance. Most clinical disorders involving magnesium, other than chronic kidney disease (CKD), result in hypomagnesemia, either from gastrointestinal or kidney losses. CKD and particularly end-stage kidney disease is the only clinical condition where sustained hypermagnesemia may occur and net magnesium balance may be positive. Methods: This review will focus on normal magnesium homeostasis and review the literature in CKD with a particular focus on end-stage kidney disease and the potential role of magnesium as a phosphate binder and in cardiovascular and bone health. Results: A number of small to medium-size interventional trials have shown that magnesium-based compounds can serve as effective phosphate binders. Observational studies suggest that higher serum magnesium concentrations in dialysis patients may improve survival and may slow the progression of vascular calcification. While a few small prospective trials support these findings, no large or long-term studies are available. Conclusions: Magnesium balance remains poorly understood in patients with end-stage kidney disease. While observational and small randomized trials suggest that exogenous administration may be useful as a phosphate binder and may have protective cardiovascular effects in terms of both arrhythmias and vascular calcification, large randomized trials are needed to test these hypotheses.

A Chemically Induced Vaccine Strategy for Prostate Cancer

Abstract: Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings.

The Treatment of Low-Energy Femoral Shaft Fractures: A Prospective Study Comparing the “Walking Spica” with the Traditional Spica Cast

Abstract: Background: A single-leg, walking hip spica cast has been shown to be a safe and effective treatment for a low-energy femoral shaft fracture in young children. We designed a prospective cohort trial comparing walking and traditional hip spica casting to determine whether a walking hip spica cast was superior to a traditional hip spica cast following a low-energy femoral shaft fracture in children one to six years old. Methods: We studied forty-five consecutive low-energy femoral shaft fractures during a three-year period in children one to six years old. Three surgeons treated their patients with a walking hip spica cast, and three other surgeons treated their patients with a traditional spica cast. Complications and subsequent interventions were recorded prospectively. Caregivers were asked to complete the validated Impact on Family Scale as well as a ten-item questionnaire developed by the authors at the time of cast removal. Results: Forty-five patients with a low-energy fracture were enrolled in the study. Nineteen patients were treated with a walking hip spica cast and twenty-six, with a traditional hip spica cast. The two cohorts were similar with respect to age, length of hospital stay, time to initial callus formation, and time to fracture union. Two children treated with a traditional hip spica cast and no children in the walking hip spica group returned to the operating room for the treatment of spontaneous loss of fracture reduction. Five of the nineteen children treated with a walking hip spica cast and one of the twenty-six treated with a traditional hip spica cast required wedge adjustment of the cast in the clinic to treat fracture malalignment (p = 0.04). One patient treated with a walking hip spica cast required repeat reduction in the operating room because of overcorrection during wedge adjustment. The malunion rate did not differ significantly between the groups (three of twenty-six in the traditional hip spica group compared with none of nineteen in the walking hip spica group). All patients treated with a walking hip spica cast were able to crawl in the cast, and 71% (twelve of seventeen) were able to walk. Use of the traditional hip spica cast resulted in a significantly greater care burden for the family as measured with use of the Impact on Family Scale (43.3 for the traditional hip spica group compared with 35.6 for the walking hip spica group, p = 0.04). Insurance-funded ambulance transportation was needed for eleven of the twenty-six patients treated with a traditional hip spica cast compared with none of the nineteen patients treated with a walking hip spica cast (p = 0.001). Conclusions: The walking hip spica cast and the traditional hip spica cast resulted in similar orthopaedic outcomes, and the walking hip spica cast resulted in a lower care burden for the family. Surgeons and families should be aware that use of a walking hip spica cast rather than a traditional hip spica cast may be associated with a greater likelihood that wedge adjustment of the cast will be necessary to treat fracture malalignment. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

A Review of Acute Stress Disorder in DSM-5

Abstract: Acute stress disorder (ASD) was introduced into DSM-IV to describe acute stress reactions (ASRs) that occur in the initial month after exposure to a traumatic event and before the possibility of diagnosing posttraumatic stress disorder (PTSD), and to identify trauma survivors in the acute phase who are high risk for PTSD. This review considers ASD in relation to other diagnostic approaches to acute stress responses, critiques the evidence of the predictive power of ASD, and discusses ASD in relation to Adjustment Disorder. The evidence suggests that ASD does not adequately identify most people who develop PTSD. This review presents a number of options and preliminary considerations to be considered for DSM-5. It is proposed that ASD be limited to describing severe ASRs (that are not necessarily precursors of PTSD). The evidence suggests that the current emphasis on dissociation may be overly restrictive and does not recognize the heterogeneity of early posttraumatic stress responses. It is proposed that A...

