Toronto aortic stenosis quality of life questionnaire (TASQ): validation in TAVI patients.

BACKGROUND: Aortic stenosis (AS) is a common cardiac condition whose prevalence increases with age. The symptom burden associated with severe aortic stenosis (AS) can introduce significant lifestyle disruptions and if left untreated can lead to a poor prognosis. Quality of life (QoL) is an important consideration in these patients. The TASQ is a QoL tool that was developed for aortic stenosis patients. We evaluated the psychometric properties of this specific questionnaire in patients who underwent transcatheter aortic valve implantation (TAVI), which is a therapeutic option for patients with severe aortic stenosis (AS). METHODS: The properties of the TASQ in measuring QoL were evaluated in AS patients undergoing TAVI. Patients presenting for the TAVI procedure (N = 62) were evaluated pre-TAVI, at discharge, 1-month, and 3-month follow-ups. Demographic information as well as caregiver status, and daily activities were recorded. In addition to the TASQ, they completed the KCCQ (Kansas City Cardiomyopathy Questionnaire) and the IIRS (Illness Intrusiveness Rating Scale). RESULTS: The TASQ is a 16-item self-administered questionnaire that assesses AS-specific QoL across five domains: physical symptoms; physical limitations; emotional impact; social limitations, and health expectations. TASQ subscales are internally consistent (α = 0.74-0.96) and showed significant improvements from baseline across assessments (p < 0.001). Construct validity evidence was demonstrated by correlations consistent with theoretically derived hypotheses across time points. CONCLUSIONS: The TASQ is a brief measure of AS-specific QoL that is sensitive to change in patients undergoing TAVI. Items on the TASQ capture important QoL concerns reported by AS patients, suggesting this is a measure of relevant and meaningful outcomes for this patient population. Detection of early improvements in QoL by the TASQ is promising, with important implications for the evaluation of procedural outcomes in this population.

Quality of life trajectories during the first year following hematopoietic cell transplantation: an inception cohort study.

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) affects quality of life (QOL). Patient-reported outcomes examine symptoms, side effects, distress, and physical and social problems, but positive outcomes have been ignored. This inception cohort study followed people over the first year following HCT to document positive and negative outcomes. METHODS: People with hematologic cancers treated by HCT completed complementary self-report instruments at four milestones: (a) pre-transplant (N = 88); (b) engraftment (N = 80); (c) short-term post-discharge (N = 60); and (d) long-term post-discharge (N = 45). We examined symptoms, side effects, illness intrusiveness, depressive symptoms, positive and negative affect, and self-esteem. We compared QOL in HCT with diverse published values. RESULTS: QOL deteriorated following HCT. Most variables returned to baseline by short-term post-discharge, but self-esteem and illness intrusiveness required more time. Illness intrusiveness at 1 year post-discharge was higher in HCT than other cancer groups; negative affect, too, was higher, but HCT survivors also reported higher positive affect. HCT and other cancer survivors reported similar depressive symptom levels. Compared to healthy people, HCT survivors reported more severe depressive symptoms, but similar positive and negative affect. CONCLUSIONS: QOL changes dramatically following HCT. People report more interference with valued activities and interests after 1 year than survivors of other cancers, but depressive symptoms are not higher. Positive and negative affect are equivalent to healthy community residents. Continued involvement in psychologically meaningful activities may preserve QOL.

A two-dimensional model of disrupted body integrity: initial evaluation in head and neck cancer.

PURPOSE: This cross-sectional study presents an initial psychometric evaluation of a two-dimensional (perceptual and evaluative) conceptualization and measure of disrupted body integrity (DBI)-illness-related disruption of the sense of the body as an integrated, smoothly functioning whole. METHODS: Male and female head and neck cancer (HNC) outpatients (N = 98) completed a questionnaire package prior to outpatient visits. MAIN OUTCOME MEASURES: The Disrupted Body Integrity Scale (DBIS) was developed to measure the perceptual and evaluative facets of DBI. Self-report measures of disfigurement, stigma, depressive symptoms, and negative affect were also completed. RESULTS: Almost all DBIS subscales demonstrated good internal consistency. Results largely supported the DBIS's construct validity. The majority of subscales correlated within the predicted range of r's = .40-.70. Almost all DBIS constructs were positively linked with either depressive symptoms or disfigurement. None correlated with positive affect, and only two subscales, abnormal sensations (perceptual) and physical vulnerability (evaluative), correlated with negative affect. DBIS constructs showed little relation with stigma, once disfigurement effects were controlled for. CONCLUSIONS: Findings offer preliminary evidence for the DBIS and the relevance of DBI in HNC. Further evaluation of DBI in disease adaptation and the DBIS's factor structure is warranted.

