Acceptability, feasibility and preliminary effects of an online group psychotherapy intervention for adolescents and young adults with cancer.

BACKGROUND: Adolescents and young adults (AYAs; ages 15-29 years) diagnosed with cancer are increasingly recognized as an oncology population with distinct psychosocial needs. However, few specialized psychosocial interventions for AYAs currently exist. This study reports on the development of a novel group-based psychotherapy intervention to address the psychosocial needs of AYAs. The objective was to evaluate the acceptability, feasibility, and preliminary effects of the intervention. METHODS: The manualized group psychotherapy program is delivered virtually over an 8-week period by registered psychologists. Four groups (n = 5-11 AYAs per group) with a total of N = 33 participants (Mage = 20.97 years, SD = 3.68, range = 15-29 years, 76% women) were conducted. Recruitment and retention data assessed intervention feasibility. Patient-reported psychosocial outcomes were measured at baseline and immediately following the intervention to assess preliminary effects. Acceptability was assessed following the intervention using a self-report measure of participant satisfaction. RESULTS: Overall, the completion rate of the intervention was 85% (n = 28). All participants "strongly agreed" (88%) or "agreed" (13%) that they were satisfied with the group. Meeting, sharing experiences, and expressing feelings with other AYAs were identified as the most helpful aspects. Participants reported significant improvements in emotional (p < 0.05) and functional (p < 0.01) quality of life from baseline to immediately post-intervention with medium effect sizes (d = 0.58-0.70). CONCLUSIONS: Findings suggest that the intervention is feasible, acceptable, and shows promise for improving psychosocial outcomes for AYAs. Further research will refine the intervention and establish efficacy in a randomized trial.

Assessing and Preparing Patients for Hematopoietic Stem Cell Transplant in Canada: An Environmental Scan of Psychosocial Care.

Recipients and caregivers of Hematopoietic Stem Cell Transplant (HCT) have extensive physical and psychosocial needs. HCT programs recognize the need to support psychosocial wellbeing. However, evidence-based guidance for pre-HCT psychosocial services is sparse. We conducted a qualitative environmental scan of programs across Canada to better understand how programs evaluate and support patients and caregivers prior to HCT. METHODS: HCT programs across Canada were contacted with a list of questions about their psychosocial assessment and preparation process with patients and caregivers. They could respond via email or participate in an interview over the phone. Descriptive qualitative content analysis was conducted, using steps outlined by Vaismoradi and colleagues (2013). RESULTS: Most participants were social workers from hospitals (64%). Four qualitative themes arose: (a) Psychosocial Team Composition. Psychosocial assessment for HCT patients was often provided by social workers, with limited availability of psychologists and psychiatrists. (b) Criteria for assessing select HCT patients. Participants prioritized psychosocial assessments for patients with higher perceived psychosocial needs or risk, and/or according to transplant type. Limited time and high psychosocial staff demands also played into decision-making. (c) Components and Practices of Pre-HCT Psychosocial Assessment. Common components and differences of assessments were identified, as well as a lack of standardized tools. (d) Patient Education Sessions. Many sites provided adjunct patient education sessions, of varying depth. CONCLUSION: Significant variation exists in the way programs across the country assess their patients' psychosocial pre-transplant needs and assist in preparing patients for the psychosocial aspects of HCT. This environmental scan identified several strategies used in diverse ways. Further in-depth research on program outcomes across Canada could help to identify which strategies are the most successful.

Racial and Socioeconomic Disparities in Long-Term Outcomes in ≥1 Year Allogeneic Hematopoietic Cell Transplantation Survivors: A CIBMTR Analysis.

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipient's ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.

Integrating Palliative Care in Hematopoietic Stem Cell Transplantation: A Qualitative Study Exploring Patient, Caregiver, and Clinician Perspectives.

PURPOSE: To explore patient, caregiver, and clinician perspectives on palliative care for patients undergoing hematopoietic stem cell transplantation (HSCT). PARTICIPANTS & SETTING: 8 patients who had undergone or would undergo HSCT, 4 caregivers, and 16 HSCT clinicians. METHODOLOGIC APPROACH: This qualitative, interpretive descriptive study used semistructured interviews conducted via telephone or videoconference. FINDINGS: Responses were categorized into the following two themes: concerns and challenges during and after HSCT, and tensions with integrating palliative care into HSCT. IMPLICATIONS FOR NURSING: The findings from this study highlight the unique and varied needs of patients and their caregivers during and after HSCT. More research is required to determine how to best integrate palliative care in this setting.

