Exploring Inflammation and Stress as Biological Correlates of Symptoms in Children With Advanced Cancer: A Longitudinal Feasibility Study.

Background: Few studies have examined biomarkers of stress and inflammation as underlying mechanisms of symptoms in adolescents and young adults with cancer. This study determined the feasibility of collecting blood and saliva samples across time, described the range and distribution of biomarkers, and explored the association of biomarkers with symptom adverse events (AEs). Method: This longitudinal, prospective repeated-measures single-site feasibility study recruited N = 10 children (M = 12.5 years) receiving treatment for advanced cancer. Symptom AE data and inflammation (cytokines and C-reactive protein) and physiologic response to stress (salivary cortisol and salivary alpha-amylase) biomarker levels were collected at three time points. Descriptive statistics were used to examine feasibility and acceptability and to summarize symptom AE, stress, and inflammatory biomarker data. A linear regression model was used to determine cortisol diurnal slopes. The relationship between symptom and inflammatory biomarker data was explored and Hedges's g statistic was used to determine its effect size. Results: Participants provided 83% of saliva samples (n = 199/240) and 185 samples were sufficient to be analyzed. Nurses collected 97% (n = 29/30) of blood samples. Participants reported the saliva collection instructions, kits, and reminders were clear and helpful. Insomnia, pain, fatigue, and anxiety demonstrated the most medium and large negative effects with inflammatory markers. Symptom AEs demonstrated the highest number of medium and large negative effects with interleukin-8 and tumor necrosis factor-alpha (-0.53 to -2.00). Discussion: The results indicate longitudinal concurrent collection of symptom and biomarker data is feasible and inflammatory and stress biomarkers merit consideration for inclusion in future studies.

The role of spirituality in pain experiences among adults with cancer: an explanatory sequential mixed methods study.

PURPOSE: Foundational research demonstrates that spirituality may affect the way people with cancer experience pain. One potential route is through alterations in thoughts and beliefs, such as pain-related catastrophizing. The purpose of this study is to understand whether spirituality impacts pain experiences through pain-related catastrophizing. METHODS: This explanatory sequential mixed methods study was informed by an adapted Theory of Unpleasant Symptoms. Data were collected via online surveys (N = 79) and follow-up qualitative interviews (N = 25). Phase 1 employed Empirical Bayesian analysis. Phase 2 used deductive content analysis. Phase 3 involved creating a mixed methods joint display to integrate findings and draw meta inferences. RESULTS: Results indicate that total spiritual well-being was directly negatively associated with pain-related catastrophizing, and indirectly negatively associated with the outcomes of pain interference, pain severity, and pain-related distress. Qualitative categories highlight the supportive role of spirituality when facing pain, while also shedding light on the limitations of spirituality in the context of some pain (i.e., severe, neuropathic, and/or chronic). Mixed methods findings reveal the importance of spirituality for some people as they face cancer and cancer-related pain, as well as the need for integrating spirituality as part of a larger pain management plan. CONCLUSIONS: This research advances supportive cancer care by exploring the complex role of spirituality in pain experiences. Findings will inform further exploration into the role of spirituality in supporting holistic symptom management in the context of cancer, as well as developing and testing interventions to enhance spirituality and address symptom-related suffering.

Mediational roles of stress-coping factors in the relationship between patient-perceived communication quality and physical functioning: racial difference between Chinese and Non-Hispanic White American breast cancer survivors.

PURPOSE: The assumption that patient-provider communication may mediate patients' sense of control over cancer to affect health outcomes has limited evidence. This study examines whether patient-perceived cancer care communication quality (PPCQ) mediates stress appraisal and coping behavior, affecting physical functioning across different racial groups. METHODS: Two hundred and twenty Chinese American and 216 non-Hispanic White (NHW) women (ages 28-80) with stage 0-III breast cancer, 1-5 years post-diagnosis, and without recurrence, enrolled and completed a cross-sectional telephone survey. Physical functioning was measured by the NIH-PROMIS short form. Validated measures of PPCQ, patients' evaluation of their socioeconomic well-being, stress appraisal (perceived severity and control), use of coping strategies, treatment-related symptoms, and comorbidities were also assessed. Path analyses were used to examine the mediation for each racial group. RESULTS: Regardless of race, treatment-related symptoms, comorbidities, and socioeconomic well-being were all directly related to physical functioning (p < 0.05). The impact of PPCQ on physical functioning was mediated by perceived control in the Chinese American group (p < 0.05), but not in the NHW group. Perceived severity and coping were not mediators of physical functioning in either group. CONCLUSIONS: The mediational pathway from PPCQ to perceived control to physical functioning in Chinese American survivors may be partially explained by their lower socioeconomic well-being and culturally valued conformity to physicians as a medical authority. These sociocultural dynamics reinforce the importance of cancer care communication. For NHW survivors, the impact of treatment-related symptoms and socioeconomic well-being on physical functioning outweighed their PPCQ and perceived control.

