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  • Kirby, A J, et al. (författare)
  • Gemini surfactants: New synthetic vectors for gene transfection
  • 2003
  • Ingår i: Angewandte Chemie International Edition in English. - : Wiley. - 0570-0833 .- 1433-7851 .- 1521-3773. ; 42:13, s. 1448-1457
  • Forskningsöversikt (refereegranskat)abstract
    • The superior surfactant properties of cationic gemini surfactants are applied to the complex problem of introducing genes into cells. Of almost 250 new compounds tested, of some 20 different structural types, a majority showed very good transfection activity in vitro. The surfactant is shown to bind and compact DNA efficiently, and structural studies and calculations provide a working picture of the lipoplex formed. The lipoplex can penetrate the outer membranes of many cell types, to appear in the cytoplasm encapsulated within endosomes. Escape from the endosome - a key step for transfection - may be controlled by changes in the aggregation behavior of the lipoplex as the pH falls. The evidence suggests that DNA may be released from the lipoplex before entry into the nucleus, where the new gene can be expressed with high efficiency.
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  • Lederman, J. S., et al. (författare)
  • International collaborative follow-up investigation of graduating high school students' understandings of the nature of scientific inquiry : is progress Being made?
  • 2021
  • Ingår i: International Journal of Science Education. - : Informa UK Limited. - 0950-0693 .- 1464-5289. ; 43:7, s. 991-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Understandings of the nature of scientific inquiry (NOSI), as opposed to engaging students in inquiry learning experiences, are included in science education reform documents around the world. However, little is known about what students have learned about NOSI during their pre-college school years. The purpose of this large-scale follow-up international project (i.e. 32 countries and regions, spanning six continents and including 3917 students for the high school sample) was to collect data on what exiting high school students have learned about NOSI. Additionally, the study investigated changes in 12th grade students' NOSI understandings compared to seventh grade (i.e. 20 countries and regions) students' understandings from a prior investigation [Lederman et al. (2019). An international collaborative investigation of beginning seventh grade students' understandings of scientific inquiry: Establishing a baseline. Journal of Research in Science Teaching, 56(4), 486-515. ]. This study documents and discusses graduating high school students' understandings and compares their understandings to seventh grade students' understandings of the same aspects of scientific inquiry for each country. It is important to note that collecting data from each of the 130+ countries globally was not feasible. Similarly, it was not possible to collect data from every region of each country. A concerted effort was made, however, to provide a relatively representative picture of each country and the world.
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  • De Baat, Esmée C., et al. (författare)
  • Risk Factors for Heart Failure among Pan-European Childhood Cancer Survivors : A PanCareSurFup and ProCardio Cohort and Nested Case-Control Study
  • 2023
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 41:1, s. 96-106
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines.METHODSThis study includes the PanCareSurFup and ProCardio cohort of ≥ 5-year childhood cancer survivors diagnosed between 1940 and 2009 in seven European countries (N = 42,361). We calculated the cumulative incidence of HF and conducted a nested case-control study to evaluate detailed treatment-related risk factors.RESULTSThe cumulative incidence of HF was 2% (95% CI, 1.7 to 2.2) by age 50 years. The case-control study (n = 1,000) showed that survivors who received a mean heart radiation therapy (RT) dose of 5 to < 15 Gy have an increased risk of HF (odds ratio, 5.5; 95% CI, 2.5 to 12.3), when compared with no heart RT. The risk associated with doses 5 to < 15 Gy increased with exposure of a larger heart volume. In addition, the HF risk increased in a linear fashion with higher mean heart RT doses. Regarding total cumulative anthracycline dose, survivors who received ≥ 100 mg/m2 had a substantially increased risk of HF and survivors treated with a lower dose showed no significantly increased risk of HF. The dose-response relationship appeared quadratic with higher anthracycline doses.CONCLUSIONSurvivors who received a mean heart RT dose of ≥ 5 Gy have an increased risk of HF. The risk associated with RT increases with larger volumes exposed. Survivors treated with < 100 mg/m2 total cumulative anthracycline dose have no significantly increased risk of HF. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.
