Cognitive Deficits in Executive and Language Functions Predict Postoperative Delirium.

OBJECTIVES: Postoperative delirium (POD) remains the most common complication in older adults, with cognitive impairment being the main risk factor. Patients with mild cognitive impairment, in particular, have much to lose from delirium; despite this, their cognitive impairment might be clinically overlooked. Understanding which cognitive domains are particularly predictive in this regard may improve the sensitivity of preoperative testing and allow for a more targeted application of resource-intensive measures to prevent delirium in the perioperative period. The authors conducted this study with the aim of identifying the most indicative cognitive domains. DESIGN: A secondary analysis of a randomized controlled trial. SETTING: At a single center, the University Medical Centre Hamburg in Hamburg, Germany. PARTICIPANTS: Patients ≥60 years without major neurocognitive disorders (dementia, Mini-Mental State Examination score ≤23) scheduled for cardiovascular surgery. MEASUREMENTS AND MAIN RESULTS: Preoperative neuropsychologic testing and delirium screening were performed twice daily until postoperative day 5. A multiple logistic regression model was applied to determine the predictive ability of test performances for the development of delirium. RESULTS: A total of 541 patients were included in the analysis; the delirium rate was 15.6%. After controlling for confounders, only low performance within the Trail Making Test B/A (odds ratio [OR] = 1.32; 95% CI: 1.05-1.66) and letter fluency (OR = 0.66; 95% CI: 0.45-0.96) predicted a particularly high risk for delirium development. The discriminative ability of the final multiple logistic regression model to predict POD had an area under the curve of 0.786. CONCLUSIONS: Impairment in the cognitive domains of executive function and language skills associated with memory, inhibition, and access speed seem to be particularly associated with the development of delirium after surgery in adults ≥65 years of age without apparent preoperative neurocognitive impairment.

Systematic Review of Patient-Reported Outcome Measures in Graft-versus-Host Disease.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. These patients face a unique challenge due to the complexity of GVHD and the toxicity of treatments received. GVHD has significant impact on quality of life (QOL), but this is not routinely evaluated formally. Despite the availability of patient-reported outcome measures (PROMs) to assess QOL, there is currently no consensus regarding the optimal PROMs that should be used to evaluate the impact of GVHD. We undertook a systematic review to determine the current evidence for the use of PROMs in assessment of QOL, symptom burden, and disease severity of patients with GVHD. A comprehensive systematic review based on the COSMIN guidelines was conducted to identify studies using PROMs (including those for QOL and symptom burden) in acute and chronic GVHD (cGVHD) patients. The following databases were searched: OVID Medline, AMED, CINAHL, Embase, PROQOLID, ProQuest, PsychINFO, and Social Sciences Citation Index from inception to May 2018. Hand searches updated the search to December 2018. Articles were screened by 2 independent reviewers, with discrepancies resolved by a third independent reviewer. Included articles were critically appraised using the COSMIN Risk of Bias tool, and relevant data on measurement properties for the included PROMs were extracted from within the target population. A total of 4545 articles were identified, and 64 articles reporting on 27 PROMs were included in this review. PROMs were separated into 5 groups; generic patient-reported measures (n = 7), cancer-specific measures (n = 4), bone marrow transplant-specific measures (n = 2), cGVHD-specific measures (n = 4), and dimension-specific measures (n = 10). Three PROMs (Human Activity Profile, Lee Symptom Scale, National Institutes of Health Eleven Point Scale) had evidence to support strong reliability (including internal consistency), responsiveness, and aspects of validity within the cGVHD population. Only 5 included PROMs were used in patients with acute GVHD. This review summarizes the current evidence regarding the use of 27 included PROMs in the context of GVHD. The choice of the most optimal PROM depends on the clinical or research context of use. Future research should comprehensively validate these tools in the GVHD population, including the testing and possible development of a PROM for use in acute GVHD, which remains a current critical gap in the existing literature.

Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Complications and Quality of Life Working Party of the European Society for Blood and Marrow Transplantation.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.