Symptom Adverse Events and Quality of Life of Children With Advanced Cancer: Results From a Longitudinal Study Using the Pediatric Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events.

Background: The presence of poorly controlled symptoms negatively impacts the quality of life (QoL) throughout cancer treatment. The purpose of this multisite study was to explore the relationship between QoL and symptom adverse events (AEs) in children with advanced cancer over 6 months. Method: A prospective and longitudinal descriptive study design was used to collect QoL and symptom AE data from children aged 2 to 18 with advanced cancer. QoL was measured using the Pediatric Quality of Life Inventory (PedsQLTM) Cancer Module 3.0 and symptom AEs were measured using the Pediatric Patient-Reported Outcome-Common Terminology Criteria for AEs (PRO-CTCAEs®). Descriptive statistics were used to describe QoL and symptom AE data. Correlational analyses and generalized linear mixed models were used to examine the relationship between symptom AEs and QoL. Results: Forty-nine children participated in the study. The mean total PedsQLTM score was 73.86 for the sample across all time points. Children diagnosed with a central nervous system (CNS) tumor reported poorer QoL compared to children diagnosed with a hematologic malignancy or non-CNS solid tumor. Symptom frequency AEs of anxiety, pain, nausea, insomnia, hot flashes, and fatigue severity demonstrated the strongest and most significant negative correlation with total QoL scores. Analyses of the relationship between QoL and symptom AEs over time revealed time-specific significant differences with children who experienced frequency AEs of nausea, and anxiety reporting poorer QoL at time point 4 (week 8). Discussion: The Ped PRO-CTCAE® and PedsQLTM can be used to evaluate the relationship between symptom AEs and QoL in practice and in future research.

The Role of Spirituality in Pain Experiences among Adults with Cancer: An Explanatory Sequential Mixed Methods Study.

Purpose: Foundational research demonstrates that spirituality may affect the way people with cancer experience pain. One potential route is through alterations in thoughts and beliefs, such as pain-related catastrophizing. The purpose of this study is to understand whether spirituality impacts pain experiences through pain-related catastrophizing. Methods: This explanatory sequential mixed methods study was informed by an adapted Theory of Unpleasant Symptoms. Data were collected via online surveys (N = 79) and follow-up qualitative interviews (N = 25). Phase 1 employed Empirical Bayesian analysis. Phase 2 used deductive content analysis. Phase 3 involved creating a mixed methods joint display to integrate findings and draw meta inferences. Results: Results indicate that spirituality was directly negatively associated with pain-related catastrophizing, and indirectly negatively associated with the outcomes of pain interference, pain severity, and pain-related distress. Qualitative categories highlight the supportive role of spirituality when facing pain, while also shedding light on the limitations of spirituality in the context of some pain (i.e., severe, neuropathic, and/or chronic). Mixed methods findings reveal the importance of spirituality for some people as they face cancer and cancer-related pain, as well as the need for integrating spirituality as part of a larger pain management plan. Conclusions: This research advances supportive cancer care by exploring the complex role of spirituality in pain experiences. Findings will inform further exploration into the role of spirituality in supporting holistic symptom management in the context of cancer, as well as developing and testing interventions to enhance spirituality and address symptom-related suffering.

A hybrid type 2 effectiveness-implementation design to evaluate a community-based, heart-healthy intervention for women of low socio-economic status.

