Search

AIM: To synthesize existing evidence on the effectiveness of speech-language teleinterventions delivered via videoconferencing to users of augmentative and alternative communication (AAC) devices. METHOD: A systematic literature search was conducted in 10 electronic databases, from inception until August 2021. Included were speech-language teleinterventions delivered by researchers and/or clinicians via videoconferencing to users of AAC devices, without restrictions on chronological age and clinical diagnosis. The quality of the studies included in the review was appraised using the Downs and Black checklist and the Single-Case Experimental Design Scale; risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies - of Interventions and the single-case design risk of bias tools. RESULTS: Six teleinterventions including 25 participants with a variety of conditions, such as Down syndrome, autism, Rett syndrome, and amyotrophic lateral sclerosis met the inclusion criteria. Five studies used a single-case experimental design and one was a cohort study. Teleinterventions included active consultation (n = 2), functional communication training (n = 2), brain-computer interface (n = 1), and both teleintervention and in-person intervention (n = 1). All teleinterventions reported an increase in participants' independent use of AAC devices during the training sessions compared to baseline, as well as an overall high satisfaction and treatment acceptability. INTERPRETATION: Speech-language teleinterventions for users of AAC devices show great potential for a successful method of service delivery. Future telehealth studies with larger sample sizes and more robust methodology are strongly encouraged to allow the generalization of results across different populations. WHAT THIS PAPER ADDS: Individuals can learn to use augmentative and alternative communication (AAC) devices independently during tele-AAC interventions. Service providers and recipients reported an overall high satisfaction and acceptability for AAC services delivered via teleinterventions. Speech-language teleinterventions may be an effective method of providing AAC intervention services.

Mobile dating applications (MDAs) have become commonly used tools to seek out dating and sexual partners online. The current review aimed to systematically synthesize empirical findings in 72 quantitative studies on mobile dating, published in ISI-ranked journals between 2014 and 2020. This review focused on summarizing different approaches toward mobile dating, identity features of quantitative research on mobile dating, and hypothesized antecedents and outcomes of mobile dating. Our findings showed, first, that the literature diverges in how mobile dating is operationalized. Second, quantitative research on mobile dating predominantly consists of cross-sectional studies that draw on theoretical insights from multiple disciplines. Third, a variety of traits and sociodemographics were associated with MDA use. In particular, using MDAs for (1) relational goals related to being male, non-heterosexual, higher levels of sociosexuality, sensation seeking, extraversion, and holding more positive peer norms about using MDAs for relational goals; (2) intrapersonal goals related to being female and having more socially impairing traits; and (3) entertainment goals related to having higher levels of sociosexuality, sensation seeking, and antisocial traits. Outcomes significantly associated with general use of MDAs were scoring higher on sexual permissiveness and on engaging in casual (unprotected) sexual intercourse, as well as having higher risk at nonconsensual sex. MDA use was also connected with increased psychological distress and body dissatisfaction. Shortcomings of the existing research approaches and measures are discussed and six methodological and theoretical recommendations for future research are provided.

Background: Persistent symptoms, described as long COVID or post-COVID-19 condition, pose a potential public health problem. Here, the design and recruitment of the PRIME post-COVID study is described. PRIME post-COVID is a large-scale population-based observational study that aims to improve understanding of the occurrence, risk factors, social, physical, mental, emotional, and socioeconomic impact of post-COVID-19 condition. Methods: An observational open cohort study was set up, with retrospective and prospective assessments on various health-conditions and health-factors (medical, demographic, social, and behavioral) based on a public health COVID-19 test and by self-report (using online questionnaires in Dutch language). Invited for participation were, as recorded in a public health registry, adults (18 years and older) who were tested for COVID-19 and had a valid Polymerase Chain Reaction (PCR) positive or negative test result, and email address. In November 2021, 61,655 individuals were invited by email to participate, these included all eligible adults who tested PCR positive between 1 June 2020 and 1 November 2021, and a sample of adults who tested negative (2:1), comparable in distribution of age, sex, municipality of residence and year-quarter of testing. New recruitment periods are planned as well. Participants are followed over time by regular follow-up measurements. Data are analyzed using the appropriate data-analyses methods. Discussion: The PRIME post-COVID study will provide insights into various health-related aspects of post-COVID-19 condition in the context of various stages of the COVID-19 pandemic. Results will inform practical guidance for society, clinical and public health practice for the prevention and care for long-term impact of COVID-19. This study was funded by the Dutch National Institute for Health and Environment, Ministry of Health, Welfare and Sport (Grant numbers: 3910090442/3910105642/3910121041). The funders had no role in the design, collection, analysis, interpretation of data, and in writing the manuscript. We gratefully acknowledge L. C. J. Steijvers for her valuable contribution to the development of the questionnaire.

Purpose: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia.Methods: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 degrees C (Best CEM43T50) < 7.2 min and >7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed.Results: TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018).Conclusions: High thermal dose (best CEM43T50 >= 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity. (C) 2021 The Authors. Published by Elsevier B.V.

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 -10 , OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10 -5 ). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A , which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A . Genomic and functional data support a causal role of WNT5A at the locus.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Embaràs i malaltia cardíaca; Resultats de l’embaràs; Transposició de les grans artèries Embarazo y enfermedad cardíaca; Resultados del embarazo; Transposición de las grandes arterias Pregnancy and cardiac disease; Pregnancy outcomes, Transposition of the great arteries Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate. Funding from “Zabawas Foundation” and “De Hoop Foundation” in addition to the support from EURObservational Research Programme (EORP) is greatly acknowledged. Since the start of EORP, the following companies have supported the program: Abbott Vascular Int (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc (2014–2016), Menarini Int Op (2009–2012), MSD‐Merck & Co (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2021), and Vifor (2019–2022).

Fremanezumab is a humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide and is approved in Europe for migraine prevention in adults with ≥4 migraine days/month. The Pan-European Real Life (PEARL) study is a 24-month, prospective, observational study of fremanezumab in chronic or episodic migraine. End points include proportion of patients with ≥50% reduction in monthly migraine days during 6 months of treatment (primary); changes in monthly migraine days, disability scores and acute headache medication use; adherence and persistence; and effectiveness in patients switching from another calcitonin gene-related peptide pathway-targeting monoclonal antibody. PEARL is being conducted in approximately 100 centers in 11 European countries (estimated n = 1100). PEARL will generate important real-world data on effectiveness of fremanezumab and treatment patterns in patients with chronic migraine or episodic migraine.Lay abstract Fremanezumab is an injectable biologic medication that targets calcitonin gene-related peptide, a substance released in the nerves and blood vessels during a migraine attack that plays a role in migraine pain. Fremanezumab is approved in Europe for preventing migraine in adults who experience ≥4 migraine days/month. The Pan-European Real Life (PEARL) study is a 24-month long study that will observe patients with migraine who are starting treatment with fremanezumab in a clinical practice setting under the care of their treating physician. The major goals of the study are to evaluate the effectiveness of fremanezumab for reducing days with migraine attacks in a month, disability associated with migraine and use of acute headache medications to treat migraine, including in patients switching from other biologic migraine therapies in the same drug class. The extent to which patients follow their recommended treatment schedule per their providers’ instructions and whether patients discontinue treatment will also be evaluated. The PEARL study will include1000 patients in 100 centers across 11 European countries. The study will provide important information on effectiveness for patients with migraine receiving fremanezumab in the normal course of their treatment, as well as on patients’ use of fremanezumab according to their prescribing physicians’ recommendations. Trial registration number: EUPAS35111 (European Network of Centres for Pharmacoepidemiology and Pharmacovigilance).

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by hepatic free cholesterol accumulation. In addition, microRNAs (miRNAs) might be involved in NAFLD development. Therefore, we systematically reviewed the literature to examine the link between miRNAs and cholesterol metabolism in NAFLD. Nineteen studies were retrieved by a systematic search in September 2022. From these papers, we evaluated associations between 13 miRNAs with NAFLD and cholesterol metabolism. Additionally, their diagnostic potential was examined. Four miRNAs (miR122, 34a, 132 and 21) were associated with cholesterol metabolism and markers for NAFLD. MiR122 was upregulated in serum of NAFLD patients, increased with disease severity and correlated with HDL-C, TAG, VLDL-C, AST, ALT, ALP, lobular inflammation, hepatocellular ballooning and NAFLD score. Serum and hepatic levels also correlated. Serum and hepatic miR34a levels were increased in NAFLD, and correlated with VLDL-C and TAG. Serum miR379 was also higher in NAFLD, especially in early stages, while miR21 gave ambiguous results. The diagnostic properties of these miRNAs were comparable to those of existing biomarkers. However, serum miR122 levels appeared to be elevated before increases in ALT and AST were evident. In conclusion, miR122, miR34a, miR21 and miR132 may play a role in the development of NAFLD via effects on cholesterol metabolism. Furthermore, it needs to be explored if miRNAs 122, 34a and 379 could be used as part of a panel in addition to established biomarkers in early detection of NAFLD.

In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p interaction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

Background/Objectives Smoking is the leading risk factor for many chronic diseases. The quantitative analysis of potential health gains from reduced smoking is important for establishing priorities in Mongolia’s health policy. This study quantifies the effect of tobacco-tax increases on future smoking prevalence and the associated smoking-related burden of disease in Mongolia. Methods The dynamic model for health impact assessment (DYNAMO-HIA) tool was used. The most recent data were used as input for evaluating tobacco-taxation scenarios. Demographic data were taken from the Mongolian Statistical Information Services. Smoking data came from a representative population-based STEPS survey, and smoking-related disease data were obtained from the health-information database of Mongolia’s National Health Center. Simulation was used to evaluate various levels of one-time price increases on tobacco products (25% and 75%) in Mongolia. Conservative interpretation suggests that the population will eventually adjust to the higher tobacco price and return to baseline smoking behaviors. Results Over a three-year period, smoking prevalence would be reduced by 1.2% points, corresponding to almost 40 thousand smokers at the population level for a price increase of 75%, compared to the baseline scenario. Projected health benefits of this scenario suggest that more than 137 thousand quality adjusted of life years would be gained by avoiding smoking-related diseases within a population of three million over a 30-year period. Discussion Prevention through effective tobacco-control policy could yield considerable gains in population health in Mongolia. Compared to current policy, tax increases must be higher to have a significant effect on population health. Implications Tobacco taxation is an effective policy for reducing the harm of tobacco smoking, while benefiting population health in countries where the tobacco epidemic is still in an early stage. Smoking prevalence and smoking behaviors in these countries differ from those in Western countries. Reducing the uptake of smoking among young people could be a particularly worthwhile benefit of tobacco-tax increases.

BACKGROUND There is increasing interest in the spatial analysis of suicide data to identify high-risk (often public) locations likely to benefit from access restriction measures. The identification of such locations, however, relies on accurately geocoded data. This study aims to examine the extent to which common completeness and positional spatial errors are present in suicide data due to the underlying geocoding process. METHODS Using Australian suicide mortality data from the National Coronial Information System for the period of 2008-2017, we compared the custodian automated geocoding process to an alternate multiphase process. Descriptive and kernel density cluster analyses were conducted to ascertain data completeness (address matching rates) and positional accuracy (distance revised) differences between the two datasets. RESULTS The alternate geocoding process initially improved address matching from 67.8% in the custodian dataset to 78.4%. Additional manual identification of nonaddress features (such as cliffs or bridges) improved overall match rates to 94.6%. Nearly half (49.2%) of nonresidential suicide locations were revised more than 1,000 m from data custodian coordinates. Spatial misattribution rates were greatest at the smallest levels of geography. Kernel density maps showed clear misidentification of hotspots relying solely on autogeocoded data. CONCLUSION Suicide incidents that occur at nonresidential addresses are being erroneously geocoded to centralized fall-back locations in autogeocoding processes, which can lead to misidentification of suicide clusters. Our findings provide insights toward defining the nature of the problem and refining geocoding processes, so that suicide data can be used reliably for the detection of suicide hotspots. See video abstract at, http://links.lww.com/EDE/B862.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high‐risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high‐risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5‐yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery‐related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: −57% for “Progressive‐only” vs −41% for “Indolent Included”). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high‐risk individuals., What's new? About 10 percent of pancreatic cancers occur in individuals with inherited risk factors. While screening such high‐risk individuals can facilitate the detection of precursor lesions and early‐stage cancer, the extent to which benefits outweigh harms, including overdiagnosis, remains unknown. Here, using a microsimulation model, the authors explored uncertainties concerning the early detection of pancreatic cancer and analyzed the impact of these uncertainties on the effect of screening. In all simulated scenarios, screening was associated with reduced pancreatic cancer mortality. The effectiveness of screening was most strongly impacted by characteristics of natural disease course and level of pancreatic cancer risk

Objective: The use of adjuvant endocrine therapy (AET) after primary treatment of hormone receptor-positive breast cancer reduces the risk of recurrence and mortality. However, non-adherence is still common. Limited consideration has been given to how users deal with AET and the role of pharmaceutical care. Therefore, this study aims to obtain insight into the needs and wishes of women using AET regarding pharmaceutical care and eHealth. Methods: This is a qualitative explorative study comprising semi-structured interviews (n = 16) and a focus group (n = 5) among women who use or used AET after primary early-stage breast cancer (EBC) treatment using a thematic analysis approach. Results: Three themes emerged from the interviews and focus group: (1) experiences with AET use, (2) experiences with provided information and (3) needs and wishes regarding pharmaceutical care. Most women were highly motivated to use AET and indicated to have received useful information on AET. However, many expressed a strong need for more elaborate tailored and timely provided information on AET. They acknowledged the accessibility of pharmacists but reported that currently, pharmacists are hardly involved in AET care. Several women considered eHealth useful to obtain counselling and reliable information. Conclusion: Women need more comprehensive information and follow-up in primary setting after initial cancer treatments. A more elaborate role for the pharmacy and eHealth/mHealth, especially with regard to counselling on side effects and side effect management, could potentially improve pharmaceutical care.

In recent publications, capacitive sensing floors have been shown to be able to localize individuals in an unobtrusive manner. This paper demonstrates that it might be possible to utilize the walking characteristics extracted from a capacitive floor to recognize subject and gender. Several neural network-based machine learning techniques are developed for recognizing the gender and identity of a target. These algorithms were trained and validated using a dataset constructed from the information captured from 23 subjects while walking, alone, on the sensing floor. A deep neural network comprising a Bi-directional Long Short-Term Memory (BLSTM) provided the most accurate identity performance, classifying individuals with an accuracy of 98.12% on the test data. On the other hand, a Convolutional Neural Network (CNN) was the most accurate for gender recognition, attaining an accuracy of 93.3%. The neural network-based algorithms are benchmarked against Support Vector Machine (SVM), which is a classifier used in many reported works for floor-based recognition tasks. The majority of the neural networks outperform SVM across all accuracy metrics.

The current food environment in The Netherlands is considered obesogenic. Eighty percent of the products in supermarkets are unhealthy. The Wheel of Five is the well-established, science-based Dutch food-based dietary guideline (FBDG) developed to stimulate healthier choices. In addition, simple directions on food packaging, such as front-of-package (FOP) health logos, could also be helpful. However, these tools should be in line with each other, in order not to confuse the consumer. To study this, we evaluated two FOP nutrient profiling systems (NPSs) for their alignment with the Wheel of Five: Choices five-level criteria and Nutri-Score. For this, a small but representative sample of 124 products was selected from the Dutch food composition database (NEVO). For these products, the scores for Choices and Nutri-Score were calculated using the published criteria, while compliance with the Wheel of Five was established by using the criteria from Netherlands Nutrition Center (NNC). The Wheel of Five food groups were used to categorize the products. Differences between the Wheel of Five and Choices are smaller than with Nutri-Score, concluding that Choices is more consistent with the Wheel of Five and might be an attractive alternation for a FOP health logo on the Dutch market.

Endometrial cancer (EC) is the most common gynaecological tumor in developed countries and its incidence is increasing. Approximately 80% of newly diagnosed EC cases are estrogen-dependent. Type 1 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD-1) is the enzyme that catalyzes the final step in estrogen biosynthesis by reducing the weak estrogen estrone (E1) to the potent estrogen 17 beta-estradiol (E2), and previous studies showed that this enzyme is implicated in the intratumoral E2 generation in EC. In the present study we employed a recently developed orthotopic and estrogen-dependent xenograft mouse model of EC to show that pharmacological inhibition of the 17 beta-HSD-1 enzyme inhibits disease development. Tumors were induced in one uterine horn of athymic nude mice by intrauterine injection of the well-differentiated human endometrial adenocarcinoma Ishikawa cell line, modified to express human 17 beta-HSD-1 in levels comparable to EC, and the luciferase and green fluorescent protein reporter genes. Controlled estrogen exposure in ovariectomized mice was achieved using subcutaneous MedRod implants that released either the low active estrone (E1) precursor or vehicle. A subgroup of E1 supplemented mice received daily oral gavage of FP4643, a well-characterized 17 beta-HSD-1 inhibitor. Bioluminescence imaging (BLI) was used to measure tumor growth non-invasively. At sacrifice, mice receiving E1 and treated with the FP4643 inhibitor showed a significant reduction in tumor growth by approximately 65% compared to mice receiving E1. Tumors exhibited metastatic spread to the peritoneum, to the lymphovascular space (LVI), and to the thoracic cavity. Metastatic spread and LVI invasion were both significantly reduced in the inhibitor-treated group. Transcriptional profiling of tumors indicated that FP4643 treatment reduced the oncogenic potential at the mRNA level. In conclusion, we show that 17 beta-HSD-1 inhibition represents a promising novel endocrine treatment for EC.

BACKGROUND AND AIMS: Patients with COVID-19 infection presents with a broad clinical spectrum of symptoms and complications. As a consequence nutritional requirements are not met, resulting in weight- and muscle loss, and malnutrition. The aim of the present study is to delineate nutritional complaints, the (course of the) nutritional status and risk of sarcopenia of COVID-19 patients, during hospitalisation and after discharge.METHODS: In this prospective observational study in 407 hospital admitted COVID-19 patients in four university and peripheral hospitals, data were collected during dietetic consultations. Presence of nutrition related complaints (decreased appetite, loss of smell, changed taste, loss of taste, chewing and swallowing problems, nausea, vomiting, feeling of being full, stool frequency and consistency, gastric retention, need for help with food intake due to weakness and shortness of breath and nutritional status (weight loss, BMI, risk of sarcopenia with SARC-F ≥4 points) before, during hospital stay and after discharge were, where possible, collected.RESULTS: Included patients were most men (69%), median age of 64.8 ± 12.4 years, 60% were admitted to ICU at any time point during hospitalisation with a median LOS of 15 days and an in-hospital mortality rate of 21%. The most commonly reported complaints were: decreased appetite (58%), feeling of being full (49%) and shortness of breath (43%). One in three patients experienced changed taste, loss of taste and/or loss of smell. Prior to hospital admission, 67% of the patients was overweight (BMI >25 kg/m2), 35% of the patients was characterised as malnourished, mainly caused by considerable weight loss. Serious acute weight loss (>5 kg) was showed in 22% of the patents during the hospital stay; most of these patients (85%) were admitted to the ICU at any point in time. A high risk of sarcopenia (SARC-F ≥ 4 points) was scored in 73% of the patients during hospital admission.CONCLUSION: In conclusion, one in five hospital admitted COVID-19 patients suffered from serious acute weight loss and 73% had a high risk of sarcopenia. Moreover, almost all patients had one or more nutritional complaints. Of these complaints, decreased appetite, feeling of being full, shortness of breath and changed taste and loss of taste were the most predominant nutrition related complaints. These symptoms have serious repercussions on nutritional status. Although nutritional complaints persisted a long time after discharge, only a small group of patients received dietetic treatment after hospital discharge in recovery phase. Clinicians should consider the risks of acute malnutrition and sarcopenia in COVID-19 patients and investigate multidisciplinary treatment including dietetics during hospital stay and after discharge.

Background and aims: Extensive research showed a diurnal rhythm of endogenous cholesterol synthesis, whereas recent research reported no diurnal rhythm of intestinal cholesterol absorption in males who consumed low-fat meals. Little is known about the acute effect of macronutrient consumption on cholesterol metabolism, and hence if meal composition may explain this absence of rhythmicity in cholesterol absorption. Therefore, we examined the effect of a high-fat, high-carbohydrate, and high-protein meal on postprandial intestinal cholesterol absorption and endogenous cholesterol synthesis in apparently healthy overweight and slightly obese males.Methods and results: Eighteen males consumed in random order an isoenergetic high-fat, high carbohydrate, and high-protein meal on three occasions. Serum total cholesterol concentrations, cholesterol absorption markers (campesterol, cholestanol, and sitosterol), and cholesterol synthesis intermediates (7-dehydrocholesterol, 7-dehydrodesmosterol, desmosterol, dihydrolanosterol, lanosterol, lathosterol, zymostenol, and zymosterol) were measured at baseline (T0) and 240 min postprandially (T240). Meal consumption did not significantly change total cholesterol concentrations and cholesterol absorption marker levels (all p > 0.05). Serum levels of 7dehydrocholesterol, lanosterol, lathosterol, zymostenol, and zymosterol decreased significantly between T0 and T240 (all p < 0.05). These decreases were not significantly different between the three meals (all p > 0.05), except for a larger decrease in dihydrolanosterol levels after the high-fat versus the high-carbohydrate meal (p Z 0.009).Conclusion: The high-fat, high-carbohydrate, and high-protein meal did not significantly influ-ence postprandial intestinal cholesterol absorption. Several cholesterol synthesis intermediates decreased postprandially, but the individual macronutrients did not differentially affect these intermediates, except for a possible effect on dihydrolanosterol.Trial registration: ClinicalTrials.gov, NCT03139890.(c) 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (pConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

IntroductionDigital technologies can be used as part of paediatric motor rehabilitation to remediate impairment, promote recovery and improve function. However, the uptake of digital technologies in this clinical field may be limited.The aim of this study is to describe and explain digital technology use for paediatric motor rehabilitation. The specific objectives will be: (1) to describe the access to, acceptance of and use of digital technologies as a function of individual factors related to professionals practicing motor rehabilitation with children, and of environmental factors related to paediatric rehabilitation practice and (2) to explain digital technology use with a causal model based on the ‘unified theory of acceptance and use of technology’.Methods and analysisRehaTech4child (Rehabilitation Technologies For children) is a cross-sectional study involving an online survey, that is sponsored by the European Academy of Childhood Disability (EACD). The survey protocol follows the Strengthening the Reporting of Observational Studies in Epidemiology and CHERRIES (Checklist for Reporting Results of Internet E-Surveys) guidelines. The survey includes 43 questions about (1) respondents’ individual and environmental characteristics; (2) the ease of access to digital technologies, and the frequency, type and purpose of use of those technologies and (3) acceptance of technologies and barriers to their use. The survey is intended for professionals involved in paediatric motor rehabilitation. It is disseminated across Europe by the EACD network in 20 languages. Participation is anonymous and voluntary. We aim to include 500 respondents to ensure sufficient precision for the description of study outcomes and to perform stratified analyses by the main determinants.Ethics and disseminationEthics approval was waived by the Brest CHRU Institutional Review Board. The study is conducted according to current French legislation (loi Jardé (n°2012-300)) and the survey is GDPR compliant. Study findings will be presented at national and international meetings and submitted for publication in a peer-reviewed journal.Trial registration numberNCT05176522.

No literature is available on the benign versus malignant breast lesion ratio in trans women (male sex assigned at birth, female gender identity). As hormone treatment in trans women results in breast tissue histologically comparable with cis (non-trans) women, breast pathology may be expected. Previously, an increased breast cancer risk compared with cis men have been observed. We aimed to investigate the frequency and outcomes of breast biopsies in trans women. Therefore, we retrospectively examined the medical files of 2616 trans women. To gain data on breast lesions, we linked our cohort to a national pathology database. In this study we found that 126 people (5%) had one or more breast biopsies (n = 139). Of these, 21 trans women had a breast biopsy before the start of hormone treatment, and 53 after the start of hormone treatment. Breast biopsies were performed predominantly because of abnormalities during physical examination (37%, n = 51/139 biopsies), or because of capsular formation or contraction (28%, n = 16/57 biopsies) in trans women with breast implants. The most common breast lesions after the start of hormone treatment were fibroadenomas (n = 20), breast cancer (n = 6), fibrosis (n = 5), cysts (n = 4), and infections (n = 4). The benign versus malignant breast biopsy ratio was 88:12, which is comparable to the ratio in cis women (90:10). This study shows breast lesions in a limited number of trans women. Since the indications and outcomes of biopsies in trans women were similar to those in cis women, it seems reasonable to follow breast care guidelines as developed for cis women.

Background: Moral courage as a part of nurses’ moral competence has gained increasing interest as a means to strengthen nurses acting on their moral decisions and offering alleviation to their moral distress. To measure and assess nurses’ moral courage, the development of culturally and internationally validated instruments is needed. Objective: The objective of this study was to validate the Dutch-language version of the four-component Nurses’ Moral Courage Scale originally developed and validated in Finnish data. Research design: This methodological study used non-experimental, cross-sectional exploratory design. Participants and research context: A total of 559 nurses from two hospitals in Flanders, Belgium, completed the Dutch-language version of the Nurses’ Moral Courage Scale. Ethical considerations: Good scientific inquiry guidelines were followed throughout the study. Permission to translate the Nurses’ Moral Courage Scale was obtained from the copyright holder, and the ethical approval and permissions to conduct the study were obtained from the participating university and hospitals, respectively. Findings: The four-component 21-item, Dutch-language version of the Nurses’ Moral Courage Scale proved to be valid and reliable as the original Finnish Nurses’ Moral Courage Scale. The scale’s internal consistency reliability was high (0.91) corresponding with the original Nurses’ Moral Courage Scale validation study (0.93). The principal component analysis confirmed the four-component structure of the original Nurses’ Moral Courage Scale to be valid also in the Belgian data explaining 58.1% of the variance. Confirmatory factor analysis based on goodness-of-fit indices provided evidence of the scale’s construct validity. The use of a comparable sample of Belgian nurses working in speciality care settings as in the Finnish study supported the stability of the structure. Discussion and conclusion: The Dutch-language version of the Nurses’ Moral Courage Scale is a reliable and valid instrument to measure nurses’ self-assessed moral courage in speciality care nursing environments. Further validation studies in other countries, languages and nurse samples representing different healthcare environments would provide additional evidence of the scale’s validity and initiatives for its further development.

Alpha-synuclein (αS) is an intrinsically disordered protein (IDP) that is abundantly present in the brain and is associated with Parkinson's disease (PD). In spite of its abundance and its contribution to PD pathogenesis, the exact cellular function of αS remains largely unknown. The ability of αS to remodel phospholipid model membranes combined with biochemical and cellular studies suggests that αS is involved in endocytosis. To unravel with which route(s) and stage(s) of the endocytic pathway αS is associated, we quantified the colocalization between αS and endocytic marker proteins in differentiated SH-SY5Y neuronal cells, using an object based colocalization analysis. Comparison with randomized data allowed us to discriminate between structural and coincidental colocalizations. A large fraction of the αS positive vesicles colocalizes with caveolin positive vesicles, a smaller fraction colocalizes with EEA1 and Rab7. We find no structural colocalization between αS and clathrin and Rab11 positive vesicles. We conclude that in a physiological context, αS is structurally associated with caveolin dependent membrane vesiculation and is found further along the endocytic pathway, in decreasing amounts, on early and late endosomes. Our results not only shed new light on the function of αS, they also provide a possible link between αS function and vesicle trafficking malfunction in PD.

Background Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8–6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

Background Medical students are expected to translate the theoretical knowledge gained during their study to practical knowledge during the clerkships. A surgical educational platform with standardized videos may be the solution. However, the effects of a structured online video-based platform in addition to the standard curriculum on students’ self-reported and tested surgical knowledge during the surgical clerkship must be assessed. Methods Fourth-year medical students (n = 178) participated in a 6-week course of theoretical and practical training followed by a 10-week in-hospital clerkship in the Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands and 11 affiliated general hospitals. Ninety students followed the usual surgical curriculum (control group), followed by 88 students who were given voluntary access to a video-based surgical educational platform of Incision Academy (video group). At the start (T0) and end (T1) of the clerkship, both groups filled out a surgical knowledge test and a survey regarding their self-reported surgical knowledge and their access to available study sources. Supervisors were blinded and surveyed concerning students’ performance and their acquired knowledge. We analyzed the data using paired and unpaired student t-tests and linear regression. Results At the end of the clerkship, students in the video group indicated that they had better resources at their disposal than the control group for surgical procedures (p = 0.001). Furthermore, students in the video group showed a greater increase in self-reported surgical knowledge during their clerkship (p = 0.03) and in more objectively tested surgical knowledge (p Conclusions An online surgical educational platform with standardized videos is a valuable addition to the current surgical curriculum according to students and their supervisors. It improves their test scores and self-reported surgical knowledge. Students feel better prepared and more able to find the information necessary to complete the clerkship. Trial registration Registry not necessary according to ICMJE guidelines.

Novel innovative drugs have improved disease control, survival and quality of life for many patients. The costs of these drugs, however, are extremely high and threaten the long-term affordability of our health care system. Efficient use of existing drugs can decrease drug expenditure whilst improving patients' quality of life at the same time. Efficiency adjustments should not compromise treatment efficacy and therefore, clinical research on the matter is crucial. In this article, we demonstrate that efficiency research is feasible, as exemplified by the SONIA study. We make the case for a 'revolving fund' in which savings from one study are used to fund a next one. A revolving fund thus stimulates efficiency research and capitalizes research investments in the interest of both patients and society.

BACKGROUND: Kidney transplant patients are at high risk for coronavirus disease 2019 (COVID-19)-related mortality. However, limited data are available on longer-term clinical, functional, and mental health outcomes in patients who survive COVID-19.METHODS: We analyzed data from adult kidney transplant patients in the European Renal Association COVID-19 Database who presented with COVID-19 between February 1, 2020, and January 31, 2021.RESULTS: We included 912 patients with a mean age of 56.7 (±13.7) y. 26.4% were not hospitalized, 57.5% were hospitalized without need for intensive care unit (ICU) admission, and 16.1% were hospitalized and admitted to the ICU. At 3 mo follow-up survival was 82.3% overall, and 98.8%, 84.2%, and 49.0%, respectively, in each group. At 3 mo follow-up biopsy-proven acute rejection, need for renal replacement therapy, and graft failure occurred in the overall group in 0.8%, 2.6%, and 1.8% respectively, and in 2.1%, 10.6%, and 10.6% of ICU-admitted patients, respectively. Of the surviving patients, 83.3% and 94.4% reached their pre-COVID-19 physician-reported functional and mental health status, respectively, within 3 mo. Of patients who had not yet reached their prior functional and mental health status, their treating physicians expected that 79.6% and 80.0%, respectively, still would do so within the coming year. ICU admission was independently associated with a low likelihood to reach prior functional and mental health status.CONCLUSIONS: In kidney transplant recipients alive at 3-mo follow-up, clinical, physician-reported functional, and mental health recovery was good for both nonhospitalized and hospitalized patients. Recovery was, however, less favorable for patients who had been admitted to the ICU.

Aims Valid health economic models are essential to inform the adoption and reimbursement of therapies for diabetes mellitus. Often existing health economic models are applied in other countries and settings than those where they were developed. This practice requires assessing the transferability of a model developed from one setting to another. We evaluate the transferability of the MICADO model, developed for the Dutch 2007 setting, in two different settings using a range of adjustment steps. MICADO predicts micro- and macrovascular events at the population level. Methods MICADO simulation results were compared to observed events in an Italian 2000–2015 cohort (Casale Monferrato Survey [CMS]) and in a Dutch 2008–2019 (Hoorn Diabetes Care Center [DCS]) cohort after adjusting the demographic characteristics. Additional adjustments were performed to: (1) risk factors prevalence at baseline, (2) prevalence of complications, and (3) all-cause mortality risks by age and sex. Model validity was assessed by mean average percentage error (MAPE) of cumulative incidences over 10 years of follow-up, where lower values mean better accuracy. Results For mortality, MAPE was lower for CMS compared to DCS (0.38 vs. 0.70 following demographic adjustment) and adjustment step 3 improved it to 0.20 in CMS, whereas step 2 showed best results in DCS (0.65). MAPE for heart failure and stroke in DCS were 0.11 and 0.22, respectively, while for CMS was 0.42 and 0.41. Conclusions The transferability of the MICADO model varied by event and per cohort. Additional adjustments improved prediction of events for MICADO. To ensure a valid model in a new setting it is imperative to assess the impact of adjustments in terms of model accuracy, even when this involves the same country, but a new time period.

To assess the association between the aortic root diameter in HLA-B27 positive (+) and HLA-B27 negative (−) ankylosing spondylitis (AS) patients from the CARDAS cohort. The CARDAS study is a cross-sectional study in AS patients between 50 and 75 years who were recruited from a large rheumatology outpatient clinic. Patients underwent cardiovascular screening including echocardiography, with 2D, spectral, and color flow Doppler measurements. The aortic root was measured at sinuses of Valsalva during diastole. The aortic root diameter was adjusted for body surface area (BSA) (aortic root index, cm/m2). 193 Consecutive AS patients were included of whom 158 (82%) were HLA-B27 positive. The aortic root index was significantly higher in HLA-B27 + patients compared to HLA-B27− patients, respectively, 1.76 cm ± 0.21 vs. 1.64 cm ± 0.14, p p = 0.8. Regression analysis showed a significant association between HLA-B27 and aortic root index corrected for age, sex and cardiovascular risk factors (β 0.091, 95% CI 0.015–0.168, p = 0.02). Especially, male HLA-B27 + patients had a significantly increased aortic root index compared to male HLA-B27− AS patients, respectively, 1.76 cm (1.63–1.88) and 1.59 cm (1.53–1.68), p

Autologous hematopoietic cell transplantation (autoHCT) is a standard initial treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient hematopoietic progenitor cells (HPCs) for 2 autoHCTs in all eligible patients. Despite a lack of published data on the utilization of HPCs stored for future use, it is common practice across transplantation programs to collect enough HPCs for 2 autoHCTs in MM patients. In this single-center retrospective study, we analyzed the utilization of HPCs collected and stored at the time of first autoHCT in patients with MM, along with the cost implications of HPC collection targets sufficient for 2 transplantations. In a cohort of 400 patients (median age, 63 years; range, 22 to 79 years), after a median follow-up of 50.4 months, 197 patients had relapsed and 36 had received HPC infusion as salvage autoHCT (n = 29) and/or HPC boost (n = 8). In this cohort, a median CD34+ cell dose of 4.3 × 106/kg (range, 1.1 to 12.94.3 × 106/kg) was used for first autoHCT, and a median of 4.4 × 106/kg (range, 1.0 to 20.2× 106/kg) CD34+ cells were stored for future use. At 6 years after the first autoHCT, the estimated cumulative incidence of salvage autoHCT was 12.0% without HPC boost and 13.9% with HPC boost. HPC utilization was significantly higher in the 60- to 64-year age group, whereas no patients who were age ≥70 years at the time of first autoHCT received salvage autoHCT. Using the CD34+ cell dose infused during the first autoHCT as the cutoff for individual patients, the estimated mean additional cost of HPC collection intended for subsequent use (over and above the HPCs used for first autoHCT) was $10,795 ($4.32 million for the entire cohort), an estimated 14% of which (ie, $583,600) was actually used up in salvage autoHCT by 6 years from first autoHCT. In conclusion, our results suggest the need for reappraisal of HPC collection targets for salvage autoHCT and argue against HPC collection and storage for salvage autoHCT in patients age ≥70 years at the time of first autoHCT.

Contains fulltext : 229899.pdf (Publisher’s version ) (Open Access) BACKGROUND: This pilot trial explores the feasibility of measuring muscle contractile properties in patients with cancer, effects of exercise during chemotherapy on muscle contractile properties and the association between changes in contractile muscle properties and perceived fatigue. METHOD: Patients who received (neo)adjuvant chemotherapy for breast or colon cancer were randomized to a 9-12 week exercise intervention or a waitlist-control group. At baseline and follow-up, we measured knee extensor strength using maximal voluntary contraction (MVC), contractile muscle properties of the quadriceps muscle using electrical stimulation, and perceived fatigue using the Multidimensional Fatigue Inventory. Feasibility was assessed by the proportion of patients who successfully completed measurements of contractile muscle properties. