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Anxiety and sleep disturbance are frequent symptoms during chemotherapy.Purposes were to identify subgroups of oncology outpatients with distinct joint anxiety and sleep disturbance profiles, as well as evaluate for differences in demographic and clinical characteristics, sleep disturbance characteristics, severity of common symptoms, and quality-of-life outcomes among these subgroups.Oncology outpatients (n = 1331) completed self-report measures of anxiety and sleep disturbance 6 times over 2 chemotherapy cycles. Latent profile analysis was done to identify subgroups of patients with distinct joint anxiety and sleep disturbance profiles.Three profiles were identified (ie, no anxiety and low sleep disturbance (59.7%), moderate anxiety and high sleep disturbance (32.5%), high anxiety and very high sleep disturbance (7.8%)). Compared with the no anxiety and low sleep disturbance class, the other 2 classes were younger; less likely to be married; had a lower annual household income; and had childcare responsibilities. Patients in the 2 worse profiles had problems with both sleep initiation and maintenance. These patients reported higher levels of depressive symptoms, trait and state anxiety, and evening fatigue, as well as lower levels of morning and evening energy, cognitive function, and poorer quality of life.More than 40% of patients had moderate or high levels of anxiety and high or very high levels of sleep disturbance. Modifiable risk factors associated with these profiles may be used to develop targeted interventions for 1 or both symptoms.Clinicians need to assess for the co-occurrence of anxiety and sleep disturbance.

Shortness of breath is a distressing symptom that occurs in 10% to 70% of oncology patients. Despite this broad range in its occurrence, little is known about inter-individual variability in shortness of breath and associated risk factors among patients receiving chemotherapy.Identify subgroups of patients with distinct shortness of breath profiles; evaluate for differences among these subgroups in demographic and clinical characteristics; evaluate for differences among symptom dimensions of shortness of breath, and evaluate for differences in quality of life outcomes.Outpatients (n=1338) completed questionnaires six times over two chemotherapy cycles. Occurrence of shortness of breath was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath profiles.Four distinct shortness of breath profiles were identified (None [70.5%], Decreasing [8.2%], Increasing [7.8%], High [13.5%]). Risk factors for membership in High class included: history of smoking, self-reported diagnosis of lung disease, having lung cancer, and receipt of a higher number of cancer treatments. Compared to the None class, High class reported poorer physical, psychological, and social functioning.Almost 14% of patients with heterogeneous types of cancer receiving chemotherapy had persistently high occurrence rates of shortness of breath for almost two months. In addition, compared to the Decreasing and Increasing classes, the High class' episodes of shortness of breath were more frequent and more severe. Clinicians need to assess all oncology patients for shortness of breath and provide targeted interventions.

While pain is a significant problem for oncology patients, little is known about interindividual variability in pain characteristics.The aims of this study were to identify subgroups of patients with distinct worst pain severity profiles and evaluate for differences among these subgroups in demographic, clinical, and pain characteristics and stress and symptom scores.Patients (n = 934) completed questionnaires 6 times over 2 chemotherapy cycles. Worst pain intensity was assessed using a 0- to 10-point numeric rating scale. Brief Pain Inventory was used to assess various pain characteristics. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles.Three worst pain profiles were identified (low [17.5%], moderate [39.9%], severe [42.6%]). Compared with the other 2 classes, severe class was more likely to be single and unemployed and had a lower annual household income, a higher body mass index, a higher level of comorbidity, and a poorer functional status. Severe class was more likely to have both cancer and noncancer pain, a higher number of pain locations, higher frequency and duration of pain, worse pain quality scores, and higher pain interference scores. Compared with the other 2 classes, severe class reported lower satisfaction with pain management and higher global, disease-specific, and cumulative life stress, as well as higher anxiety, depression, fatigue, sleep disturbance, and cognitive dysfunction scores.Unrelieved pain is a significant problem for more than 80% of outpatients.Clinicians need to perform comprehensive pain assessments; prescribe pharmacologic and nonpharmacologic interventions; and initiate referrals for pain management and psychological services.

Unrelieved chemotherapy-induced nausea (CIN) occurs 48% of patients undergoing chemotherapy and is one of the most debilitating symptoms that patients report.The aims of this study were to identify subgroups of patients with distinct CIN profiles and determine how these subgroups differed on demographic and clinical characteristics; severity, frequency, and distress of CIN; and the co-occurrence of common gastrointestinal symptoms.Patients (n = 1343) completed demographic questionnaire and Memorial Symptom Assessment Scale 6 times over 2 cycles of chemotherapy. Latent class analysis was used to identify subgroups of patients with distinct CIN profiles. Differences among these subgroups were evaluated using parametric and nonparametric statistics.Four distinct CIN profiles were identified: none (40.8%), increasing-decreasing (21.5%), decreasing (8.9%), and high (28.8%). Compared with the none class, patients in the high class were younger, had a lower annual household income, had child care responsibilities, had a lower Karnofsky Performance Status score and a higher Self-administered Comorbidity Questionnaire score, and were more likely to have received chemotherapy on a 14-day cycle and a highly emetogenic chemotherapy regimen. In addition, patients in the high class reported high occurrence rates for dry mouth, feeling bloated, diarrhea, lack of appetite, abdominal cramps, difficulty swallowing, mouth sores, weight loss, and change in the way food tastes.That 60% of the patients reported moderate to high CIN occurrence rates confirms that this unrelieved symptom is a significant clinical problem.Nurses need to evaluate patients' level of adherence to their antiemetic regimen and make appropriate referrals for physical therapy, psychological services, and dietary counseling.

Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This study's purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.

Sleep disturbance is a common problem in patients receiving chemotherapy. Purpose was to evaluate for perturbations in immune-inflammatory pathways between oncology patients with low versus very high levels of sleep disturbance.Sleep disturbance was evaluated using the General Sleep Disturbance Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct sleep disturbance profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 198) and microarray (n = 162) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between Low versus Very High sleep disturbance classes.In the RNA sequencing and microarray samples, 59.1% and 51.9% of patients were in the Very High sleep disturbance class, respectively. Thirteen perturbed pathways were related to immune-inflammatory mechanisms (i.e., endocytosis, phagosome, antigen processing and presentation, natural killer cell mediated cytotoxicity, cytokine-cytokine receptor interaction, apoptosis, neutrophil extracellular trap formation, nucleotide-binding and oligomerization domain-like receptor signaling, Th17 cell differentiation, intestinal immune network for immunoglobulin A production, T-cell receptor signaling, complement and coagulation cascades, and tumor necrosis factor signaling).First study to identify perturbations in immune-inflammatory pathways associated with very high levels of sleep disturbance in oncology outpatients. Findings suggest that complex immune-inflammatory interactions underlie sleep disturbance.

Unrelieved pain occurs in 55% of cancer patients. Identification of molecular mechanisms for pain may provide insights into therapeutic targets. Purpose was to evaluate for perturbations in neuroinflammatory pathways between oncology patients with and without severe pain. Worst pain severity was rated using a 0 to 10 numeric rating scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 192) and microarray (n = 197) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between None versus the Severe pain classes. In the RNA sequencing and microarray samples, 62.5% and 56.3% of patients were in the Severe pain class, respectively. Nine perturbed pathways were related to neuroinflammatory mechanisms (i.e., retrograde endocannabinoid signaling, gamma-aminobutyric acid synapse, glutamatergic synapse, Janus kinase-signal transducer and activator of transcription signaling, phagosome, complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling, calcium signaling). First study to identify perturbations in neuroinflammatory pathways associated with severe pain in oncology outpatients. Findings suggest that complex neuroimmune interactions are involved in the maintenance of chronic pain conditions. Perspective: In this study that compared oncology patients with none versus severe pain, nine perturbed neuroinflammatory pathways were identified. Findings suggest that complex neuroimmune interactions are involved in the maintenance of persistent pain conditions.

The embryonic environment can modify cancer cell metabolism, and it is reported to induce the loss of tumorigenic properties and even affect the differentiation of cancer cells into normal tissues. The cellular mechanisms related to this remarkable phenomenon, which is likely mediated by cell-to-cell communication, have been previously investigated with particular focus on the proteins and genes involved. In this study we report the optimization and results of a straightforward

/Background - Depression and sleep disturbance are significant problems during chemotherapy. Study purposes were to identify subgroups of patients with distinct joint depression AND sleep disturbance profiles and evaluate for differences in demographic and clinical characteristics, severity of symptoms, and quality of life (QOL) outcomes among these subgroups.Oncology outpatients (n = 1331) completed measures of depression and sleep disturbance six times over two chemotherapy cycles. Latent profile analysis, that modeled the two symptoms together, was done to identify the distinct joint depression and sleep disturbance profiles.Five distinct profiles were identified (i.e., no depression or sleep disturbance (None, 21.4%); no depression and moderate sleep disturbance (32.3%); subsyndromal depression and very high sleep disturbance (20.4%); moderate depression and moderate sleep disturbance (17.7%); and high depression and very high sleep disturbance (8.2%)). Compared to the None class, the other four classes were more likely to be female; less likely to be employed; had a higher comorbidity burden; and had a lower functional status. Patients in the two very high sleep disturbance classes had problems with both sleep initiation and maintenance. These patients reported higher levels of depressive symptoms, trait and state anxiety, and fatigue as well as lower levels of energy, cognitive function, and poorer QOL.Over 45% of the patients had subsyndromal to high levels of depression AND moderate or very high levels of sleep disturbance. Characteristics associated with the higher risk profiles can be used to screen patients at increased risk for both symptoms.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide’s Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.

Background Depression is the leading cause of disease burden among women worldwide. However, an understanding of symptom profiles among women at risk of mood disorders is limited. We determined distinct profiles of affective symptoms among high risk women, along with their distinguishing characteristics. Methods Women were recruited from 17 clinical sites affiliated with the National Network of Depression Centers. They completed measures of depression (Patient Health Questionnaire – 9) and anxiety (Generalized Anxiety Disorder – 7) as well as questions regarding demographics, reproductive status, behavioral/mental health history, and life stress/adversity. Latent class analysis and multinomial logistic regression were used to identify and characterize symptom profiles. Results 5792 women participated, ages 18 to 90 (M = 38). Three latent classes were identified: generally asymptomatic (48%), elevated symptoms of comorbid anxiety and depression (16%), and somatic symptoms (36%). Financial security and greater social support were protective factors that distinguished asymptomatic women. The profile of the class with elevated anxiety/depressive symptoms constituted a complex mix of adverse social determinants and potentially heritable clinical features, including a diagnosis of Bipolar Disorder. Women in the 3rd latent class were characterized by menstrual irregularity and a stronger expression of neurovegetative symptoms, especially sleep disturbance and fatigue. Limitations Limitations included less than optimal racial diversity of our sample and reliance on self-report. Conclusions Different symptom profiles may reflect distinct subtypes of women at risk of mood disorders. Understanding the etiology and mechanisms underlying clinical and psychosocial features of these profiles can inform more precisely targeted interventions to address women's diverse needs.

