Life partnerships in childhood cancer survivors, their siblings, and the general population

Background: Life partnerships other than marriage are rarely studied in childhood cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in CCS and compare them to life partnerships in siblings and the general population; and (2) to identify socio-demographic and cancer-related factors associated with life partnership and marriage. Methods: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20–40 years) registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at diagnosis, who had survived ≥5 years. The proportion with life partner or married was compared between CSS and siblings and participants in the Swiss Health Survey (SHS). Multivariable logistic regression was used to identify factors associated with life partnership or marriage. Results: We included 1,096 CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%) than siblings (61%, P < 0.001) had life partners, and fewer CCS were married (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P < 0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners. CCS who had undergone radiotherapy, bone marrow transplants (global PTreatment = 0.018) or who had a CNS diagnosis (global PDiagnosis < 0.001) were less likely to have life partners. Conclusion: CCS are less likely to have life partners than their peers. Most CCS with a life partner were not married. Future research should focus on the effect of these disparities on the quality of life of CCS.

Information provision and information needs in adult survivors of childhood cancer

BACKGROUND Knowledge about their past medical history is central for childhood cancer survivors to ensure informed decisions in their health management. Knowledge about information provision and information needs in this population is still scarce. We thus aimed to assess: (1) the information survivors reported to have received on disease, treatment, follow-up, and late effects; (2) their information needs in these four domains and the format in which they would like it provided; (3) the association with psychological distress and quality of life (QoL). PROCEDURE As part of the Follow-up survey of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all survivors (≥18 years) who previously participated to the baseline survey, were diagnosed with cancer after 1990 at an age of <16 years. RESULTS Most survivors had received oral information only (on illness: oral: 82%, written: 38%, treatment: oral: 79%, written: 36%; follow-up: oral: 77%, written: 23%; late effects: oral: 68%, written: 14%). Most survivors who had not previously received any information rated it as important, especially information on late effects (71%). A large proportion of survivors reported current information needs and would like to receive personalized information especially on late effects (44%). Survivors with higher information needs reported higher psychological distress and lower QoL. CONCLUSIONS Survivors want to be more informed especially on possible late effects, and want to receive personalized information. Improving information provision, both qualitatively and quantitatively, will allow survivors to have better control of their health and to become better decision makers. Pediatr Blood Cancer 2014;61:312-318. © 2013 Wiley Periodicals, Inc.

Do childhood cancer survivors with physical performance limitations reach healthy activity levels?

BACKGROUND The extent to which physical performance limitations affect the ability of childhood cancer survivors to reach healthy activity levels is unknown. Therefore this study aims to describe the effect of different types of limitations on activity levels in survivors. PROCEDURE Within the Swiss Childhood Cancer Survivor Study we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2005 aged <16 years. We measured healthy activity levels using international guidelines and assessed different kinds of performance limitations (visual impairment, weight and endurance problems, cardiorespiratory, musculoskeletal, and neurological problems, pain and fatigue syndromes). RESULTS The sample included 1,560 survivors (75% response rate), of whom 209 (13.5%) reported they have performance limitations. Forty-two percent of survivors with limitations reached healthy activity levels, compared to 57% of survivors without limitations. Least active were survivors with vision impairments (25% active), weight and endurance problems (27.3%), cardiorespiratory problems (36.4%), and musculoskeletal problems (43.1%). After adjusting for socio-demographic variables and type of cancer, we found that survivors with limitations were 1.4 (95%CI 1.0-2.0; P = 0.047) times more likely to be inactive. CONCLUSIONS Although many survivors with physical performance limitations maintain healthy activity levels, there is room for improvement. Adapted and targeted physical activity counseling for survivors with performance limitations might help them to raise level of activity and pursue a healthy lifestyle.

General practitioner involvement in follow-up of childhood cancer survivors: a systematic review

BACKGROUND An increasing number of childhood cancer survivors need long-term follow-up care. Different models address this problem, including that of follow-up by general practitioners (GP). We describe models that involve GPs in follow-up for childhood cancer survivors, their advantages and disadvantages, clinics that employ these models, and the elements essential to high-quality, GP-led follow-up care. PROCEDURE We searched four databases (PubMed [including Medline], Embase, Cochrane, and CINAHL) without language restrictions. RESULTS We found 26 publications, which explicitly mentioned GP-led follow-up. Two models were commonly described: GP-only, and shared care between GP and pediatric oncology or late effects clinic. The shared care model appears to have advantages over GP-only follow-up. We found four clinics using models of GP-led follow-up, described in five papers. We identified well-organized transition, treatment summary, survivorship care plan, education of GPs and guidelines as necessary components of successful follow-up. CONCLUSION Scarcity of literature necessitated a review rather than a meta-analysis. More research on the outcomes of GP-led care is necessary to confirm the model for follow-up of childhood cancer survivors in the long term. However, with the necessary elements in place, the model of GP-led follow-up, and shared care in particular, holds promise.

