A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects.

BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.

Patients With Advanced Cancer and Minor Children: An Exploratory Study of Health-Related Quality of Life and Satisfaction With Care.

OBJECTIVES: Patients with advanced cancer and minor children experience high rates of depression and anxiety. However, associations between parental status and other aspects of the patient experience are not well understood. This study compared patient-reported outcomes of patients with and without minor children. SAMPLE & SETTING: This was a retrospective analysis of 448 adults with stage III or IV solid tumors from a public research registry. METHODS & VARIABLES: Multiple linear regression models or modified Poisson regression models were fitted to evaluate differences in health-related quality of life, global health, and patient satisfaction scores between patients living with and without minors. RESULTS: One in five patients lived with minor children. They reported significantly worse health-related quality of life, global physical health, and global mental health. They also expressed lower satisfaction with time spent with their provider, communication, and financial aspects. IMPLICATIONS FOR NURSING: Patients with minor children may benefit from earlier identification and support for their psychosocial needs and concerns.

A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To determine if high dose intravenous (IV) thiamine can prevent delirium during hospitalization following allogeneic HSCT. Secondarily, we evaluated the effects of high dose IV thiamine on thiamine levels and explored risk factors for delirium. METHODS: Randomized, double-blind, placebo-controlled trial in patients undergoing allogeneic HSCT at a U.S. academic medical center between October 2017 and March 2020. 64 participants were randomized 1:1 to thiamine 200 mg IV three times daily for 7 days or placebo. We used the Delirium Rating Scale to assess for delirium. Delirium incidence was compared between groups using the chi-square test. Group differences in time to onset and duration of delirium were compared using the Kaplan-Meier method. Fisher's Exact and Wilcoxon Rank Sum tests were used to examine associations between pre-transplantation variables and delirium. RESULTS: 61 participants were analyzed. Delirium incidence (25% vs. 21%, Chi-square (df = 1) = 0.12, p = 0.73), time to onset, duration, and severity were not different between study arms. Immediately following the intervention, thiamine levels were higher in the thiamine arm (275 vs. 73 nmol/L, t-test (df = 57) = 13.63, p < 0.0001), but not predictive of delirium. Variables associated with delirium in our sample included disease severity, corticosteroid exposure, infection, and pre-transplantation markers of nutrition. CONCLUSION: High dose IV thiamine did not prevent delirium in patients receiving allogeneic HSCT. Given the multiple contributors to delirium in this population, further research regarding the efficacy of multicomponent interventions may be needed. TRIAL REGISTRATION: Clinical Trials NCT03263442. FUNDING: Rising Tide Foundation for Clinical Cancer Research.

Addressing the needs of parents with advanced cancer: Attitudes, practice behaviors, and training experiences of oncology social workers.

OBJECTIVE: Advanced cancer patients who are parents of minor children experience heightened psychosocial distress. Oncology social workers (OSWs) are essential providers of psychosocial support to parents with advanced cancer. Yet, little is known about the experiences and approaches of OSWs in addressing these patients' unique needs. The purpose of this study was to characterize the attitudes, practice behaviors, and training experiences of OSWs who provide psychosocial care for advanced cancer patients with minor children. METHOD: Forty-one OSWs participated in a cross-sectional survey addressing multiple facets of their psychosocial care for parents with advanced cancer. The five assessed domains of psychosocial support were communication support, emotional support, household support, illness and treatment decision-making support, and end-of-life planning. RESULTS: Participants reported greatest confidence in counseling patients on communication with children about illness and providing support to co-parents about parenting concerns. OSWs reported less confidence in counseling parents on end-of-life issues and assisting families with non-traditional household structures. The majority of participants reported needing more time in their clinical practice to sufficiently address parents' psychosocial needs. Nearly 90% of participants were interested in receiving further training on the care of parents with advanced cancer. SIGNIFICANCE OF RESULTS: To improve the care of parents with advanced cancer, it is critical to understand how the psychosocial oncology workforce perceives its clinical practice needs. Study findings suggest an opportunity for enhanced training, particularly with respect to end-of-life needs and in response to the changing household structure of American families.

Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer.

BACKGROUND: Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. MATERIALS AND METHODS: Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. RESULTS: In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36-3.45) and anxiety (RR, 1.48; 95% CI, 1.05-2.09). CONCLUSION: Oncologists frequently underestimate patients' depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. IMPLICATIONS FOR PRACTICE: In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients' mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients' psychological health.