Holding at room temperature is the first step in most boar semen cryopreservation protocols. It is well accepted that a holding time (HT) of 24 h increases sperm cryotolerance. However, the effect of HT on ejaculates with different freezability is not entirely clear. The aim of this study was to understand how HT influences spermatic and seminal plasma metabolite profiles of boar ejaculates and how these possible changes affect freezability. A total of 27 ejaculates were collected and extended to 1:1 (v: v) with BTS and split into two aliquots. The first aliquot was cryopreserved without HT (0 h), and the second was held at 17°C for 24 h before cryopreservation. Spermatozoa and seminal plasma were collected by centrifugation at two times, before HT (0 h) and after HT (24 h), and subsequently frozen until metabolite extraction and UPLC–MS analysis. After thawing, the semen samples were evaluated for kinetics, membrane integrity, mitochondrial potential, membrane lipid peroxidation, and fluidity. The ejaculates were then allocated into two phenotypes (good ejaculate freezers [GEF] and poor ejaculate freezers [PEF]) based on the percent reduction in sperm quality (%RSQ) as determined by the difference in total motility and membrane integrity between raw and post-thaw samples cryopreserved after 24 h of HT. The metabolic profile of the seminal plasma did not seem to influence ejaculate freezability, but that of the spermatozoa were markedly different between GEF and PEF. We identified a number of metabolic markers in the sperm cells (including inosine, hypoxanthine, creatine, ADP, niacinamide, spermine, and 2-methylbutyrylcarnitine) that were directly related to the improvement of ejaculate freezability during HT; these were components of metabolic pathways associated with energy production. Furthermore, PEF showed an upregulation in the arginine and proline as well as the glutathione metabolism pathways. These findings help to better understand the effect of HT on boar sperm freezability and propose prospective metabolic markers that may predict freezability; this has implications in both basic and applied sciences.

BackgroundEarly detection and intervention research is expected to improve the outcomes for patients with high grade muscle invasive urothelial carcinoma (InvUC). With limited patients in suitable high-risk study cohorts, relevant animal model research is critical. Experimental animal models often fail to adequately represent human cancer. The purpose of this study was to determine the suitability of dogs with high breed-associated risk for naturally-occurring InvUC to serve as relevant models for early detection and intervention research. The feasibility of screening and early intervention, and similarities and differences between canine and human tumors, and early and later canine tumors were determined.MethodsSTs (n=120) ≥ 6 years old with no outward evidence of urinary disease were screened at 6-month intervals for 3 years with physical exam, ultrasonography, and urinalysis with sediment exam. Cystoscopic biopsy was performed in dogs with positive screening tests. The pathological, clinical, and molecular characteristics of the “early” cancer detected by screening were determined. Transcriptomic signatures were compared between the early tumors and published findings in human InvUC, and to more advanced “later” canine tumors from STs who had the typical presentation of hematuria and urinary dysfunction. An early intervention trial of an oral cyclooxygenase inhibitor, deracoxib, was conducted in dogs with cancer detected through screening.ResultsBiopsy-confirmed bladder cancer was detected in 32 (27%) of 120 STs including InvUC (n=29, three starting as dysplasia), grade 1 noninvasive cancer (n=2), and carcinoma in situ (n=1). Transcriptomic signatures including druggable targets such as EGFR and the PI3K-AKT-mTOR pathway, were very similar between canine and human InvUC, especially within luminal and basal molecular subtypes. Marked transcriptomic differences were noted between early and later canine tumors, particularly within luminal subtype tumors. The deracoxib remission rate (42% CR+PR) compared very favorably to that with single-agent cyclooxygenase inhibitors in more advanced canine InvUC (17-25%), supporting the value of early intervention.ConclusionsThe study defined a novel naturally-occurring animal model to complement experimental models for early detection and intervention research in InvUC. Research incorporating the canine model is expected to lead to improved outcomes for humans, as well as pet dogs, facing bladder cancer.

Background The impact of research findings on clinical practice usually remains uncertain and unmeasured. To address this problem, we examined the long-term clinical and economic impact of the Initiating Dialysis Early and Late (IDEAL) trial using data from the Australia and New Zealand Dialysis and Transplant Registry. Methods We performed a registry-based study including all incident adult dialysis patients in Australia and New Zealand from July 2000 to June 2018. A piecewise linear regression model was used to examine differences in mean estimated glomerular filtration rate (eGFR) at dialysis commencement for the years prior to (2000–2010) and following (2010–2018) publication of the IDEAL trial results. The return on investment (ROI) was calculated using the total cost of performing the IDEAL trial and the cost or savings accruing in Australia and New Zealand from changes in dialysis initiation practice. Results From July 2000 to June 2010, mean eGFR at dialysis commencement increased at a rate of 0.21 mL/min/1.73 m2/year [95% confidence interval (CI) 0.19–0.23]. After the IDEAL trial results were published, mean eGFR at dialysis commencement did not show any temporal change [−0.01 mL/min/1.73 m2/year (95% CI −0.03–0.01)]. The ROI of the IDEAL trial was AU$35.70/AU$1 spent, an estimated savings to the Australian and New Zealand health systems of up to AU$84 million/year. Conclusions The previous trend to higher eGFR at dialysis commencement changed following publication of the IDEAL trial results to a steady eGFR that has continued for a decade, avoiding unnecessary dialysis treatments and accruing savings to the Australian and New Zealand health systems.

