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  • Bergman, Peter, et al. (author)
  • Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
  • 2021
  • In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
  • Journal article (peer-reviewed)abstract
    • Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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  • Cernvall, Martin, 1980-, et al. (author)
  • Avoidance and hyperarousal mediates the relationship between reexperiencing and dysphoria in parents of children with cancer : a longitudinal analysis
  • 2012
  • In: 12th International Congress of Behavioral Medicine.
  • Conference paper (peer-reviewed)abstract
    • There is little theoretical and empirical work regarding the mechanisms underlying the development of traumatic stress among parents of children with cancer. Such work would add to the understanding of this phenomenon and could inform intervention strategies for this group. Cognitive processing theory stipulates that avoidance mediates the relationship between intrusive thoughts about trauma and psychological distress (Creamer, et al., 1992). Evidence also suggests that hyperarousal predicts emotional numbing in response to trauma (Litz, et al., 1997; Weems, et al., 2003). The purpose of this study was to investigate the mediating role of avoidance and hyperarousal in the relationship between reexperiencing and dysphoria among parents of children on cancer treatment.We used data from a longitudinal study with three assessment points: T1 = 2 weeks after the child´s diagnosis (n = 249), T2 = two months after the child´s diagnosis (n = 234), and T3 = four months after diagnosis (n = 203). The PTSD-Checklist Civilian was used as a measure of symptoms of traumatic stress interpreted with Simms et al. (2002) four-factor theory of traumatic stress. Two models were evaluated with mediation analysis using bias corrected bootstrap estimation of indirect effects and 95% confidence intervals (CI; Preacher and Hayes, 2008). The first model included two indicators of avoidance at T2 as mediators of the relationship between reexperiencing at T1 and dysphoria at T3, while controlling for initial levels of included variables and gender. In the second model hyperarousal at T2 was added as a mediator.In the first model there was a significant total indirect effect from reexperiencing to dysphoria via avoidance (0.048, CI = 0.012-0.116). However, only avoidance of activities or situations reminding of the child´s disease had a significant specific indirect effect (0.044, CI = 0.009-0.097). In the second model there was a significant total indirect effect from reexperiencing to dysphoria via avoidance and hyperarousal (0.140, CI = 0.076-0.233). However, only hyperarousal contributed with a significant specific indirect effect (0.110, CI = 0.061-0.212).The current analyses suggest that avoidance and hyperarousal both are important targets for intervention in this population.
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  • Cernvall, Martin, et al. (author)
  • Experiential avoidance and rumination in parents of children on cancer treatment : relationships with posttraumatic stress symptoms and symptoms of depression
  • 2016
  • In: Journal of clinical psychology in medical settings. - : Springer Science and Business Media LLC. - 1068-9583 .- 1573-3572. ; 23:1, s. 67-76
  • Journal article (peer-reviewed)abstract
    • We conducted a cross-sectional survey study to investigate whether there is a relationship between experiential avoidance (EA), rumination, post-traumatic stress symptoms (PTSS), and symptoms of depression, in parents of children on cancer treatment. Data from 79 parents (55 mothers) of 79 children with a median of three months since their cancer diagnosis were included in cross-sectional analyses. EA and rumination were positively correlated with PTSS and symptoms of depression. EA and rumination did not provide incremental explained variance in PTSS over and above that explained by symptoms of depression, while controlling for symptoms of anxiety and demographic characteristics. However, EA and rumination provided incremental explained variance in symptoms of depression over and above that explained by PTSS, while controlling for symptoms of anxiety and demographic characteristics. Rumination and EA are important constructs in the understanding of PTSS and symptoms of depression in parents of children on cancer treatment. Future research should delineate the temporal relationships between these constructs.
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  • Cernvall, Martin, et al. (author)
  • Internet-based guided self-help for parents of children diagnosed with cancer : Long-term follow-up of a randomized controlled trial
  • 2016
  • In: EABCT 2016 Abstract Book. ; , s. 470-470
  • Conference paper (other academic/artistic)abstract
    • Background: A considerable proportion of parents of children on cancer treatment experience distress such as symptoms of posttraumatic stress (PTSS), depression and anxiety. The purpose was to investigate the long-term efficacy of Internetbased guided self-help for these parents.Methods: 58 parents of children on cancer treatment (median months since diagnosis = 3) were randomized to receive 10 weeks of guided self-help via the Internet or to wait-list (intervention n = 31, wait-list n = 27). The intervention utilized principles from cognitive behavior therapy and included psychoeducation, relaxation training, coping with thoughts and feelings, problem solving, and emotional writing. Weekly support via e-mail was provided. Outcomes included PTSS (PCL-C), depression (BDI-II) and anxiety (BAI) and were assessed at pre and post intervention and at one-year follow-up.Results: 18 participants completed the intervention. 16 participants in the intervention condition and 16 participants in the wait-list condition participated in the one-year follow-up. Intention-to-treat analyses indicated significant time*group interactions for all three outcomes with reductions favoring the intervention group: PCL-C; F = 10.9, < .001, BDI-II; F = 12.0, < .001, BAI; F = 14.6, < .001. At the one-year follow-up there were large between-group effect sizes for all three outcomes (Cohens d 0.8 to 1.1).Conclusions: The high drop-out rate warrants caution in interpretation of the findings. However, Internet-based guided self-help may be an accessible alternative for some parents of children on cancer treatment and findings indicate that short-term efficacy can be maintained in the long term.