CD56bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft-versus-host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results.

Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow were grouped together, a higher chronic graft-versus-host disease frequency was associated with lower proportions of CD56bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.

Balancing give and take between patients and their spousal caregivers in hematopoietic stem cell transplantation.

OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) is a demanding treatment. Spouses of HSCT patients assume caregiving responsibilities that can induce feelings of burden and disrupt relationship equity. On the basis of equity theory, we propose a conceptual framework examining the individual and dyadic experience of HSCT patients and their caregivers. The model includes feelings of inequity, patient self-perceived burden, caregiver burden, and distress. METHODS: The HSCT patients and their spousal caregivers were recruited prior to HSCT between March 2011 and September 2012. Each member of the dyad self-administered a questionnaire package. RESULTS: Seventy-two dyads were included in the path analyses. Our model demonstrated an inadequate statistical fit; however, with one modification, an adequate to good fit was obtained: χ2 (df) = 6.01(5), normed χ2  = 1.20, standardized root mean square residual = 0.048, comparative fit index = 0.99, Tucker-Lewis index = 0.96, and root-mean-square error of approximation = 0.05 (90% CI, 0.00-0.18). As hypothesized, pre-HSCT caregiver burden mediates the relationship between caregiver underbenefit and caregiver distress. However, patient self-perceived burden was not associated with patient distress; rather, patient perception of overbenefit was related to patient distress. In our modified model, the results demonstrate that patient overbenefit influenced caregiver burden; however, there was not a reciprocal influence, because caregiver variables did not affect patient variables. CONCLUSIONS: Our proposed theoretical framework describes patients' and caregivers' individual experience of distress before HSCT but does not as clearly encompass the dyadic experience. Addressing perceived imbalances and providing psycho-education on role changes within HSCT dyads before transplantation may be a useful prehabilitation strategy for preventing distress.

Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial.

BACKGROUND: Pretreatment with anti-thymocyte globulin (ATG) decreases the occurrence of chronic graft-versus-host disease (CGVHD) after haemopoietic cell transplantation from an unrelated donor, but evidence of patient benefit is absent. We did a study to test whether ATG provides patient benefit, particularly in reducing the need for long-term immunosuppressive treatment after transplantation. METHODS: We did a phase 3, multicentre, open-label, randomised controlled trial at ten transplant centres in Canada and one in Australia. Eligible patients were aged 16 to 70 years with any haematological malignancy and a Karnofsky score of at least 60 receiving either myeloablative or non-myeloablative (or reduced intensity) conditioning preparative regimens before haemopoietic cell transplantation from an unrelated donor. We allocated patients first by simple randomisation (1:1), then by a minimisation method, to either pretransplantation rabbit ATG plus standard GVHD prophylaxis (ATG group) or standard GVHD prophylaxis alone (no ATG group). We gave a total dose of ATG of 4·5 mg/kg intravenously over 3 days (0·5 mg/kg 2 days before transplantation, 2·0 mg/kg 1 day before, and 2·0 mg/kg 1 day after). The primary endpoint was freedom from all systemic immunosuppressive drugs without resumption up to 12 months after transplantation. Analysis was based on a modified intention-to-treat method. This trial was registered at ISRCTN, number 29899028. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and assigned 203 eligible patients to treatment (101 to ATG and 102 to no ATG). 37 (37%) of 99 patients who received ATG were free from immunosuppressive treatment at 12 months compared with 16 (16%) of 97 who received no ATG (adjusted odds ratio 4·25 [95% CI 1·87-9·67]; p=0·00060. The occurrence of serious adverse events (Common Terminology Criteria grades 4 or 5) did not differ between the treatment groups (34 [34%] of 99 patients in the ATG group vs 41 [42%] of 97 in the no ATG group). Epstein-Barr virus reactivation was substantially more common in patients who received ATG (20 [one of whom died-the only death due to an adverse event]) versus those who did not receive ATG (two [no deaths]). No deaths were attributable to ATG. INTERPRETATION: ATG should be added to myeloblative and non-myeloblative preparative regimens for haemopoietic cell transplantation when using unrelated donors. The benefits of decreases in steroid use are clinically significant. Epstein-Barr virus reactivation is increased, but is manageable by prospective monitoring and the use of rituximab. Future trials could determine whether the doses of ATG used in this trial are optimum, and could also provide additional evidence of a low relapse rate after non-myeloablative regimens. FUNDING: The Canadian Institutes of Health Research and Sanofi.

Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

Illness intrusiveness and subjective well-being in patients with glioblastoma.

Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on quality of life (QOL) is poorly understood. In other patient populations, illness intrusiveness (the extent to which disease and treatment disrupts valued activities and interests) is associated with low subjective well-being, after controlling for disease and treatment variables. In this cross-sectional cohort study, we examined the relations among illness intrusiveness, disease burden, and subjective well-being in GBM. 73 GBM patients completed validated self-report measures of depression, positive affect, illness intrusiveness, and health-related QOL. Responses were compared to data from six other cancer groups using repeated measures analyses of variance. Hierarchical multiple-regression analyses tested the hypothesis that illness intrusiveness accounts for well-being after controlling for the effects of disease burden. GBM patients reported less positive affect, more depression, and more illness intrusiveness than people with other cancers. Illness intrusiveness correlated with depression and (low) positive affect. Associations among cancer symptoms, depression, and positive affect decreased when illness intrusiveness was added to regression equations. Good performance status and high cancer-symptom burden were associated with illness intrusiveness and depression. GBM patients report greater distress, lower positive affect, and more illness intrusiveness than people with other cancers. Subjective well-being is mediated in part by illness intrusiveness in this population. In addition to medical treatment, efforts to help patients remain engaged in valued activities and interests may help preserve QOL after the diagnosis of a GBM.

Empirical validation of the English version of the Fear of Cancer Recurrence Inventory.

PURPOSE: Cancer patients report that help in managing fear of cancer recurrence (FCR) is one of their greatest unmet needs. Research on FCR has been limited by the very few validated, multi-dimensional measures of this construct. One exception is the Fear of Cancer Recurrence Inventory (FCRI), originally developed and empirically validated in French. The present study validated the English version of the FCRI. METHODS: The FCRI was translated into English using a forward-backward translation procedure and pilot-tested with 17 English-speaking cancer patients. Cross-cultural equivalency of the French and English versions was established by administering both forms to 42 bilingual cancer patients. Last, 350 English-speaking breast, colon, prostate, or lung cancer patients were asked to complete the FCRI. A subsample (n = 135) was mailed the FCRI again one month later to evaluate test-retest reliability. RESULTS: The English translation of the FCRI was well accepted by participants. There was no item-bias when comparing bilingual participants' answers on both versions. A confirmatory factor analysis supported the hypothesized seven-factor structure. The English version has high internal consistency (α = .96 for the total scale and .71-.94 for the subscales) and test-retest reliability (r = .88 for the total scale and 56-.87 for the subscales). CONCLUSIONS: The English version of the FCRI is a reliable and valid measure of FCR applicable to breast, colon, prostate, and lung cancer patients. Its multi-dimensional nature makes it an attractive research and clinical tool to further our knowledge of FCR.

Do stigma and its psychosocial impact differ between Asian-born Chinese immigrants and Western-born Caucasians with head and neck cancer?

Stigma appears to influence emotional distress and well-being in cancer survivors, but cross-cultural differences have been ignored. Previous studies suggest that stigma may be especially relevant for survivors of Asian origin. However, their study designs (e.g. focused on female cancers, qualitative designs, and an absence of comparison groups) limit the strength of this conclusion. We hypothesized that (1) Asian-born Chinese immigrants (AI) would report more perceived cancer-related stigma than Western-born Caucasians (WBC); and (2) the impact of stigma on emotional distress and well-being would be greater in AI as compared to WBC. Head and neck cancer survivors (n = 118 AI and n = 404 WBC) completed measures of well-being, emotional distress, and a three-item indicator of stigma in structured interviews. The majority of respondents (59%) reported one or more indicators of stigma. Stigma correlated significantly with emotional distress (r = .13, p = .004) and well-being (r = -.09, p = .032). Contrary to our hypotheses, WBCs and AIs did not differ in reported stigma nor did we detect differences in its psychosocial impact. Stigma exerts a deleterious psychosocial impact on head and neck cancer survivors. It did not differ significantly between AI and WBC survivors.

Distancing, self-esteem, and subjective well-being in head and neck cancer.