Cognitive function in patients prior to undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: Cognitive impairment is common and consequential in patients with cancer who undergo allogeneic hematopoietic stem cell transplantation (HSCT). However, there is no standard of care for evaluating cognition in patients prior to or after receiving HSCT, and it is not known which patients are at highest risk for cognitive impairment. The objectives of this study were to describe cognitive function in patients prior to allogeneic HSCT and identify demographic, disease-related, and psychosocial factors associated with cognitive function. METHODS: Prior to HSCT, participants completed the Montreal Cognitive Assessment (MoCA). We assessed bivariable associations between continuous MoCA scores and demographic, disease-related, and psychosocial variables using linear regression. Variables significant at the p < 0.2 level were adjusted for age, sex, and years of education in multiple linear regression analyses. RESULTS: Over 50% of participants demonstrated evidence of cognitive impairment (MoCA < 26) prior to transplantation. When adjusted for demographic variables, two characteristics were significantly associated with worse cognitive function: the hematopoietic cell transplantation-comorbidity index score (p = 0.01) and history of alcohol or substance abuse (p = 0.02). Pre-HSCT cancer and cancer treatment-specific variables were not associated with cognitive function. CONCLUSION: Cognitive impairment is common in patients scheduled to receive HSCT. Pre-transplantation evaluation of medical comorbidities and history of substance abuse may be important in identifying patients at risk for cognitive impairment. Further research characterizing the trajectory and impact of cognitive impairment on patient symptom burden and function may help improve outcomes.

Design of a randomized placebo controlled trial of high dose intravenous thiamine for the prevention of delirium in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Delirium is a highly prevalent and preventable neuropsychiatric condition with major health consequences. Thiamine deficiency is a well-established cause of delirium in those with chronic, severe alcoholism, but there remains an underappreciation of its significance in non-alcoholic populations, including patients with cancer. Treatment of suspected thiamine-related mental status changes with high dose intravenous (IV) thiamine has preliminary evidence for improving a variety of cognitive symptoms in oncology inpatient settings but has never been studied for the prevention of delirium in any population. OBJECTIVES: The primary objective of this clinical trial is to determine if high dose IV thiamine can prevent delirium in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for treatment of cancer. Secondary objectives are to determine if thiamine status is predictive of delirium onset and if high dose IV thiamine can attenuate the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and long-term neuropsychiatric outcomes. METHODS: In this phase II study, we are recruiting 60 patients undergoing allogeneic HSCT, randomizing them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluating all participants for delirium and related comorbidities. We use the Delirium Rating Scale to measure the severity and duration of delirium during hospitalization for HSCT. We obtain thiamine levels weekly during the transplantation hospitalization. We assess HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to and at one, three, and six months after transplantation.

Psychiatric Care in Hematopoietic Stem Cell Transplantation.

BACKGROUND: Patients with cancer frequently experience neuropsychiatric symptoms due to their medical illness or its treatment. In recent decades, psychiatrists have become increasingly involved in the care of patients with cancer. However, psychiatrists may be less familiar with hematopoietic stem cell transplantation (HSCT), a distinct cancer treatment modality associated with multiple neuropsychiatric sequelae. OBJECTIVE: To provide an overview of HSCT, and describe the prevalence, impact, risk factors, and suggested management of psychiatric consequences of HSCT. METHODS: We performed literature searches in PubMed and PsychInfo to identify articles describing neuropsychiatric symptoms, including depression, anxiety, distress, post-traumatic stress disorder, delirium and cognitive impairment, resulting from HSCT in adults. Those articles most relevant to this manuscript were included. RESULTS: Psychiatrists may be involved in the treatment of patients before, during, or after inpatient hospitalization for HSCT. Each phase of treatment introduces unique stressors that may lead to or exacerbate psychiatric disorders. Appropriate management requires evaluation of HSCT-related medications, an understanding of the impact of complications from HSCT, and consideration of how the patient's underlying medical condition should influence psychiatric recommendations. CONCLUSION: To optimize patient outcomes, consulting psychiatrists should be familiar with the basic principles of HSCT, and the neuropsychiatric sequelae that may result from treatment. Further research is needed to identify strategies to manage psychiatric complications in this unique population.