Meta-analyses of randomized controlled trials (RCTs) have shown that exercise has beneficial effects on quality of life (QoL) in patients with breast cancer. However, these effects were often small. ...Blinding in an exercise trial is not possible, which has the possible disadvantage of difficult accrual, drop-out after randomization to control and contamination between study groups (controls adopting the behaviour of the intervention group). The cohort multiple randomized controlled trial (cmRCT) is an alternative for conventional RCTs and has the potential to overcome these disadvantages.
This cmRCT will be performed within the Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA). Patients with breast cancer who visit the radiotherapy department of the University Medical Center Utrecht are asked to participate in UMBRELLA. Patients give consent for collection of medical information, providing patient-reported outcomes through regular questionnaires and randomization into future intervention studies. Patients who fulfill the UMBRELLA Fit study eligibility criteria (12 to 18 months post inclusion in UMBRELLA, low physical activity level) will be randomly allocated to the intervention or control group (1:1 ratio). Patients randomized to the intervention group will be offered a 12-week exercise programme. The control group will not be informed. Regular cohort measurements will be used for outcome assessment. Feasiblity (including participation, contamination, generalizability and retention) of the cmRCT design and effects of the intervention on QoL will be evaluated.
We will examine the feasibility of the cmRCT design in exercise-oncology research and compare this with conventional RCTs. Furthermore, the effectiveness of an exercise intervention on the QoL of patients with breast cancer in the short term (6 months) and long term (24 months) will be studied.
Netherlands Trial Register, NTR5482/NL.52062.041.15 . Retrospectively registered on 7 December 2015.
Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to ...improve early detection and reduce interval breast cancers in such patients.
In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period.
The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval CI, 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.
The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE ClinicalTrials.gov number, NCT01315015.).
Lateral distributions for electrons and muons in extensive air showers measured with the array of the KASCADE experiment are compared to results of simulations based on the high-energy hadronic ...interaction models QGSJet and SIBYLL. It is shown, that the muon distributions are well described by both models. Deviations are found for the electromagnetic component, where both models predict a steeper lateral shape than observed in the data. For both models the observed lateral shapes of the electron component indicate a transition from a light to a more heavy composition of the cosmic ray spectrum above the knee.
The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after ...which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients’ recollection, understanding, and acceptance of broad consent in a clinical oncology setting.
We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12–18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1–6 months after cohort enrollment).
Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of “not being selected for an intervention while your data were being used in comparison with patients receiving interventions,” 10% felt reassured (6/62) and 2% scared/insecure (2/62).
Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications.
Using data measured by the KASCADE-Grande air shower array, an upper limit to the flux of ultra-high energy gamma-rays in the primary cosmic-ray flux is determined. KASCADE-Grande measures the ...electromagnetic and muonic components for individual air showers in the energy range from 10 PeV up to 1 EeV. The analysis is performed by selecting air showers with low muon contents. A preliminary result on the 90% C.L. upper limit to the relative intensity of gamma-ray with respect to cosmic ray primaries is presented and compared with limits reported by other measurements.
Previous results obtained by KASCADE-Grande using the QGSjetII-02 hadronic interaction model have shown that the energy spectrum of cosmic rays between 1016eV and 1018eV exhibits a significant ...hardening at approximately 2×1016eV and a slight but statistically significant steepening close to 1017eV. Moreover, the analysis with QGSjetII-02 suggests that the break observed around 1017eV is caused by the heavy component of primary cosmic rays. In this paper, we report on the results of similar analyses performed using the SIBYLL 2.1 and EPOS 1.99 hadronic interaction models to interpret the data. The present results confirm qualitatively the previous findings. However, the intensity of the all-particle spectrum, the positions of the hardening and steepening of the spectrum, as well as the relative abundance of the heavy and light mass groups depend on the hadronic interaction model used to interpret the data.
Left-sided pancreatic lesions are often treated surgically. Accurate diagnostic work-up is therefore essential to prevent futile major abdominal surgery. Large series focusing specifically on the ...preoperative work-up of left-sided pancreatic lesions are lacking. This surgical cohort analysis describes the sensitivity of CT, MRI, and EUS-FNA/B in the diagnostic work-up of left-sided pancreatic lesions.
We performed a post-hoc analysis of patients who underwent surgery for a left-sided pancreatic lesion between April 2010 and August 2017 and participated in the randomized CPR trial. Primary outcome was the sensitivity of CT, MRI, and EUS-FNA/B. Sensitivity was determined as the most likely diagnosis of each modality compared with the postoperative histopathological diagnosis. Additionally, the change in sensitivity of EUS versus EUS-FNA/B (i.e., cyst fluid analysis, and/or tissue acquisition) was measured.