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  • Cernvall, Martin, et al. (author)
  • Internet‐based guided self‐help for parents of children on cancer treatment : a randomized controlled trial
  • 2015
  • In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 24:9, s. 1152-1158
  • Journal article (peer-reviewed)abstract
    • ObjectiveThe aim of the study was to investigate the feasibility and preliminary efficacy of an Internet‐based guided self‐help intervention for posttraumatic stress symptoms (PTSS) and related symptoms in parents of children on cancer treatment.MethodsParents of children on cancer treatment, who fulfilled the modified symptom criteria on the PTSD Checklist, were randomly allocated to the intervention or to a wait‐list control condition. The intervention group accessed a 10‐week guided self‐help program via the Internet based on principles from cognitve behavior therapy. The primary outcome PTSS and the secondary outcomes depression and anxiety were assessed by self‐report preintervention and postintervention.ResultsSeven hundred forty‐seven parents were approached and informed about the study, 92 were assessed for eligibility, and 58 were included and randomized to the intervention (n  = 31) or wait list (n  = 27). Eightteen participants completed the intervention. Intention‐to‐treat analyses indicated a significant effect of the intervention on PTSS with a large between‐group effect size at postassessment (Cohen's d  = 0.88). The intervention group reported reductions in PTSS with a large within‐group effect size (d  = 1.62) compared with a minimal reduction in the wait‐list group (d  = 0.09). There was a significant intervention effect on depression and anxiety and reductions in the intervention group with large within‐group effect sizes (d  = 0.85–1.09).ConclusionsFindings indicate a low enrollment rate and considerable attrition but also that Internet‐based guided self‐help shows promise for parents of children on cancer treatment who report a high level of PTSS and would like to take part in an Internet‐based intervention. 
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  • Cernvall, Martin, 1980-, et al. (author)
  • Posttraumatic stress and attentional bias towards cancer-related stimuli in parents of children recently diagnosed with cancer
  • 2016
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:4
  • Journal article (peer-reviewed)abstract
    • Objectives: To investigate whether posttraumatic stress symptoms (PTSS) are related to attentional bias towards cancer-related stimuli among parents of children recently diagnosed with cancer.Methods: Sixty-two parents completed questionnaires measuring PTSS, depression, and anxiety and the emotional Stroop task via the Internet. The emotional Stroop task included cancer-related words, cardiovascular disease-related words, and neutral words.Results: Participants were split in two groups based on the median of PTSS: High-PTSS and Low-PTSS. There was a significant interaction between word-type and group and a planned contrast test of this interaction indicated that the High-PTSS group had longer response latencies on cancer-related words compared to the other word-type and group combinations.Conclusions: Findings suggest that PTSS are related to attentional bias towards cancer-related stimuli among parents of children recently diagnosed with cancer. Implications of this finding for the understanding of PTSS in this population, future research, and clinical practice are discussed.
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  • Cernvall, Martin, 1980-, et al. (author)
  • The relationship between traumatic stress, experiential avoidance, and depression in parents of children recently diagnosed with cancer
  • 2012
  • In: 12th international Congress of Behavioral Medicine, 29 August - 1 September 2012, Budapest Hilton Hungary. ; , s. 138-138
  • Conference paper (peer-reviewed)abstract
    • Parents of children recently diagnosed with cancer can experience severe psychosocial distress. Experiential avoidance has been defined as the tendency to avoid or escape from certain private experiences (e.g., thoughts, feelings, memories) or contexts that elicit them (Hayes et al., 1996). This construct has been shown to be linked to distress in several populations and has received increased interest as a target for intervention. The purpose of this study was to investigate the relationship between traumatic stress, experiential avoidance, and depression in parents of children recently diagnosed with cancer. It was hypothesized that experiential avoidance would account for the relationship between traumatic stress and depression. 48 parents (33 mothers and 15 fathers) of children recently diagnosed with cancer and who participated in the screening/pre-assessment of a RCT of a psychosocial intervention were included in the current cross-sectional study. The mean (SD) of months since the child’s diagnosis was 3.5 (1.8). Parents provided self-report of demographic characteristics, general anxiety, traumatic stress, experiential avoidance, and depression.Hierarchical regression was used with depression as dependent variable. In step 1 demographic variables and general anxiety was entered (∆R2 = .57, p < .001). In step 2 traumatic stress was added resulting in a significant increase in explained variance (∆R2 = .04, p < .05, β for traumatic stress = 0.39, p < .05). In step 3 experiential avoidance was added resulting in a significant increase in explained variance (∆R2 = .06, p < .05, β for experiential avoidance = 0.35, p < .05). Furthermore, traumatic stress was no longer a significant predictor of depression (β = 0.15, p = 40). Total R2 in the final model was .68. Mediation analysis (Preacher & Hayes, 2008) confirmed a significant indirect effect from traumatic stress to depression via experiential avoidance (estimate = 0.21, bootstrap 95% CI = 0.03-0.38). The current results suggest that experiential avoidance accounts for the relationship between traumatic stress and depression in parents of children recently diagnosed with cancer. Experiential avoidance could be a potential target in psychosocial interventions for this group.