Cancer-and-treatment-specific distress and its impact on posttraumatic stress in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

BACKGROUND: In this prospective multicenter study, we investigated cancer-and-treatment-specific distress (CTXD) and its impact on symptoms of posttraumatic stress disorder (PTSD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Patients were consulted before (T0, N = 239), 3 (T1, N = 150), and 12 months (T2, N = 102) after HSCT. Medical (eg, diagnosis and pretreatment) and demographic information, CTXD and PTSD (PCL-C) were assessed. RESULTS: Random intercept models revealed that the sum score of CTXD was highest pre-HSCT (T0), decreased by T1 (γ = -.18, 95% CI [-.26/-.09]), and by T2 (γ = -.10, 95% CI [-.20/-.00]). Uncertainty, family strain, and health burden were rated most distressing during HSCT. Uncertainty and family strain decreased from T0 to T1 (γ = -.30, 95% CI [-.42/-.17]; γ = -.10, 95% CI [-.20/-.00]) and health burden from T1 to T2 (γ = -.21, 95% CI [-.36/.05]). Women were more likely to report uncertainty (γ = .38, 95% CI [.19/.58]), family strain (γ = .38, 95% CI [.19/.58]), and concerns regarding appearance and sexuality (γ = .31, 95% CI [.14/.47]) than men. Uncertainty (γ = .18, 95% CI [.12/.24]), appearance and sexuality (γ = .09, 95% CI [.01/.16]), and health burden (γ = .21, 95% CI [.14/.27]) emerged as predictors of PTSD symptomatology across the 3 assessment points. CONCLUSIONS: Our data provide first evidence regarding the course of 6 dimensions of CTXD during HSCT and their impact on PTSD symptomatology. Specifically, results emphasize the major burden of uncertainty pre-HSCT and the impact of uncertainty and concerns regarding appearance and sexuality on PTSD symptomatology.

Distress, anxiety and depression in patients with brain metastases before and after radiotherapy.

BACKGROUND: Many patients with cancer suffer from distress, anxiety and depression. However, studies on patients with brain metastases are lacking. In this exploratory study we prospectively assessed distress, anxiety and depression in patients with brain metastases from different solid primary tumour treated with radiotherapy to the brain. METHODS: Patients were recruited between May 2008 and December 2010. Distress, anxiety and depression were subjectively evaluated before radiotherapy, 6 weeks, 3 months and 6 months after radiotherapy using the validated National Comprehensive Cancer Network Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). The treatment group consisted of adult patients (n = 67) with brain metastases who were treated with whole-brain radiotherapy (n = 40) or hypofractionated stereotactic radiotherapy (n = 27). The control group comprised of patients (n = 32) diagnosed with breast cancer without cranial involvement who received adjuvant whole breast radiotherapy. Forty-six patients (24 in the treatment group) completed the study after six months. RESULTS: Before radiotherapy, the treatment group experienced higher distress than the control group (p = 0.029). Using a cut-off ≥ 5, 70% of the treatment group were suffering from significant distress (66% of the control group). No significant time-by-group interaction on distress, anxiety and depression was observed. At all time points, a high proportion of patients reported psychological stress which featured more prominently than most of the somatic problems. Global distress correlated strongly with the Hospital Anxiety score before radiotherapy, but only moderately or weakly with both HADS scores after radiotherapy with the weakest association 6 months after radiotherapy. CONCLUSION: In conclusion, the course of distress, anxiety and depression does not differ significantly between patients with brain metastases and breast cancer patients without cranial involvement. This finding suggests that both groups need similar psychological support during their treatment. Both screening instruments should be used as they cover different facets of distress.

Cognitive functioning in allogeneic hematopoietic stem cell transplantation recipients and its medical correlates: a prospective multicenter study.