BACKGROUND: Women of low socioeconomic status continue to experience a disproportionate burden of cardiovascular disease. To respond to their unique needs, we adapted the intervention and implementation strategy of an effective theory-based psychoeducational intervention for improving heart-healthy behaviors. Study aims were to evaluate implementation (i.e., reach, fidelity, acceptability, appropriateness) and effectiveness (i.e., perceived stress, common physical symptoms in primary care, physical activity, diet) of the adapted program we called mySTEPS. METHOD: We used a hybrid type 2 effectiveness-implementation approach. To evaluate implementation, we conducted a process evaluation using data from research records, observation rubrics, and pre-/post-intervention surveys. To evaluate potential effectiveness, we used a one-group, pre-/post-test design with three, sequential offerings (16 weeks each) in unique settings, used standardized, quantitative measures at 8 weeks post-intervention, and calculated effect sizes. RESULTS: Forty-two women were included in the evaluation. For reach, 66 % and 61 % of participants attended adequate numbers of educational and coaching sessions. Supporting fidelity of delivery, nurse implementers addressed 85-98 % of required criteria. Supporting fidelity of receipt, participants' pre- to post- knowledge scores increased and other scores revealed that nurse-implementers had interacted supportively throughout mySTEPS. Participants rated the acceptability and appropriateness of components positively. Effect-sizes revealed moderate decreases in stress, moderate increases in physical activity, and modest decreases in the number of physical symptoms. Dietary scores did not change. CONCLUSIONS: The effectiveness and implementation of mySTEPS were positive overall. After strengthening the dietary component, more extensive evaluation of mySTEPS can be conducted to explain mechanisms of action. MESH HEADINGS: Health behavior, prevention, self-determination theory, self-regulation theory, cardiovascular diseases, implementation strategies.

Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized, placebo-controlled 36-month study of safety and efficacy.

BACKGROUND CONTEXT PURPOSE: Evaluate the safety and efficacy of a single intradiscal injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with degenerative disc disease (DDD) through 36-month follow-up. STUDY DESIGN/SETTING: A multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and 1 in Australia). SUBJECT SAMPLE: A total of 100 subjects with chronic low back pain associated with moderate DDD (modified Pfirrmann score of 3-6) at one level from L1 to S1 for at least 6 months and failing 3 months of conservative treatment, including physical therapy were randomized in a 3:3:2:2 ratio to receive 6 million MPCs with HA, 18 million MPCs with HA, HA vehicle control, or saline control (placebo) treatment. OUTCOME MEASURES: Subjects were clinically and radiographically evaluated at 1, 3, 6, 12, 24, and 36 months postinjection. Subject-reported outcomes including adverse events, LBP on a Visual Analog Scale (VAS), Oswestry Disability Index (ODI), SF-36 and Work Productivity and Activity Index were collected. METHODS: Clinical and radiographic measures were collected at each visit. All randomized subjects were included in the safety assessments and analyzed based on the treatment received. Safety assessments included assessments of AEs, physical and radiographic examinations and laboratory testing. Efficacy assessments evaluated changes in VAS, ODI, and modified Pfirrmann (MP) scores between all active and control groups, respectively. Assessments included least squares mean (Mean), LS mean change from baseline (Mean Change) and responder analyses in order to assess the clinical significance of observed changes from baseline. The population for efficacy assessments was adjusted for the confounding effects of post-treatment interventions (PTIs). This study was conducted under an FDA Investigational New Drug application sponsored and funded by Mesoblast. RESULTS: There were significant differences between the control and MPC groups for improvement in VAS and ODI. The PTI-corrected VAS and ODI Means and Mean Change analyses; the proportion of subjects with VAS ≥30% and ≥50% improvement from baseline; absolute VAS score ≤20; and ODI reduction ≥10 and ≥15 points from baseline showed MPC therapy superior to controls at various time points through 36 months. Additionally, the proportion of subjects achieving the minimally important change and clinically significant change composite endpoints for the MPC groups was also superior compared with controls at various time points from baseline to 36 months. There were no significant differences in change in MP score from baseline across the groups. There were also no statistically significant differences in change in modified MP score at the level above or below the level treated between study arms. Both the procedure and treatment were well tolerated and there were no clinical symptoms of immune reaction to allogeneic MPCs. There was a low rate of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events, and the rates of these events in the MPC groups were not significantly different from the control groups. One TEAE of severe back pain was possibly related to study agent and one TEAE of implantation site infection was considered to be related to the study procedure. CONCLUSIONS: Results provide evidence that intradiscal injection of MPCs could be a safe, effective, durable, and minimally invasive therapy for subjects who have CLBP associated with moderate DDD.