Overall, 181 patients were included (benign: 23%, premalignant: 27%, malignant: 50%). Most patients had solid lesions (65%). Preoperative imaging included CT (86%), MRI (41%), EUS (68%). Overall, CT and EUS-FNA/B reached a sensitivity of both 71%, compared with 66% for MRI. When EUS was combined with FNA/B, sensitivity rose from 64% to 71%. For solid lesions, CT reached the highest sensitivity (75%) when compared with MRI (70%) and EUS-FNA/B (69%). For cystic lesions, EUS-FNA/B reached the highest sensitivity (75%) when compared with CT and MRI (both 62%).
CT is the most sensitive diagnostic modality for solid and EUS-FNA/B for cystic left-sided pancreatic lesions. EUS-FNA/B was associated with an increased sensitivity when compared to EUS alone.
Outcome measures in Angelman syndrome Hagenaar, Doesjka A; Bindels-de Heus, Karen G C B; van Gils, Maud M ...
Journal of neurodevelopmental disorders,
03/2024, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral ...challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children's functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials.
Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype.
The study sample consisted of 28 children with AS aged 2-18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored.
Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD).
Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition.
Registered d.d. 23-04-2020 under number 'NL8550' in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075.
To improve the specificity in prostate cancer diagnosis and to prevent unnecessary prostate biopsies, especially in the serum prostate-specific antigen (PSA) "gray zone" between 3 and 15 ng/mL, the ...implementation of prostate cancer-specific markers is urgently needed. The recently discovered prostate cancer antigen 3 (PCA3) is such a promising prostate cancer marker. In a previous single institution study, the PCA3 urine test clearly proved to be of diagnostic value. Therefore, the diagnostic performance of the PCA3 urine test was validated in a multicenter study.
The first voided urine after digital rectal examination was collected from a total of 583 men with serum PSA levels between 3 and 15 ng/mL who were to undergo prostate biopsies. We determined the PCA3 score in these samples and correlated the results with the results of the prostate biopsies.
A total of 534 men (92%) had an informative sample. The area under the receiver-operating characteristic curve, a measure of the diagnostic accuracy of a test, was 0.66 for the PCA3 urine test and 0.57 for serum PSA. The sensitivity for the PCA3 urine test was 65%, the specificity was 66% (versus 47% for serum PSA), and the negative predictive value was 80%.
In this multicenter study, we validated the diagnostic performance of the PCA3 urine test in the largest group studied thus far using a PCA3 gene-based test. This study shows that the PCA3 urine test, when used as a reflex test, can improve the specificity in prostate cancer diagnosis and could prevent many unnecessary prostate biopsies.
Background: Physical activity has been shown to reduce side-effects of breast cancer and its treatment. As physical activity levels of patients with breast cancer are largely unknown, we investigated ...these levels and compared them to women from the general population.
Methods: In this prospective cohort study, physical activity levels of women with breast cancer participating in the UMBRELLA cohort were assessed at radiotherapy intake and thereafter every 6 months up to 3 years with the SQUASH questionnaire, which was also used in a random sample of the Dutch population. We compared physical activity levels (no activity, low, moderate or high levels of sports, leisure time or total activity) between patients and the Dutch female population using multinomial logistic regression. Standardized Prevalence Ratios (SPR) were calculated to compare adherence to Dutch physical activity guidelines.
Results: Women with breast cancer (n
baseline
= 1655, n
6 months
= 1414, n
12 months
= 1186, n
18 months
= 957, n
24 months
= 744, n
30 months
= 555, and n
36 months
= 377) were less likely to spend time in physical activity compared to the general population (n = 11,710) until 3 years post-diagnosis, especially after 6 months (OR
high-vs.-no activity
= 0.34, 95% CI: 0.28-0.41). From 12 months onwards, patients were more likely to perform sports compared to the general population, especially patients who underwent systemic therapy. Guideline adherence was significantly lower in patients at baseline and 6 months (SPR
baseline
= 89, 95% CI: 82-97; SPR
6 months
= 88, 95% CI: 81-96), and comparable to the general population at 12-36 months, especially in older women.
Conclusions: Physical activity levels in women with breast cancer during and after treatment were lower compared to the Dutch female population. Three years post-treatment, they were still less physically active, although they spend more time in sport activities. As about half of the patients did not perform any sports, physical activity needs to be stimulated during and after treatment.
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