BACKGROUND: Distancing (i.e. construing oneself as dissimilar to a negatively-stereotyped group) preserves self-esteem and may benefit other domains of subjective well-being. Head and neck cancer (HNC) is stigmatized because major risk factors include avoidable lifestyle variables (smoking, alcohol consumption, and human papilloma virus). Because the benefits of coping efforts, such as distancing, are most evident when people are under stress, we hypothesize that the psychosocial benefits of distancing will be most pronounced when cancer and its treatment interfere substantially with participation in valued activities and interests (i.e. high illness intrusiveness). OBJECTIVE: To test whether distancing preserves self-esteem and other domains of subjective well-being (SWB) in HNC, especially when illness intrusiveness is high. METHODS: Five hundred and twenty-two HNC outpatients completed a semantic-differential measure of perceived similarity to the 'cancer patient' and measures of illness intrusiveness, self-esteem, depressive symptoms, and psychological well-being in structured interviews. Evaluations of the 'cancer patient' reflected cancer stereotypes. RESULTS: A statistically significant interaction supported the central hypothesis: When people held negative stereotypes, those who construed themselves as similar to the 'cancer patient' reported lower self-esteem than those who construed themselves as dissimilar. Distancing did not benefit other SWB variables. Some results were counter-intuitive: e.g. Emotional distress increased with increasing illness intrusiveness when people did not hold negative cancer stereotypes, but when they held highly negative stereotypes, distress decreased with increasing illness intrusiveness. CONCLUSIONS: Overall, distancing preserved self-esteem in people with HNC and was associated with benefits in other SWB domains.

The psychosocial impact of stigma in people with head and neck or lung cancer.

BACKGROUND: Lung and head and neck cancers are widely believed to produce psychologically destructive stigma because they are linked to avoidable risk-producing behaviors and are highly visible, but little research has tested these ideas. We examined cancer-related stigma, its determinants, and its psychosocial impact in lung (n = 107) and head and neck cancer survivors (n = 99) ≤ 3 years post-diagnosis. We investigated cancer site, self-blame, disfigurement, and sex as determinants, benefit finding as a moderator, and illness intrusiveness as a mediator of the relation between stigma and its psychosocial impact. METHODS: Prospective participants received questionnaire packages 2 weeks before scheduled follow-up appointments. They self-administered widely used measures of subjective well-being, distress, stigma, self-blame, disfigurement, illness intrusiveness, and post-traumatic growth. RESULTS: As hypothesized, stigma correlated significantly and uniquely with negative psychosocial impact, but contrary to common beliefs, reported stigma was comparatively low. Reported stigma was higher in (i) men than women, (ii) lung as compared with head and neck cancer, and (iii) people who were highly disfigured by cancer and/or its treatment. Benefit finding buffered stigma's deleterious effects, and illness intrusiveness was a partial mediator of its psychosocial impact. CONCLUSIONS: Stigma exerts a powerful, deleterious psychosocial impact in lung and head and neck cancers, but is less common than believed. Patients should be encouraged to remain involved in valued activities and roles and to use benefit finding to limit its negative effects.

Routine screening for suicidal intention in patients with cancer.

OBJECTIVES: Suicide rates are elevated in individuals with cancer, although suicidal intention is not typically assessed in cancer centers. We evaluated in a large comprehensive cancer center the utility of an electronic Distress Assessment and Response Tool (DART), in which suicidal intention is assessed with a single item. METHODS: Patients attending cancer clinics completed DART as part of routine care. DART includes measures of physical symptoms, depression, anxiety, social difficulties, and practical concerns. Medical variables were obtained from the Princess Margaret Cancer Registry, the data warehouse of cancer patient statistics. A Generalized Estimating Equation (GEE) model was used to assess factors associated with suicidal intention. RESULTS: Between September 2009 and March 2012, 4822/5461 patients (88.3%) who completed DART consented to the use of their data for research. Amongst the latter, 280 (5.9%) of the 4775 patients who answered the question reported suicidal ideation, which was related to physical and psychological distress, and social difficulties (ps < 0.0001). Amongst those with ideation who responded to the intention question, 20/186 (10.8%) reported suicidal intention. Of respondents with more severe suicidal ideation, 12/49 (24.5%) reported suicidal intention. Using a GEE model, suicidal intention in those with ideation was significantly associated with male sex, difficulty making treatment decisions, and with everyday living concerns. CONCLUSIONS: Suicidal ideation is reported on an electronic distress screening tool (DART) by almost 6% of cancer patients, of whom almost 11% report suicidal intention and 33% decline to indicate intention. DART demonstrated utility in identifying patients who may be at highest risk of completed suicide and who require urgent clinical assessment.