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  • van Atteveld, J. E., et al. (författare)
  • Risk and determinants of low and very low bone mineral density and fractures in a national cohort of Dutch adult childhood cancer survivors (DCCSS-LATER): a cross-sectional study
  • 2023
  • Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 11:1, s. 21-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Childhood cancer survivors are at risk of developing skeletal comorbidities later in life. We aimed to assess risk factors for low and very low bone mineral density (BMD), and the risk of and risk factors for any fractures and vertebral fractures in a national cohort of Dutch adult childhood cancer survivors. Methods In this cross-sectional study, we used data from the DCCSS LATER cohort, which comprised individuals who were alive for at least 5 years after diagnosis of childhood cancer (ie, histologically confirmed malignancies or Langerhans cell histiocytosis), were diagnosed before the age of 19 years, and who had been treated at one of seven Dutch paediatric oncology centres between 1963 and 2002 (hereafter referred to as survivors). For this study, we invited survivors aged 18-45 years, who were alive as of Oct 10, 2016, living in the Netherlands, and who were deemed eligible by their treating physician to participate. We assessed BMD using dual-energy x-ray absorptiometry (DXA). Self-reported fractures that occurred at least 5 years after cancer diagnosis were assessed using available medical history and compared with population-level data from the Swedish national registry. We assessed vertebral fractures in a subset of participants using a vertebral fracture assessment. We assessed associations between the occurrence of low (Z-score of <=-1) or very low (Z-score of <=-2) BMD, fractures, and vertebral fractures and demographic, treatment -related, endocrine, and lifestyle-related factors using logistic regression analysis. Findings Between April 29, 2016, and Jan 22, 2020, 3996 (64 center dot 8%) of 6165 individuals from the DCCSS LATER cohort were invited to participate, of whom 2003 (50 center dot 1%) were enrolled (mean age at participation was 33 center dot 1 years [SD 7 center dot 2], 966 [48 center dot 2%] were female, and 1037 [51 center dot 8%] were male [data on ethnicity and race were not available due to national policies]). 1548 (77 center dot 3%) had evaluable DXA scans for assessment of BMD, 1892 (94 center dot 5%) provided medical history of fractures, and 249 (12 center dot 4%) were assessed for vertebral fractures. 559 (36 center dot 1%) of 1548 had low BMD at any site, and 149 (9 center dot 6%) had very low BMD at any site. The standardised incidence ratio of any first fracture was 3 center dot 53 (95% CI 3 center dot 06-4 center dot 06) for male participants and 5 center dot 35 (4 center dot 46-6 center dot 52) for female participants. 33 (13 center dot 3%) of 249 participants had vertebral fractures. Male sex, underweight, high carboplatin dose, any dose of cranial radiotherapy, hypogonadism, hyperthyroidism, low physical activity, and severe vitamin D deficiency were associated with low BMD at any site and male sex, underweight, cranial radiotherapy, growth hormone deficiency, and severe vitamin D deficiency were associated with very low BMD at any site. Additionally, male sex, former and current smoking, and very low lumbar spine BMD were associated with any fractures, whereas older age at follow-up, previous treatment with platinum compounds, growth hormone deficiency, and low physical activity were specifically associated with vertebral fractures. Interpretation Survivors of childhood cancer are at increased risk of any first fracture. Very low lumbar spine BMD was associated with fractures, highlighting the importance of active BMD surveillance in high-risk survivors (ie, those treated with cranial, craniospinal, or total body irradiation). Moreover, our results indicate that intensive surveillance and timely interventions for endocrine disorders and vitamin deficiencies might improve bone health in childhood cancer survivors, but this needs to be assessed in future studies.
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  • Verbruggen, Lisanne C., et al. (författare)
  • Guidance regarding COVID-19 for survivors of childhood, adolescent, and young adult cancer : A statement from the International Late Effects of Childhood Cancer Guideline Harmonization Group
  • 2020
  • Ingår i: Pediatric Blood and Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 67:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood, adolescent, and young adult (CAYA) cancer survivors may be at risk for a severe course of COVID-19. Little is known about the clinical course of COVID-19 in CAYA cancer survivors, or if additional preventive measures are warranted. We established a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) to summarize existing evidence and worldwide recommendations regarding evidence about factors/conditions associated with risk for a severe course of COVID-19 in CAYA cancer survivors, and to develop a consensus statement to provide guidance for healthcare practitioners and CAYA cancer survivors regarding COVID-19.