BACKGROUND: Owing to its neurotoxicity, allogeneic hematopoietic stem cell transplantation (HSCT) carries risks for cognitive impairment. In this multicenter study, we prospectively evaluated cognitive functioning and its medical and demographic correlates in patients undergoing allogeneic HSCT. METHODS: A total of 102 patients were consecutively assessed prior to (T0 ), 100 ± 20 days (T1 ) after, and 12 ± 1 months (T2 ) after HSCT (61% men, 41% acute myeloid leukemia). A comprehensive neuropsychological test battery was applied to evaluate attention, memory, executive function, and fine motor function, summing up into 14 test scores. RESULTS: Before and after HSCT, patients performed below test norms in up to 50% of the test scores. Patients were mostly impaired on word fluency (24%, T0 ), fine motor function, and verbal delayed recall (19% each, T2 ). Impairment on ≥ 1/5 cognitive domains occurred in 47% (T0 ) and 41% (T2 ) of the patients. Performance (mean z-scores) partially improved over time (i.e., visual span forward, verbal learning, and word fluency). However, from baseline to T2 , 16% of the patients showed reliable decline on ≥ 3/14 test scores (reliable change index method). For the majority of neuropsychological subtests, no associations with conditioning intensity, total body irradiation, graft-versus-host disease, cyclosporine treatment, and length of hospital stay were found. Age and premorbid intelligence level were consistently associated with cognition. CONCLUSIONS: Below average cognitive performance is common in this patient group. In addition, a subgroup shows reliable cognitive decline after allogeneic HSCT. Healthcare professionals should be aware of these treatment-related cognitive side effects.

[Psychological distress in adults with neurofibromatosis type 1: a longitudinal study]. / Psychische Belastung von Erwachsenen mit Neurofibromatose Typ 1: Eine Längsschnittstudie.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder with an autosomal dominant inheritance. It is a chronic condition that affects mostly the skin and causes it to grow multiple tumors and also affects the nervous system. The clinical picture is complex with highly variable symptoms and clinical severity. This study explores the psychological distress in 129 adult patients with NF1. It turned out that adults with NF1 have a higher level of psychological distress compared to the general population. The psychological distress is stable within a year. Physicians treating patients with NF1 should consider the psychological distress in NF1 patients. Psychotherapy, psychiatric treatment and psychosocial offers are therefore essential.

Identifying children and adolescents with cognitive dysfunction following mild traumatic brain injury--preliminary findings on abbreviated neuropsychological testing.

OBJECTIVE: Studies on cognitive function in paediatric patients suffering head trauma suggest neuropsychological impairment even after mild traumatic brain injury (MTBI). The present study examined the feasibility of abbreviated neuropsychological testing in different settings in children and adolescents following MTBI. METHODS: Within the scope of two prospective studies on psychosocial and cognitive outcome, 71 school-aged children with mild, moderate or severe TBI were assessed. In addition, 15 healthy children were included in the study. The abbreviated instrument comprises three standardized tests measuring attention and memory functions (Digit Symbol, Digit Span, learning trials of the German Auditory Verbal Learning Test). Impairment rates were calculated according to a defined cut-off score for clinically significant cognitive impairment. RESULTS: Abbreviated testing could easily be implemented both in the acute and post-acute clinical setting. Out of the children with MTBI, 12% (shortly after injury) and 30% (2 months after injury), respectively, were classified as cognitively impaired. Following moderate or severe TBI, impairment occurred in 50% of the patients. Healthy children showed the best performance, while children with severe TBI performed worst. CONCLUSION: Results suggest that abbreviated testing allows detection of MTBI-related cognitive dysfunction. Identified children should be referred to a clinical neuropsychologist for comprehensive assessment.

Return to Work in Patients with Hematological Cancers 1 Year after Treatment: A Prospective Longitudinal Study.