Negative cancer stereotypes and disease-specific self-concept in head and neck cancer.

BACKGROUND: Life-threatening diseases, such as head and neck cancer (HNCa), can stimulate the emergence of a new disease-specific self-concept. We hypothesized that (i) negative cancer-stereotypes invoke distancing, which inhibits the adoption of a disease-specific self-concept and (ii) patient characteristics, disease and treatment factors, and cancer-related stressors moderate the phenomenon. METHODS: Head and neck cancer outpatients (N = 522) completed a semantic-differential measure of disease-specific self-concept (perceived similarity to the 'cancer patient') and other self-report measures in structured interviews. Negative cancer-stereotypes were represented by the number of semantic-differential dimensions (0-3) along which respondents evaluated the stereotypic 'cancer patient' negatively (i.e., negative valence). We tested the two-way interactions between negative valence and hypothesized moderator variables. RESULTS: We observed significant negative valence × moderator interactions for the following: (i) patient characteristics (education, employment, social networks); (ii) disease and treatment factors (cancer-symptom burden); and (iii) cancer-related stressors (uncertainty, lack of information, and existential threats). Negative cancer stereotypes were consistently associated with distancing of self from the stereotypic 'cancer patient,' but the effect varied across moderator variables. All significant moderators (except employment and social networks) were associated with increasing perceived similarity to the 'cancer patient' when respondents maintained negative stereotypes; perceived similarity decreased when people were employed or had extensive social networks. Moderator effects were less pronounced when respondents did not endorse negative cancer stereotypes. DISCUSSION: When they hold negative stereotypes, people with HNCa distance themselves from a 'cancer patient' identity to preserve self-esteem or social status, but exposure to cancer-related stressors and adaptive demands may attenuate these effects.

The burden of stress in head and neck cancer.

BACKGROUND: Head and neck cancer (HNCa) introduces numerous stressors. We developed the Cancer-Related Stressors Checklist (CRSC), which documents exposure to seven categories of common stressors and emotional distress. We surveyed HNCa survivors and examined associations among exposure to cancer-related stressors, illness intrusiveness (i.e., cancer-induced interference with lifestyles, activities, and interests), and distress. We also investigated whether reported exposure rates differ between self-administered and interviewer-administered measures. METHODS: Respondents included HNCa survivors, stratified by sex, who participated in one of two clinical studies (N1 = 162; N2 = 408) examining the psychosocial impact of illness intrusiveness. All completed the CRSC, the Center for Epidemiologic Studies Depression Scale, and the Illness Intrusiveness Ratings Scale. Study 1 respondents self-administered the instruments; an interviewer administered them in Study 2. We gathered clinical data by self-report and from medical records. RESULTS: High inter-rater reliability corroborated the 8-subscale structure of the CRSC (Krippendorff alpha = .92). Cancer-related stressor exposures differed significantly across categories (interpersonal stressors were most common). Controlling for empirically identified covariates and distress, exposure to each cancer-related stressor correlated significantly and uniquely with illness intrusiveness. All stressor categories correlated significantly with distress, but coefficients were low to moderate, substantiating incremental validity. Respondents reported fewer exposures when materials were self-administered as compared with interviewer-administered, but reported distress levels did not differ by mode of administration. CONCLUSIONS: Cancer-related stressors are common and burdensome in HNCa and, therefore, merit clinical attention. Identifying specific stressors will allow more targeted and effective interventions to alleviate and prevent distress.

Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. METHODS: This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60­7·60]; p=0·0016). At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9­23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9­25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2­29·2) versus 31·3% (21·9­40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5­35·1) in the anti-thymocyte globulin group and 41·3% (31·3­51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 70·6% (95% CI 60·6­78·6) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 53·3% (42·8­62·8) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35­0·90]; p=0·017). Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient in the anti-thymocyte globulin plus GVHD prophylaxis group died of Epstein-Barr virus hepatitis, but no deaths were attributable to anti-thymocyte globulin. INTERPRETATION: The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including decreases in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin should be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. FUNDING: Canadian Institutes of Health Research and Sanofi.

Cultural syndromes and age moderate the emotional impact of illness intrusiveness in rheumatoid arthritis.