Decisional Conflict During Major Medical Treatment Decision-making: a Survey Study.

BACKGROUND: Both patients and surrogate decision-makers experience decisional conflict when making a major medical treatment decision with life or death implications. The relationship between health literacy and decisional conflict while making a major medical treatment decision is not understood. OBJECTIVE: To identify the prevalence of individuals making major medical treatment decisions for themselves or someone else and to explore the relationships between decisional conflict and circumstances of the decision as well as the decision-maker. DESIGN: Two-phase survey study: in phase 1, we screened for who made a major treatment decision; in phase 2, we asked eligible respondents about their experience making the decision. PARTICIPANTS: Address-based random sample of 4000 Wisconsin residents; 1072 completed phase 1 and 464 completed phase 2. MAIN MEASURES: We asked respondents about types of decisions made, the most difficult decision made, and characteristics of the decision-maker and the decision. We included the Decisional Conflict Scale and four domains of the Health Literacy Questionnaire. Open-ended questions also allowed respondents to describe their experiences. KEY RESULTS: About 43% of respondents reported making a major medical treatment decision. Decisions about major surgery and life support were regarded as the most difficult decisions. Respondents who made the decision for a spouse/partner (ß = 6.65, p = 0.012), parent (ß = 9.27, p < 0.001), or someone else (ß = 10.7, p < 0.001) had higher decisional conflict. Respondents who reported higher ability to actively engage with healthcare providers (ß = - 5.24, p = 0.002) and to understand health information well enough to know what to do (ß = - 6.12, p = 0.001) had lower decisional conflict. CONCLUSIONS: The need to make major treatment decisions is likely to increase and making decisions on someone else's behalf appeared to be especially difficult. Improving communication to encourage patient and family engagement in the decision-making conversation, particularly for individuals with limited health literacy, may be helpful.

Perceived Stress Can Mediate the Associations between a Lifestyle Intervention and Fat and Fast Food Intakes.

This secondary analysis study addressed a gap of knowledge: whether perceived stress reduction created by a lifestyle intervention might serve as a mediator for reducing fat and fast food intakes in low-income overweight or obese mothers of young children. This analysis included 338 low-income overweight or obese mothers of young children who completed a phone interview immediately after the 16-week lifestyle intervention. Valid surveys were used to assess perceived stress and fat and fast food intakes. Composite indicator structural equation modeling was performed to test the mediation effects. The overall effect of the intervention was not significant for fat intake but was significant for fast food intake (B = -0.53, p < 0.05). When assessing the potential role of perceived stress as a mediator, the indirect effects of the intervention on fat (B = -0.39, p < 0.01) and fast food (B = -0.27, p < 0.01) intakes were both significant. Future dietary intervention studies aimed to reduce fat and fast food intakes in low-income overweight or obese mothers of young children might consider including practical strategies aimed at reducing perceived stress.

Effects of Massage on Postoperative Pain in Infants With Complex Congenital Heart Disease.

BACKGROUND: Pain management is an essential component of care for pediatric patients following surgery. Massage reduces self-reported postoperative pain in adults with heart disease but has received little attention in postoperative pediatric patients with complex congenital heart disease (CCHD). OBJECTIVES: The aim of the study was to evaluate the effectiveness of massage compared to a rest period on postoperative pain scores and physiological responses in infants with CCHD. METHODS: We used a two-group randomized clinical trial design with a sample of 60 infants with CCHD between 1 day and 12 months of age following their first cardiothoracic surgery. Both groups received standard postoperative care. Group 1 received a daily 30-minute restriction of nonessential caregiving (quiet time), and Group 2 received a daily 30-minute massage. Interventions continued for seven consecutive days. Pain was measured six times daily using the Face, Legs, Activity, Cry, Consolability Pain Assessment Tool (FLACC). Average daily doses of analgesics were recorded. Heart rates (HRs), respiratory rates (RRs), and oxygen saturations (SpO2) were recorded continuously. Daily averages, pre- and postintervention FLACC scores, and physiological responses were analyzed using descriptive statistics, generalized linear mixed models repeated measures, latent growth models, and/or regression discontinuity analysis. Fentanyl-equivalent narcotic values were used as a time-varying covariate. RESULTS: Adjusted pain scores were lower for the massage group on all days except Day 7. Overall, there were no group effects on level of pain or differential rate of change in pain. However, the massage group had lower daily pain scores with small to medium effect size differences, largest at Days 4, 5, and 6, and lower average daily HR and RR. There was little difference between groups in SpO2. Infants demonstrated immediate effects of massage, with HR and RR decreasing and oxygen saturations increasing. DISCUSSION: This study provides beginning evidence that postoperative massage may reduce pain and improve physiological parameters in infants with congenital heart disease. This nonpharmacological adjunct to pain management may provide a particular benefit for this population by reducing demand on the cardiorespiratory system.