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  • Cernvall, Martin, 1980-, et al. (author)
  • Twelve-Month Follow-Up of a Randomized Controlled Trial of Internet-Based Guided Self-Help for Parents of Children on Cancer Treatment
  • 2017
  • In: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 19:7
  • Journal article (peer-reviewed)abstract
    • Background: A substantial proportion of parents of children on cancer treatment report psychological distress such as symptoms of post-traumatic stress (PTSS), depression, and anxiety. During their child’s treatment many parents also experience an economic burden.Objective: The aim of this study was to evaluate the long-term efficacy of Internet-based guided self-help for parents of children on cancer treatment.Methods: This study was a parallel randomized controlled trial comparing a 10-week Internet-based guided self-help program, including weekly support from a therapist via encrypted email, with a wait-list control condition. The intervention was based on cognitive behavior therapy (CBT) and focused on psychoeducation and skills to cope with difficult thoughts and feelings. Primary outcome was self-reported PTSS. Secondary outcomes were self-reported symptoms of depression, anxiety, health care consumption, and sick leave during the past month. Outcomes were assessed pre- and postintervention and at 12-month follow-up. Parents of children on cancer treatment were invited by health care personnel at pediatric oncology centers, and parents meeting the modified symptom criteria on the PCL-C were included in the study. Self-report assessments were provided on the Web.Results: A total of 58 parents of children on cancer treatment (median months since diagnosis=3) were included in the study (intervention n=31 and control n=27). A total of 18 participants completed the intervention, and 16 participants in each group participated in the 12-month follow-up. Intention-to-treat analyses revealed significant effects in favor of the intervention on the primary outcome PTSS, with large between-group effect sizes at postassessment (d=0.89; 95% CI 0.35-1.43) and at 12-month follow-up (d=0.78; 95% CI 0.25-1.32). Significant effects in favor of the intervention on the secondary outcomes depression and anxiety were also observed. However, there was no evidence for intervention efficacy on health care consumption or sick leave.Conclusions: Using the Internet to provide psychological interventions shows promise as an effective mode of delivery for parents reporting an increased level of PTSS and who consider Internet-based interventions as a viable option. Future research should corroborate these findings and also develop and evaluate interventions and policies that may help ameliorate the economic burden that parents may face during their child’s treatment for cancer.
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  • Hovén, Emma, et al. (author)
  • Increased risk of mental health problems after cancer during adolescence : a register based cohort study.
  • 2020
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:12, s. 3349-3360
  • Journal article (peer-reviewed)abstract
    • In this nationwide, register-based study, we estimated the risk of mental health problems in 2,822 individuals diagnosed with cancer in adolescence (13-19 years). Mental health problems were assessed by psychiatric diagnoses and/or prescribed psychotropic drugs. Cox proportional hazards models estimated hazard ratio (HR) for a psychiatric diagnosis and prescription of psychotropic drug compared to a matched comparison group (n=28,220). Estimates were adjusted for calendar period and parent characteristics (e.g., history of psychiatric diagnosis, education, country of birth). We found an increased risk of a psychiatric diagnosis during the first five years after the cancer diagnosis (females: HR 1.23, 95% CI, 1.06-1.44; males: HR 1.32, 95% CI, 1.11-1.56), and at >five years after diagnosis (females: HR 1.31, 95% CI, 1.09-1.58, males: HR 1.45, 95% CI, 1.18-1.77). The risk of being prescribed antidepressant- (females: HR 1.54, 95% CI, 1.30-1.84, males: HR 2.06, 95% CI, 1.66-2.55), antipsychotic- (females: HR 2.28, 95% CI, 1.56-3.34, males: HR 3.07, 95% CI, 2.13-4.42), anxiolytic- (females: HR 1.95, 95% CI, 1.64-2.31, males: HR 4.02, 95% CI, 3.34-4.84), and sedative drugs (females: HR 2.24, 95% CI, 1.84-2.72, males: HR 3.91, 95% CI, 3.23-4.73) were higher than for comparisons during the first five years after diagnosis. Median age at first psychiatric diagnosis and first prescribed psychotropic drug was 18 years. In conclusion, cancer during adolescence is associated with increased risk of mental health problems that may develop in close proximity to treatment. The findings emphasize the need for comprehensive care during treatment and follow-up.