Mothers with Cancer: An Intersectional Mixed-Methods Study Investigating Role Demands and Perceived Coping Abilities.

Mothers with cancer report guilt associated with failing to successfully balance their parental roles and cancer. This study utilized a cross-sectional mixed-methods design and intersectional framework to investigate the multiple roles that mothers with cancer assume and their perceived coping ability. Participants included mothers diagnosed with any type or stage of cancer, in treatment or ≤3 years post-treatment, and experiencing cancer-related disability with a dependent child (<18 years, living at home). Participants completed a questionnaire battery, semi-structured interview, and optional focus group. Descriptive statistics, correlations, and thematic inductive analyses are reported. The participants' (N = 18) mean age was 45 years (SD = 5.50), and 67% were in active treatment. Their role participation (M = 42.74, ±6.21), role satisfaction (M = 43.32, ±5.61), and self-efficacy (M = 43.34, ±5.62) were lower than the general population score of 50. Greater role participation and higher role satisfaction were positively correlated (r = 0.74, p ≤ 0.001). A qualitative analysis revealed that the mothers retained most roles, and that their quality of life depended on their capacity to balance those roles through emotion-focused and problem-focused coping. We developed the intersectional Role Coping as a Mother with Cancer (RCMC) model, which has potential research and clinical utility.

Program Evaluation of a Class Addressing Psychosocial Topics in Preparation for Hematopoietic Cell Transplantation: a Brief Report.

Patients undergoing hematopoietic cell transplantation (HCT) and their caregivers can experience psychosocial complications pre-, during, and post-transplant. To meet the needs of the most patients and caregivers, a class was developed to prepare patients and caregivers to prevent and manage common psychosocial challenges. We evaluated the feasibility and acceptability of the class over a 5-month pilot period. Attendance in this class became part of standard pre-transplant care. Attendees were invited to complete a questionnaire (Likert-scale and open-ended questions) to evaluate the feasibility and acceptability of this class. Data were collected over a 5-month period. Descriptive analysis was completed. Patients (n = 41) and caregivers (n = 40) were satisfied to very satisfied with the class. Patients (80%) and caregivers (65%) reported that the class met their expectations, with several describing it as worthwhile and informative. Information relating to finances and benefits were considered most helpful, followed by emotional support resources. Patients (73%) and caregivers (93%) reported that they would recommend the class to others. This education class should be provided as early as possible to ensure that psychosocial needs are addressed. Future research initiatives include further assessing the perspectives of patients, clinicians, and other stakeholders; evaluating delivery methods; and collaborating with other centers.

Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis.

Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.

Community health status and outcomes after allogeneic hematopoietic cell transplantation in the United States.

BACKGROUND: The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes. METHODS: This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied. RESULTS: The median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM. CONCLUSIONS: Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.

Association of Mindfulness-Based Interventions With Anxiety Severity in Adults With Cancer: A Systematic Review and Meta-analysis.

