Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial.

CONTEXT: Tissue plasminogen activator is the only thrombolytic agent approved in the United States for treatment of acute ischemic stroke, and has limitations. Aptiganel hydrochloride is a novel and selective ligand for the ion-channel site of the N-methyl-D-aspartate receptor-channel complex and a promising neuroprotective agent in animal models of focal brain ischemia. OBJECTIVE: To determine whether aptiganel improves the clinical outcome for acute ischemic stroke patients. DESIGN: Nested phase 2/phase 3 randomized controlled trial conducted between July 1996 and September 1997. SETTING: One hundred fifty-six medical centers in the United States, Canada, Australia, South Africa, England, and Scotland. PARTICIPANTS: A total of 628 patients with hemispheric ischemic stroke (50.3% male; mean age, 71.5 years). INTERVENTIONS: Patients were randomly assigned within 6 hours of stroke to receive 1 of 3 treatment regimens: high-dose aptiganel (5-mg bolus followed by 0.75 mg/h for 12 hours; n = 214); low-dose aptiganel (3-mg bolus followed by 0.5 mg/h for 12 hours; n = 200); or placebo (n = 214). MAIN OUTCOME MEASURES: The primary efficacy end point was the Modified Rankin Scale score at 90 days after stroke onset. Secondary end points included mortality and change in National Institutes of Health (NIH) Stroke Scale score at 7 days after stroke. RESULTS: The trial was suspended by the sponsor and the independent data and safety monitoring board because of both a lack of efficacy and a potential imbalance in mortality. There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06). Mortality in the low-dose aptiganel group was 22.5% (P =.39 vs placebo). CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.

Bone marrow transplantation: support of the patient and his/her family.

Bone marrow transplantation (BMT) has evolved over the last decade from a controversial research procedure to a standard therapeutic modality, becoming an important innovative treatment for hematological malignancies, solid tumors, immunodeficiency diseases and metabolic disorders. Historically in research and clinical literature, the BMT procedure is divided into several stages, each accompanied by particular emotional tones and psychological issues. In providing care for transplant recipients, donors, and families, caregivers must be familiar with the psychological stages of the procedure, the psychological themes such as body image, and the patient's mechanisms of coping with the stress of such protocols. BMT's complex regimens of high-dose chemotherapy and total-body irradiation, germ-free environments, graft-versus-host disease, and total parenteral nutrition can precipitate significant psychological sequelae in some patients with acute and long-term consequences. In response to their illness, transplant patients may also develop emotional disturbances of anxiety, depression, agitation, and non-compliance. This paper will address the psychological care of the patient, donor and family from pre-BMT consultation, through informed consent, hospitalization and convalescence. Various psychotherapeutic, pharmacological and behavioral interventions will be briefly described. Finally, areas of research in quality of life after BMT and factors that may predict BMT adjustment and outcome will be explored. We hope this brief paper will familiarize the reader with this psychologically intriguing field and will provide a departure point for future reading, study, research, and patient/family care.

Lives in a balance: perceived family functioning and the psychosocial adjustment of adolescent cancer survivors.

Childhood cancer patients have a greater likelihood of long-term survival than ever before. This study examined both the perceived family functioning of adolescents who had successfully completed treatment for pediatric cancer and the relationship between family functioning and post-treatment adjustment. Eighty-eight adolescent survivors of hematologic malignancies were assessed regarding their family functioning, mental health, self-esteem, global competence, and problem behaviors. Contrary to expectations about the influence of cancer on these families, adolescent cancer survivors reported lower levels of family cohesion than the normative sample of healthy adolescents and their families. While current age, gender, age at diagnosis, and time since treatment completion were generally not associated with adolescents' adjustment, perceived family cohesion and adaptability were strongly related to post-treatment psychological adjustment.

Long-term psychological adjustment of acute leukemia survivors: impact of bone marrow transplantation versus conventional chemotherapy.

