Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Liraglutide and cardiovascular outcomes in adults with overweight or obesity: A post hoc analysis from SCALE randomized controlled trials.

The cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist approved for weight management at a dose of 3.0 mg, was evaluated post hoc using data from 5908 participants in 5 randomized, double-blind, placebo-controlled clinical trials. Participants were randomized to liraglutide or a comparator group (placebo or orlistat). The objective was to evaluate whether cardiovascular risk was increased with liraglutide treatment. The primary composite outcome of this time-to-event analysis was the first occurrence of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. These cardiovascular events were adjudicated prospectively for three of the trials and retrospectively for two trials by an event adjudication committee. The primary outcome was analyzed using a Cox proportional hazards model, stratified by trial. With liraglutide 3.0 mg, 8 participants had positively adjudicated cardiovascular events (1.54 events/1000 person-years) compared to 10 participants in the comparators group (3.65 events/1000 person-years). The hazard ratio for liraglutide 3.0 mg compared to comparators was 0.42 (95% confidence interval, 0.17-1.08). In this analysis, liraglutide 3.0 mg treatment was not associated with excess cardiovascular risk. However, the wide confidence intervals and retrospective adjudication of events in two of the trials are limitations of the analysis.

Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer: Aggregate data and individual patient data meta-analyses.

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer.

PURPOSE: Clinical reports suggest that many breast cancer patients experience persistent fatigue as a long-term side effect of adjuvant chemotherapy treatment. To investigate this issue further, we examined the characteristics and correlates of fatigue in women who had completed adjuvant chemotherapy for breast cancer and in a comparison group of women with no history of cancer. PATIENTS AND METHODS: Participants were 61 women with breast cancer who had completed chemotherapy an average of 471 days previously and 59 women with no history of cancer. All participants completed standardized self-report measures of fatigue, sleep quality, menopausal symptoms, and coping and were administered a structured clinical interview to identify current and past psychiatric disorder. RESULTS: Compared with women with no history of cancer, former adjuvant chemotherapy patients reported more severe fatigue (P < .01) and worse quality of life because of fatigue (P < .05). More severe fatigue among patients was significantly (P < .05) related to poorer sleep quality, more menopausal symptoms, greater use of catastrophizing as a coping strategy, and current presence of a psychiatric disorder. CONCLUSION: These findings support the view that many breast cancer patients experienced heightened fatigue after completion of adjuvant chemotherapy treatment. Results yield a profile of women who are at increased risk for heightened fatigue after chemotherapy and suggest ways to intervene clinically to prevent or reduce fatigue in this patient population.

Characteristics and correlates of cognitive functioning following bone marrow transplantation.

Patients who undergo bone marrow transplantation (BMT) often report cognitive problems following treatment. This study used cognitive tests and a self-report measure of subjective cognitive complaints to determine (1) the rate of objective cognitive impairment in a sample of 65 BMT patients, and (2) the correspondence of patients' cognitive complaints to their actual cognitive performance. At 6 months following BMT, patients were assessed in seven cognitive domains--attention, verbal learning, verbal memory, visual memory, simple executive function, complex executive function, and psychomotor speed. Cognitive complaints were likewise assessed. In all, 51% had at least mild impairment (-1 standard deviation (s.d.) below published norms) in one or more cognitive domains, with 28% demonstrating moderate-to-severe impairment (-2 s.d.). Older patients and patients with lower IQ were more likely to score in the impaired range on objective cognitive tests, with males and the less educated showing trends toward scores in the impaired range. Younger patients made significantly more cognitive complaints. Total cognitive complaints were unrelated to average cognitive performance, and complaints in specific cognitive domains were largely unrelated to objective performance on corresponding domains. Findings suggest that patients who complain about their cognitive performance following BMT differ from those who experience actual deficits.

Pilot study of a home-based aerobic exercise program for sedentary cancer survivors treated with hematopoietic stem cell transplantation.