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  • Wang, Yuehan, et al. (författare)
  • Male breast cancer after childhood cancer : Systematic review and analyses in the PanCareSurFup cohort
  • 2022
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 165, s. 27-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Breast cancer is a well-recognised late adverse effect in female childhood cancer survivors (CCSs), especially after chest radiotherapy; information on subsequent male breast cancer (SMBC) is limited. We summarised the existing evidence on SMBC after childhood cancer in a systematic review and investigated the risk of SMBC among males in a Pan-European cohort. Methods: We searched Medline/PubMed for cohort studies and case reports/series that assessed SMBC after childhood cancer (≤21 years). Furthermore, we analysed data on SMBC in the PanCareSurFup cohort, reporting standardised incidence ratios (SIRs), absolute excess risks (AERs), and 5- and 10-year survival rates. Results: The systematic review included 38 of 7080 potentially eligible articles. Cohort-specific SMBC frequencies were 0–0.40% (31 studies). SMBC occurred after a follow-up ranging from 24.0 to 42.0 years. Nine case reports/series described 11 SMBC cases, occurring 11.0–42.5 years after primary childhood cancer. In the PanCareSurFup cohort (16 SMBC/37,738 males; 0.04%), we observed a 22.3-fold increased risk of SMBC relative to the general male population (95% CI 12.7–36.2; absolute excess risk/100,000 person-years: 2.3, 95% CI 1.3–3.7). The five- and ten-year survival rates after SMBC diagnosis were 60.3% (95% CI 35.6%–85.0%) and 43.0% (95% CI 16.1%–69.9%), respectively. Clear evidence of risk factors did not emerge from these comprehensive efforts. Conclusions: Compared to the general population, male CCSs have an elevated risk of developing subsequent breast cancer, although the absolute risk is low. Health care providers should be aware of this rare yet serious late effect; male CCSs with symptoms potentially related to SMBC warrant careful examination.
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  • Bright, Chloe J, et al. (författare)
  • Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe
  • 2018
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 110:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer.Methods: We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated.Results: Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma.Conclusions: For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.
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  • Dixon, Stephanie B., et al. (författare)
  • The Future of Childhood Cancer Survivorship : Challenges and Opportunities for Continued Progress
  • 2020
  • Ingår i: Pediatric Clinics of North America. - : Elsevier BV. - 0031-3955. ; 67:6, s. 1237-1251
  • Forskningsöversikt (refereegranskat)abstract
    • As treatment evolves and the population who survive childhood cancer ages and increases in number, researchers must use novel approaches to prevent, identify and mitigate adverse effects of treatment. Future priorities include collaborative efforts to pool large cohort data to improve detection of late effects, identify late effects of novel therapies, and determine the contribution of genetic factors along with physiologic and accelerated aging among survivors. This knowledge should translate to individual risk prediction and prevention strategies. Finally, we must utilize health services research and implementation science to improve adoption of survivorship care recommendations outside of specialized pediatric oncology centers.
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  • Dudley, Isabelle M., et al. (författare)
  • Risk of subsequent primary lymphoma in a cohort of 69,460 five-year survivors of childhood and adolescent cancer in Europe : The PanCareSurFup study
  • 2023
  • Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:3, s. 426-440
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survivors of Hodgkin lymphoma (HL) are at risk of developing non-Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer survivors worldwide. Methods: The Pan-European Network for Care of Survivors After Childhood and Adolescent Cancer (PanCare) Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 69,460 five-year survivors of childhood cancer, diagnosed during 1940 through 2008, from 12 European countries. Risks of SPLs were quantified by standardized incidence ratios (SIRs) and relative risks (RRs) using multivariable Poisson regression. Results: Overall, 140 SPLs, including 104 NHLs and 36 HLs, were identified. Survivors were at 60% increased risk of an SPL compared with the general population (SIR, 1.6; 95% confidence interval [CI], 1.4–1.9). Survivors were twice as likely to develop NHL (SIR, 2.3; 95% CI, 1.9–2.8), with the greatest risks among survivors of HL (SIR, 7.1; 95% CI, 5.1–10.0), Wilms tumor (SIR, 3.1; 95% CI, 1.7–5.7), leukemia (SIR, 2.8; 95% CI, 1.8–4.4), and bone sarcoma (SIR, 2.7; 95% CI, 1.4–5.4). Treatment with chemotherapy for any cancer doubled the RR of NHL (RR, 2.1; 95% CI, 1.2–3.9), but treatment with radiotherapy did not (RR, 1.2; 95% CI, 0.7–2.0). Survivors were at similar risk of developing a subsequent HL as the general population (SIR, 1.1; 95% CI, 0.8–1.5). Conclusions: In addition to HL, the authors show here for the first time that survivors of Wilms tumor, leukemia, and bone sarcoma are at risk of NHL. Survivors and health care professionals should be aware of the risk of NHL in these survivors and in any survivors treated with chemotherapy.