BACKGROUND: Although hematological cancer survivors have a high risk of disability, data on work-related issues are scarce for this population. METHODS: We investigated return to work (RTW) and work ability (Work Ability Index, WAI) in hematological cancer patients 6 months and 1 year after cancer treatment. We explored associations between baseline sociodemographic and medical characteristics and RTW as well as work ability at follow-up. RESULTS: The participation rate was 42% (baseline n = 91, after 12 months n = 40 (44%)). 6 months after cancer treatment, 33% (95% confidence interval 21%-46%) of the remaining patients had returned to work. After 12 months, the RTW rate was 58% (42%-73%). Mean WAI sum score ± SD significantly increased from 18.5 ± 7.3 at baseline to 28.3 ± 8.3 after 12 months (p = 0.001). Patients with lymphoma (r = 0.31, p = 0.02) and patients who received radiation therapy (r = 0.29, p = 0.04) were significantly more likely to return to work. Work ability after 6 months was most strongly associated with higher education (r = 0.60, p < 0.01). Patients' subjective prognosis of gainful employment before cancer treatment predicted work ability after 6 (r = 0.62, p < 0.01) and 12 months (r = 0.51, p < 0.01). CONCLUSION: The chance of returning to work of hematological malignancy survivors is similar to that of other cancer patients.

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

The association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life in breast cancer survivors following standard adjuvant versus high-dose chemotherapy.

OBJECTIVE: The possible association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life has been studied in high-risk breast cancer survivors 5 years following standard adjuvant (n=23) versus high-dose chemotherapy (n=24) and in early-stage breast cancer patients (n=29) (comparison group) following radiation therapy. METHODS: A neuropsychological assessment covering attention, memory and executive functions was used together with the questionnaire for self-perceived deficits in attention (FEDA), the multidimensional fatigue inventory (MFI-20) and the EORTC-QLQ-C30. RESULTS: Findings have shown that neuropsychological impairment is not directly associated with self-perceived cognitive deficits, fatigue and HRQOL. However, 46% of patients reported self-perceived cognitive deficits and 82% of the patients complained about cancer related fatigue. Except for reduced activity we did not find significant group differences, even though patients who received standard-dose chemotherapy had consistently higher levels of self-perceived cognitive deficits and fatigue, and the lowest HRQOL. CONCLUSION: Results emphasize the need for psychosocial counseling and support during treatment phase and follow up care as well. Sensitive cancer-specific measures for the assessment of self-perceived cognitive deficits in different cognitive domains according to neuropsychological measurements are required. PRACTICE IMPLICATIONS: The role of self-perceived cognitive deficits and fatigue should be considered in educational interventions and counseling. Specific rehabilitation measures should be developed, implemented and evaluated in order to meet the needs of these patients and to decrease the frequency of cognitive deficits following cancer treatment.

Stability and Priority of Symptoms and Symptom Clusters Among Allogeneic HSCT Patients Within a 5-Year Longitudinal Study.

CONTEXT: Due to toxicity and invasiveness, allogeneic hematopoietic stem cell transplantation causes severe and longstanding symptom burden. Longitudinal studies on symptoms and symptom clusters (SC) would be helpful to optimize symptom control but are rare to date. OBJECTIVES: The objective of this study was to investigate stability of symptoms, extract time stable SC, and determine their priority in symptom management. METHODS: In this multicenter study, patients diagnosed with hematologic cancer were assessed before conditioning (T0) and three months (T1), one year (T2), and five years (T3) after transplantation. Symptoms were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Symptoms were stable when rated as present at three consecutive time points. Applying factor analysis, stable SC were composed of symptoms loading on the same factor across all time points. Priority in symptom management was derived from a combination of severity and predictive power for quality of life (QoL). RESULTS: Two hundred thirty-nine patients participated at T0, 150 (63%) at T1, 102 (43%) at T2, and 45 (19%) at T3. We identified three stable SC, composed of rest-tired-weak-dyspnea-loss of appetite (exhausted), tense-worried-irritable-depressed (affective), and nausea-vomiting (gastrointestinal). Fatigue was most persistent and also most severe and predictive for QoL, both as symptom and in cluster (exhausted). CONCLUSION: Given its high stability, severity, and impact on QoL, fatigue should have priority in symptom management. The treatment of this symptom could be enhanced by also incorporating interventions addressing dyspnea and loss of appetite.

Posttraumatic stress disorder symptomatology in the course of allogeneic HSCT: a prospective study.

