255 research outputs found

    Модель взаємовідносин між державою та фінансово-промисловими групами для різних бізнес-систем

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    Мета дослідження - визначення пріоритетів та стратегічних напрямків формування ефективної моделі взаємодії української держави з вітчизняними фінансово-промисловими групами в сучасних умовах економічного розвитку

    Cardiorespiratory fitness and physical activity in children with cancer

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    Purpose: This study assessed cardiorespiratory fitness (CRF), physical activity (PA), and sedentary behavior (SB), as well as factors associated with these outcomes in children during or shortly after cancer treatment. Methods: Cross-sectionally, CRF data, obtained by the cardiopulmonary exercise test, and PA and SB data, obtained by an accelerometer, were assessed in children with cancer (8–18 years old). Linear regression models were used to determine associations between CRF, PA, or SB and patient characteristics. Results: Among 60 children with cancer, mean age 12.6 years, 35 boys, 28 % were during cancer treatment. CRF, reported as the z score of VO2peak, showed that 32 children had a VO2peakz score which was −2 below the predicted value. CRF was significantly associated with PA and SB: eac

    Dutch–Flemish translation of nine pediatric item banks from the Patient-Reported Outcomes Measurement Information System (PROMIS)®

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    Purpose: The Patient-Reported Outcomes Measurement Information System (PROMIS®) is a new, state-of-the-art assessment system for measuring patient-reported health and well-being of adults and children. It has the potential to be more valid, reliable, and responsive than existing PROMs. The items banks are designed to be self-reported and completed by children aged 8–18 years. The PROMIS items can be administered in short forms or through computerized adaptive testing. This paper describes the translation and cultural adaption of nine PROMIS item banks (151 items) for children in Dutch–Flemish. Methods: The translation was performed by FACITtrans using standardized PROMIS methodology and approved by the PROMIS Statistical Center. The translation included four forward translations, two back-translations, three independent reviews (at least two Dutch, one Flemish), and pretesting in 24 children from the Netherlands and Flanders. Results: For some items, it was necessary to have separate translations for Dutch and Flemish: physical function—mobility (three items), anger (one item), pain interference (two items), and asthma impact (one item). Challenges faced in the translation process included scarcity or overabundance of possible translations, unclear item descriptions, constructs broader/smaller in the target language, difficulties in rank ordering items, differences in unit of measurement, irrelevant items, or differences in performance of activities. By addressing these challenges, acceptable translations were obtained for all items. Conclusion: The Dutch–Flemish PROMIS items are linguistically equivalent to the original USA version. Short forms are now available for use, and entire item banks are ready for cross-cultural validation in the Netherlands and Flanders

    Clinical characteristics and survival patterns of subsequent sarcoma, breast cancer, and melanoma after childhood cancer in the DCOG-LATER cohort

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    PURPOSE: Childhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma, breast cancer, or melanoma) and a population-based sample of similar first malignant neoplasm (FMN) patients.METHODS: We assembled three case series of solid SMNs observed in a cohort of 5-year Dutch childhood cancer survivors diagnosed 1963-2001 and followed until 2014: sarcoma (n = 45), female breast cancer (n = 41), and melanoma (n = 17). Each SMN patient was sex-, age-, and calendar year-matched to 10 FMN patients in the population-based Netherlands Cancer Registry. We compared clinical and histopathological characteristics by Fisher's exact tests and survival by multivariable Cox regression and competing risk regression analyses.RESULTS: Among sarcoma-SMN patients, overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.23-2.87] and sarcoma-specific mortality (HR 1.91, 95% CI 1.16-3.13) were significantly worse compared to sarcoma-FMN patients (foremost for soft-tissue sarcoma), with 15-year survival rates of 30.8% and 61.6%, respectively. Overall survival did not significantly differ for breast-SMN versus breast-FMN patients (HR 1.14, 95% CI 0.54-2.37), nor for melanoma-SMN versus melanoma-FMN patients (HR 0.71, 95% CI 0.10-5.00). No significant differences in tumor characteristics were observed between breast-SMN and breast-FMN patients. Breast-SMN patients were treated more often with mastectomy without radiotherapy/chemotherapy compared to breast-FMN patients (17.1% vs. 5.6%).CONCLUSIONS: Survival of sarcoma-SMN patients is worse than sarcoma-FMN patients. Although survival and tumor characteristics appear similar for breast-SMN and breast-FMN patients, treatment differs; breast-SMN patients less often receive breast-conserving therapy. Larger studies are necessary to substantiate these exploratory findings.</p