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  • Feijen, Elizabeth A M, et al. (författare)
  • Late cardiac events after childhood cancer : Methodological aspects of the pan-european study pancaresurfup
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aim Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup. Methods Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors. Data onsymptomatic heart failure, ischemia, pericarditis, valvular disease and arrhythmia were collected and graded according to the Criteria for Adverse Events. Detailed treatment data, data on potential confounders, lifestyle related risk factors and general health problems were collected. Results The PanCareSurFup cardiac cohort consisted of 59,915 5-year childhood cancer survivors with malignancies diagnosed between 1940 and 2009 and classified according to the International Classification of Childhood Cancer 3. Different strategies were used to identify cardiac events such as record linkage to population/ hospital or regional based databases, and patient-And general practitioner-based questionnaires. Conclusion The cardiac study of the European collaborative research project PanCareSurFup will provide the largest cohort of 5-year childhood cancer survivors with systematically ascertained and validated data on symptomatic cardiac events. The result of this study can provide information to minimize the burden of cardiac events in childhood cancer survivors by tailoring the follow-up of childhood cancer survivors at high risk of cardiac adverse events, transferring this knowledge into evidence-based clinical practice guidelines and providing a platformfor future research studies in childhood cancer patients.
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  • Heymer, Emma J., et al. (författare)
  • Cumulative Absolute Risk of Subsequent Colorectal Cancer After Abdominopelvic Radiotherapy Among Childhood Cancer Survivors : A PanCareSurFup Study
  • 2024
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 42:3, s. 336-347
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study. METHODS Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area. RESULTS Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected). CONCLUSION We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.
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  • Heymer, Emma J., et al. (författare)
  • Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study
  • 2024
  • Ingår i: British Journal of Cancer. - 0007-0920. ; 130:6, s. 976-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.
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  • Mulder, Renée L., et al. (författare)
  • Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer : recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
  • 2021
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:2, s. 68-80
  • Forskningsöversikt (refereegranskat)abstract
    • Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.
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  • Ratajczak-Tretel, B., et al. (författare)
  • Atrial fibrillation in cryptogenic stroke and TIA patients in the nordic atrial fibrillation and stroke The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study : Main results
  • 2023
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 148-156
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA₂DS₂-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.
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21.
  • Ratajczak-Tretel, B, et al. (författare)
  • Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke : results from the NOR-FIB Study
  • 2023
  • Ingår i: Journal of Neurology. - 1432-1459. ; 270:8, s. 4049-4059
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study.METHOD: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA 2DS 2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. RESULTS: In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7.CONCLUSION: Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.
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22.
  • Ratajczak-Tretel, B, et al. (författare)
  • Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study : the importance of comprehensive clinical evaluation
  • 2023
  • Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management.METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis.RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA 2DS 2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal.TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.
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23.
  • Sieberts, SK, et al. (författare)
  • Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
  • 2016
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
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24.
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25.
  • Sunguc, Ceren, et al. (författare)
  • Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study
  • 2023
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 128:1, s. 80-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks. Methods: The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. Results: One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4–5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6–25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7–11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9–9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0–8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3–44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6–100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1–70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6–23.7). Conclusions: Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early.
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26.
  • van Atteveld, Jenneke E., et al. (författare)
  • Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors : evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
  • 2021
  • Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:9, s. 622-637
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dualenergy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > -1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.
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27.
