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Biomedical subjects

Tim A Ahles

Publications and source records attributed to Tim A Ahles.

At least 19 recordsLinked to original sources

Cognitive-behavioral management of chemotherapy-related cognitive change.

Adjuvant chemotherapy can produce mild cognitive decline among breast cancer survivors which adversely effects function and quality of life. However, no treatment to date has been proposed or developed for this problem despite large numbers of cancer patients who report post-treatment memory dysfunction. This paper presents data from a single arm pilot study of a brief cognitive-behavioral treatment aimed at helping breast cancer survivors manage cognitive dysfunction associated with adjuvant chemotherapy (Memory and Attention Adaptation Training; MAAT). Participants were twenty-nine women who were an average of 8 years post-chemotherapy for stage I and II breast cancer. All had reported complaints regarding memory and attention. Improvements in self-report of cognitive function, quality of life and standard neuropsychological test performance were observed at post-treatment, 2-month and 6-month follow-up. Participants also reported high treatment satisfaction and rated MAAT as helpful in improving ability to compensate for memory problems. Given these results, the treatment appears to be a feasible and practical cognitive-behavioral program that warrants continued evaluation among cancer survivors who experience persistent cognitive dysfunction.

Adult↗

Distress, psychiatric syndromes, and impairment of function in women with newly diagnosed breast cancer.

BACKGROUND: Emotional distress and psychiatric syndromes are prevalent in the breast cancer population at large. However, to date there is a paucity of literature specifically concerning presurgical breast cancer patients. METHODS: The authors assessed 236 newly diagnosed patients at the time of their presurgical consultation at the Comprehensive Breast Cancer Program of Dartmouth-Hitchcock Medical Center in Lebanon, NH. RESULTS: Of patients in this study, 41% rated their distress in the clinically significant range on the Distress Thermometer (ie, >5, 0-10 scale). Nearly one-half (47%) of patients met established thresholds for positivity on 1 or more screens for distress or psychiatric disorders. Prevalence rates were 11% for major depression (60% of these patients were moderately severe to severely depressed) and were 10% for posttraumatic stress disorder (PTSD). Emotional symptoms markedly interfered with daily function in both groups. Of depressed patients, 56% were already taking a psychotropic medication, yet they still met screening criteria for major depression. CONCLUSIONS: Emotional distress and psychiatric syndromes (major depression and PTSD) were prevalent in this population. Markedly impaired function was evident for both depressed and PTSD patients. Future research should refine current screening procedures and develop interventions to better address emotional distress and psychiatric disorders in newly diagnosed breast cancer patients.

Affective Symptoms↗

Palliative care program effectiveness research: developing rigor in sampling design, conduct, and reporting.

Research on palliative care presents some unique sampling challenges. The purpose of this paper is to articulate the sampling challenges that palliative care researchers face during phases of study design, conduct, and the reporting of results. Challenges include identifying a target population, avoiding selection bias in the face of clinician and patient denial of serious illness, developing eligibility criteria for a seriously ill population, minimizing high patient refusals due to illness, and accurate reporting of all screened and eligible participants. These challenges are explored within the context of a randomized clinical trial testing a palliative care intervention. Suggestions for improving scientific rigor in sampling design include 1) defining a target population that is consistent with research goals; 2) identifying eligibility criteria that are objective and understandable to clinicians to yield the desired sample; and 3) reporting results about the target population, sample eligibility/exclusions, and participation using standardized criteria.

Biomedical Research↗

Quality of life of long-term survivors of breast cancer and lymphoma treated with standard-dose chemotherapy or local therapy.

