Search

Contains fulltext : 294556.pdf (Publisher’s version ) (Open Access) BACKGROUND: Desmoid-type fibromatosis (DTF) has a highly variable clinical course with varying intensity of symptoms. The objectives of this study were to identify subgroups of DTF patients based on physical symptom burden and to compare symptom burden subgroups on health-related quality of life (HRQoL) and healthcare use (univariate and multivariate). METHODS: Desmoid-type fibromatosis patients from the United Kingdom and the Netherlands received cross-sectional questionnaires on HRQoL (EORTC QLQ-C30), DTF-specific HRQoL (DTF-QoL) and healthcare utilisation. Latent class cluster analysis was performed to identify subgroups based on patients' symptom burden using EORTC QLQ-C30 and DTF-QoL physical symptom items. Multivariate linear and logistic regression analyses were conducted to examine associations of symptom burden with HRQoL and healthcare utilisation, respectively. RESULTS: Among 235 DTF patients, four symptom burden clusters were identified, with low symptom burden (24%), intermediate symptom burden-low pain (20%), intermediate symptom burden-high pain (25%) and high symptom burden (31%). DTF patients with high symptom burden had clinically relevant lower HRQoL scores compared to patients with low and intermediate symptom burden (p

Aim: To assess whether infants with colic (IC) demonstrate persisting developmental dysregulation into childhood, manifested as behavioural problems, and to determine if these behavioural problems are associated with parenting factors. Methods: Preschool children with a history of IC at the age of 0–3 months, as defined by the Wessel criteria, were invited to participate in an observational follow-up study, in which their caregivers completed the Child Behaviour Checklist (CBCL). Raw scores and clinical-range scores on the internalising, externalising and total behavioural problems scales were compared with a Dutch normative sample using independent t-tests and Chi-square tests. For the clinical-range scores, multivariable logistic regressions (odds ratios [99% confidence interval, CI]) were used to adjust for confounders and to identify variables associated with behavioural problems. Results: Two hundred and fifty-eight children with a history of IC (median age 5.1 (interquartile range, IQR 4.6–5.5) years, 51.9% boys) were included. The cases had a significantly higher adjusted risk (adjusted odds ratios (aORs) [99% CI]) of scoring in the clinical range of the emotionally reactive, internalising and total problems scale (2.96 [1.24–7.06]; 2.50 [1.35–4.62]; 2.98 [1.46-6.07], respectively). Internalising (P < 0.001), externalising (P < 0.001) and total (P < 0.001) behavioural problems in children with a history of IC were associated with higher parenting stress scores. Conclusions: Children with a history of IC demonstrated significantly more internalising behavioural problems at preschool age compared to the norm sample. Specific advice and support need to be available for parents to understand and regulate the behaviour of their child, from infancy to childhood.

ABSTRACT INTRODUCTIONPractice nurses in general practice are ideally placed to deliver weight management treatments. Teaching people to eat according to their appetite, based on measurements of blood glucose (‘hunger training’), is known to lead to weight loss and improved eating behaviour. To effectively translate this research to primary care requires understanding of key stakeholder perspectives. AIMThe aim of this study was to explore the perspectives of practice nurses on the suitability of using hunger training as a weight management intervention in general practice. METHODSTen nurses trialled hunger training for 1 week, followed by a semi-structured interview where they were asked about their experience; perceived patient interest; enablers and barriers; and suggested changes to hunger training. RESULTSAll nurses were positive about hunger training and wanted to use it with their patients. They thought it was a useful method for teaching patients about eating according to their appetite, and the impact of food choices on glucose. Motivation was seen to be both an important potential barrier and enabler for patients. Other anticipated patient enablers included the educational value of hunger training and ease of the programme. Other barriers included lack of time and cost of equipment and appointments. For most nurses, 1 week of following hunger training was sufficient training to deliver the intervention. Suggested refinements included adding nutrition advice to the booklet, incorporating other health goals and enabling social support. DISCUSSIONThese findings suggest that hunger training could be translated to primary care with minor modifications.

Background Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma. Methods Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months. Results A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid. Conclusion Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.

