Sleep disturbance in patients with cancer: a feasibility study of multimodal therapy.

BACKGROUND: Our aim was to determine feasibility and effect sizes of bright light therapy (BLT), melatonin (MLT), methylphenidate (MP) and eight combinations (BLT+MLT+MP, BLT+MLT, BLT+MP, BLT alone, MLT+MP, MLT alone, MP alone, placebo for BLT, MLT and MP) defined as multimodal therapy (MMT), to improve sleep quality (SQ) (Pittsburgh Sleep Quality Index (PSQI)) from baseline to day 15. We also examined the effects of MMT on insomnia, fatigue, depression, quality of life and actigraphy. METHODS: Patients with advanced cancer with poor SQ (PSQI ≥5) were eligible. Using a double-blind randomised factorial study design, patients were randomised into 1 of the 8 arms for 2 weeks. Feasibility and effect sizes were assessed. RESULTS: 81% (54/67) of randomised patients completed the study. There were no differences in the demographics and SQ between groups. The adherence rates for BLT, MLT and MP were 93%, 100% and 100%, respectively. BLT+MLT+placebo of MP; BLT+placebo of MLT+placebo of MP; BLT+MLT+MP showed an effect size (Cohen's d) for change in PSQI scores of 0.64, 0.57 and 0.63, respectively. PSQI change using linear regression showed BLT (n=29) has effect size of 0.46, p=0.017; MLT (n=26), 0.24, p=0.20; MP (n=26), 0.06, p=0.46. No significant differences were observed in scores for insomnia, fatigue, depression, quality of life and actigraphy. There were no differences in adverse events by groups(p=0.80). CONCLUSIONS: The use of MMT to treat SQ disturbance was feasible. BLT+MLT showed the most promising effect size in improvement in SQ, and additional larger studies are needed. TRIAL REGISTRATION NUMBER: NCT01628029.

Pleural Fluid Cytokine Levels at Baseline and Over Time are Associated With Time to IPC Removal: An Exploratory Study.

BACKGROUND: The behavior of pleural fluid cytokine (PFCs) levels and their association with pleurodesis after indwelling pleural catheter (IPC) placement is unknown. OBJECTIVE: A prospective exploratory study was conducted to obtain preliminary data on PFC levels after IPC placement. METHODS: The PFC panel consisted of 4 cytokines [interleukin -8 (IL-8), vascular endothelial growth factor, total (but not activated) transforming growth factor betas, and basic fibroblast growth factor], measured across 5 time points (T0: insertion; T1: 24 to 48 h; T2: 72 to 96 h; T3: 1 wk; and T4: 2 wk). Profile plots were used to identify patterns of change of PFC levels. Correlation matrices for each PFC over time were computed, and area under the curve (AUC) categories were used to compare the cumulative incidence of IPC removal. Auto pleurodesis was defined as elective catheter removal because of decreased drainage within 90 days of insertion. RESULTS: A total of 22 patients provided complete data. Except for IL-8, the majority of PFCs demonstrated strong positive correlations across measurement time points. Patients with high AUCs for IL-8, basic fibroblast growth factor, and vascular endothelial growth factor had a higher cumulative incidence of IPC removal by 90 days than did patients with low AUCs. CONCLUSION: This is the first study to evaluate longitudinal changes of pleural cytokine levels with respect to the likelihood of IPC removal and provide early evidence that the cytokine profile may be associated with the outcome of pleurodesis induced by IPCs. However, this is an exploratory study and further studies are needed to assess if these findings can be validated in further studies.

Cancer-related fatigue and sleep deficiency in cancer care continuum: concepts, assessment, clusters, and management.

Throughout the cancer continuum, patients are faced with the cancer- and treatment-related side effects that can have a negative impact on their overall quality of life. Cancer-related fatigue (CRF) and sleep deficiency are among the symptoms that patients and their caregivers most often experience. An increasing body of literature suggests that a strong correlation between CRF and sleep deficiency exists, indicating that they may be reciprocally related and that they may have similar underlying etiology. This paper aims at bringing together the opinions of leading cancer control (i.e., CRF and sleep) and oncology experts in order to increase the understanding of CRF and sleep deficiency's assessment, associated symptom clustering, symptom burden shared by caregivers, and CRF and sleep deficiency management in the cancer care context.

Patient-reported sleep disturbance in advanced cancer: frequency, predictors and screening performance of the Edmonton Symptom Assessment System sleep item.