Properties of the Early Symptom Measurement of Post-Stroke Depression: Concurrent Criterion Validity and Cutoff Scores.

BACKGROUND: Early-stage post-stroke depression (PSD) increases the risk of stroke-related disability and mortality in the first year of recovery. Presently available screening measures were developed to assess major depression, and none used a PSD screening criterion that was systematically developed and tested in populations of patients with acute stroke. PURPOSE: The purpose of this study was to evaluate the concurrent criterion validity and cutoff scoring of the Early Symptom Measurement of Post-Stroke Depression (ESM-PSD) instrument in hospitalized patients with acute stroke. METHODS: Purposive recruitment of newly admitted patients yielded a qualified sample of 139 nonaphasic participants who were 7-30 days post mild-to-moderate stroke confirmed by computed tomography and magnetic resonance images. Participants responded to the ESM-PSD and Hamilton Rating Scale for Depression-24 (HAMD-24). RESULTS: The mean number of post-stroke days was 11.99 (SD = 7.68). Cronbach's alpha estimates of internal consistency were ESM-PSD = .90 and HAMD-24 = .76. ESM-PSD measurement sensitivity and specificity were superior. The following three ESM-PSD cutoff scores, determined by the receiver operating characteristic curve, were used to assess clinically relevant early-symptom levels: no PSD < 14.5, low PSD = 14.5-25.5, moderate PSD = 25.5-45.5, high PSD ≥ 45.5. CONCLUSION/IMPLICATIONS FOR PRACTICE: ESM-PSD cutoff scores show the expected correspondence with mild-moderate-severe HAMD-24 symptoms, which was evidenced by the high area under the receiver operating characteristic curve. Planned follow-up research will assess the efficacy of using ESM-PSD scores to detect increased risk of major depression onset in patients with acute stroke.

Factors associated with Chinese American and White cancer survivors' physical and psychological functioning.

OBJECTIVE: To examine whether health-related stressors and resources are associated with physical function, depression, and anxiety in Chinese American and White breast cancer survivors. METHOD: During 2011-2013, this cross-sectional study enrolled Chinese American and White women from California cancer registries diagnosed with Stage 0-III breast cancer between 2006 and 2012. Survivors completed a telephone survey assessing health-related factors including comorbidity, treatment-related symptoms, medical communication, perceived threat, use of coping, and social support resources. Outcomes were assessed using the Patient-Reported Outcome Measurement Information System® (PROMIS®) short forms. Chinese were classified as low- or high-acculturated based on English proficiency, years in the United States, and interview language. Analyses were conducted using Tobit regression models. RESULTS: Low-acculturated Chinese (n = 136) had worse physical functioning than Whites (n = 216), controlling for demographics, cancer stage, and time since diagnosis (ß = -3.33, p = .01). This disparity was attenuated after adjusting for comorbidity and symptoms (ß = -1.63, p = .18). Perceived threat, disengagement coping, and lack of social support were associated with poorer psychological outcomes, regardless of ethnicity. Although low-acculturated Chinese had lower scores on all health-related factors than Whites, the former reported significantly lower level of depression (ß = -3.23) and anxiety (ß = -5.8) after adjusting for covariates (both p < .05). High-acculturated Chinese (n = 84) did not differ from Whites except that the former had significantly lower anxiety. CONCLUSION: Low-acculturated Chinese may benefit from interventions aimed to improve their physical problems. However, despite experiencing greater psychosocial stress, they reported better emotional functioning. Whether Chinese culture shapes this resiliency, or if it is a reporting bias will need further investigation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Impact of Intermediate Cystic Fibrosis Classification on Parents' Perceptions of Child Vulnerability and Protectiveness.