Renger de Bruin und Maarten Brinkman (Hrsg.): Friedensstädte. Die Verträge von Utrecht, Rastatt und Baden 1713–1714. Ausstellungskatalog. Michael Imhof Verlag Petersberg 2013. 192 Seiten mit 121 farbigen Abbildungen. Broschur € 30,80. ISBN 978-3-86568-896-5

Introduction The influence of screens and technology on adolescent well-being is controversial and there is a need to improve methods to measure these behaviors. This study examines the feasibility and acceptability of using automated wearable cameras to measure evening screen use in adolescents. Methods A convenience sample of adolescents (aged 13–17 years, n=15) wore an automated camera for 3 evenings from 5:00 pm to bedtime. The camera (Brinno TLC120) captured an image every 15 seconds. Fieldwork was completed between October and December 2017, and data analyzed in 2018. Feasibility was examined by quality of the captured images, wear time, and whether images could be coded in relation to contextual factors (e.g., type of screen and where screen use occurred). Acceptability was examined by participant compliance to the protocol and from an exit interview. Results Data from 39 evenings were analyzed (41,734 images), with a median of 268 minutes per evening. The camera was worn for 78% of the evening on Day 1, declining to 51% on Day 3. Nearly half of the images contained a screen in active use (46%), most commonly phones (13.7%), TV (12.6%), and laptops (8.2%). Multiple screen use was evident in 5% of images. Within the exit interview, participants raised no major concerns about wearing the camera, and data loss because of deletions or privacy concerns was minimal (mean, 14 minutes, 6%). Conclusions Automated cameras offer a feasible, acceptable method of measuring prebedtime screen behavior, including environmental context and aspects of media multitasking in adolescents.

Background: Capivasertib (AZD5363), an AKT1,2,3 inhibitor, significantly improved progression-free and overall survival when added to paclitaxel in triple negative breast cancer (BC) patients (Schmid et al. ASCO 2018). We have previously reported in STAKT, robust target inhibition at 480mg BD versus placebo, including significant decreases in the primary biomarkers (PBs) - Ki67, pPRAS40 & pGSK3β - in primary BCs (Robertson et al. SABCS 2017). We now report the dose- and exposure-response relationship of capivasertib and the correlation between primary and secondary (pAKT, pS6, nuclear FOXO3a) tumor biomarkers. Design: STAKT was a two-stage, double blind, randomized, placebo controlled 'window-of-opportunity' trial in newly diagnosed ER+ BC patients. Stage 1 assessed capivasertib at a dose of 480mg BD p.o. versus placebo. Stage 2 assessed capivasertib at two lower doses 360mg and 240mg BD. Tumor biopsies were taken prior to 1st dose and after 4.5 days of dosing. Evaluable patients (who required pre-defined minimum baseline PD values for PBs) included placebo (n=11), capivasertib at 480mg (n=17), 360mg (n=5) and 240mg (n=6). Blood samples for pharmacokinetic (PK) studies were scheduled at pre-dose; 2, 4, optional 6 & 8 hrs post first dose on Day 1; ˜2-4 h post last dose on Day 5 (before biopsy). The % change from baseline for PBs were evaluated against the following exposure variables (placebo=0): i) Dose, ii) Observed Cmax Day 1 (˜2h post-dose), iii) Observed plasma concentration on Day 5, iv) Model-predicted plasma concentration Day 5 at time of biopsy, and v) Model-predicted AUC on Day 5. Spearman correlation coefficient measured the strength and direction of association between biomarkers. Results: · Significant mean reductions in % change from baseline were observed for the PBs pGSK3β (-39%; p · Dose-response relationships for individual % change from baseline could be described by an Emax model for all PBs. Overall, the correlation to PK exposure (observed or predicted) was similar to the correlation to dose. · Correlation coefficient analyses between biomarkers at capivasertib 480mg BD identified- i) Positive correlations for pGSK3β with Ki67 (ρ = 0.52, p-value < 0.05) & with pS6 (ρ = 0.54, p-value Conclusions · Capivasertib caused dose- and concentration- dependent effects on biomarkers after only 4.5 days. · Significant changes in the PBs were demonstrated at 480 mg BD. Biomarker changes was observed at 360mg and 240mg BD, but statistical analysis was limited by the small sample size at lower doses. · Correlation between a number of tumor biomarkers (relative changes) were identified for capivasertib 480mg BD. Citation Format: Gee J, Coleman RE, Cheung KL, Evans A, Holcombe C, Skene A, Rea D, Ahmed S, Jahan A, Horgan K, Rauchhaus P, Littleford R, Finlay P, Cheung A, Cullberg M, de Bruin E, Foxley A, Koulai L, Pass M, Schiavon G, Rugman P, Deb R, Robertson JFR. Dose- and exposure-response relationship and biomarker correlation analysis in breast tumors from patients treated with capivasertib, an AKT inhibitor, in the STAKT randomized, placebo controlled pre-surgical study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-12-01.