As increasing numbers of patients survive acute leukemia, it has become important to study the long-term psychological and social adjustment of patients who have successfully completed their leukemia treatment. An important aspect of this inquiry is comparing the long-term psychosocial impact of two treatments for acute leukemia: chemotherapy and bone marrow transplantation. This study examines the psychosocial adjustment of 70 acute leukemia survivors who received either conventional chemotherapy alone (N = 49) or chemotherapy and an allogeneic bone marrow transplantation (N = 21). At the time of assessment, patients were an average of 31 years old, had completed treatment 5 years ago and were physically healthy (mean Karnofsky score of 97). Psychometrically sound, self-report questionnaires assessed global and illness-specific psychological distress and social adjustment. Despite the additional strain and longer hospitalization associated with bone marrow transplantation, there was no difference found between BMT survivors and those treated with conventional chemotherapy alone in current psychological and social functioning. Both groups, however, had significantly greater levels of distress than that observed in normal physically healthy samples. The distress neither reached a psychiatric threshold nor significantly interfered with social adjustment. These data suggest that, irrespective of treatment, acute leukemia survivors experience overall psychological well-being and social adjustment even though they still carry a psychological burden that should be recognized in their continuing follow-up and care.

Long-term psychosexual adjustment of acute leukemia survivors: impact of marrow transplantation versus conventional chemotherapy.

Psychosexual sequelae associated with surviving acute leukemia treated with conventional chemotherapy or with chemotherapy followed by bone marrow transplantation (BMT) were investigated in 70 patients who were off treatment for at least 1 year. Assessment of psychosexual function included frequency of sexual activity, satisfaction, body image, gender role identity, and adjustment in sexual relations. No differences between BMT and conventional chemotherapy survivors were found on any of these measures, despite the high probability of gonadal impairment with BMT. Compared with physically healthy norms, women survivors generally reported decreased sexual frequency and satisfaction, whereas both men and women survivors reported poorer body image. Longer time since completing cancer treatment predicted greater frequency of sexual activity in women but poorer body image for both men and women. Those survivors who reported decreased sexual frequency, satisfaction, and poorer body image reported greater psychological distress and decreased energy. Results indicate that psychosexual sequelae in survivors of leukemia occur frequently and warrant intensive investigation, particularly to address the need for an intervention in those most distressed.

Psychosocial correlates of physician-patient communication at time of informed consent for bone marrow transplantation.

In obtaining informed consent for bone marrow transplantation (BMT) oncologist-investigators may feel that they engender emotional distress in patients due to the disclosure of potentially lethal complications associated with BMT. However, little is known regarding the psychological profile of BMT patients at the time of informed consent or what impact the consent process has upon the physician-patient relationship. The purpose of this study was to assess (1) the psychological symptom profile of patients consenting to BMT and (2) the relationship of behavioral and psychological factors to patients' perceptions of the quality of communication between physician and patient. The results indicated that adult BMT patients experienced significant psychological distress at the time at which they provided written consent for BMT. Two factors were positively related to perceived quality of communication between physician and patient: problem-focused coping style and perceived autonomy in decision making. These findings are interpreted in relation to the goals of informed consent and its implications for the physician-patient relationship.

Psychological distress in parents consenting to child's bone marrow transplantation.

The purpose of this study was to determine the nature and prevalence of the psychological symptomatology in parents of children undergoing bone marrow transplantation (BMT) and to investigate the manner in which certain psychosocial factors are related to parental distress associated with the informed consent process. A total of 61 parents (46 mothers and 15 fathers) were assessed with respect to psychological distress, coping styles, quality of physician-patient communication, and recall of BMT information after providing written consent for their child to have BMT. Forty-seven percent of fathers and 60% of mothers exhibited significant psychological distress of a generalized nature. Mothers exhibited a broader range of specific psychological symptomatology and more severe levels of depression and phobic anxiety than did fathers. The level of parents' distress was unrelated to characteristics of their child's disease or treatment milieu, or to parents' recall of BMT information. However, emotional coping was positively related to psychological distress whereas the quality of the communication between physician and parent was inversely related. The findings from this study suggest that approximately 50% of all parents could benefit from psychological interventions which promote the efficient utilization of coping strategies and highlight the importance of the nature of the communication style used by oncologist-investigators in obtaining informed consent.