This cross-sectional, mixed-method study examined factors associated with parent perceptions of child vulnerability and protectiveness in three groups: cystic fibrosis (CF-group, n = 40), intermediate CF classification (I-group, n = 20), and healthy (H-group, n = 50). A composite indicator structural equation (CISE) using Bayesian estimation tested two mediational models: psychological and biological. Significant results ( p < .05) from the psychological model showed I-group and CF-group parents perceived their children to be more vulnerable than H-group parents but reported lower levels of protectiveness than H-group parents. Perceptions of vulnerability mediated protectiveness for CF- and I-groups. The biological model showed I-group children had significantly less severe genotype and phenotype, and lower sweat chloride levels than the CF-group; I-group parents had lower expectations about children developing CF symptoms. Both models showed negative associations between children's ages and protectiveness. Psychological factors explained perceptions of child vulnerability and protectiveness; biological factors explained protectiveness. Parent perceptions of vulnerability and protectiveness are separate, independent constructs.

Epigenetic silencing of SOCS5 potentiates JAK-STAT signaling and progression of T-cell acute lymphoblastic leukemia.

Activating mutations in cytokine receptors and transcriptional regulators govern aberrant signal transduction in T-cell lineage acute lymphoblastic leukemia (T-ALL). However, the roles played by suppressors of cytokine signaling remain incompletely understood. We examined the regulatory roles of suppressor of cytokine signaling 5 (SOCS5) in T-ALL cellular signaling networks and leukemia progression. We found that SOCS5 was differentially expressed in primary T-ALL and its expression levels were lowered in HOXA-deregulated leukemia harboring KMT2A gene rearrangements. Here, we report that SOCS5 expression is epigenetically regulated by DNA methyltransferase-3A-mediated DNA methylation and methyl CpG binding protein-2-mediated histone deacetylation. We show that SOCS5 negatively regulates T-ALL cell growth and cell cycle progression but has no effect on apoptotic cell death. Mechanistically, SOCS5 silencing induces activation of JAK-STAT signaling, and negatively regulates interleukin-7 and interleukin-4 receptors. Using a human T-ALL murine xenograft model, we show that genetic inactivation of SOCS5 accelerates leukemia engraftment and progression, and leukemia burden. We postulate that SOCS5 is epigenetically deregulated in T-ALL and serves as an important regulator of T-ALL cell proliferation and leukemic progression. Our results link aberrant downregulation of SOCS5 expression to the enhanced activation of the JAK-STAT and cytokine receptor-signaling cascade in T-ALL.

Predicting postoperative delirium severity in older adults: The role of surgical risk and executive function.

OBJECTIVES: Delirium is an important postoperative complication, yet predictive risk factors for postoperative delirium severity remain elusive. We hypothesized that the NSQIP risk calculation for serious complications (NSQIP-SC) or risk of death (NSQIP-D), and cognitive tests of executive function (Trail Making Tests A and B [TMTA and TMTB]), would be predictive of postoperative delirium severity. Further, we demonstrate how advanced statistical techniques can be used to identify candidate predictors. METHODS/DESIGN: Data from an ongoing perioperative prospective cohort study of 100 adults (65 y old or older) undergoing noncardiac surgery were analyzed. In addition to NSQIP-SC, NSQIP-D, TMTA, and TMTB, participant age, sex, American Society of Anesthesiologists (ASA) score, tobacco use, surgery type, depression, Framingham risk score, and preoperative blood pressure were collected. The Delirium Rating Scale-R-98 (DRS) measured delirium severity; the Confusion Assessment Method (CAM) identified delirium. LASSO and best subsets linear regression were employed to identify predictive risk factors. RESULTS: Ninety-seven participants with a mean age of 71.68 ± 4.55, 55% male (31/97 CAM+, 32%), and a mean peak DRS of 21.5 ± 6.40 were analyzed. LASSO and best subsets regression identified NSQIP-SC and TMTB to predict postoperative delirium severity (P < 00.001, adjusted R2 : 0.30). NSQIP-SC and TMTB were also selected as predictors for postoperative delirium incidence (AUROC 0.81, 95% CI, 0.72-0.90). CONCLUSIONS: In this cohort, we identified NSQIP risk score for serious complications and a measure of executive function, TMT-B, to predict postoperative delirium severity using advanced modeling techniques. Future studies should investigate the utility of these variables in a formal delirium severity prediction model.