Importance: Mindfulness-based interventions (MBIs), grounded in mindfulness, focus on purposely paying attention to experiences occurring at the present moment without judgment. MBIs are increasingly used by patients with cancer for the reduction of anxiety, but it remains unclear if MBIs reduce anxiety in patients with cancer. Objective: To evaluate the association of MBIs with reductions in the severity of anxiety in patients with cancer. Data Sources: Systematic searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and SCOPUS were conducted from database inception to May 2019 to identify relevant citations. Study Selection: Randomized clinical trials (RCTs) that compared MBI with usual care, waitlist controls, or no intervention for the management of anxiety in cancer patients were included. Two reviewers conducted a blinded screening. Of 101 initially identified studies, 28 met the inclusion criteria. Data Extraction and Synthesis: Two reviewers independently extracted the data. The Cochrane Collaboration risk-of-bias tool was used to assess the quality of RCTs, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Summary effect measures were reported as standardized mean differences (SMDs) and calculated using a random-effects model. Main Outcomes and Measures: Our primary outcome was the measure of severity of short-term anxiety (up to 1-month postintervention); secondary outcomes were the severity of medium-term (1 to ≤6 months postintervention) and long-term (>6 to 12 months postintervention) anxiety, depression, and health-related quality of life of patients and caregivers. Results: This meta-analysis included 28 RCTs enrolling 3053 adults with cancer. None of the trials were conducted in children. Mindfulness was associated with significant reductions in the severity of short-term anxiety (23 trials; 2339 participants; SMD, -0.51; 95% CI, -0.70 to -0.33; I2 = 76%). The association of mindfulness with short-term anxiety did not vary by evaluated patient, intervention, or study characteristics. Mindfulness was also associated with the reduction of medium-term anxiety (9 trials; 965 participants; SMD, -0.43; 95% CI, -0.68 to -0.18; I2 = 66%). No reduction in long-term anxiety was observed (2 trials; 403 participants; SMD, -0.02; 95% CI, -0.38 to 0.34; I2 = 68%). MBIs were associated with a reduction in the severity of depression in the short term (19 trials; 1874 participants; SMD, -0.73; 95% CI; -1.00 to -0.46; I2 = 86%) and the medium term (8 trials; 891 participants; SMD, -0.85; 95% CI, -1.35 to -0.35; I2 = 91%) and improved health-related quality of life in patients in the short term (9 trials; 1108 participants; SMD, 0.51; 95% CI, 0.20 to 0.82; I2 = 82%) and the medium term (5 trials; 771 participants; SMD, 0.29; 95% CI, 0.06 to 0.52; I2 = 57%). Conclusions and Relevance: In this study, MBIs were associated with reductions in anxiety and depression up to 6 months postintervention in adults with cancer. Future trials should explore the long-term association of mindfulness with anxiety and depression in adults with cancer and determine its efficacy in more diverse cancer populations using active controls.

Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.

Inferior Access to Allogeneic Transplant in Disadvantaged Populations: A Center for International Blood and Marrow Transplant Research Analysis.

Allogeneic hematopoietic cell transplantation (alloHCT) is offered in a limited number of medical centers and is associated with significant direct and indirect costs. The degree to which social and geographic barriers reduce access to alloHCT is unknown. Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) were integrated to determine the rate of unrelated donor (URD) alloHCT for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) performed between 2000 and 2010 in the 612 counties covered by SEER. The total incidence of AML, ALL, and MDS was determined using SEER, and the number of alloHCTs performed in the same time period and geographic area were determined using the CIBMTR database. We then determined which sociodemographic attributes influenced the rate of alloHCT (rural/urban status, median family size, percentage of residents below the poverty line, and percentage of minority race). In the entire cohort, higher levels of poverty were associated with lower rates of alloHCT (estimated rate ratio [ERR], .86 for a 10% increase in the percentage of the population below the poverty line; P < .01), whereas rural location was not (ERR, .87; P = .11). Thus, patients from areas with higher poverty rates diagnosed with ALL, AML, and MDS are less likely patients from wealthier counties to undergo URD alloHCT. There is need to better understand the reasons for this disparity and to encourage policy and advocacy efforts to improve access to medical care for all.

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

Exploring the screening capacity of the Fear of Cancer Recurrence Inventory-Short Form for clinical levels of fear of cancer recurrence.