Anticipatory immune suppression and nausea in women receiving cyclic chemotherapy for ovarian cancer.

Nausea and immune function were assessed in 20 cancer patients in the hospital prior to chemotherapy and compared with assessments conducted at home. Proliferative responses to T-cell mitogens were lower for cells isolated from hospital blood samples than for home samples obtained several days earlier. Patients also experienced increased nausea in the hospital. Hierarchical multiple regression analyses indicated that decreased immune function in the hospital was not related to increased anxiety. The observed anticipatory immune suppression is consistent with the hypothesis that chemotherapy patients may develop conditioned immune suppression as well as conditioned nausea after repeated pairings of hospital stimuli with the emetic and immunosuppressive effects of chemotherapy.

Psychiatric aspects of adult leukemia.

This report has discussed the normal psychological responses associated with diagnosis and treatment of leukemia, specific psychological disorders that are encountered in the context of treatment, and psychological issues that develop after definitive treatment as patients become survivors from leukemia. Psychopharmacologic and psychotherapeutic strategies to treat the specific disorders of anxiety, depression, and delirium have been outlined. Similarly, survival issues have been considered as an ever-growing number of patients are cured of leukemia.

Surviving hematological malignancies: stress responses and predicting psychological adjustment.

Within the adolescent survivor sample, the psychosocial response of having been diagnosed and successfully treated for cancer is not universal as evidenced by the variability in psychosocial adjustment. Data from the MHI suggests that adolescent cancer survivors do experience more global psychological distress than a comparison group of healthy adolescents. In addition, the majority of these patients reported persistent, intrusive thoughts about their illness and its treatment. Conversely, the adolescent cancer survivors did not differ from a normative sample on social competence, manifestation of problems behaviors, or school achievement. Thus, our data suggest that adjustment in this population is multi-dimensional with variability. While they are functioning quite adequately at school and in social situation, they continue to experience heightened and persistent distress of both a global and illness-specific quality. A number of factors that are conducive to psychosocial intervention appear to be related to adjustment. Family communication and family cohesion were significantly related to the mental health of the adolescent survivors, suggesting a need to further explore the family context of adolescent adjustment. The present work also represents the first attempt to directly examine the psychosocial functioning of young adult, acute leukemia survivors. When compared with normative samples of nonpatients, these survivors (taken as a whole group), reported heightened levels on several indicators of psychological distress. While not entirely consistent across different psychological measures, these young people were generally one standard deviation above the mean for psychological distress. But when compared to normative samples of psychiatric outpatients, our survivors reported significantly less psychological distress. For instance, leukemia survivors reported less intrusive and avoidant cognitions associated with the stressor of being diagnosed and treated for cancer than those associated with patients experiencing traumatic stress disorders. In aggregate, these findings again suggest that the psychosocial adjustment of leukemia survivors is quite variable. Finally, while group comparisons shed light on the psychosocial functioning of leukemia survivors, in general, wide variability in psychosocial adjustment may mask identification of a cohort of cancer survivors most at-risk for psychosocial dysfunction. Sociodemographic, disease/treatment and psychological distress variables only partially explain this variability. The findings from our data suggest several clinical recommendations. First, the prevalence of persistent, psychiatric comorbidity is quite low among long-term survivors of hematologic malignancies survivors. Second, if survivors do experience some psychological distress, usually, it is of non-psychopathological proportions.(ABSTRACT TRUNCATED AT 400 WORDS)

Psychosocial issues in the diagnosis and management of cancer cachexia and anorexia.