  • van den Oever, Selina R., et al. (författare)
  • Childhood cancer survivorship care during the COVID-19 pandemic : an international report of practice implications and provider concerns
  • 2022
  • Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 16:6, s. 1390-1400
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Long-term follow-up (LTFU) care is essential to optimise health outcomes in childhood cancer survivors (CCS). We aimed to assess the impact of the COVID-19 pandemic on LTFU services and providers. Methods: A COVID-19 working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) distributed a questionnaire to LTFU service providers in 37 countries across Europe, Asia, North America, Central/South America, and Australia. The questionnaire assessed how care delivery methods changed during the pandemic and respondents’ level of worry about the pandemic’s impact on LTFU care delivery, their finances, their health, and that of their family and friends. Results: Among 226 institutions, providers from 178 (79%) responded. Shortly after the initial outbreak, 42% of LTFU clinics closed. Restrictions during the pandemic resulted in fewer in-person consultations and an increased use of telemedicine, telephone, and email consultations. The use of a risk assessment to prioritise the method of LTFU consultation for individual CCS increased from 12 to 47%. While respondents anticipated in-person consultations to remain the primary method for LTFU service delivery, they expected significantly increased use of telemedicine and telephone consultations after the pandemic. On average, respondents reported highest levels of worry about psychosocial well-being of survivors. Conclusions: The pandemic necessitated changes in LTFU service delivery, including greater use of virtual LTFU care and risk-stratification to identify CCS that need in-person evaluations. Implications for Cancer Survivors: Increased utilisation of virtual LTFU care and risk stratification is likely to persist post-pandemic.
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28.
  • van Kalsbeek, Rebecca J., et al. (författare)
  • The PanCareFollowUp Care Intervention : A European harmonised approach to person-centred guideline-based survivorship care after childhood, adolescent and young adult cancer
  • 2022
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 162, s. 34-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Long-term follow-up (LTFU) care, although endorsed, is not available for the majority of adult survivors of childhood, adolescence and young adult (CAYA) cancer. Barriers to implementation include lack of time, knowledge, personnel and funding. Sustainable solutions are urgently needed to address the needs of CAYA cancer survivors to improve the quality of life and reduce the burden of late effects on survivors, health care systems and society. The European Union–funded PanCareFollowUp project, initiated by the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer, was established to facilitate the implementation of person-centred survivorship care across Europe. Patients and methods: The PanCareFollowUp Care Intervention was co-developed with survivors as part of the PanCareFollowUp project. It is a person-centred approach to survivorship care, supported by guidelines and with flexibility to adapt to local health care settings. The Care Intervention consists of three steps: (1) previsit completion of a Survivor Questionnaire (by the survivor) and Treatment Summary (by the health care provider [HCP]), (2) a clinic visit including shared decision-making, and (3) a follow-up call to finalise the individualised Survivorship Care Plan. Results: We developed the key components of the PanCareFollowUp Care Intervention: a PanCareFollowUp Survivor Questionnaire, Treatment Summary template, Survivorship Care Plan template, and educational materials for HCPs and survivors. Wide implementation of the PanCareFollowUp Care Intervention will be supported with a freely distributed Replication Manual on completion of the PanCareFollowUp project. Conclusions: The PanCareFollowUp Care Intervention will support the implementation of person-centred, guideline-based LTFU care in different health care settings across Europe to improve survivors’ health and well-being.
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29.
  • Abu-Hayyeh, S., et al. (författare)
  • Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum
  • 2016
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 63:4, s. 1287-1298
  • Tidskriftsartikel (refereegranskat)abstract
    • A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP.
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30.
  • Astuto, L. M., et al. (författare)
  • CDH23 mutation and phenotype heterogeneity : a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness
  • 2002
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:2, s. 262-275
  • Tidskriftsartikel (refereegranskat)abstract
    • Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.
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31.
  • Bouwman, Eline, et al. (författare)
  • Healthcare professionals' perceived barriers and facilitators of health behavior support provision : A qualitative study
  • 2023
  • Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 12:6, s. 7414-7426
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Childhood cancer survivors (CCSs) have an increased risk of developing chronic health conditions. Evidence suggests that poor health behaviors further increase health risks. Healthcare professionals (HCPs) involved in survivorship care have a key role in providing health behavior support (HBS) but can feel limited in their ability to do so. This study aims to explore European HCPs perceived facilitators and barriers to providing HBS to CCSs. Methods: Five focus groups with 30 HCPs from survivorship care clinics across Europe were conducted. Topic guides were informed by the Theoretical Domains Framework (TDF) to capture domains that may influence provision of HBS. Focus groups were analyzed with thematic analysis. Transcripts were inductively coded, after which axial coding was applied to organize codes into categories. Finally, categories were mapped onto the TDF domains. Results: Nine TDF domains were identified in the data. The most commonly reported TDF domains were “Knowledge”, “Skills”, and “Environmental context and resources”. HCPs indicated that their lack of knowledge of the association between late effects and health behaviors, besides time restrictions, were barriers to HBS. Facilitators for HBS included possession of skills needed to pass on health behavior information, good clinic organization, and an established network of HCPs. Conclusions: This study identified education and training of HCPs as key opportunities to improve HBS. Survivorship care clinics should work towards establishing well-integrated structured care with internal and external networks including HBS being part of routine care. Proper understanding of facilitators and barriers should lead to better survivorship care for CCSs.