AIMS: Sleep Disturbance (SD) is a severe debilitating symptom in advanced cancer patients (ACP). However, routine screening of SD is uncommon. The primary aim of this study was to determine the optimal cutoff score for SD screening for Edmonton Symptom Assessment system (ESAS) sleep item using Pittsburgh Sleep Quality Index (PSQI) as a gold standard. We also determined the frequency of SD, obstructive sleep apnea symptoms (OSA) and restless leg syndrome (RLS) and factors associated with SD. METHODS: We prospectively surveyed 180 consecutive ACP. Patients completed validated assessment for symptoms. We determined epidemiological performance, receiver operating characteristics, and correlations of SD. RESULTS: SD according to PSQI was diagnosed in 112/180 (62%), and median (IQR) ESAS sleep was 5 (2-7). ESAS sleep ≥ 4 had a sensitivity of 74% and 80%, and specificity of 71% and 64% in the training and validation samples, respectively for screening of SD. The frequency of OSA was 61%; RLS was 38%. ESAS sleep was associated [r, p-value] with PSQI (0.61, <0.0001), pain (0.4, <0.0001); fatigue (0.35, <0.0001); depression (0.20, 0.006); anxiety (0.385, <0.0001); drowsiness (0.385, <0.0001), shortness of breath (0.24, <0.0014); anorexia (0.32, <0.0001), well-being (0.36, <0.0001). Multivariate analysis found well-being (OR per point 1.34, p=0.0003), pain (OR 1.21, p<0.0037), dyspnea (OR 1.16, p=0.027), and OSA (OR 0.31, P=0.003) as independent predictors of SD. There was no association between SD and survival. CONCLUSIONS: SD is frequent and ESAS SD item ≥ 4 has good sensitivity for SD screening.

Fatal hemorrhagic pneumonia: Don't forget Stenotrophomonas maltophilia.

We present a case of fatal hemorrhagic pneumonia secondary to Stenotrophomonas maltophilia in a patient with acute myeloid leukemia. S. maltophilia is commonly a non-virulent pathogen. However, in the immunocompromised, it is generally associated with bacteremia after central venous catheter placement or pneumonia. Hemorrhagic pneumonia is a rare presentation of this bacteria, with only 31 cases reported in the literature, and has 100% mortality within 72 hours. Rapid recognition and early suspicion should be key in the treatment of these patients.

Association between Daytime Activity, Fatigue, Sleep, Anxiety, Depression, and Symptom Burden in Advanced Cancer Patients: A Preliminary Report.

BACKGROUND: There is limited research in advanced cancer patients (ACP) regarding association between objectively measured daytime activity and sleep (as measured by actigraphy), patient characteristics, and cancer symptoms (fatigue, sleep, anxiety, depression, cachexia, and symptom distress scores [SDSs]). OBJECTIVES: Our aim of the study was to determine the association between mean daytime activity (MDTA) and the following items: fatigue (FACIT-F), SDSs (Edmonton Symptom Assessment Scale [ESAS]), sleep quality (Pittsburg Sleep Quality Index [PSQI]), objective sleep variables (OSV) (sleep onset, sleep efficacy, wake after sleep onset, total sleep time), anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), body composition scores, and overall survival (OS). We also examined the association between sleep [PSQI and OSV scores] and FACIT-F, HADS, and ESAS. METHODS: Secondary analysis of a recent clinical trial of cancer-related fatigue in advanced cancer (NCT00424099). Association between MDTA and OSV (measured by actigraphy) during the first week of the study and patient characteristics, symptoms (FACIT-F, ESAS, HADS, and PSQI), and OS were analyzed. RESULTS: Seventy-nine eligible patients were evaluable. The median age was 57 years. Median MDTA was 248.43 counts/minute. Multivariate analysis shows that low MDTA was significantly associated with age, gender, Functional Assessment of Cancer Therapy (FACT)-Functional Well-Being (FWB), ESAS dyspnea, HADS-anxiety, and total sleep time. MDTA was not associated with FACIT-F (p = 0.997) and OS (p = 0.18). Sleep quality (PSQI) was significantly associated with FACIT-F, HADS, ESAS anxiety, and depression, but none of these variables was associated with OSV. CONCLUSION: In ACP, lower MDTA was significantly associated with age, gender, FACT-FWB, ESAS dyspnea, HADS-anxiety, and total sleep time. Both sleep quality and cancer-related fatigue scores were strongly associated with depression and anxiety. More research is needed.

Quality-adjusted survival following treatment of malignant pleural effusions with indwelling pleural catheters.

BACKGROUND: Malignant pleural effusions (MPEs) are a frequent cause of dyspnea in patients with cancer. Although indwelling pleural catheters (IPCs) have been used since 1997, there are no studies of quality-adjusted survival following IPC placement. METHODS: With a standardized algorithm, this prospective observational cohort study of patients with MPE treated with IPCs assessed global health-related quality of life using the SF-6D to calculate utilities. Quality-adjusted life days (QALDs) were calculated by integrating utilities over time. RESULTS: A total of 266 patients were enrolled. Median quality-adjusted survival was 95.1 QALDs. Dyspnea improved significantly following IPC placement (P < .001), but utility increased only modestly. Patients who had chemotherapy or radiation after IPC placement (P < .001) and those who were more short of breath at baseline (P = .005) had greater improvements in utility. In a competing risk model, the 1-year cumulative incidence of events was death with IPC in place, 35.7%; IPC removal due to decreased drainage, 51.9%; and IPC removal due to complications, 7.3%. Recurrent MPE requiring repeat intervention occurred in 14% of patients whose IPC was removed. Recurrence was more common when IPC removal was due to complications (P = .04) or malfunction (P < .001) rather than to decreased drainage. CONCLUSIONS: IPC placement has significant beneficial effects in selected patient populations. The determinants of quality-adjusted survival in patients with MPE are complex. Although dyspnea is one of them, receiving treatment after IPC placement is also important. Future research should use patient-centered outcomes in addition to time-to-event analysis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01117740; URL: www.clinicaltrials.gov.

Incorporation of a decorin biomimetic enhances the mechanical properties of electrochemically aligned collagen threads.

Orientational anisotropy of collagen molecules is integral to the mechanical strength of collagen-rich tissues. We have previously reported a novel methodology to synthesize highly oriented electrochemically aligned collagen (ELAC) threads with mechanical properties approaching those of native tendon. Decorin, a small leucine-rich proteoglycan (SLRP), binds to fibrillar collagen and has been suggested to enhance the mechanical properties of tendon. Based on the structure of natural decorin, we have previously designed and synthesized a peptidoglycan (DS-SILY) that mimics decorin both structurally and functionally. In this study, we investigated the effect of the incorporation of DS-SILY on the mechanical properties and structural organization of ELAC threads. The results indicated that the addition of DS-SILY at a molar ratio of 30:1 (collagen:DS-SILY) significantly enhanced the ultimate stress and ultimate strain of the ELAC threads. Furthermore, differential scanning calorimetry revealed that the addition of DS-SILY at a molar ratio of 30:1 resulted in a more thermally stable collagen structure. However, addition of DS-SILY at a higher concentration (10:1 collagen:DS-SILY) yielded weaker threads with mechanical properties comparable to collagen control threads. Transmission electron microscopy revealed that the addition of DS-SILY at a higher concentration (10:1) resulted in pronounced aggregation of collagen fibrils. More importantly, these aggregates were not aligned along the long axis of the ELAC, thereby compromising the overall tensile properties of the material. We conclude that incorporation of an optimal amount of DS-SILY is a promising approach to synthesize mechanically competent collagen-based biomaterials for tendon tissue engineering applications.

Prospective, randomized, controlled trial of parathyroidectomy versus observation in patients with "asymptomatic" primary hyperparathyroidism.

BACKGROUND: Disruptions in cognitive function have been described in the constellation of symptoms associated with "asymptomatic" primary hyperparathyroidism (PHPT). The aim of this study was to determine the impact of parathyroidectomy (PTX) on brain function and sleep in "asymptomatic" PHPT patients. METHODS: We conducted a prospective, randomized trial comparing immediate PTX with observation in patients with asymptomatic PHPT. We performed functional magnetic resonance imaging (fMRI) of the brain, sleep assessment, and validated neuropsychological battery at baseline, 6 weeks, and 6 months. Wilcoxon rank-sum and Pearson and Spearman correlations were used. RESULTS: A total of 18 patients were randomized. Subjective sleepiness correlated with worse performance on executive function tests during fMRI at 6 weeks (Pearson, -0.473; P = .047) and 6 months (Pearson, -0.673; P = .002). Total sleep time correlated with PTH levels at both 6 weeks (Pearson, 0.518; P = .048) and 6 months (Pearson, 0.567; P = .018). At 6 weeks, hypersomnolence as measured subjectively was decreased in the PTX group, but increased in those observed (-2.56 vs 2.22; P = .03) CONCLUSION: This prospective, randomized trial for asymptomatic PHPT patients demonstrated an association of sleep with brain function. Sleep seemed to be an indicator of brain activation in the anterior cingulate gyrus and precentral cortex. Subjective sleepiness was associated with executive function. The results of this pilot study suggest that decreased serum PTH levels correlate with improved sleep and that PTX decreases sleepiness in patients with asymptomatic PHPT.