PURPOSE: This study compared the quality of life (QOL) of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors (mean, 10.0 +/- 5.3 years after treatment) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast, n = 141, age = 57.0 +/- 10.1 years; lymphoma, n = 66, age = 55.8 +/- 13.5 years) or local therapy only (breast, n = 294, age = 65.8 +/- 9.1 years; lymphoma, n = 37, age = 50.4 +/- 12.8 years) were interviewed by phone using the Quality of Life-Cancer Survivors Tool. RESULTS: Multivariate analysis of covariance, controlling for sex, age, education, stage of disease, and time since last treatment, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on overall QOL compared with survivors treated with local therapy only (P = .04). Analysis of covariance on the subscale scores revealed that, compared with survivors who received local therapy, survivors treated with chemotherapy scored significantly lower on the Social subscale (P < .0001), but no differences emerged on the Psychological or Spiritual subscales. There was a statistically significant interaction between treatment and diagnosis (P = .01), as measured by the Physical subscale, indicating that lymphoma survivors treated with chemotherapy scored worse than all other groups. CONCLUSION: Important QOL differences emerged between the chemotherapy and local therapy groups, suggesting that long-term QOL may vary depending on the type of treatment and diagnosis.

Adaptation, Psychological↗

Partner-guided cancer pain management at the end of life: a preliminary study.

This preliminary study tested the efficacy of a partner-guided cancer pain management protocol for patients who are at the end of life. Seventy-eight advanced cancer patients meeting criteria for hospice eligibility and their partners were randomly assigned to a partner-guided pain management training intervention, or usual care control condition. The partner-guided pain management training protocol was a three-session intervention conducted in patients' homes that integrated educational information about cancer pain with systematic training of patients and partners in cognitive and behavioral pain coping skills. Data analyses revealed that the partner-guided pain management protocol produced significant increases in partners' ratings of their self-efficacy for helping the patient control pain and self-efficacy for controlling other symptoms. Partners receiving this training also showed a trend to report improvements in their levels of caregiver strain. Overall, the results of this preliminary study suggest that a partner-guided pain management protocol may have benefits in the context of cancer pain at the end of life. Given the significance of pain at the end of life, future research in this area appears warranted.

Adaptation, Psychological↗

Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480.

BACKGROUND: Research has suggested that men with hormone-refractory prostate carcinoma have a lower quality of life (QOL) compared with men who have hormone-sensitive prostate carcinoma and that quality of life (QOL) steadily declines over the last year of life for men with prostate carcinoma. The primary purpose of the current study was to evaluate whether there was evidence of palliative effects associated with suramin at any of the three doses administered in the original clinical trial. METHODS: Patients with histologically confirmed advanced hormone-refractory adenocarcinoma of the prostate were randomized to receive suramin at a low dose (n = 129; median age, 69 years), an intermediate dose (n = 129; median age, 71 years), or a high dose (n = 127; median age, 70 years) as part of the Intergroup 0159/Cancer and Leukemia Group B 9480 trial. Patients completed a battery of assessment tools, including the Functional Assessment of Cancer Therapy (FACT)-Prostate, the Center for Epidemiological Studies-Depression Scale (CES-D), the Brief Pain Inventory, and an opioid medication log, at baseline, on Day 1 of the sixth week of active therapy, during the second week after treatment termination, and 3 months after administration of the final suramin dose. RESULTS: Patients who received low-dose suramin reported improvement in QOL (FACT-General: P < 0.01; FACT-Treatment Outcome Index: P < 0.01) and decreased levels of depression (CES-D: P < 0.0006) during treatment compared with patients in the intermediate- and high-dose arms. After treatment, all groups experienced equal decreases in FACT and CES-D scores. CONCLUSIONS: The pattern of results suggests that the lowest dose of suramin administered had a palliative effect in terms of improvement in QOL and decreased levels of depression and that this effect was lost once suramin was discontinued.

Adenocarcinoma↗

Cognitive impairment associated with chemotherapy for cancer: report of a workshop.

Cognitive dysfunction may occur in some patients who receive chemotherapy. We provide a summary of an April 2003 workshop on this topic, that included medical oncologists, radiologists, clinical and experimental psychologists, and patient advocates. Current studies indicate that cognitive deficits are often subtle, although they are observed consistently in a proportion of patients, may be durable, and can be disabling. Deficits have been observed in a range of cognitive functions. Underlying mechanisms are unknown, although preliminary studies suggest there may be genetic predisposition and that cognitive impairment may be accompanied by changes in the brain detectable by neuroimaging. The following priorities were established for future research: (1) large-scale clinical studies that use both a longitudinal design and concurrent evaluation of patients with cancer who do not receive chemotherapy-such studies should address the probability and magnitude of cognitive deficits, factors that predict them, and underlying mechanisms; (2) exploration of discrepancies between subjective reports of cognitive dysfunction and the objective results of cognitive testing; (3) studies of cognitive function in patients receiving treatment for diseases other than breast cancer, and in both men and women, to address the hypothesis that underlying mechanisms relate to changes in serum levels of sex hormones and/or to chemotherapy-induced menopause; (4) development of interventions to alleviate these problems; and (5) development of animal models and the use of imaging techniques to address mechanisms that might cause cognitive impairment associated with chemotherapy.