En depit des changements radicaux de 2006 concernant ses statuts, l’ordre teutonique du bailliage d’Utrecht est toujours defini par son ethique protestante et son enracinement dans l’ancienne noblesse, identite qui remonte a presque quatre siecles. Fonde au xiiie siecle, comme une branche de l’Ordre militaire, le bailliage avait a l’origine une identite purement catholique. Durant la Reforme, le bailliage resta catholique pendant une periode remarquablement longue, puis se detacha completement du pouvoir central de l’Ordre en Allemagne, devenant une institution pour les aristocrates maries protestants. Les conditions pour ceux qui souhaitaient le rejoindre etaient d’avoir quatre quartiers de noblesse et d’appartenir a l’Eglise reformee. De cette facon, l’Ordre s’insera sans heurt dans les structures des Provinces-unies. En 1795, apres le renversement de la Republique par les armees revolutionnaires francaises, l’Ordre survecut en maintenant son ancien critere d’entree. Apres l’introduction d’une constitution liberale en 1848, la noblesse protestante assuma un role directeur dans la defense des valeurs traditionnelles. L’identite protestante renforcee du bailliage d’Utrecht completa le tableau. Au xxe siecle, cette identite s’exprima en particulier a travers une politique de donations d’une importance croissante.

BACKGROUND Epilepsy is a common symptom in glioma patients, requiring antiepileptic drug (AED) treatment. However, comprehensive data on the efficacy and tolerability of AED treatment is currently lacking. In this systematic review we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma. METHODS Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane library were searched up to April 2020. Three different outcomes were extracted from all eligible articles: (I) seizure freedom; (II) ≥50% reduction in seizure frequency; and (III) treatment failure. To overcome variation with respect to sample sizes, weighted averages (WA) were calculated for outcomes at 6 and 12 months. RESULT A total of 64 studies were included. For monotherapy, the 6-months seizure freedom rate was highest for phenytoin (WA=72%), whereas the 12-months seizure freedom rate was highest for pregabalin (WA=75%). For achieving ≥ 50% seizure reduction, levetiracetam was the most effective AED at 6 and 12 months, with WA of 82 and 97% respectively. Considering the provided polytherapy combinations, levetiracetam combined with phenytoin was most effective followed by levetiracetam with valproic acid. Seizure freedom rates with polytherapy at 6 months and 12 months were highest for combinations with phenytoin and topiramate, respectively. For achieving a ≥ 50% seizure reduction, combinations with perampanel were found to be the most effective at 6 and 12 months. CONCLUSION Based on the current literature, phenytoin, levetiracetam and pregabalin are most effective as AED monotherapy in glioma patients with epilepsy. Well-controlled prospective studies are needed to help further guide clinician’s treatment choices.

This abstract was withdrawn by the authors.

The risk of infection with avian influenza viruses for poultry workers is relatively unknown in China, and study results are often biased by the notification of only the severe human cases. Protein microarray was used to detect binding antibodies to 13 different haemagglutinin (HA1-part) antigens of avian influenza A(H5N1), A(H7N7), A(H7N9) and A(H9N2) viruses, in serum samples from poultry workers and healthy blood donors collected in the course of 3 years in Guangdong Province, China. Significantly higher antibody titre levels were detected in poultry workers when compared to blood donors for the most recent H5 and H9 strains tested. These differences were most pronounced in younger age groups for antigens from older strains, but were observed in all age groups for the recent H5 and H9 antigens. For the H7 strains tested, only poultry workers from two retail live poultry markets had significantly higher antibody titres compared to blood donors.

Background In electroconvulsive therapy (ECT), a generalized seizure is provoked under general anesthesia. Standard airway management is done by face mask ventilation, but this is difficult during generalized seizure. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a method to increase apnea tolerance and permit apnea oxygenation. We hypothesize that THRIVE can oxygenate the patient during ECT and that it is comfortable for patients. Methods In this single-center feasibility study, 13 patients with a pharmacotherapy-resistant depressive disorder underwent 20 ECT sessions with the use of THRIVE. They received general anesthesia under standard monitoring and transcutaneous carbon dioxide monitoring. Afterward, they completed a survey comparing their prior experience with face mask oxygenation. Results There were no desaturations during the procedure, and patient comfort showed no difference in comparison to face mask. Compared with data from earlier ECT with face mask ventilation in the same patient, THRIVE did not seem to shorten seizure duration. Conclusions THRIVE is a novel, safe oxygenation method during ECT.