We report a pilot study of a home-based aerobic exercise program in a group of 17 adult hematopoietic stem cell transplant (HSCT) recipients. Participants had received no cancer treatment for at least 6 months and reported leisure time physical activity less than 20 min per day and fewer than three times a week during the previous month. Following baseline assessments of aerobic fitness, fatigue symptoms, and quality of life, participants were placed on home-based aerobic exercise programs consisting of 20-40 min of activity in the target heart rate zone (40-60% predicted heart rate reserve) delivered in three to five sessions per week for 12 weeks. Subjects were supplied with electronic heart rate monitors and we encouraged program adherence using weekly telephone contacts and exercise diaries. In all, 32 of the 42 qualified candidates consented (acceptance=76%). Of these, 17 kept appointments for baseline assessments, four did not complete the study (attrition=46%), and no exercise-related adverse events were reported. Scores on measures of aerobic fitness, fatigue severity, and physical well-being improved (signed ranks test; P<0.05) during program participation. Our findings suggest that individually prescribed, home-based aerobic exercise is an acceptable, safe, and potentially effective intervention for improving physical functioning and fatigue in sedentary HSCT recipients.

Characteristics of psychiatric consultations in a pediatric cancer center.

Data on psychiatric consultations with 58 pediatric cancer patients are summarized. Although most patients received DSM-III axis I diagnoses, adjustment disorder was diagnosed in 30 cases (52%). The patients with primarily depressive features were significantly older than those with anxious features.

Temperature-induced chromatin changes in ethanol-fixed cells.

We studied the chromatin structure of rat thymocytes fixed in 70% ethanol at 0-44 degrees C by flow cytometry and gel electrophoresis. The fluorescence of the DNA-specific dye mithramycin increased by 93% when thymocytes were exposed at 44 degrees C in the fixative compared to cells kept at 0 degrees C. Antibody labeling (X-ANA) of the core histones was 65% lower for the 44 degrees C-treated cells compared to the control cells (0 degree C). The emission anisotropies of the DNA-specific dye Hoechst 33258 bound to chromatin were 0.341 and 0.318 for thymocytes fixed at 0 degree C and 44 degrees C, respectively. Increased mobility of DNA in chromatin of 44 degrees C-treated cells, as revealed by the emission anisotropy of Hoechst 33258, was not due to denaturation of DNA but was probably caused by removal of constraints situated at short intervals (less than or equal to 50 BP) along the DNA helix. The short intervals between these constraints in chromatin fixed at 0 degree C suggests that they were histones. PAGE of 0.5 N H2SO4-extracted histones showed that the 44 degrees C treatment reduced total core histone content by 65% and that the different histones were lost in unequal amounts. The loss was about 75% and 54% for the histone pairs H3/H4 and H2A/H2B, respectively. The amount of H1 was reduced by about 25% on temperature treatment. The temperature-induced change in the chromatin structure of the cells in 70% ethanol was biphasic. A change in the three-dimensional structure of chromatin occurred for temperatures up to 20 degrees C (no histones were released but binding of mithramycin increased by approximately 15%, whereas the binding of X-ANA decreased by the same amount). Sixty-five percent of core histones were released in the second phase (20-44 degrees C), which may explain the further increase and decrease in the binding of mithramycin and X-ANA, respectively.

Quality of life following bone marrow transplantation for breast cancer: a comparative study.

As more women are treated with bone marrow transplantation (BMT) for breast cancer, there is growing interest in quality of life (QOL) following treatment. Although there have been some clinical studies of QOL following BMT, this area has received little systematic attention. In particular, it is unclear how QOL for women treated with BMT for breast cancer differs from that which might be expected for 'healthy' women of about the same age. To address this issue, we compared QOL reported by women treated with autologous BMT for breast cancer with that of a group of women of similar age with no history of cancer. In addition, we examined the relationship of demographic factors, medical factors, and self-reported symptom prevalence, severity, and distress to QOL in post-BMT patients. All participants completed the SF-36 Health Survey developed from the Medical Outcomes Study (SF-36). Post-BMT patients also completed the ECOG Performance Status Rating Scale (PSR) and the Memorial Symptom Assessment Scale (MSAS). Results indicated that, compared to the women with no cancer history, post-BMT patients reported significantly impaired physical functioning, physical role functioning, general health, vitality, social functioning, and emotional role functioning. Impaired QOL following BMT was significantly associated with lower income, a longer time to engraftment, longer hospital stay, poor performance status, and greater symptom prevalence, severity, and distress. The problems identified in this study may be important targets for intervention when trying to improve QOL following BMT.