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  • Hovén, Emma, 1983-, et al. (author)
  • Losing a child to adolescent cancer : A register‐based cohort study of psychotropic medication use in bereaved parents
  • 2023
  • In: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:5, s. 6148-6160
  • Journal article (peer-reviewed)abstract
    • PurposeTo investigate the short- and long-term risk of psychotropic medication use in parents who lose a child to cancer diagnosed in adolescence.MethodsThis is a Swedish nationwide register-based study including 184 bereaved mothers and 184 bereaved fathers of 184 children diagnosed with cancer in adolescence. Logistic regression analyses, adjusted for sociodemographic characteristics and history of mental health problems, were performed to estimate risk of a prescription of psychotropic medication (anxiolytics, hypnotics/sedatives, antidepressants) in cancer-bereaved parents from 1 year before to 5 years after the child's death, with a general population sample of non-bereaved parents (n = 3291) as referents.ResultsAt the year of the child's death, 28%–36% of mothers and 11%–20% of fathers had a prescription of anxiolytics, hypnotics/sedatives or antidepressants. The corresponding percentages for non-bereaved mothers and fathers were 7%–12% and 4%–7%, respectively. Compared to non-bereaved mothers, bereaved mothers showed higher odds of prescriptions from 1 year before up to four (anxiolytics) and 5 years (hypnotics/sedatives and antidepressants) after the child's death. Bereaved fathers showed higher odds than non-bereaved fathers of prescriptions from 1 year before up to the year of (anxiolytics and hypnotics/sedatives) and 1 year after (antidepressants) the child's death. No differences in odds between bereaved and non-bereaved fathers were found at 2 years after the child's death. Being unmarried, born outside Sweden, and having a history of mental health problems were associated with higher odds of prescribed medications.ConclusionsIndicative of mental health problems of clinical importance, cancer-bereaved parents had a higher prevalence of use of psychotropic medication. A decrease in medication use was evident with time, but still at 5 years after the child's death mothers displayed a higher use while fathers showed no difference to non-bereaved fathers after 2 years.
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  • Leijonhufvud, Gustaf, et al. (author)
  • Better detection of Torque teno virus in children with leukemia by metagenomic sequencing than by quantitative PCR
  • 2022
  • In: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 94:2, s. 634-641
  • Journal article (peer-reviewed)abstract
    • Torque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study.
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  • Ljungman, Gustaf, et al. (author)
  • Incidence and Survival Analyses in Children with Solid Tumours Diagnosed in Sweden 1983-2007.
  • 2011
  • In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 100:5, s. 750-757
  • Journal article (peer-reviewed)abstract
    • Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population-based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: 2 487 children (< 15 years) were diagnosed with solid tumours in Sweden 1983 - 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3/million children. The survival rates at 10 years follow up have improved significantly when comparing the two time periods 1983-95 and 1995-2007 (76 vs. 82%; p<0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/ million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow up were 80, 79 and 76%, respectively.
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  • Ljungman, Gustaf, et al. (author)
  • Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 2007
  • 2011
  • In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:5, s. 750-757
  • Journal article (peer-reviewed)abstract
    • Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: Two thousand four hundred and eighty-seven children (< 15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p < 0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively.
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  • Ljungman, Lisa, 1981-, et al. (author)
  • An open trial of individualized face-to-face cognitive behavior therapy for psychological distress in parents of children after end of treatment for childhood cancer including a cognitive behavioral conceptualization
  • 2018
  • In: PeerJ. - : PeerJ. - 2167-8359. ; 6
  • Journal article (peer-reviewed)abstract
    • ObjectiveA subgroup of parents of children who have been treated for childhood cancer report high levels of psychological distress. To date there is no empirically supported psychological treatment targeting cancer-related psychological distress in this population. The aim of the current study was to test the feasibility and preliminarily evaluate the effect of individualized face-to-face cognitive behavior therapy (CBT) for parents of children after the end of treatment for childhood cancer. A secondary aim was to present a cognitive behavioral conceptualization of cancer-related distress for these parents.MethodsAn open trial was conducted where 15 parents of children who had completed successful treatment for cancer three months to five years earlier and who reported psychological distress related to a child’s previous cancer disease were provided CBT at a maximum of 15 sessions. Participants were assessed at baseline, post-intervention, and three-month follow-up using self-reported psychological distress (including posttraumatic stress symptoms (PTSS), depression, and anxiety) and the diagnostic Mini-International Neuropsychiatric Interview. Feasibility outcomes relating to recruitment, data collection, and delivery of the treatment were also examined. Individual case formulations for each participant guided the intervention and these were aggregated and presented in a conceptualization detailing core symptoms and their suggested maintenance mechanisms.ResultsA total of 93% of the participants completed the treatment and all of them completed the follow-up assessment. From baseline to post-assessment, parents reported significant improvements in PTSS, depression, and anxiety with medium to large effect sizes (Cohen’s d = 0.65–0.92). Results were maintained or improved at a three-month follow-up. At baseline, seven (47%) participants fulfilled the diagnostic criteria for major depressive disorder and four (29%) fulfilled the criteria for posttraumatic stress disorder, compared to none at a post-assessment and a follow-up assessment. The resulting cognitive behavioral conceptualization suggests traumatic stress and depression as the core features of distress, and avoidance and inactivity is suggested as the core maintenance mechanisms.ConclusionThe treatment was feasible and acceptable to the participants. Significant improvements in distress were observed during the study. Overall, results suggest that the psychological treatment for parents of children after end of treatment for childhood cancer used in the current study is promising and should be tested and evaluated in future studies.