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32.
  • Bouwman, Eline, et al. (författare)
  • Perceived barriers and facilitators to health behaviors in European childhood cancer survivors : A qualitative PanCareFollowUp study
  • 2023
  • Ingår i: Cancer Medicine. - 2045-7634. ; 12:11, s. 12749-12764
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Healthy behaviors, that is, engaging in regular physical activities, maintaining a healthy diet, limiting alcohol consumption, and avoiding tobacco and drug use, decrease the risk of developing late adverse health conditions in childhood cancer survivors. However, childhood cancer survivors may experience barriers to adopting and maintaining healthy behaviors. This study aimed to assess these barriers and facilitators to health behavior adoption and maintenance in childhood cancer survivors. Methods: A focus group (n = 12) and semi-structured telephone interviews (n = 20) were conducted with a selected sample of European and Dutch childhood cancer survivors, respectively. The Theoretical Domains Framework (TDF) was used to inform the topic guide and analysis. Inductive thematic analysis was applied to identify categories relating to barriers and facilitators of health behavior adoption and maintenance, after which they were deductively mapped onto the TDF. Results: Ten TDF domains were identified in the data of which “Knowledge,” “Beliefs about consequences,” “Environmental context and resources,” and “Social influences” were most commonly reported. Childhood cancer survivors expressed a need for knowledge on the importance of healthy behaviors, possibly provided by healthcare professionals. They indicated physical and long-term benefits of healthy behaviors, available professional support, and a supporting and health-consciously minded work and social environment to be facilitators. Barriers were mostly related to a lack of available time and an unhealthy environment. Lastly, (social) media was perceived as both a barrier and a facilitator to healthy behaviors. Conclusion: This study has identified education and available professional support in health behaviors and the relevance of healthy behaviors for childhood cancer survivors as key opportunities for stimulating health behavior adoption in childhood cancer survivors. Incorporating health behavior support and interventions for this population should therefore be a high priority.
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33.
  • Byrne, Julianne, et al. (författare)
  • The PanCareSurFup consortium : research and guidelines to improve lives for survivors of childhood cancer
  • 2018
  • Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 103:Nov, s. 238-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.
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34.
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35.
  • Fidler, Miranda M., et al. (författare)
  • Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe
  • 2018
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 110:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors.Methods: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided.Results: Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk.Conclusions: For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer.
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36.
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37.
  • Grabow, Desiree, et al. (författare)
  • The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer : a cohort from 12 European countries
  • 2018
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 33:3, s. 335-349
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.
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38.
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39.
  • Kremer, B, et al. (författare)
  • Influence of lamotrigine on progression of early Huntington disease : a randomized clinical trial.
  • 1999
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 53:5, s. 1000-11
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess the efficacy of lamotrigine, a novel antiepileptic drug that inhibits glutamate release, to retard disease progression in Huntington disease (HD).BACKGROUND: Excitatory amino acids may cause selective neuronal death in HD, and lamotrigine may inhibit glutamate release in vivo.METHODS: A double-blinded, placebo-controlled study was conducted of 64 patients with motor signs of less than 5 years' duration who were randomly assigned to either placebo or lamotrigine and assessed at 0 (baseline), 12, 24, and 30 months. The primary response variable was total functional capacity (TFC) score. Secondary response variables included the quantified neurological examination and a set of cognitive and motor tests. Repeated fluorodeoxyglucose measurements of regional cerebral metabolism using PET also were included.RESULTS: Fifty-five patients (28 on lamotrigine, 27 on placebo) completed the study. Neither the primary response variable nor any of the secondary response variables differed significantly between the treatment groups. Both the lamotrigine and the placebo group deteriorated significantly on the TFC, in the lamotrigine group by 1.89 and the placebo group by 2.11 points. No effect of CAG size on the rate of deterioration could be detected.CONCLUSIONS: There was no clear evidence that lamotrigine retarded the progression of early Huntington disease over a period of 30 months. However, more patients on lamotrigine reported symptomatic improvement (53.6 versus 14.8%; p = 0.006), and a trend toward decreased chorea was evident in the treated group (p = 0.08). The study also identified various indices of disease progression, including motor tests and PET studies, that were sensitive to deterioration over time.