To evaluate for inter-individual differences in financial distress and identify demographic, clinical, and symptom characteristics associated with higher levels of financial distress. Patients (n = 387) were enrolled prior to breast cancer surgery and followed for 12 months. Financial distress was measured using a 0 (no problem) to 10 (severe problem) numeric rating scale. Hierarchical linear modeling was used to evaluate for inter-individual differences in trajectories of financial distress and characteristics associated with financial distress at enrollment and over 12 months. Patients’ mean age was 55.0 (± 11.7) years and the majority underwent breast conservation surgery (80.6%). Mean financial distress score prior to surgery was 3.3 (± 3.4; range 0 to 10). Unconditional model for financial distress demonstrated no significant changes over time (-0.006/month). Younger age, lower income, receipt of an axillary lymph node dissection and adjuvant chemotherapy, and lower attentional function were associated with higher preoperative levels of financial distress. Risk factors identified in this study can be used to inform clinicians regarding the need to initiate financial discussions and social work referrals for some patients. Additional clinical or system level interventions should be considered for vulnerable groups with these risk factors.

Patients with gastrointestinal cancers experience diurnal variations in fatigue severity during chemotherapy that decrease their functional status and quality of life.Study purposes were to identify subgroups of patients with distinct co-occurring morning and evening fatigue profiles and evaluate for differences among these subgroups in demographic, clinical, stress, and symptom characteristics.Patients with gastrointestinal cancers (n = 405) completed questionnaires 6 times over 2 cycles of chemotherapy. The Lee Fatigue Scale was used to evaluate diurnal variations in fatigue severity. Latent profile analysis was used to identify subgroups of patients with distinct co-occurring morning AND evening fatigue profiles. Differences among the subgroups in demographic, clinical, stress, and symptom characteristics at enrollment were evaluated using parametric and nonparametric analyses.Two classes were identified, namely: low morning and moderate evening fatigue (ie, Low-Moderate, 60.0%) and high morning and high evening fatigue (ie, Both High, 40.0%). Compared with the Low-Moderate class, the Both High class was significantly younger, female, unmarried, and unemployed and lacked regular exercise. In addition, they had childcare responsibilities, lower annual income, lower functional status, higher comorbidity burden, and self-reported anemia and depression. Patients in the Both High class reported higher levels of anxiety, depressive symptoms, sleep disturbance, pain, and stress, and lower levels of energy and cognitive function.Findings provide new insights into the risk factors for higher levels of co-occurring morning and evening fatigue in patients with gastrointestinal cancers.Clinicians can use this information to identify high-risk patients and develop personalized symptom management interventions.

Cognitive and physical fatigue are common symptoms experienced by oncology patients. Exposure to stressful life events (SLE), cancer-related stressors, coping styles, and levels of resilience may influence the severity of both dimensions of fatigue.Evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and coping in oncology patients (n=1332) with distinct cognitive fatigue AND evening physical fatigue profiles.Latent profile analysis, which combined the two symptom scores, identified three subgroups of patients with distinct cognitive fatigue AND evening physical fatigue profiles (i.e., Low, Moderate, High). Patients completed measures of global, cancer-specific, and cumulative life stress as well measures of resilience and coping. Differences among the latent classes in the various measures were evaluated using parametric and nonparametric tests.Compared to Low class, the other two classes reported higher global and cancer-specific stress. In addition, they reported higher occurrence rates for sexual harassment and being forced to touch prior to 16 years of age. Compared to the other two classes, High class reported lower resilience scores and higher use of denial, substance use, and behavioral disengagement.To decrease both cognitive and evening physical fatigue, clinicians need to assess for relevant stressors and initiate interventions to increase resilience and the use of engagement coping strategies. Additional research is warranted on the relative contribution of various social determinants of health to both cognitive and physical fatigue in oncology patients receiving chemotherapy.

The purpose was to model cognitive fatigue and evening physical fatigue together to determine subgroups of patients with distinct cognitive fatigue AND evening physical fatigue profiles. Once these profiles were identified, differences among the subgroups in demographic and clinical characteristics, co-occurring symptoms, and quality of life outcomes were evaluated. Oncology patients (n = 1332) completed self-report measures of cognitive fatigue and evening physical fatigue, six times over two cycles of chemotherapy. Latent profile analysis, which combined the two symptom scores, was done to identify subgroups of patients with distinct cognitive fatigue AND evening physical fatigue profiles. Three distinct profiles (i.e., Low [20.5%], Moderate [39.6%], and High [39.6%]) were identified. Compared to the Low class, patients in the High class were younger, female, and more likely to live alone and had a higher comorbidity burden and a lower functional status. In addition, these patients had a higher symptom burden and a poorer quality of life. Based on clinically meaningful cutoff scores, 80% of the patients in this study had moderate to high levels of both cognitive fatigue and evening physical fatigue. In addition, these patients experienced high levels of other common symptoms (e.g., anxiety, depression, sleep disturbance, and pain). These co-occurring symptoms and other modifiable characteristics associated with membership in the Moderate and High classes may be potential targets for individualized symptom management interventions.