Predictors of Mindfulness Meditation and Exercise Practice, from MEPARI-2, a randomized controlled trial.

OBJECTIVES: Health-supporting behaviors can be challenging to initiate and maintain. Data from the MEPARI-2 randomized trial were used to assess predictors of sustained exercise and meditation practice. METHODS: Adults aged 30 to 69 years not exercising regularly and without prior meditation training were randomized to 8-week trainings in mindfulness meditation, moderate intensity exercise, or observational control, and monitored for 8 months. Exercise participants reported day-to-day minutes of moderate and vigorous activity; mindfulness meditation participants reported minutes of informal and formal practice. Demographic characteristics and psychosocial factors were assessed as predictors of practice. Growth mixture modeling was used to identify higher and lower practice subgroups. RESULTS: 413 participants (75.8% female; mean (SD) age 49.7 (11.6) years) were randomized to exercise (137), mindfulness meditation (138), or control (138), with 390 (95%) completing the study. Seventy-nine percent of exercisers and 62% of meditators reported ≥150 minutes/week practice for at least half of the 37 weeks monitored. Self-reported minutes of mindfulness meditation and/or exercise practice were significantly (p<0.01) predicted by baseline levels of: general mental health, self-efficacy, perceived stress, depressive symptoms, openness, neuroticism, physical activity, smoking status, and number of social contacts. Growth mixture modeling identified subsets of people with moderate (100-200 min/week) and high (300-450 min/week) levels of self-reported practice for both mindfulness meditation (62% moderate; 38% high) and exercise (71% moderate; 29% high). CONCLUSIONS: In this sample, participants randomized to behavioral trainings reported high levels of practice sustained over 37 weeks. Baseline psychosocial measures predicted practice levels in expected directions.

Reducing Symptom Distress in Patients With Advanced Cancer Using an e-Alert System for Caregivers: Pooled Analysis of Two Randomized Clinical Trials.

BACKGROUND: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could. OBJECTIVE: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient's symptoms, as reported by a family caregiver. METHODS: A pooled analysis from two randomized clinical trials (NCT00214162 and NCT00365963) compared outcomes at 12 months for two unblinded groups: a control group (Comprehensive Health Enhancement Support System [CHESS]-Only) that gave caregivers access to CHESS, an online support system, and an experimental group (CHESS+CR [Clinician Report]), which also had CHESS but with a CR that automatically alerted clinicians if symptoms exceeded a predetermined threshold of severity. Participants were dyads (n=235) of patients with advanced lung, breast, or prostate cancer and their respective family caregivers from 5 oncology clinics in the United States of America. The proportion of improved patient threshold symptoms was compared between groups using area-under-the-curve analysis and binomial proportion tests. The proportion of threshold symptoms out of all reported symptoms was also examined. RESULTS: When severe caregiver-reported symptoms were shared with clinicians, the symptoms were more likely to be subsequently reported as improved than when the symptoms were not shared with clinicians (P<.001). Fewer symptom reports were completed in the group of caregivers whose reports went to clinicians than in the CHESS-Only group (P<.001), perhaps because caregivers, knowing their reports might be sent to a doctor, feared they might be bothering the clinician. CONCLUSIONS: This study suggests that an eHealth system designed for caregivers that alerts clinicians to worrisome changes in patient health status may lead to reduced patient distress. TRIAL REGISTRATION: Clinicaltrials.gov NCT00214162; https://clinicaltrials.gov/ct2/show/NCT00214162 (Archived by WebCite at http://www.webcitation.org/6nmgdGfuD) and Clinicaltrials.gov NCT00365963; https://clinicaltrials.gov/ct2/show/NCT00365963 (Archived by WebCite at http://www.webcitation.org/6nmh0U8VP).

Are Parents Who Feel the Need to Watch Over Their Children's Care Better Patient Safety Partners?

