| 1. |
- Bergman, Peter, et al.
(author)
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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
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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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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| 2. |
- Hovén, Emma, et al.
(author)
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Increased risk of mental health problems after cancer during adolescence : a register based cohort study.
- 2020
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:12, s. 3349-3360
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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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| 3. |
- Hovén, Emma, 1983-, et al.
(author)
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Losing a child to adolescent cancer : A register‐based cohort study of psychotropic medication use in bereaved parents
- 2023
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In: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:5, s. 6148-6160
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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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| 4. |
- Leijonhufvud, Gustaf, et al.
(author)
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Better detection of Torque teno virus in children with leukemia by metagenomic sequencing than by quantitative PCR
- 2022
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In: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 94:2, s. 634-641
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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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| 5. |
- Martinez-Monleon, Angela, et al.
(author)
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Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup
- 2022
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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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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| 6. |
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| 7. |
- Wikman, Anna, et al.
(author)
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Psychotropic medication use in parents of survivors of adolescent cancer : A register-based cohort study
- 2022
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In: Cancer Medicine. - : Wiley. - 2045-7634. ; 11:22, s. 4341-4353
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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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| 8. |
- Blacker, Christopher, et al.
(author)
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Primary evaluation of an air-cooling device to reduce oral mucositis : a pilot study in healthy volunteers
- 2020
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In: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 37:12
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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.
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| 9. |
- Blacker, C, et al.
(author)
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Randomized cross-over study investigating the tolerability and side effects of an intra-oral air-cooling device compared to ice in healthy volunteers
- 2023
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In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 40
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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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| 10. |
- Cederved, Catarina, 1979-
(author)
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Alleviating anxiety in children with cancer facing radiotherapy : The creation of a serious game
- 2023
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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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