OBJECTIVE: The authors investigated cultural syndromes (multidimensional vectors comprising culturally based attitudes, values, and beliefs) and age as moderators of the emotional impact of illness intrusiveness--illness-induced lifestyle disruptions--in rheumatoid arthritis (RA) and examined illness intrusiveness effects in total and separately for three life domains (relationships and personal development, intimacy, and instrumental). RESEARCH METHOD/DESIGN: People with RA (n = 105) completed the Illness Intrusiveness Ratings, Individualism-Collectivism, and Center for Epidemiologic Studies--Depression scales in a one-on-one interview. RESULTS: Controlling for disease and background characteristics, the association between illness intrusiveness (total score and the Relationships and Personal Development subscale) and distress was inverse when young adults with RA endorsed high horizontal individualism. Illness intrusiveness into intimacy was associated with increased distress, and this intensified when respondents endorsed high vertical individualism, horizontal collectivism, vertical collectivism, or low horizontal individualism. The negative emotional impact of illness intrusiveness into intimacy diminished with increasing age. CONCLUSION: Given an aging and increasingly pluralistic society, diversity can no longer be ignored in addressing the psychosocial impact of chronic, disabling disease.

Development of a psychoeducational intervention for people affected by pancreatic cancer.

BACKGROUND: Pancreatic cancer has one of the highest mortality rates of any malignancy, placing a substantial burden on patients and families with high unmet informational and supportive care needs. Nevertheless, access to psychosocial and palliative care services for the individuals affected is limited. There is a need for standardized approaches to facilitate adjustment and to improve knowledge about the disease and its anticipated impact. In this intervention-development paper guided by implementation science principles, we report the rationale, methods, and processes employed in developing an interdisciplinary group psychoeducational intervention for people affected by pancreatic cancer. The acceptability and feasibility of implementation will be evaluated as a part of a subsequent feasibility study. METHODS: The Schofield and Chambers framework for designing sustainable self-management interventions in cancer care informed the development of the intervention content and format. The Consolidated Framework for Implementation Research served as an overarching guide of the implementation process, including the development phase and the formative evaluation plan of implementation. RESULTS: A representative team of stakeholders collaboratively developed and tailored the intervention content and format with attention to the principles of implementation science, including available resourcing. The final intervention prototype was designed as a single group-session led by an interdisciplinary clinical team with expertise in caring for patients with pancreatic cancer and their families and in addressing nutrition guidelines, disease and symptom management, communication with family and health care providers, family impact of cancer, preparing for the future, and palliative and supportive care services. CONCLUSIONS: The present paper describes the development of a group psychoeducational intervention to address the informational and supportive care needs of people affected by pancreatic cancer. Consideration of implementation science during intervention development efforts can optimize uptake and sustainability in the clinical setting. Our approach may be utilized as a framework for the design and implementation of similar initiatives to support people affected by diseases with limited prognoses.

Predicting stress-related problems in long-term breast cancer survivors.

INTRODUCTION: Little is known about the early clinical and psychosocial factors associated with subsequent stress-related problems in breast cancer survivors. METHODS: We used data collected at 3, 7, 11, and 15 months post-diagnosis to predict stress-related problems in 86 breast cancer survivors at 6 years post-diagnosis. We examined two common stress-related problems: (a) emotional distress and (b) intrusion and avoidance. Hypothesized risk factors included perceived stressfulness of the cancer; fear of the future; poor perceived health; initial stress-related problems; avoidance coping; and second cancer experience. Hypothesized protective factors included active coping (seeking social support; positive problem solving); optimism; and social support. RESULTS: Hierarchical multiple regression analyses, controlling for age and education, indicated that positive problem-solving coping at 3 months and emotional distress at 7 months significantly predicted 6-year emotional distress (R(2)=.24, P<.01). Second cancer experience and 3-month intrusion and avoidance significantly predicted 6-year intrusion and avoidance (R(2)=.38, P<.001). In both cases, risk and/or protective factors measured at 11 and 15 months did not add significantly to the regression equations. DISCUSSION/CONCLUSION: Symptoms of intrusion and avoidance should be monitored carefully during the first 3 months following diagnosis because they signal the risk that these symptoms will persist in the long-term. Elevated emotional distress at 7-months post-diagnosis and second-cancer experiences may signal the need for psychosocial intervention. Overreliance on positive problem solving to cope early in the disease trajectory may be detrimental in the longer term.