Antineoplastic Agents↗

Cognitive effects of cytotoxic cancer chemotherapy: predisposing risk factors and potential treatments.

Increasing evidence suggests that systemic cancer chemotherapy can have significant long-term effects on cognition, particularly on verbal learning, memory, attention, and speed of information processing. These deficits can be a source of significant distress to survivors. There is much less known about the mechanisms, predisposing vulnerabilities, and treatment of these deficits. We will summarize current knowledge of chemotherapy-associated cognitive deficits. Emerging theories about the role of selected genetic polymorphisms in heightening the vulnerability to chemotherapy-induced cognitive decline will be described.

Antineoplastic Combined Chemotherapy Protocols↗

The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy.

PURPOSE: The primary purpose of this study was to compare the neuropsychological performance of long-term survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the epsilon 4 allele of the Apolipoprotein E (APOE) gene to those who carry other APOE alleles. PATIENTS AND METHODS: Long-term survivors (mean=8.8+/-4.3 years post-treatment) of breast cancer (N=51, age=55.9+/-8.8) or lymphoma (N=29, age=55.8+/-11.6) who had been treated with standard-dose chemotherapy completed a standardized battery of neuropsychological and psychological tests. Survivors were also classified into two groups based on the presence (N=17) or absence (N=63) of at least one epsilon 4 allele of APOE. RESULTS: Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest (a proxy measure of baseline IQ), indicated that survivors with at least one epsilon 4 allele scored significantly lower in the visual memory (p<0.03) and the spatial ability (p<0.05) domains and tended to score lower in the psychomotor functioning (p<0.08) domain as compared to survivors who did not carry an epsilon 4 allele. No group differences were found on depression, anxiety, or fatigue. CONCLUSIONS: The results of this study provide preliminary support for the hypothesis that the epsilon 4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive decline.

Adult↗

Low neuropsychologic performance among adult cancer survivors treated with chemotherapy.

Decline in neuropsychologic test performance following adjuvant chemotherapy for various types of cancer has gained much research attention over the past decade. From available data, about one fourth to one third of individuals undergoing systemic chemotherapy exhibit measurable decrements in performance of standard tests of cognitive function. Many cancer survivors report that cognitive problems interfere with function and compromise quality of life. However, these declines appear subtle and there are little available longitudinal data examining pre- to post-treatment cognitive change. Further, there is little available evidence identifying the causes of cognitive decline. This paper reviews current literature on low neuropsychologic performance following systemic chemotherapy and hypotheses on the causes of cognitive symptoms following chemotherapy. Future research directions, with emphasis on longitudinal research design as well as treatment implications, are discussed.

Adult↗

The self-efficacy of family caregivers for helping cancer patients manage pain at end-of-life.

This preliminary study examined the self-efficacy of family caregivers with regard to helping cancer patients manage pain at end of life. A sample of 63 family caregivers of hospice-eligible cancer patients with pain provided ratings of their self-efficacy in assisting the patient in pain management and rated their own mood and level of caregiver strain. Patients completed measures of pain and quality of life. Data analyses revealed that caregivers who rated their self-efficacy as high reported much lower levels of caregiver strain as well as decreased negative mood and increased positive mood. Caregiver self-efficacy in managing the patient's pain was related to the patient's physical well-being. In dyads where the caregiver reported high self-efficacy, the patient reported having more energy, feeling less ill, and spending less time in bed. Considered overall, the results of this study suggest that caregiver self-efficacy in pain management is important in understanding how caregivers adjust to the demands of caring for cancer patients who have pain at the end of life.

Adult↗

Ongoing distress from emotional trauma is related to pain, mood, and physical function in a primary care population.