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40.
  • Lesur, I, et al. (författare)
  • A sample view of the pedunculate oak (Quercus robur) genome from the sequencing of hypomethylated and random genetic libraries
  • 2011
  • Ingår i: Tree Genetics & Genomes. - : Springer Science and Business Media LLC. - 1614-2942 .- 1614-2950. ; 7:6, s. 1277-1285
  • Tidskriftsartikel (refereegranskat)abstract
    • Genomic resources have recently been developed for a number of species of Fagaceae, with the purpose of identifying the genetic factors underlying the adaptation of these long-lived, biologically predominant, commercially and ecologically important species to their environment. The sequencing of genomes of the size of the oak genome (740 Mb/C) is now becoming both possible and affordable due to breakthroughs in sequencing technology. However, an understanding of the composition and structure of the oak genome is required before launching a sequencing initiative. We constructed random (Rd) and hypomethylated (Hp) genomic libraries for pedunculate oak (Quercus robur) and carried out a sample sequencing of 2.33 and 2.36 Mb of shotgun DNA from the Rd and Hp libraries, respectively, to provide a first insight into the repetitive element and gene content of the oak genome. We found striking similarities between Rd sequences and previously analyzed BAC end sequences of pedunculate oak, with a similar percentage of known repeat elements (5.56%), an almost identical simple sequence repeat density (i.e., 29 SSRs per 100 kb), an identical profile of SSR motifs (in descending order of frequency—dinucleotide, pentanucleotide, trinucleotide, tetranucleotide, and hexanucleotide motifs). Conversely, the Hp fraction was, as expected, enriched in nuclear genes (2.44-fold enrichment). This enrichment was associated with a lower frequency of retrotransposons than for Rd sequences. We also identified twice as many SSR motifs in the Rd library as in the Hp library. This work provides useful information before opening a new chapter in oak genome sequencing.
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41.
  • Lynch, Kate D, et al. (författare)
  • Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases.
  • 2020
  • Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n= 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P= .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P= .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
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42.
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43.
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44.
  • Reulen, RC, et al. (författare)
  • Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study
  • 2021
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1520-1528
  • Tidskriftsartikel (refereegranskat)abstract
    • Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.MethodsThe PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence.Results427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN—comparable to the risk among members of the general population with at least two first-degree relatives affected.ConclusionsColonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.
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45.
  • Skinner, Roderick, et al. (författare)
  • Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors : a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium
  • 2017
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:2, s. 75-90
  • Forskningsöversikt (refereegranskat)abstract
    • Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.
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46.
  • van Dalen, Elvira C., et al. (författare)
  • Coronary artery disease surveillance among childhood, adolescent and young adult cancer survivors : A systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
  • 2021
  • Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 156, s. 127-137
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking. Aim: To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers. Methods: A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations. Results: 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses >15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations. Conclusion: These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors.
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47.
  • Van Dorp, Wendy, et al. (författare)
  • Recommendations for premature ovarian insufficiency surveillance for female survivors of childhood, adolescent, and young adult cancer : A report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup consortium
  • 2016
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 34:28, s. 3440-3450
  • Forskningsöversikt (refereegranskat)abstract
    • Purpose: Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were treated with alkylating agents and/or radiation, with potential exposure of the ovaries, have an increased risk of premature ovarian insufficiency (POI). Clinical practice guidelines can facilitate these survivors' access to optimal treatment of late effects that may improve health and quality of survival; however, surveillance recommendations vary among the existing long-term follow-up guidelines, which impedes the implementation of screening. Patients and Methods: The present guideline was developed by using an evidence-based approach and summarizes harmonized POI surveillance recommendations for female survivors of CAYA cancer who were diagnosed at age < 25 years. The recommendations were formulated by an international multidisciplinary panel and graded according to the strength of the evidence and the potential benefit gained from early detection and intervention. The harmonized POI surveillance recommendations were developed by using a transparent process and are intended to facilitate care for survivors of CAYA cancer. Results and Conclusion: The harmonized set of POI surveillance recommendations is intended to be scientifically rigorous, to positively influence health outcomes, and to facilitate the care for female survivors of CAYA cancer.