BACKGROUND Patients with gynecologic cancer undergoing chemotherapy experience multiple co-occurring symptoms. Understanding how symptom clusters change over time is essential to the development of interventions that target multiple co-occurring symptoms. OBJECTIVE The aim of this study was to assess the relative stability of symptom clusters across a chemotherapy cycle in patients with gynecologic cancer. METHODS This is a longitudinal, descriptive study. Eligible patients (n = 232) were English-speaking adults (≥18 years old) with gynecologic cancer. Data were collected in the week before patients' second or third cycle of chemotherapy (T1) and at 1 (T2) and 2 (T3) weeks after chemotherapy. Three dimensions of the symptom experience (occurrence, severity, and distress) were assessed using a modified version of the Memorial Symptom Assessment Scale. Symptom clusters for each dimension and time point were identified through exploratory factor analysis. RESULTS A 5-factor solution was selected for each exploratory factor analysis. Hormonal, respiratory, and weight change clusters were identified across all dimensions and time points. A psychological symptom cluster was identified at T1 for occurrence and severity and at T2 and T3 for all 3 dimensions. A gastrointestinal symptom cluster was identified at T1 for occurrence and at T2 and T3 for all 3 dimensions. The hormonal, respiratory, psychological, and weight change symptom clusters exhibited common symptoms across dimensions and time points. CONCLUSIONS Hormonal, respiratory, weight change, and psychological symptom clusters are relatively stable across a cycle of chemotherapy in patients with gynecologic cancer. IMPLICATIONS FOR PRACTICE Clinicians need to assess patients for multiple co-occurring symptoms and initiate multimodal interventions.

Identify subgroups of gastrointestinal (GI) cancer patients with distinct multiple co-occurring symptom profiles and evaluate for differences among these subgroups in demographic and clinical characteristics and quality of life (QOL) outcomes. Patients with GI cancers (n = 399) completed the Memorial Symptom Assessment Scale (MSAS) that was used to assess for multiple co-occurring symptoms. Latent class analysis (LCA) was used to identify subgroups of patients with distinct symptom profiles using symptom occurrence ratings. Differences in demographic and clinical characteristics and QOL outcomes among the subgroups were evaluated using parametric and nonparametric tests. All Low (36.6%), Moderate (49.4%), and All High (14.0%) classes were identified. Compared to the All Low class, patients in the other two classes were significantly younger and were more likely to report depression and back pain. Compared to the other two classes, patients in the All High class had fewer years of education and a higher number of comorbidities. Significant differences were found among the three classes for comorbidity burden and total number of MSAS symptoms (i.e., All Low Moderate > All High). A higher symptom burden was associated with poorer QOL outcomes. The first study to identify subgroups of patients with GI cancers based on distinct symptom profiles. LCA allowed for the identification of risk factors associated with a higher symptom burden. Clinicians can use this information to identify high-risk patients and develop personalized symptom management interventions.

Background: Fatigue is the most common and debilitating symptom experienced by oncology patients undergoing chemotherapy. Little is known about patient characteristics that predict changes in fatigue severity over time. Purpose: To predict the severity of evening fatigue in the week following the administration of chemotherapy using machine learning approaches. Methods: Outpatients with breast, gastrointestinal, gynecological, or lung cancer (N = 1217) completed questionnaires one week prior to and one week following administration of chemotherapy. Evening fatigue was measured with the Lee Fatigue Scale (LFS). Separate prediction models for evening fatigue severity were created using clinical, symptom, and psychosocial adjustment characteristics and either evening fatigue scores or individual fatigue item scores. Prediction models were created using two regression and three machine learning approaches. Results: Random forest (RF) models provided the best fit across all models. For the RF model using individual LFS item scores, two of the 13 individual LFS items (i.e. ‘worn out’, ‘exhausted’) were the strongest predictors. Conclusion: This study is the first to use machine learning techniques to predict evening fatigue severity in the week following chemotherapy from fatigue scores obtained in the week prior to chemotherapy. Our findings suggest that the language used to assess clinical fatigue in oncology patients is important and that two simple questions may be used to predict evening fatigue severity.