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  • Ljungman, Lisa, et al. (author)
  • Does time heal all wounds? A longitudinal study of the development of posttraumatic stress symptoms in parents of survivors of childhood cancer and bereaved parents
  • 2015
  • In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 24:12, s. 1792-1798
  • Journal article (peer-reviewed)abstract
    • Background: A lack of longitudinal studies has hampered the understanding of the development of posttraumatic stress symptoms (PTSS) in parents of children diagnosed with cancer. This study examines level of PTSS and prevalence of posttraumatic stress disorder (PTSD) from shortly after diagnosis up to 5 years after end of treatment or child’s death, in mothers and fathers. Methods: A design with seven assessments (T1–T7) was used. T1–T3 were administered during treatment and T4–T7 after end of treatment or child’s death. Parents (N = 259 at T1; n = 169 at T7) completed the PTSD Checklist Civilian Version. Latent growth curve modeling was used to analyze the development of PTSS. Results: A consistent decline in PTSS occurred during the first months after diagnosis; thereafter the decline abated, and from 3 months after end of treatment only minimal decline occurred. Five years after end of treatment, 19% of mothers and 8% of fathers of survivors reported partial PTSD. Among bereaved parents, corresponding figures were 20% for mothers and 35% for fathers, 5 years after the child’s death. Conclusions: From 3 months after end of treatment the level of PTSS is stable. Mothers and bereaved parents are at particular risk for PTSD. The results are the first to describe the development of PTSS in parents of children diagnosed with cancer, illustrate that end of treatment is a period of vulnerability, and that a subgroup reports PTSD 5 years after end of treatment or child’s death.
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  • Ljungman, Lisa, et al. (author)
  • Long-term positive and negative psychological late effects for parents of childhood cancer survivors: A systematic review
  • 2014
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
  • Journal article (peer-reviewed)abstract
    • Increasing survival rates in childhood cancer have yielded a growing population of parents of childhood cancer survivors (CCSs). This systematic review compiles the literature on positive and negative long-term psychological late effects for parents of CCSs, reported at least five years after the child’s diagnosis and/or two years after the end of the child’s treatment. Systematic searches were made in the databases CINAHL, EMBASE, PsycINFO, and PubMed. Fifteen studies, published between 1988 and 2010, from 12 projects were included. Thirteen studies used quantitative methodology, one quantitative and qualitative methodology, and one qualitative methodology. A total of 1045 parents participated in the reviewed studies. Mean scores were within normal ranges for general psychological distress, coping, and family functioning. However, a substantial subgroup reported a clinical level of general psychological distress, and 21–44% reported a severe level of posttraumatic stress symptoms. Worry, disease-related thoughts and feelings, marital strains, as well as posttraumatic growth was reported. Several factors were associated with the long-term late effects, such as parents’ maladaptive coping during earlier stages of the childs disease trajectory and children’s current poor adjustment. Quality assessments of reviewed studies and clinical implications of findings are discussed and recommendations for future research are presented.
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  • Martinez-Monleon, Angela, et al. (author)
  • Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup
  • 2022
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Journal article (peer-reviewed)abstract
    • In neuroblastoma, MYCN amplification and 11q-deletion are important, although incomplete, markers of high-risk disease. It is therefore relevant to characterize additional alterations that can function as prognostic and/or predictive markers. Using SNP-microarrays, a group of neuroblastoma patients showing amplification of one or multiple 12q loci was identified. Two loci containing CDK4 and MDM2 were commonly co-amplified, although amplification of either locus in the absence of the other was observed. Pharmacological inhibition of CDK4/6 with ribociclib or abemaciclib decreased proliferation in a broad set of neuroblastoma cell lines, including CDK4/MDM2-amplified, whereas MDM2 inhibition by Nutlin-3a was only effective in p53(wild-type) cells. Combined CDK4/MDM2 targeting had an additive effect in p53(wild-type) cell lines, while no or negative additive effect was observed in p53(mutated) cells. Most 12q-amplified primary tumors were of abdominal origin, including those of intrarenal origin initially suspected of being Wilms' tumor. An atypical metastatic pattern was also observed with low degree of bone marrow involvement, favoring other sites such as the lungs. Here we present detailed biological data of an aggressive neuroblastoma subgroup hallmarked by 12q amplification and atypical clinical presentation for which our in vitro studies indicate that CDK4 and/or MDM2 inhibition also could be beneficial.
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  • Wikman, Anna, et al. (author)
  • Parents of children diagnosed with cancer : work situation and sick leave, a five-year post end-of-treatment or a child's death follow-up study
  • 2016
  • In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:9-10, s. 1152-1157
  • Journal article (peer-reviewed)abstract
    • Background: Cancer in a child is associated with a significant impact on parental employment. We assessed the proportions of parents of survivors and bereaved parents working and reporting sick leave five years after end of successful treatment (ST)/child's death (T7) compared with one year after end of ST/child's death (T6) and the association between partial post-traumatic stress disorder (PTSD) and work situation and sick leave at T7.Participants and procedure: The sample included 152 parents of survivors (77 mothers, 75 fathers) and 42 bereaved parents (22 mothers, 20 fathers) of children diagnosed with cancer in Sweden.Results: The proportions of parents working or reporting sick leave did not differ among mothers and fathers of survivors (92% vs. 96% working, 20% vs. 18% on sick leave) or among bereaved mothers and fathers (91% vs. 90% working, 14% vs. 20% on sick leave) at T7. There was no change from T6 to T7 in the proportion of fathers working (fathers of survivors 91% vs. 96%, bereaved fathers 95% vs. 90%). Although more mothers of survivors (92% vs. 82%) and bereaved mothers (91% vs. 77%) worked at T7 than at T6, this increase was not significant. Fewer bereaved mothers reported sick leave at T7 than at T6 (14% vs. 59%, p<0.05). Although more fathers reported sick leave at T7 than at T6 (fathers of survivors 18% vs. 8%, bereaved fathers 20% vs. 15%), this was not significant. Partial PTSD was not associated with parents' work situation or sick leave at T7.Conclusion: Results suggest little adverse effect on work situation and sick leave among parents of survivors and bereaved parents five years after end of ST/child's death from cancer. However, the pattern of change observed differed between parents, which could potentially indicate possible delayed consequences for fathers not captured in the present paper.
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34.
  • Wikman, Anna, et al. (author)
  • Psychotropic medication use in parents of survivors of adolescent cancer : A register-based cohort study
  • 2022
  • In: Cancer Medicine. - : Wiley. - 2045-7634. ; 11:22, s. 4341-4353
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The aim was to investigate psychotropic medication use in parents of survivors of adolescent cancer from the acute post-diagnostic phase and up to 2 years following the cancer diagnosis.METHODS: This study had a nationwide register-based cohort design comparing psychotropic medication use in parents of adolescent survivors of cancer (n = 2323) to use in parents of cancer-free controls (n = 20,868). Cox proportional hazards models, adjusted for cancer diagnostic group, parents' age, country of birth, education level, marital status and previous mental health problems estimated the risk of use from the time of the cancer diagnosis up to 2 years later.RESULTS: During the first 6 months after the cancer diagnosis, both mothers and fathers had an increased risk of use of anxiolytics (mothers: HRadj 1.71, 95% CI 1.30-2.25; fathers: HRadj 1.57, 95% CI 1.10-2.45) and hypnotics/sedatives (mothers: HRadj 1.53, 95% CI 1.23-1.90; fathers: HRadj 1.32, 95% CI 1.00-1.75). For fathers with a prescription of psychotropic medication during the first 6 months after the cancer diagnosis, the risk remained increased after 6 months (HRadj 1.66, 95% CI 1.04-2.65). From 6 months after the cancer diagnosis, only the risk of antidepressant use among mothers was increased (HRadj 1.38, 95% CI 1.08-1.76). Risk factors included being divorced/widowed, born in a non-Nordic country, older age and having had previous mental health problems.CONCLUSION: Our study results show that during the immediate post-diagnostic phase, mothers and fathers of survivors of adolescent cancer are at increased risk of use of anxiolytics and sedatives, whereas only mothers are at increased risk of antidepressant use from 6 months until 2 years after the diagnosis. Further, previous mental health problems were shown to be the strongest risk factor for psychotropic medication use in both mothers and fathers, pointing to the particular vulnerability of these parents.
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35.
  • Ander, Malin, 1983- (author)
  • Cancer during adolescence : Psychological consequences and development of psychological treatment
  • 2017
  • Doctoral thesis (other academic/artistic)abstract
    • The overall aim of the present thesis was to examine long-term psychological distress following cancer during adolescence and to develop a tailored psychological intervention to reduce cancer-related distress experienced by young survivors of adolescent cancer that was feasible and acceptable.Study I adopted a longitudinal design, assessing health-related quality of life (HRQOL) and symptoms of anxiety and depression among adolescents diagnosed with cancer from shortly after diagnosis (n=61) up to 10 years after diagnosis (n=28). Findings suggest that development of HRQOL and anxiety and depression is not linear and whilst the majority adjust well, a subgroup report long-term elevated distress. In Study II, experiences of cancer-related psychological distress were explored using unstructured interviews. Participants described cancer treatment as a mental challenge, felt marked and hindered by the cancer experience, and struggled with feelings of inadequacy and insecurity, existential issues, and difficulties handling emotions. Study III was a preliminary investigation of individualised cognitive behavioural therapy (CBT), alongside the identification and conceptualisation of cancer-related concerns using cognitive-behavioural theory. Significant difficulties with recruitment were encountered. Participants reported cancer-related concerns conceptualised as social avoidance, fear and avoidance of emotions and bodily symptoms, imbalance in activity, and worry and rumination. In Study IV, the acceptability and feasibility of an internet-administered CBT based self-help intervention (ICBT) for young persons diagnosed with cancer during adolescence was examined using an uncontrolled design and embedded process evaluation. The study protocol for Study IV was included in this thesis along with preliminary findings demonstrating significant difficulties with recruitment.Overall, findings suggest that whilst the majority of survivors of adolescent cancer adjust well over time a subgroup report elevated levels of distress and a range of distressing cancer-related experiences. A number of cancer-related difficulties were identified in Study II and III, which may be used to inform the development of future psychological treatments for the population. Preliminary investigation of the psychological interventions examined within this thesis further highlights the need for future development work to enhance the feasibility and acceptability of psychological support for the population. 
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36.
  • Ander, Malin, et al. (author)
  • Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence : a 10-year follow-up study
  • 2016
  • In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 25:5, s. 582-589
  • Journal article (peer-reviewed)abstract
    • Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer
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37.
  • Ander, Malin, et al. (author)
  • Guided Internet-Administered Self-Help to Reduce Symptoms Of Anxiety and Depression Among Adolescents and Young Adults Diagnosed With Cancer During Adolescence (U-CARE: YoungCan) : study protocol for a feasibility trial
  • 2017
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Introduction A subgroup of adolescents and young adults diagnosed with cancer during adolescence reports elevated levels of anxiety and depressive symptoms and unmet needs for psychological support. Evidence-based psychological treatments tailored for this population are lacking. This protocol describes a feasibility study of a guided-internet-administered self-help programme (YoungCan) primarily targeting symptoms of anxiety and depression among young persons diagnosed with cancer during adolescence and of the planned study procedures for a future controlled trial. Methods/analysis The study is an uncontrolled feasibility trial with a pre-post and 3-month follow-up design. Potential participants aged 15-25years, diagnosed with cancer during adolescence, will be identified via the Swedish Childhood Cancer Registry. 30 participants will be included. Participants will receive YoungCan, a 12-week therapist-guided, internet-administered self-help programme consisting primarily of cognitive-behavioural therapy organised into individually assigned modules targeting depressive symptoms, worry and anxiety, body dissatisfaction and post-traumatic stress. Interactive peer support and psychoeducative functions are also available. Feasibility outcomes include: recruitment and eligibility criteria; data collection; attrition; resources needed to complete the study and programme; safety procedures; participants' and therapists' adherence to the programme; and participants' acceptability of the programme and study methodology. Additionally, mechanisms of impact will be explored and data regarding symptoms of anxiety, depression, post-traumatic stress, body dissatisfaction, reactions to social interactions, quality of life, axis I diagnoses according to the Mini International Neuropsychiatric Interview and healthcare service use will be collected. Exploratory analyses of changes in targeted outcomes will be conducted. Ethics/dissemination This feasibility protocol was approved by the Regional Ethical Review Board in Uppsala, Sweden (ref: 2016/210). Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences.
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38.
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39.
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40.
  • Bergh, Jonas, et al. (author)
  • Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer : A randomised trial
  • 2000
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 356:9239, s. 1384-1391
  • Journal article (peer-reviewed)abstract
    • Background: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. Methods: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. Findings: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. Interpretation: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.
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41.
  •  
42.
  • Beziat, Vivien, et al. (author)
  • NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs
  • 2013
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:14, s. 2678-2688
  • Journal article (peer-reviewed)abstract
    • Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human KIR-ome at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.
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43.
  •  
44.
  • Blacker, Christopher, et al. (author)
  • Primary evaluation of an air-cooling device to reduce oral mucositis : a pilot study in healthy volunteers
  • 2020
  • In: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 37:12
  • Journal article (peer-reviewed)abstract
    • Oral mucositis is a common side effect of chemo and radiotherapy causing painful ulcers in the oral mucosa. One of the preventive treatments recommended in international guidelines is oral cryotherapy (OC). Randomized clinical trials on OC have used ice and ice-chips to cool the mouth, but this cooling method can be difficult for the patients to tolerate. Studies have shown that OC with ice for a period of 60 min reduces the oral temperature by 12.9 degrees C. The aim of this pilot study was to evaluate the temperature reduction and tolerability of OC using an intra-oral air-cooling (IOAC) device in healthy volunteers. Twelve healthy volunteers, mean age 35.4 years, were included in the study. They were treated with OC using the IOAC device for 60 min. Measurements of temperature were obtained at baseline, 5 and 60 min using a FLIR (R) C2 camera. After the OC session, tolerability and adverse events were documented using a questionnaire. All participants were able to use the device for 60 min. The overall temperature reduction after 5 min of OC was 10.7 degrees C (p < 0.01) and after 60 min 14.5 degrees C (p < 0.01). The most common adverse events were bad fit of the mouthpiece (n = 6), hypersalivation (n = 6), and difficulties swallowing (n = 5). The oral device reduced the temperature of the oral mucosa as much as treatment with ice with tolerable adverse events. The mouthpiece will be remodeled to improve tolerability before further studies are conducted.
  •  
45.