Patients' psychosocial concerns following stem cell transplantation.

Information regarding the nature, frequency, correlates and temporal trajectory of concerns of stem cell transplantation (SCT) recipients is critical to the development of interventions to enhance quality of life (QOL) in these individuals. This study examined psychosocial concerns in 110 SCT (87% autologous) recipients drawn from two SCT centers. Participants were a mean of 46 years of age and 17 months post-SCT (range 3-62 months). Information regarding current and past SCT-related concerns, performance status, and demographic characteristics was collected by telephone interview or questionnaire. Recipients reported a wide variety of psychosocial concerns following SCT. Recipients who were younger, female and evidenced a poorer performance status reported a larger number of post-SCT concerns. Examination of the temporal trajectory of concerns suggests that some concerns are salient throughout the course of post-SCT recovery (eg disease recurrence, energy level, 'returning to normal'), some are salient early in the course of recovery (eg quality of medical care, overprotectiveness by others), and others emerge later in the course of recovery (eg feeling tense or anxious, sexual life, sleep, relationship with spouse/partner, ability to be affectionate). Implications for the development of interventions to enhance post-SCT QOL are identified.

Anticipatory anxiety in women receiving chemotherapy for breast cancer.

This study examined (a) the prevalence and course of anxiety before the 1st 6 infusions of cancer chemotherapy and (b) the contribution of trait anxiety, side effect expectations, and prior occurrence of posttreatment side effects to anxiety before infusions. Fifty-three women receiving adjuvant chemotherapy for breast cancer participated. Anxiety was most prevalent and intense before the 1st infusion. Trait anxiety predicted anxiety before both the 1st and subsequent infusions. Prior occurrence of posttreatment nervousness also predicted anxiety before subsequent infusions, even after accounting for trait anxiety and other posttreatment side effects. Results are discussed in terms of the role that anxiety proneness, response expectancy, and classical conditioning may play in the development of anxiety before repeated chemotherapy infusions.

Analysis of child and parent behavior during painful medical procedures.

Examined (a) the impact of demographic, medical, and psychological factors on overall child distress during an invasive medical procedure required for pediatric cancer treatment and (b) the relationship of individual parent behaviors to child distress across phases of the procedure. Seventy 3- to 10-year-old pediatric cancer patients receiving outpatient venipuncture and their parents participated. Overall distress was greater in younger children who had fewer previous venipunctures and poorer venous access and whose parents rated them prior to the procedure as less likely to be cooperative. Providing explanations regarding the procedure was the parent behavior most clearly associated with child distress. The impact of parent explanation depended on when the explanation was given and on the child's level of distress at the time.

Adult-child interaction during invasive medical procedures.

Adult-child interactions during stressful medical procedures were investigated in 43 pediatric patients videotaped during a venipuncture procedure in the course of cancer treatment. Relations among six adult behavior categories (explain, distract, command to engage in coping behavior, give control to the child, praise, and criticize/threat/bargain) and three child behavior categories (momentary distress, cry/scream, and cope) were examined using correlational and sequential analysis. Results indicated that adult distraction resulted in increased child coping and reduced momentary distress and crying. Adult explanations, although a likely response to child distress and crying, did not result in a reduction of these behaviors. Attempts to give the child control reduced child crying. Implications for clinical interventions during painful medical procedures are discussed.

An analysis of a behavioral intervention for children undergoing venipuncture.

An examination of factors was conducted to determine the effectiveness of the distraction component of a behavioral intervention (use of a party blower). In one condition, parents were instructed to coach children in the use of a party blower and to praise child cooperation. In a second condition, nurses were instructed to assist parents in coaching the child. Parents used the coaching skills they learned and got their children to use the distraction technique. Use of the distraction technique was associated with less crying. Encouragement from a health care professional and intervention early in the procedure did not enhance the intervention's effectiveness. Older children and children who were less distressed during the initial phase of the procedure were less likely to reject the intervention.

High performance liquid chromatography with multiwavelength detection: a technique for identification of iodinated x-ray contrast agents in human body fluids and brain tissue.