The relationship of trauma history to physical and emotional functioning in primary care pain patients was examined. Data were drawn from a mailed screening questionnaire for a larger study designed to evaluate an intervention for improving pain management in primary care. Results indicated that 50.4% of the pain patients reported experiencing at least one previous emotionally traumatic event. Further, 31% of patients with trauma history continued to be bothered by that experience. Finally, patients who continued to be significantly bothered by the trauma reported more pain, emotional distress, poorer social functioning, and more difficulty with engaging in their daily activities than did patients with either no trauma history or who had a trauma history but did not have bothersome thoughts of the trauma. These preliminary findings suggest that the experience of trauma alone was not related to additional impairments in physical and psychosocial functioning. However, the report that one continued to be bothered by thoughts of a trauma was associated with greater impairments in functioning.

Adult↗

Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives.

Recent studies have indicated the frequent occurrence of neuropsychologic deficits and cognitive complaints after systemic cancer chemotherapy. Most early reports were retrospective, but prospective longitudinal studies are underway. Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information. We review the minimal imaging data available at present and also note studies of other brain disorders or treatment effects that might serve as a model for imaging chemotherapy-induced changes. Large-scale prospective studies are needed to help isolate the pathophysiological mechanisms underlying the cognitive deficits associated with chemotherapy.

Antineoplastic Agents↗

Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma.

PURPOSE: The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/- 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 +/- 10.5 years; lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study-Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). RESULTS: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P <.04), particularly in the domains of verbal memory (P <.01) and psychomotor functioning (P <.03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P <.01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P <.02). CONCLUSION: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy.

Adult↗

Expressive disclosure and health outcomes in a prostate cancer population.

OBJECTIVE: This pilot study explored the feasibility and the efficacy of a brief, well-defined psychosocial intervention (expressive disclosure) in improving behavioral, medical, immunological, and emotional health outcomes in men with diagnosed prostate cancer. METHOD: Thirty prostate cancer patients receiving outpatient oncology care were randomized into experimental (disclosure) and control (non-disclosure) groups. All had been previously treated by surgery or radiation within the last 4 years and were being monitored without further intervention for change in PSA levels. Psychological and physical health surveys were administered and peripheral blood for PSA levels and immune assays was obtained upon study enrollment and again at 3 and 6 months post enrollment. Multivariate analyses were used to examine how the expressive disclosure impacted the hypothesized domains of functioning: physical and psychological symptoms; health care utilization; and immunocompetence. RESULTS: Compared to controls, patients in the expressive disclosure condition showed improvements in the domains of physical symptoms and health care utilization, but not in psychological variables nor in disease relevant aspects of immunocompetence. CONCLUSIONS: Study results support the feasibility of an expressive disclosure intervention for men with prostate cancer. The intervention was well accepted by this population, and participation/adherence was quite high. Results provide only limited support for the hypothesis that a written emotional disclosure task can positively impact health outcomes in a cancer population. However, this pilot study may have lacked adequate power to detect possible intervention benefits. Further studies with larger samples are needed to better assess the intervention's impact on psychological well-being and immunocompetence.

Affect↗

Breast cancer chemotherapy-related cognitive dysfunction.

Cognitive side effects of systemic chemotherapy have become an increasing concern among breast cancer survivors, their families, and health care professionals. A growing body of research supports the hypothesis that chemotherapy can produce long-term cognitive changes in at least a subgroup of cancer survivors. We review evidence implicating systemic chemotherapy as the cause of cognitive changes; describe the limitations due to lack of longitudinal studies and gaps in knowledge (ie, no clear mechanism by which chemotherapy can produce cognitive changes has been proposed); discuss possible factors like age, intelligence quotient/education, and psychological, genetic, and hormonal factors that might increase risk for chemotherapy-induced cognitive changes; and outline future directions for research. Such future research includes large-scale, longitudinal studies of pretreatment neuropsychological assessments, use of imaging techniques and the development of animal models to study the mechanisms of chemotherapy-induced changes in cognitive functioning, and the development of interventions to prevent or reduce the negative cognitive effects of chemotherapy

Antineoplastic Combined Chemotherapy Protocols↗