Reduction in total plasma ghrelin levels following catecholamine depletion: relation to bulimic and depressive symptoms

There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between peprandial and postprandial plasma ghrelin levels (p < 0.0001) and a postprandial rise in plasma PYY levels (p < 0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p < 0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p < 0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p < 0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms.

Restoring tactile awareness through the rubber hand illusion in cervical spinal cord injury

BACKGROUND Bodily sensations are an important component of corporeal awareness. Spinal cord injury can leave affected body parts insentient and unmoving, leading to specific disturbances in the mental representation of one's own body and the sense of self. OBJECTIVE Here, we explored how illusions induced by multisensory stimulation influence immediate sensory signals and tactile awareness in patients with spinal cord injuries. METHODS The rubber hand illusion paradigm was applied to 2 patients with chronic and complete spinal cord injury of the sixth cervical spine, with severe somatosensory impairments in 2 of 5 fingers. RESULTS Both patients experienced a strong illusion of ownership of the rubber hand during synchronous, but not asynchronous, stroking. They also, spontaneously reported basic tactile sensations in their previously numb fingers. Tactile awareness from seeing the rubber hand was enhanced by progressively increasing the stimulation duration. CONCLUSIONS Multisensory illusions directly and specifically modulate the reemergence of sensory memories and enhance tactile sensation, despite (or as a result of) prior deafferentation. When sensory inputs are lost, and are later illusorily regained, the brain updates a coherent body image even several years after the body has become permanently unable to feel. This particular example of neural plasticity represents a significant opportunity to strengthen the sense of the self and the feelings of embodiment in patients with spinal cord injury.

Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) associated with severe, acquired ADAMTS13 deficiency is uncommonly reported in children. The incidence, demographic, and clinical features of these children, compared to adults, have not been described. PROCEDURES This study focused on children (<18 years old) and adults with TTP associated with severe, acquired ADAMTS13 deficiency, defined as activity <10%. The incidence rates for TTP in children and adults were calculated from patients enrolled in the Oklahoma TTP-HUS (Hemolytic-Uremic syndrome) Registry, 1996-2012. To describe demographic and clinical features, children with TTP were also identified from a systematic review of published reports and from samples sent to a reference laboratory for analysis of ADAMTS13. RESULTS The standardized annual incidence rate of TTP in children was 0.09 × 10(6) children per year, 3% of the incidence rate among adults (2.88 × 10(6) adults per year). Among the 79 children who were identified (one from the Oklahoma Registry, 55 from published reports, 23 from the reference laboratory), TTP appeared to be more common among females, similar to the relative increased frequency of women among adults with TTP, and more common in older children. Clinical data were available on 52 children; the frequency of severe renal failure, relapse, treatment with rituximab, and systemic lupus erythematosus in these children was similar to adults with TTP. CONCLUSIONS TTP associated with severe, acquired ADAMTS13 deficiency is uncommon in children. The demographic and clinical features of these children are similar to the features of adults with TTP.

Practices of pediatric oncology and hematology providers regarding fertility issues: A European survey.

BACKGROUND Fertility is impaired in many survivors of childhood cancer following treatment. Preservation of fertility after cancer has become a central survivorship concern. Nevertheless, several doctors, patients, and families do not discuss fertility and recommendations for fertility preservation in pediatrics are still lacking. Recommendations based on scientific evidence are needed and before their development we wanted to assess the practice patterns of fertility preservation in Europe. PROCEDURES On behalf of the PanCare network, we sent a questionnaire to pediatric onco-hematology institutions across Europe. The survey consisted of 21 questions assessing their usual practices around fertility preservation. RESULTS One hundred ninety-eight institutional representatives across Europe received the survey and 68 (response rate 34.3%) responded. Pre-treatment fertility counseling was offered by 64 institutions. Counseling was done by a pediatric onco-hematologist in 52% (33/64) and in 32% (20/64) by a team. The majority of institutions (53%) lacked recommendations for fertility preservation. All 64 centers offered sperm banking; eight offered testicular tissue cryopreservation for pre-pubertal males. For females, the possibility of preserving ovarian tissue was offered by 40 institutions. CONCLUSIONS There is a high level of interest in fertility preservation among European centers responding to our survey. However, while most recommended sperm cryopreservation, many also recommended technologies whose efficacy has not been shown. There is an urgent need for evidence-based European recommendations for fertility preservation to help survivors deal with the stressful topic of fertility. Pediatr Blood Cancer 2014;9999:1-5. © 2014 Wiley Periodicals, Inc.

Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial

BACKGROUND Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. METHODS We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. FINDINGS Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014). INTERPRETATION In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study. FUNDING Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

The views of European clinicians on guidelines for long-term follow-up of childhood cancer survivors.