PURPOSE: Several cases of a severe adverse reaction, referred to as "ascending tonic-clonic seizure syndrome," have been reported after administration of water-soluble iodinated x-ray contrast agents for myelographic examinations. Because of the bizarre reactions, the identities of the causative contrast media were questioned. METHODS: Analyses of biologic materials from four of these patients were performed by using reverse-phase high-performance liquid chromatography. The chromatographic system was equipped with a fast-scanning UV-visible detector for the analysis of the UV-spectra of the chromatographic peaks. RESULTS: The analyses revealed that the nonionic contrast agents iohexol or ioversol were not present in detectable amounts in any of the samples. On the other hand, the chromatographic analyses revealed peaks that cochromatographed with and showed the same UV-spectra as the ionic agents diatrizoate, metrizoate, and ioxitalamate. CONCLUSION: The results indicate inadvertent injection of ionic contrast medium in all four cases.

Behavioral and psychological responses to HIV antibody testing.

The development of tests to identify the antibody to human immunodeficiency virus (HIV) has made it possible to diagnose infection with the virus prior to the development of physical symptoms. The introduction of these tests raises questions regarding the effects of informing individuals of their antibody status. These issues include the emotional impact of telling individuals that they have been infected with a fatal virus and the usefulness of antibody testing in promoting behaviors that would reduce the spread of acquired immunodeficiency syndrome (AIDS). Research that has examined changes in psychological distress and in behaviors associated with HIV infection among individuals who have undergone antibody testing is reviewed. Methodological issues encountered in studying behavioral and psychological responses to antibody testing are identified, and directions for future research are offered.

Behavioral intervention to reduce child and parent distress during venipuncture.

This study investigated a behavioral intervention incorporating parent coaching, attentional distraction, and positive reinforcement to control child distress during invasive cancer treatment. Children (N = 23) requiring physical restraint to complete venipuncture were alternately assigned to either a behavioral intervention or an attention control condition. Child distress behaviors were recorded, and self-reports of parent, child, and nurse distress were obtained. Parent and nurse also rated child distress. Results of planned comparisons indicate that observed child distress, parent-rated child distress, and parent ratings of his/her own distress were significantly reduced by behavioral intervention and were maintained across the course of three intervention trials. The use of physical restraint to manage child behavior was also significantly reduced. Child self-reported pain and nurse ratings of child distress were not significantly affected.

Conditioned emotional distress in women receiving chemotherapy for breast cancer.

This study investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Women scheduled to begin chemotherapy were randomly assigned either to an experimental group (exposed to a distinctive stimulus before each chemotherapy infusion) or a control group. After repeated infusions of chemotherapy, patients' responses to the distinctive stimulus were assessed in a location not associated with chemotherapy administration. At the test trial, experimental group patients showed evidence of increased emotional distress (self-reported on a visual analog scale) after the presentation of the distinctive stimulus, whereas control group patients did not. Post hoc analyses indicated that these increases in distress were not secondary to other conditioned responses (e.g., nausea, taste aversion). Thus, results supported the hypothesis that the pairing of a distinctive stimulus with chemotherapy would result in the development of a conditioned emotional response.

Family caregiver quality of life: differences between curative and palliative cancer treatment settings.

To compare the impact of cancer caregiving in curative and palliative settings on family caregiver quality of life (QOL), 267 family caregivers of cancer patients receiving curative treatment were compared to 134 family caregivers of cancer patients receiving palliative treatment through hospice. Both groups completed a demographic profile in addition to two self-report QOL questionnaires. Patient performance status and disease site were also recorded. Family caregivers of patients receiving palliative care had significantly lower QOL scores and lower scores on physical health. Hierarchical multiple regressions showed that after accounting for patient performance status, treatment status accounted for no additional significant variability in QOL scores. After accounting for caregiver level of education, treatment status accounted for no additional significant variability in physical health. These results suggest that the lower QOL scores of caregivers in the palliative setting are a reflection of the patients' poorer performance status. The lower physical health scores of caregivers in the palliative setting appear to be a reflection of their lower educational level. Additional research is needed to evaluate the influence of specific demands of caregiving and emotional distress of the caregiver on caregiver QOL.