BackgroundOne in five patients experience chronic pain 12months following total knee arthroplasty (TKA). This longitudinal study used a person-centred approach to identify subgroups of patients with distinct chronic pain profiles following TKA and identified preoperative characteristics associated with these profiles.MethodsOn the day before surgery, 202 patients completed questionnaires that assessed pain, interference with functioning, fatigue, anxiety, depression and illness perceptions. Average and worst pain were assessed prior to surgery, on postoperative day 4, at 6week and at 3 and 12months following surgery. Using growth mixture modelling, two subgroups with distinct average and worst pain profiles were identified.ResultsPatients in the "lower average" and "lower worst" pain classes had moderate preoperative pain scores that decreased over the remaining 9months following TKA. Patients in the "higher average" and "higher worst" pain classes had relatively higher preoperative pain scores that increased during the first three months and then decreased slightly over the remaining 9months. Patients in the higher pain classes had higher interference with function scores; used opioids prior to surgery more often, were more likely to receive a continuous nerve block and ketamine; had higher preoperative fatigue severity and interference scores; and had worse perceptions of illness than patients in the lower pain classes.ConclusionsThese risk factors may be used to identify subgroups of patients at higher risk for more severe pain after TKA. Future studies should test whether modifying these risk factors can improve patients' outcomes after TKA.Significance statementThe present study provides a novel and original analysis of pain profiles following total knee arthroplasty that may contribute to our understanding of the transition from acute to chronic pain. Our results may be used to identify patients at higher risk for poorer outcomes based on preoperative risk factors.

The objective of this study was to characterize and compare the dry-aging flavor precursors and their liberation mechanisms in beef aged with different methods. Thirteen paired loins were collected at 5 days postmortem, divided into four sections, and randomly assigned into four aging methods (wet-aging (WA), conventional dry-aging (DA), dry-aging in a water-permeable bag (DWA), and UV-light dry-aging (UDA)). All sections were aged for 28 days at 2 °C, 65% RH, and a 0.8 m/s airflow before trimming and sample collection for chemical, metabolomics, and microbiome analyses. Higher concentrations of free amino acids and reducing sugars were observed in all dry-aging samples (p < 0.05). Similarly, metabolomics revealed greater short-chain peptides in the dry-aged beef (p < 0.05). The DWA samples had an increase in polyunsaturated free fatty acids (C18:2trans, C18:3n3, C20:2, and C20:5; p < 0.05) along with higher volatile compound concentrations compared to other aging methods (aldehyde, nonanal, octanal, octanol, and carbon disulfide; p < 0.05). Microbiome profiling identified a clear separation in beta diversity between dry and wet aging methods. The Pseudomonas spp. are the most prominent bacterial species in dry-aged meat, potentially contributing to the greater accumulation of flavor precursor concentrations in addition to the dehydration process during the dry-aging. Minor microbial species involvement, such as Bacillus spp., could potentially liberate unique and potent flavor precursors.

OBJECTIVES: Older adults with serious mental illness (SMI) are more likely to have high body mass index (BMI) and chronic conditions such as cardiovascular disease and diabetes. A sedentary lifestyle, which may be attributed to pharmacologic side effects and the symptoms of mental illness, has been difficult to treat. Patients experiencing negative symptoms (e.g., apathy, anhedonia) may be more likely to exercise in a group setting with activities that are designed to stimulate the mind and encourage engagement. “Exergames,” or exercise-based videogames, are an interactive and stimulating method to provide aerobic activities. Exercise has also been shown to reduce the symptoms of depression. The purpose of this study is to evaluate the impact of a 10-week exergame program on depressive and negative symptoms in older adults with SMI. MATERIALS AND METHODS: A single-group pretest posttest study was conducted with 52 older adults diagnosed with SMI. Participants engaged in group exergame activities for 50-minute sessions three times a week for 10 weeks. The Patient Reported Outcome Measurement Information System (PROMIS) and the Scale for the Assessment of Negative Symptoms (SANS) were conducted at enrollment, 5 weeks, and 10 weeks. RESULTS: Participants achieved statistically significant reductions in self-reported depressive symptoms (−0.83, LL −1.46, UL −0.12) and observed negative symptoms (−5.29, LL −7.67, UL −3.14) over a 10-week period. CONCLUSIONS: Our results suggest utilization of exergames as an adjunct treatment can be an effective, engaging, and cost-efficient method to reducing depressive and negative symptoms in older adults with SMI.

Background Sepsis is associated with ascorbic acid (AA) depletion and critical illness‐related corticosteroid insufficiency (CIRCI) in humans. Hypotheses Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. Animals Thirty‐two healthy horses. Methods Randomized placebo‐controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were administered 1 hour after completion of LPS infusion. Clinical signs, clinicopathological variables, pro‐inflammatory cytokine gene expression and production, and plasma AA concentrations were assessed at various time points. Serum cortisol concentrations and ACTH stimulation tests were used to detect CIRCI. Results There was no effect of drug on clinical signs or pro‐inflammatory cytokine gene expression or production compared to controls at any time point. Administration of AA was associated with higher blood neutrophil counts 6 hours after LPS infusion (11.01 ± 1.02 K/μl) compared to other groups (8.99 ± 0.94 K/μL; P

Patients with colorectal cancer (CRC) experience multiple symptoms. Resilience is a positive health outcome that can assist patients to face and adapt to their disease.The purpose of this study was to evaluate a proposed resilience model for patients with CRC.Patients (n = 416), who were given a diagnosis of stage Ι to III CRC within the past 5 years, were recruited from 2 medical centers in Northern Taiwan. Symptom Severity Scale, Fatigue Symptom Inventory, and Center for Epidemiological Studies Depression scale were used to assess the risk factors of symptom severity, fatigue, and depressive symptoms, respectively. Cancer Behavior Inventory and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale were used to assess the protective factors of self-efficacy for coping with cancer and spiritual well-being, respectively. Resilience was assessed using the Resilience Scale. Structural equation modeling was used to evaluate the proposed resilience model for patients with CRC.The initial structural equation modeling fit indices did not support the proposed model. In the revised model, depressive symptoms was a partial mediator between protective factors and resilience with an acceptable model fit (comparative fit index, 0.968; root mean square error of approximation, 0.085; standardized root mean square residual, 0.034).Patients with CRC who had higher levels of protective factors had higher levels of resilience. This study provides new information on the role of depressive symptoms as a partial mediator between protective factors and resilience.Oncology nurses need to evaluate for depressive symptoms as well as protective factors and resilience in patients with CRC.