PURPOSE: Despite the life-threatening character of allogeneic hematopoietic stem cell transplantation (allogeneic HSCT), very few longitudinal research exists on posttraumatic stress disorder (PTSD) symptomatology in this patient group. We investigated prevalence, temporal course and predictors of PTSD symptomatology in this population. METHODS: Patients were assessed before conditioning (T0), 100 days (T1), and 12 months after HSCT (T2). PTSD symptomatology was measured with the PTSD Checklist-Civilian Version. We conducted multilevel modeling and multiple regression analyses. RESULTS: Two hundred thirty-nine patients participated at baseline, 150 at T1, and 102 at T2. Up to 15 % met the criteria for PTSD at least once during the course of assessment. Fifty-two percent showed diagnostic relevant levels of intrusion, 30 % of avoidance, and 33 % of arousal at least once. Apart from arousal, which increased between T0 and T1 (γ = 0.56, p = 0.03), no other severity score significantly differed between time points. Being impaired by pain (γ = 2.89, p < 0.01), pain level (γ = 0.63, p = 0.02), and being female (γ = 3.81, p < 0.01) emerged as significant predictors of PTSD symptomatology when taking into account all time points. Acute plus chronic graft-versus-host-disease and longer hospital stay predicted PTSD symptomatology at T2 (γ = 3.39, p = 0.04; γ = 0.1, p = 0.03). CONCLUSIONS: A considerable number of patients undergoing allogeneic HSCT met the criteria for PTSD. PTSD symptomatology is prominent at all assessment points. Burden of pain, being female, and medical complications are risk factors for elevated levels of PTSD symptomatology. IMPLICATIONS FOR CANCER SURVIVORS: Psychological support should be offered not only after treatment but also in the long-term and even before HSCT. Professionals should be aware of the psychological consequences accompanied by pain and complications.

Self-reported cognitive outcomes in patients with brain metastases before and after radiation therapy.

PURPOSE: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. METHODS AND MATERIALS: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). RESULTS: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. CONCLUSION: Self-reported attention declined in patients with brain metastases after RT to the brain, whereas it remained relatively stable in breast cancer patients.

Health-related quality of life and psychosocial consequences after mild traumatic brain injury in children and adolescents.

BACKGROUND: Little is known about the course of health-related quality of life (HRQOL) and functional outcome parameters in children and adolescents with TBI. In addition, a neuropsychological screening instrument would be useful for routine clinical care. OBJECTIVE: To describe health-related quality of life and psychosocial consequences following mild traumatic brain injury (TBI). METHODS: One chose a prospective, longitudinal design (two measurement time points). Methods included a telephone interview and a questionnaire, which was mailed to the parents whose children (older than 4 years of age) were admitted (with TBI) to a collaborating hospital. In addition, a feasibility study for screening children for cognitive side effects, attention and memory tasks was conducted. A group of 59 parents filled out questionnaires assessing health-related quality of life (KINDL), behavioural problems (SDQ) and health status (FS-II-R). Ten families participated in the feasibility study. RESULTS: Results indicated that HRQOL, behavioural problems and health status remained stable over time. Compared to the reference groups, no significant differences in HRQOL were noted. Thirty per cent of the children screened were classified as being cognitively impaired. CONCLUSION: Mild TBI resulted in no decline in the children's health outcome after injury. The cognitive screening approach proved itself to be a useful instrument for routine clinical care.

Post-acute service utilisation and parental satisfaction with health care services after mild traumatic brain injury in children and adolescents.

The objectives of this study were to describe and analyse the current aftercare practise following define TBI in four German cities. A retrospective, cross-sectional design was chosen in order to investigate the research questions. Methods and procedures included a questionnaire mailed to parents whose children were admitted with TBI to one of seven collaborating hospitals. A total of 564 parents participated in the study. The results indicate that aftercare services were rarely utilised. Furthermore, it was found that the behaviour of the physician in charge had a great impact on parental satisfaction with healthcare services. In conclusion, the findings described in this article underline the need to improve communication between acute and post-acute services.