OBJECTIVES: Many parents report needing to watch over their child's hospital care to prevent mistakes. In this study, we assessed whether needing to watch over care predicts parent performance of recommended safety behaviors to reduce medication errors and health care-associated infections. METHODS: At admission, we surveyed 170 parents about their need to watch over care, demographics, and hospitalization factors. At discharge, parents were surveyed about medication awareness and hand hygiene behaviors. Logistic regression was used to examine how parents' need to watch over care predicted each behavior, adjusting for demographics and hospitalization factors. RESULTS: Thirty-eight percent of parents reported needing to watch over care. Most parents (77%) reported frequently or very frequently asking providers for drug names or doses. Fewer parents asked to check drug or infusion accuracy (29%) or to show or read aloud medication labels (21%). Few parents reminded providers to clean hands (4%), but most stated they would be comfortable asking (82%) and likely to speak up if a provider did not (78%). After adjustment, parents needing to watch over care were significantly more likely to ask providers to check drug or infusion accuracy (adjusted odds ratio = 4.59, 95% confidence interval 2.14-9.94) and for drug name or dose (adjusted odds ratio = 3.04, 95% confidence interval 1.25-7.39). CONCLUSIONS: Parents who report the need to watch over care are more likely to perform behaviors specific to safe medication use (but not hand hygiene) compared with those not reporting this need. Opportunities exist to engage parents as safety partners by leveraging their need to watch over care toward system-level safety initiatives.

Optimized approach for Ion Proton RNA sequencing reveals details of RNA splicing and editing features of the transcriptome.

RNA-sequencing (RNA-seq) has become the standard method for unbiased analysis of gene expression but also provides access to more complex transcriptome features, including alternative RNA splicing, RNA editing, and even detection of fusion transcripts formed through chromosomal translocations. However, differences in library methods can adversely affect the ability to recover these different types of transcriptome data. For example, some methods have bias for one end of transcripts or rely on low-efficiency steps that limit the complexity of the resulting library, making detection of rare transcripts less likely. We tested several commonly used methods of RNA-seq library preparation and found vast differences in the detection of advanced transcriptome features, such as alternatively spliced isoforms and RNA editing sites. By comparing several different protocols available for the Ion Proton sequencer and by utilizing detailed bioinformatics analysis tools, we were able to develop an optimized random primer based RNA-seq technique that is reliable at uncovering rare transcript isoforms and RNA editing features, as well as fusion reads from oncogenic chromosome rearrangements. The combination of optimized libraries and rapid Ion Proton sequencing provides a powerful platform for the transcriptome analysis of research and clinical samples.

Do Work Condition Interventions Affect Quality and Errors in Primary Care? Results from the Healthy Work Place Study.

BACKGROUND: While primary care work conditions are associated with adverse clinician outcomes, little is known about the effect of work condition interventions on quality or safety. DESIGN: A cluster randomized controlled trial of 34 clinics in the upper Midwest and New York City. PARTICIPANTS: Primary care clinicians and their diabetic and hypertensive patients. INTERVENTIONS: Quality improvement projects to improve communication between providers, workflow design, and chronic disease management. Intervention clinics received brief summaries of their clinician and patient outcome data at baseline. MAIN MEASURES: We measured work conditions and clinician and patient outcomes both at baseline and 6-12 months post-intervention. Multilevel regression analyses assessed the impact of work condition changes on outcomes. Subgroup analyses assessed impact by intervention category. KEY RESULTS: There were no significant differences in error reduction (19 % vs. 11 %, OR of improvement 1.84, 95 % CI 0.70, 4.82, p = 0.21) or quality of care improvement (19 % improved vs. 44 %, OR 0.62, 95 % CI 0.58, 1.21, p = 0.42) between intervention and control clinics. The conceptual model linking work conditions, provider outcomes, and error reduction showed significant relationships between work conditions and provider outcomes (p ≤ 0.001) and a trend toward a reduced error rate in providers with lower burnout (OR 1.44, 95 % CI 0.94, 2.23, p = 0.09). LIMITATIONS: Few quality metrics, short time span, fewer clinicians recruited than anticipated. CONCLUSIONS: Work-life interventions improving clinician satisfaction and well-being do not necessarily reduce errors or improve quality. Longer, more focused interventions may be needed to produce meaningful improvements in patient care. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov # NCT02542995.