Anorexia with its associated decreased food intake and weight loss is a common and profoundly important symptom in cancer, and one which has at times a psychological as well as physical component. When it is physical in origin it may be caused directly or indirectly by the disease process or treatment. Most poorly understood is the anorexia-cachexia syndrome of advanced disease. Psychological causes often reflect anxiety about cancer, its possible progression, depression, anticipatory phenomena, and learned food adversions. Pre-existing psychiatric disorders, especially anorexia nervosa or paranoid states, can substantially complicate cancer treatment. Learned food aversions, which can further restrict limited intake, have been demonstrated in children receiving chemotherapy and may also contribute to aversions of specific foods seen among adult patients after chemotherapy or radiation. Regardless of etiology, psychological management of the anorexia is often helpful. Optimal management often involves use of a combination of modalities: psychotherapeutic, behavioral and/or pharmacologic supplemented by education, counseling and support. Behavioral techniques such as relaxation exercises are useful tools to alter this response as well as to relieve the anxiety precipitated by the patient's concerns about anorexia and weight loss. Environmental interventions and nutritional advice can also be of considerable value in reversing the negative effects of this distressing symptom in cancer.

Patients', parents', and oncologists' perceptions of informed consent for bone marrow transplantation.

Bone marrow transplantation (BMT) is gaining increasing acceptance as a therapeutic treatment modality and is being offered to patients even in the early stages of disease in the presence of minimal debilitating symptoms. Despite this, little is known regarding patients' and physicians' perceptions of the process in which informed consent for this controversial and potentially lethal procedure is obtained. Thirty-nine adult BMT patients and the parents of 61 children undergoing BMT and each of their physicians completed a questionnaire concerning their perceptions of the discussion in which consent for BMT was obtained and their evaluation of the consent document. In addition, the factors influencing patients' and parents' decision to accept BMT and the nature and amount of BMT information retained by patients and parents were assessed. The results indicate that on the whole patients and parents evaluated the BMT consultation and consent document favorably, were motivated by their trust in the physician and their belief in BMT as a cure, retained information regarding major points of informed consent from both the consent document and physician discussion, and had considerable difficulty with recall of the specific toxic side effects associated with BMT. Physicians' perceptions, on the other hand, reflected a less positive view of the extent to which patients and parents were actively involved in the consent process and the readability of the consent document. Perceptions of the informed consent process on the part of oncologist-investigators and patients which could impede the goals of informed consent and implications for facilitating the process are discussed.

Psychosocial problems in cancer survivors.

Cancer is a disease with both physical and psychosocial sequelae. While much is being learned about the physical late effects of cancer and its treatment, less is known about its psychosocial morbidity. Research shows that cancer survivors typically function quite adequately in their daily lives but may experience distress related to their past illness. The cancer survivor's self-image is crucial to the way he or she reenters and adapts to family and social life, school, or work, and this reentry and adaptation in turn influences self-image. The physician plays as important a role in the survivor's psychosocial healing as he did in the patient's physical treatment.

Psychological aspects of patients in germ-free isolation: a review of child, adult, and patient management literature.

Life-threatening medical conditions such as severe combined immunodeficiency disease, leukemia, severe aplastic anemia, radiation injury, burns, organ transplantation, and aggressive administration of chemotherapy often necessitate the isolation of the patient in a protected germ-free environment for weeks or months. This treatment milieu has the effect of extensive psychological and physical isolation from family and staff. A review of the literature was undertaken to investigate the psychological implications of such treatment and to question the possibility that this isolation therapy might produce a unique type of psychological stress. Most authors agree that patients are able to withstand the emotional stress of germ-free isolation and that behavioral changes relate more to the severity of the illness rather than to the isolation. However, there may be inherent stresses related to isolator therapy that can be alleviated by environmental manipulation. Case vignettes are included and patient management in such an environment is outlined.

Three cases of female anorgasmia associated with MAOIs.

Monoamine oxidase inhibitors have been associated with male retarded ejaculation and impotence. The authors describe three cases of female anorgasmia secondary to this class of antidepressants. To the author's knowledge only one incidental finding of this kind has been reported.