BACKGROUND Evidence-based guidelines are needed to guide effective long-term follow-up (LTFU) of childhood cancer survivors (CCS) at risk of late adverse effects (LAEs). We aimed to ascertain the use of LTFU guidelines throughout Europe, and seek views on the need for pan-European LTFU guidelines. PROCEDURES One expert clinician from each of 44 European countries was invited to participate in an online survey. Information was sought regarding the use and content of LTFU guidelines in the respondent's centre and country, and their views about developing pan-European LTFU guidelines. RESULTS Thirty-one countries (70%) responded, including 24 of 26 full EU countries (92%). LTFU guidelines were implemented nationally in 17 countries (55%). All guidelines included recommendations about physical LAEs, specific risk groups and frequency of surveillance, and the majority about psychosocial LAEs (70%), and healthy lifestyle promotion (65%). A minority of guidelines described recommendations about transition to age-appropriate LTFU services (22%), where LTFU should be performed (22%) and by whom (30%). Most respondents (94%) agreed on the need for pan-European LTFU guidelines, specifically including recommendations about surveillance for specific physical LAEs (97%), action to be taken if a specific LAE is detected (90%), minimum requirements for LTFU (93%), transition and health promotion (both 87%). CONCLUSIONS Guidelines are not universally used throughout Europe. However, there is strong support for developing pan-European LTFU guidelines for CCS. PanCareSurFup (www.pancare.eu) will collaborate with partners to develop such guidelines, including recommendations for hitherto relatively neglected topics, such as minimum LTFU requirements, transition and health promotion.

Concentration, Working Speed and Memory: Cognitive Problems in Young Childhood Cancer Survivors and Their Siblings.

BACKGROUND Cognitive problems can have a negative effect on a person's education, but little is known about cognitive problems in young childhood cancer survivors (survivors). This study compared cognitive problems between survivors and their siblings, determined if cognitive problems decreased during recent treatment periods and identified characteristics associated with the presence of a cognitive problem in survivors. METHODS As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was sent to all survivors, aged 8-20 years, registered in the Swiss Childhood Cancer Registry, diagnosed at age <16 years, who had survived ≥5 years. Parent-reported (aged 8-15 years) and self-reported (aged 16-20 years) cognitive problems (concentration, working speed, memory) were compared between survivors and siblings. Multivariable logistic regression was used to identify characteristics associated with cognitive problems in survivors. RESULTS Data from 840 survivors and 247 siblings were analyzed. More often than their siblings, survivors reported problems with concentration (12% vs. 6%; P = 0.020), slow working speed (20% vs. 8%; P = 0.001) or memory (33% vs. 15%; P < 0.001). Survivors from all treatment periods were more likely to report a cognitive problem than were siblings. Survivors of CNS tumors (OR = 2.82 compared to leukemia survivors, P < 0.001) and those who had received cranial irradiation (OR = 2.10, P = 0.010) were most severely affected. CONCLUSION Childhood cancer survivors, even those treated recently (2001-2005), remain at risk to develop cognitive problems, suggesting a need to improve therapies. Survivors with cognitive problems should be given the opportunity to enter special education programs. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children

BACKGROUND Despite substantial evidence supporting a pharmacogenetic approach to warfarin therapy in adults, evidence on the importance of genetics in warfarin therapy in children is limited, particularly for clinical outcomes. We assessed the contribution of CYP2C9/VKORC1/CYP4F2 genotypes and variation in other genes involved in vitamin K and coagulation pathways to warfarin dose and related clinical outcomes in children. PROCEDURE Clinical and genetic data for 93 children (age ≤ 18 years) who received warfarin therapy were obtained. DNA was genotyped for 93 selected single nucleotide polymorphisms using a custom assay. RESULTS With a median age of 4.8 years, our cohort included more young children than most previous studies. Overall, 76.3% of dose variability was explained by weight, indication, VKORC1-1639G/A and CYP2C9 *2/*3, with genotypes accounting for 21.1% of variability. There was a strong correlation (R(2) = 0.68; P < 0.001) between actual and predicted warfarin dose using a pediatric genotype-based dosing model. VKORC1 genotype had a significant impact on time to therapeutic international normalized ratio (INR) (P = 0.047) and time to over-anticoagulation (INR > 4; P = 0.024) during the initiation of therapy. CYP2C9*3 carriers were also at increased risk of major bleeding while receiving warfarin (adjusted OR = 11.28). An additional variant in CYP2C9 (rs7089580) was significantly associated with warfarin dose (P = 0.020) in a multivariate clinical and genetic model. CONCLUSIONS This study confirms the importance of VKORC1/CYP2C9 genotypes for warfarin dosing in a young pediatric cohort and demonstrates an impact of genetic factors on clinical outcomes in children. Furthermore, we identified an additional variant in CYP2C9 of potential relevance for warfarin dosing in children.