Cortisol outcomes among caucasian and latina/hispanic women caring for a family member with dementia: a preliminary examination of psychosocial predictors and effects of a psychoeducational intervention

Abstract: A host of interventions are now known to be helpful to alleviate subjective distress and improve well-being in dementia caregivers. However, few intervention studies have focused on measures of physical health, and none have examined cortisol as an outcome—despite the fact that cortisol is regarded as a crucial biological intermediary by which chronic stress leads to disease. In this study, we examined demographic and psychosocial factors as predictors of salivary cortisol at a baseline assessment, among a sample of 175 Latino/Hispanic and Caucasian women caring for a family member with dementia. We also examined the influence of a cognitive–behaviour-based psychoeducational intervention (Coping with Caregiving) on cortisol at a post-treatment assessment, compared with a minimal support condition. Results revealed that caregivers with high intensity caregiving situations, characterized by long hours of care and co-residence with the care recipient, tended to have less adaptive cortisol patterns. However, these ‘at-risk’ caregivers benefited most from the Coping with Caregiving intervention and had more normal cortisol patterns at post-treatment, compared with caregivers in the control condition. Copyright © 2011 John Wiley & Sons, Ltd.

Racial disparities in traumatic stress in prostate cancer patients: secondary analysis of a National URCC CCOP Study of 317 men

Abstract: African American men have the highest rates of prostate cancer of any racial group, but very little is known about the psychological functioning of African American men in response to prostate cancer diagnosis and treatment. In this secondary analysis of a national trial testing a psychological intervention for prostate cancer patients, we report on the traumatic stress symptoms of African American and non-African American men. This analysis includes 317 men (African American: n = 30, 9%; non-African American: n = 287, 91%) who were enrolled in the intervention trial, which included 12 weeks of group psychotherapy and 24 months of follow-up. Using mixed model analysis, total score on the Impact of Events Scale (IES) and its Intrusion and Avoidance subscales were examined to determine mean differences in traumatic stress across all time points (0, 3, 6, 12, 18, and 24 months). In an additional analysis, relevant psychosocial, demographic, and clinical variables were added to the model. Results showed significantly higher levels of traumatic stress for African American men compared to non-African American men in all models independently of the intervention arm, demographics, and relevant clinical variables. African Americans also had a consistently higher prevalence of clinically significant traumatic stress symptoms (defined as IES total score ≥27). These elevations remained across all time points over 24 months. This is the first study to show a racial disparity in traumatic stress specifically as an aspect of overall psychological adjustment to prostate cancer. Recommendations are made for appropriate assessment, referral, and treatment of psychological distress in this vulnerable population.

Perceived Benefits and Psychosocial Outcomes of a Brief Existential Family Intervention for Cancer Patients/Survivors:

Abstract: This study assessed a range of benefits from participation in a brief existential intervention consisting of a semi-structured videotaped interview with cancer patients and their families designed to illuminate a life legacy for the family (the Life Tape Project [LTP]). Results indicated the majority reported intervention-specific benefits, especially in the areas of symbolic immortality (passing on personal values and philosophy), self-reflection and growth, and improved family cohesion and communication. Participants, particularly those who had perceived their cancer as a threat of death, serious injury, or threat to their physical integrity, and responded with intense fear or helplessness, also reported more general reductions in mood disturbance, improvements in aspects of well-being (including overall quality of life), satisfaction with the understanding they received, and enhanced cancer-related posttraumatic growth. In short, the LTP is a brief, inexpensive, existential intervention that can yield ...

Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus

Abstract: The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM- HI's, function through orthogonal pathways, by inhibiting the gpl20-CD4 interaction, and by recruiting anti-DNP antibodies to gpl20-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gpl20 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gpl20-expressing cells. Compounds and methods are described herein.