Chemotherapy-induced diarrhea (CID) is a common symptom that occurs in 50 to 80% of patients. Given that the majority of the data on the occurrence and severity of CID is based on physician-rated toxicity criteria, this study’s purposes were to identify subgroups of patients with distinct CID profiles and determine how these subgroups differ in terms of demographic and clinical characteristics; severity, frequency, and distress of CID; the co-occurrence of common GI symptoms; and QOL. Patients (n = 1133) completed the Memorial Symptom Assessment Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct diarrhea profiles. Differences among these subgroups were evaluated using parametric and nonparametric statistics. Four distinct diarrhea profiles were identified: none (58.3%), decreasing (22.0%), increasing (5.2%), and high (14.5%). Compared with the none class, patients in the high class had a lower functional status, a worse comorbidity profile, were more likely to have gastrointestinal cancer, and were more likely to receive chemotherapy on a 14-day cycle. No differences were found among the classes in the percentages of patients who received chemotherapy with a targeted therapy. Given that CID occurred in over 40% of the patients, clinicians should assess for this symptom and other common GI symptoms and initiate appropriate pharmacologic and dietary interventions.

BackgroundStudy purposes were to identify subgroups of patients with breast cancer with distinct self-reported financial distress (FD) profiles and determine which demographic, clinical and symptom characteristics, as well as quality of life (QOL) outcomes were associated with subgroup membership.MethodsPatients (n=391) who were assessed for changes in FD a total of 10 times from prior to through 12 months after breast cancer surgery. Latent profile analysis was used to identify subgroups of patients with distinct FD profiles.ResultsThree distinct FD profiles (ie, None (14.6%), Low (52.7%), High (32.7%)) were identified. Compared with None and/or Low subgroups, patients in the High subgroup were more likely to report a lower annual household income and performance status; had a higher body mass index, axillary lymph node dissection and more advanced stage disease; had a longer time from cancer diagnosis to surgery; and had received neoadjuvant or adjuvant chemotherapy. In addition, patients in the High subgroup reported higher fatigue, sleep disturbance, state/trait anxiety, depressive symptom scores, and lower attentional function and QOL scores.ConclusionThis study provides new insights on risk factors for and evidence of a higher symptom burden associated with FD. Findings from this study provide clinicians with information on how to identify high-risk patients and to recommend appropriate interventions for both symptom management and FD. Additional research on the mechanisms that underlie the relationships among FD and common physical and psychological symptoms may inform future interventions.

Use of electronic nicotine delivery systems (ENDS) is becoming increasingly prevalent. ENDS aerosols contain a variety of toxic components that may adversely impact health. Although exposure to traditional cigarette smoke is a risk factor for periodontal disease, the effects of ENDS on oral health have not been adequately examined. To evaluate potential oral health effects associated with ENDS use, a pilot study was performed with 14 current ENDS users and 16 never tobacco users. Participants completed questionnaires about their ENDS use and overall health. Saliva samples were assessed for differential biomarkers of inflammation, toxicity, and disease development. This included evaluation of specific inflammatory cytokines and the global assessment of alterations in metabolites. ENDS users were determined to have elevated saliva levels of interleukin-1β and tumor necrosis factor-α indicative of inflammation. Metabolite profiling determined 368 metabolites were differentially expressed in the saliva of ENDS users versus never tobacco users. Cotinine, the primary metabolite of nicotine, was the most significantly altered metabolite between the groups. Increased levels of prostaglandins and leukotrienes indicated that ENDS users exhibited increased arachidonic acid metabolism compared to never tobacco users. Additionally, a variety of other metabolites known to be involved in immune signaling such as gangliosides, ceramides, angiotensin, and others were also different between groups. Overall, our pilot study demonstrates differential saliva component profiles in current ENDS users, which may contribute to periodontal disease development. These alterations suggest specific pathways of oral disease induced by ENDS use and could be utilized as potential future biomarkers. Impact statement The use of traditional tobacco products is a known risk factor for the development of diseases including periodontal disease. To date, the potential oral health effects related to electronic nicotine delivery systems (ENDS) use is unknown. This study collected saliva from ENDS users and never tobacco users to examine differences in the oral cavity of inflammatory cytokines and metabolites. The identification and measurement of these ENDS-related changes provide insight into disease pathways potentially associated with ENDS use. The utilization of saliva samples collected from human participates enhances the application of the findings compared to the majority of studies using cell culture and animal models. In addition, these foundational findings can inform future studies to examining specific pathways identified, interventional approaches, and application of translatable biomarkers of ENDS use.