OBJECTIVE: Fear of cancer recurrence (FCR) is a common concern among cancer survivors. Identifying survivors with clinically significant FCR requires validated screening measures and clinical cut-offs. We evaluated the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) clinical cut-off in 2 samples. METHODS: Level of FCR in study 1 participants (from an Australian randomized controlled trial: ConquerFear) was compared with FCRI-SF scores. Based on a biopsychosocial interview, clinicians rated participants as having nonclinical, subclinical, or clinical FCR. Study 2 participants (from a Canadian FCRI-English validation study) were classified as having clinical or nonclinical FCR by using the semistructured clinical interview for FCR (SIFCR). Receiver operating characteristic analyses evaluated the screening ability of the FCRI-SF against clinician ratings (study 1) and the SIFCR (study 2). RESULTS: In study 1, 167 cancer survivors (mean age: 53 years, SD = 10.1) participated. Clinicians rated 43% as having clinical FCR. In study 2, 40 cancer survivors (mean age: 68 years, SD = 7.0) participated; 25% met criteria for clinical FCR according to the SIFCR. For both studies 1 and 2, receiver operating characteristic analyses suggested a cut-off ≥22 on the FCRI-SF identified cancer survivors with clinical levels of FCR with adequate sensitivity and specificity. CONCLUSIONS: Establishing clinical cut-offs on FCR screening measures is crucial to tailoring individual care and conducting rigorous research. Our results suggest using a higher cut-off on the FCRI-SF than previously reported to identify clinically significant FCR. Continued evaluation and validation of the FCRI-SF cut-off is required across diverse cancer populations.

Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Complications and Quality of Life Working Party of the European Society for Blood and Marrow Transplantation.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.

Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases.

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029-$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time.

Phosphorylated Histone 3 at Serine 10 Identifies Activated Spinal Neurons and Contributes to the Development of Tissue Injury-Associated Pain.

Transcriptional changes in superficial spinal dorsal horn neurons (SSDHN) are essential in the development and maintenance of prolonged pain. Epigenetic mechanisms including post-translational modifications in histones are pivotal in regulating transcription. Here, we report that phosphorylation of serine 10 (S10) in histone 3 (H3) specifically occurs in a group of rat SSDHN following the activation of nociceptive primary sensory neurons by burn injury, capsaicin application or sustained electrical activation of nociceptive primary sensory nerve fibres. In contrast, brief thermal or mechanical nociceptive stimuli, which fail to induce tissue injury or inflammation, do not produce the same effect. Blocking N-methyl-D-aspartate receptors or activation of extracellular signal-regulated kinases 1 and 2, or blocking or deleting the mitogen- and stress-activated kinases 1 and 2 (MSK1/2), which phosphorylate S10 in H3, inhibit up-regulation in phosphorylated S10 in H3 (p-S10H3) as well as fos transcription, a down-stream effect of p-S10H3. Deleting MSK1/2 also inhibits the development of carrageenan-induced inflammatory heat hyperalgesia in mice. We propose that p-S10H3 is a novel marker for nociceptive processing in SSDHN with high relevance to transcriptional changes and the development of prolonged pain.

Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

BACKGROUND: To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. METHODS: We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. RESULTS: The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). CONCLUSION: Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is at risk for post-transplant complications. Cancer 2017;123:1828-1838. © 2017 American Cancer Society.

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.

Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study.

INTRODUCTION: In patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue-haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised data compare different thresholds for administering prophylactic platelets or prophylactic versus therapeutic platelet transfusions. An alternative strategy involves prescribing prophylactic antifibrinolytic agents such as tranexamic acid to prevent bleeding. METHODS AND ANALYSIS: This report describes the design of an open-labelled randomised pilot study comparing the prophylactic use of oral tranexamic acid with platelet transfusions in the setting of autologous HSCT. In 3-5 centres, 100 patients undergoing autologous HSCT will be randomly assigned to either a prophylactic tranexamic acid or prophylactic platelets bleeding prevention strategy-based daily platelet values up to 30 days post-transplant. The study will be stratified by centre and type of transplant. The primary goal is to demonstrate study feasibility while collecting clinical outcomes on (1) WHO and Bleeding Severity Measurement Scale (BSMS), (2) transplant-related mortality, (3) quality of life, (4) length of hospital stay, (5) intensive care unit admission rates, (6) Bearman toxicity scores, (7) incidence of infections, (8) transfusion requirements, (9) adverse reactions and (10) economic analyses. ETHICS AND DISSEMINATION: This study is funded by a peer-reviewed grant from the Canadian Institutes of Health Research (201 503) and is registered on Clinicaltrials.gov NCT02650791. It has been approved by the Ottawa Health Science Network Research Ethics Board. Study results will presented at national and international conferences. Importantly, the results of this trial will inform the feasibility and conduct of a larger study. TRIAL REGISTRATION NUMBER: NCT02650791; Pre-results.

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.