Inhibidor de l'AKT; PIK3CA; Capivasertib Inhibidor de AKT; PIK3CA; Capivasertib AKT inhibitor; PIK3CA; Capivasertib Background BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1–3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer, and in a phosphoinositide 3-kinase, catalytic, alpha polypeptide mutation sub-population (PIK3CA+). Patients and methods BEECH consisted of an open-label, phase Ib safety run-in (part A) in 38 patients with advanced breast cancer, and a randomised, placebo-controlled, double-blind, phase II expansion (part B) in 110 women with ER+/HER2− metastatic breast cancer. In part A, patients received paclitaxel 90 mg/m2 (days 1, 8 and 15 of a 28-day cycle) with capivasertib taken twice daily (b.i.d.) at two intermittent ascending dosing schedules. In part B, patients were randomly assigned, stratified by PIK3CA mutation status, to receive paclitaxel with either capivasertib or placebo. The primary end point for part A was safety to recommend a dose and schedule for part B; primary end points for part B were progression-free survival (PFS) in the overall and PIK3CA+ sub-population. Results Capivasertib was well tolerated, with a 400 mg b.i.d. 4 days on/3 days off treatment schedule selected in part A. In part B, median PFS in the overall population was 10.9 months with capivasertib versus 8.4 months with placebo [hazard ratio (HR) 0.80; P = 0.308]. In the PIK3CA+ sub-population, median PFS was 10.9 months with capivasertib versus 10.8 months with placebo (HR 1.11; P = 0.760). Based on the Common Terminology Criteria for Adverse Event v4.0, the most common grade ≥3 adverse events in the capivasertib group were diarrhoea, hyperglycaemia, neutropoenia and maculopapular rash. Dose intensity of paclitaxel was similar in both groups. Conclusions Capivasertib had no apparent impact on the tolerability and dose intensity of paclitaxel. Adding capivasertib to weekly paclitaxel did not prolong PFS in the overall population or PIK3CA+ sub-population of ER+/HER2− advanced/metastatic breast cancer patients. This study was supported by AstraZeneca (no grant number applies).

Background Dynamic changes in circulating tumour DNA (ctDNA) levels may predict long-term outcome. We utilised samples from a phase I/II randomised trial (BEECH) to assess ctDNA dynamics as a surrogate for progression-free survival (PFS) and early predictor of drug efficacy. Patients and methods Patients with estrogen receptor-positive advanced metastatic breast cancer (ER+ mBC) in the BEECH study, paclitaxel plus placebo versus paclitaxel plus AKT inhibitor capivasertib, had plasma samples collected for ctDNA analysis at baseline and at multiple time points in the development cohort (safety run-in, part A) and validation cohort (randomised, part B). Baseline sample ctDNA sequencing identified mutations for longitudinal analysis and mutation-specific digital droplet PCR (ddPCR) assays were utilised to assess change in ctDNA abundance (allele fraction) between baseline and 872 on-treatment samples. Primary objective was to assess whether early suppression of ctDNA, based on pre-defined criteria from the development cohort, independently predicted outcome in the validation cohort. Results In the development cohort, suppression of ctDNA was apparent after 8 days of treatment (P = 0.014), with cycle 2 day 1 (4 weeks) identified as the optimal time point to predict PFS from early ctDNA dynamics. In the validation cohort, median PFS was 11.1 months in patients with suppressed ctDNA at 4 weeks and 6.4 months in patients with high ctDNA (hazard ratio = 0.20, 95% confidence interval 0.083–0.50, P

Background: Community participation can provide increased understanding and more effective implementation of strategies that seek to improve outcomes for women and newborns. There is limited knowledge on how participatory processes take place and how this affects the results of an intervention.Objective: This paper presents the results of two years of implementing (2013–2015) community groups for maternal health care in Magu District, Tanzania.Method: A total of 102 community groups were established, and 77 completed the four phases of the participatory learning and action cycle. The four phases included identification of problems during pregnancy and childbirth (phase 1), deciding on solutions and planning strategies (phase 2), implementation of strategies (phase 3) and evaluation of impact (phase 4). Community group meetings were facilitated by 15 trained facilitators and groups met monthly in their respective villages. Data was collected as an ongoing process from facilitator and meeting reports, through interviews with facilitators and local leaders and from focus group discussions with community group participants.Results: The majority of groups prioritized problems related to the availability of and accessibility to health services. The most commonly actioned solution was the provision of health education to the community. Almost all groups (95%) experienced a positive impact on the community as results of their actions, including increased maternal health knowledge and positive behaviour changes among health care workers. Facilitators were positive about the community groups, stating that they were grateful for the gained knowledge on maternal health, and positively regarded the involvement of men in community groups, which are traditionally women-only.Conclusion: The process of establishing and undertaking community groups in itself appeared to have a positive perceived impact on the community. However, sustained behaviour change, power dynamics and financial incentives need to be carefully considered during implementation and sustaining the community groups.