  •  
48.
  • van Kalsbeek, Rebecca J., et al. (författare)
  • European PanCareFollowUp Recommendations for surveillance of late effects of childhood, adolescent, and young adult cancer
  • 2021
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 154, s. 316-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Long-term follow-up (LTFU) care for childhood, adolescent, and young adult (CAYA) cancer survivors is essential to preserve health and quality of life (QoL). Evidence-based guidelines are needed to inform optimal surveillance strategies, but many topics are yet to be addressed by the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG). Therefore, the PanCareFollowUp Recommendations Working Group collaborated with stakeholders to develop European harmonised recommendations in anticipation of evidence-based IGHG guidelines. Methods: The PanCareFollowUp Recommendations Working Group, consisting of 23 late effects specialists, researchers, and survivor representatives from nine countries, collaborated in the first Europe-wide effort to provide unified recommendations in anticipation of evidence-based guidelines. A pragmatic methodology was used to define recommendations for topics where no evidence-based IGHG recommendations exist. The objective was to describe the surveillance requirements for high-quality care while balancing the different infrastructures and resources across European health care systems. The process included two face-to-face meetings and an external consultation round involving 18 experts from 14 countries. Results: Twenty-five harmonised recommendations for LTFU care were developed collaboratively and address topics requiring awareness only (n = 6), awareness, history and/or physical examination (n = 9), or additional surveillance tests (n = 10). Conclusions: The PanCareFollowUp Recommendations, representing a unique agreement across European stakeholders, emphasise awareness among survivors and health care providers in addition to tailored clinical evaluation and/or surveillance tests. They include existing IGHG guidelines and additional recommendations developed by a pragmatic methodology and will be used in the Horizon 2020–funded PanCareFollowUp project to improve health and QoL of CAYA cancer survivors.
  •  
49.
  • Van Kalsbeek, Rebecca J., et al. (författare)
  • Evaluating the feasibility, effectiveness and costs of implementing person-centred follow-up care for childhood cancer survivors in four European countries : the PanCareFollowUp Care prospective cohort study protocol
  • 2022
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Long-term survival after childhood cancer often comes at the expense of late, adverse health conditions. However, survivorship care is frequently not available for adult survivors in Europe. The PanCareFollowUp Consortium therefore developed the PanCareFollowUp Care Intervention, an innovative person-centred survivorship care model based on experiences in the Netherlands. This paper describes the protocol of the prospective cohort study (Care Study) to evaluate the feasibility and the health economic, clinical and patient-reported outcomes of implementing PanCareFollowUp Care as usual care in four European countries. Methods and analysis In this prospective, longitudinal cohort study with at least 6 months of follow-up, 800 childhood cancer survivors will receive the PanCareFollowUp Care Intervention across four study sites in Belgium, Czech Republic, Italy and Sweden, representing different healthcare systems. The PanCareFollowUp Care Intervention will be evaluated according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Clinical and research data are collected through questionnaires, a clinic visit for multiple medical assessments and a follow-up call. The primary outcome is empowerment, assessed with the Health Education Impact Questionnaire. A central data centre will perform quality checks, data cleaning and data validation, and provide support in data analysis. Multilevel models will be used for repeated outcome measures, with subgroup analysis, for example, by study site, attained age, sex or diagnosis. Ethics and dissemination This study will be conducted in accordance with the guidelines of Good Clinical Practice and the Declaration of Helsinki. The study protocol has been reviewed and approved by all relevant ethics committees. The evidence and insights gained by this study will be summarised in a Replication Manual, also including the tools required to implement the PanCareFollowUp Care Intervention in other countries. This Replication Manual will become freely available through PanCare and will be disseminated through policy and press releases. Trial registration number Netherlands Trial Register (NL8918; https://www.trialregister.nl/trial/8918).
  •  
50.
  • Winther, Jeanete F., et al. (författare)
  • Childhood cancer survivor cohorts in Europe
  • 2015
  • Ingår i: Acta Oncologica. - 1651-226X. ; 54:5, s. 655-668
  • Forskningsöversikt (refereegranskat)abstract
    • With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.
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