  • Blacker, C, et al. (author)
  • Randomized cross-over study investigating the tolerability and side effects of an intra-oral air-cooling device compared to ice in healthy volunteers
  • 2023
  • In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 40
  • Journal article (peer-reviewed)abstract
    • Oral cryotherapy (OC) is a common preventive treatment of oral mucositis (OM) and is recommended in international guidelines. Ice and air OC have previously been shown to result in temperature reductions of 8.1-12.9 degrees C, and 14.5 degrees C, respectively, in healthy volunteers. However, no direct comparison between these two modalities has been performed. The primary aim was to investigate the tolerability and side effects of air OC using an intra-oral air-cooling (IOAC) device compared with ice OC. The secondary aim was to evaluate the temperature reduction in the mouth for the two respective methods. Cross-over study with randomization to order of treatment, in 15 healthy volunteers. We evaluated the self-reported intensity, frequency, and discomfort for 13 pre-defined side effects used in previous studies. All participants were able to complete both OC sessions, although one participant required reduced airflow in the air OC arm. The subjects reported more discomfort from being cold, having sensitive teeth, and numbness in the ice OC group, while they reported more discomfort from swallowing when subjected to air OC. No significant difference in the median temperature reduction was detected in the two modalities, except for the dorsal posterior part of the tongue where temperature reduction was larger in the ice OC group. We found that oral cooling using a new IOAC device was tolerated and seems to be safe in healthy volunteers.
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46.
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47.
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48.
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49.
  • Cederved, Catarina, et al. (author)
  • Acceptability and potential impact on perceived anxiety of a serious game about radiotherapy in children aged 5 to 14 years : A feasibility and randomized controlled pilot trial
  • Other publication (other academic/artistic)abstract
    • A web-based serious game was developed as psychological preparation for children who are going to undergo radiotherapy. The game was developed together with children with experience of radiotherapy. The study aimed to investigate the feasibility in terms of reach, usability, and acceptability, of a serious game about radiotherapy, and to evaluate whether it can decrease anxiety levels in children aged 5 to14 years undergoing radiotherapy. The study was designed as a randomized controlled pilot trial with predefined feasibility criteria. Twenty-eight children were assessed for eligibility and 23 were found to meet the inclusion criteria. They were consecutively randomized into one of two study arms. One child was excluded after randomization due to language difficulties. If randomized into Group 1, the children received the intervention (serious game) before treatment started. Children in Group 2 received the intervention after three days of treatment. Questionnaires with fixed answers were used to assess anxiety levels (an adapted version of STAIC) and experiences of gameplay (an adapted version of PENS). The predefined feasibility criterion that the children should play the game for 20 minutes or more was not met. The second criterion, that 70% or more of the participants should return all of the questionnaires was not met either, however, more than 80% returned the PENS questionnaires. All feasibility criteria set for the study were not meet, suggesting that adaptions need to be made if a future study is going to be undertaken. There was no indication that playing the serious game decreased the children’s stated anxiety. When combining the two groups, a pattern emerged that anxiety levels decreased over time. The PENS questionnaire adapted for children showed promising results regarding player satisfaction when using the serious game within healthcare. The trial was registered at ClinicalTrials.gov:NCT04728555
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50.
  • Cederved, Catarina, 1979- (author)
  • Alleviating anxiety in children with cancer facing radiotherapy : The creation of a serious game
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • Children undergoing radiotherapy (RT) can experience anxiety, and explaining the procedure through a serious game could be a means to alleviate anxiety. Children have the right to take part in research that concerns them. Through co-creation stakeholders can be part of the process and thereby ensure that the developed product is suitable for the end users. The overarching aim was to investigate the developmental process of a serious game about RT, with a focus on the influence of co-creation, the feasibility of the game, and the game’s effects on self-rated anxiety by children undergoing RT.The thesis consists of four studies, where the first three describes the developmental process of the serious game from different aspects. Study I describes the children’s and their parents’ contributions to the game development based on data from interviews, audio recordings from workshops, and filmed gameplay. Nine children participated, 7 to 10 years old. Study II describes the experiences of seven parents who participated in the first study through interviews. Study III consist of interviews made with thirteen researchers, game designers and hospital staff. The interviews describe the participants’ experiences of taking part in the developmental process of the game. In study IV, reach and acceptability of the game was tested through a feasibility study at one clinic. . It was a randomized pilot, waiting list based study where 22 children participated. Analyses were performed by thematic analysis (Study I and III), content analysis (Study II) and statistical calculations (Study IV).The results showed that every participant involved in the development of the game contributed to the process. The method used in study I can be applied by researchers to co-create serious games with children. The children were active participants and had a consulting and informative role in the development, and their participation led to numerous changes. The interdisciplinary work was challenging but with ample time and an open climate it worked. A majority of children reported anxiety at the start of RT. In conclusion, the children’s participation impacted the game’s design and its content. The children’s abilities to participate in workshops was affected by their disease. Not all of the feasibility criteria set for study IV were reached. There were too few participants enrolled in the study to conclusively answer if the game had an effect on self-reported anxiety.
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