    The Dutch LATER physical outcomes set for self-reported data in survivors of childhood cancer

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    Purposes: Studies investigating self-reported long-term morbidity in childhood cancer survivors (CCS) are using heterogeneous outcome definitions, which compromises comparability and include (un)treated asymptomatic and symptomatic outcomes. We generated a Dutch LATER core set of clinically relevant physical outcomes, based on self-reported data. Clinically relevant outcomes were defined as outcomes associated with clinical symptoms or requiring medical treatment. Methods: First, we generated a draft outcome set based on existing questionnaires embedded in the Childhood Cancer Survivor Study, British Childhood Cancer Survivor Study, and Dutch LATER study. We added specific outcomes reported by survivors in the Dutch LATER questionnaire. Second, we selected a list of clinical relevant outcomes by agreement among a Dutch LATER experts team. Third, we compared the proposed clinically relevant outcomes to the severity grading of the Common Terminology Criteria for Adverse Events (CTCAE). Results: A core set of 74 self-reported long-term clinically relevant physical morbidity outcomes was established. Comparison to the CTCAE showed that 36% of these clinically relevant outcomes were missing in the CTCAE. Implications for Cancer Survivors: This proposed core outcome set of clinical relevant outcomes for self-reported data will be used to investigate the self-reported morbidity in the Dutch LATER study. Furthermore, this Dutch LATER outcome set can be used as a starting point for international harmonization for long-term outcomes in survivors of childhood cancer

    Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

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    Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes.Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls.Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation.All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (&lt; p10) 10.1 [95% CI 4.9; 20.6]; low AFC (&lt; p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (&gt; 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (&lt; 20 ng/l) 3.6 [95% CI 1.7; 7.7], p &lt; 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy &gt; 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score.Conclusion: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.</p

    TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response

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    SummaryPARP1 is the main sensor of single- and double-strand breaks in DNA and, in building chains of poly(ADP-ribose), promotes the recruitment of many downstream signaling and effector proteins involved in the DNA damage response (DDR). We show a robust physical interaction between PARP1 and the replication fork protein TIMELESS, distinct from the known TIMELESS-TIPIN complex, which activates the intra-S phase checkpoint. TIMELESS recruitment to laser-induced sites of DNA damage is dependent on its binding to PARP1, but not PARP1 activity. We also find that the PARP1-TIMELESS complex contains a number of established PARP1 substrates, and TIMELESS mutants unable to bind PARP1 are impaired in their ability to bind PARP1 substrates. Further, PARP1 binding to certain substrates and their recruitment to DNA damage lesions is impaired by TIMELESS knockdown, and TIMELESS silencing significantly impairs DNA double-strand break repair. We hypothesize that TIMELESS cooperates in the PARP1-mediated DDR

    Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study

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    Purpose: To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes. Methods: The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population. Results: Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4–0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3–3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2–2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes. Conclusion: CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated

    Chronic fatigue in childhood cancer survivors is associated with lifestyle and psychosocial factors; a DCCSS LATER study

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    Background: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). Patients and methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the ‘fatigue severity subscale’ of the Checklist Individual Strength (‘CIS-fatigue’). CF was defined as scoring ≥35 on the ‘CIS-fatigue’ and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. Results: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P &lt; 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37). Conclusion: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS.</p
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