CONTEXT. While ~75% of breast cancer patients report changes in attentional function, little is known about how demographic, clinical, symptom, and psychosocial adjustment (e.g., coping) characteristics influence changes in the trajectories of attentional function over time. OBJECTIVES. This study evaluated inter-individual variability in the trajectories of self-reported attentional function and determined which demographic, clinical, symptom, and psychosocial adjustment characteristics were associated with initial levels and with changes in attentional function from prior to through 12 months after breast cancer surgery. METHODS. Prior to surgery, 396 women were enrolled. Attentional Function Index (AFI) was completed prior to and nine times within the first 12 months after surgery. Hierarchical linear modeling (HLM) was used to determine which characteristics were associated with initial levels and trajectories of attentional function. RESULTS. Given an estimated preoperative AFI score of 6.53, for each additional month, the estimated linear rate of change in AFI score was an increase of 0.054 (p

Context Cancer and its treatment are inherently stressful and stress impacts important patient outcomes. Patients vary considerably in their response to stress. Understanding this variability requires a patient-centered multidimensional approach. Objectives The objectives of this study were to identify and characterize patient subgroups with distinct multidimensional stress profiles (stress appraisal, exposure, and adaptation) during cancer treatment. Methods Among 957 patients undergoing chemotherapy for breast, gastrointestinal, gynecological, or lung cancer, latent profile analysis was performed to identify patient subgroups using concurrent evaluations of global (Perceived Stress Scale) and cancer-specific (Impact of Events Scale–Revised) stress, lifetime stress exposure (Life Stressor Checklist–Revised), and resilience (Connor-Davidson Resilience Scale-10). Results Three latent classes were identified: “Normative” (54.3%; intermediate global stress and resilience, lower cancer-related stress, lowest life stress); “Stressed” (39.9%; highest global and cancer-specific stress scores, lowest resilience, most life stress); and “Resilient” (5.7%; lowest global stress, cancer-specific stress comparable to Normative class, highest resilience, intermediate life stress). Characteristics that distinguished the Stressed from the Normative class included the following: younger age, female gender, lower socioeconomic status, unmarried/partnered, living alone, poorer functional status, and higher comorbidity burden. Compared to Stressed patients, Resilient patients were more likely to be partnered, to not live alone, and had a higher functional status. No demographic or clinical characteristics differentiated Normative from Resilient patients. Exposure to specific life stressors differed significantly among the classes. Conclusion A subset of patients warrants intensive psychosocial intervention to reduce stress and improve adaptation to cancer. Intervention efforts may be informed by further study of Resilient patients.

Context Patients with end-stage renal disease undergoing dialysis experience multiple concurrent symptoms. These symptoms cluster together and have negative impacts on patient outcomes. However, information on changes in symptom clusters over time is limited. Objectives This longitudinal study examined the stability of symptom clusters and their impacts on health-related quality of life and functional status over a period of one year. Methods Eligibility criteria were patients diagnosed with end-stage renal disease; had received dialysis consecutively for at least three months; and had given written informed consent. Dialysis Symptom Index, Kidney Disease Quality of Life 36, and Karnofsky Performance Status Scale were used to evaluate the impacts of symptom clusters and outcomes. Exploratory factor analyses and multiple regression analyses were used to determine symptom clusters and their associations with patient outcomes. Results Among the 354 recruited patients, 271 completed the 12-month assessment. Four symptom clusters were identified across the three assessments, namely, uremic, gastrointestinal, skin, and emotional. Within each cluster, the specific symptoms were varied. The uremic symptom cluster accounted for the largest amount of variability. Across the three assessments, a higher uremic cluster factor score was associated with poorer physical well-being, whereas a higher emotional cluster factor score was consistently associated with poorer mental well-being. Conclusion Symptoms in patients on dialysis clustered in relatively stable patterns. The four symptom clusters identified had consistent negative effects on various aspects of patients' well-being. Our findings suggest the need for ongoing symptom assessment and early recognition of symptoms that may contribute to adverse patient outcomes.

BACKGROUND Patients with gastrointestinal cancers experience moderate to high levels of sleep disturbance during chemotherapy that decreases their functional status and quality of life (QOL). OBJECTIVE The objectives of this study were to identify subgroups of patients with gastrointestinal cancers with distinct sleep disturbance profiles and evaluate for differences among these subgroups in demographic, clinical, and sleep characteristics, as well as co-occurring symptoms and QOL outcomes. METHODS Patients (n = 405) completed questionnaires 6 times over 2 cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct sleep disturbance profiles. RESULTS Three distinct sleep disturbance profiles (ie, low, high, very high) were identified. Compared with the low class, patients in the other 2 classes were significantly younger and less likely to be married and to exercise on a regular basis and received a higher number of previous treatments. Compared with the low class, patients in the other 2 classes reported higher levels of anxiety, depressive symptoms, morning and evening fatigue, and pain and lower levels of attentional function and QOL scores at enrollment. CONCLUSIONS This study is the first to use latent profile analysis to identify subgroups of patients with gastrointestinal cancers with distinct sleep disturbance profiles. Findings provide new insights on the associations between sleep disturbance and multiple co-occurring symptoms in these patients. IMPLICATIONS FOR PRACTICE Clinicians can identify patients who are at the highest risk for sleep disturbance and recommend a variety of sleep hygiene interventions (eg, establishment of a bedtime routine), as well as initiate interventions for other co-occurring symptoms.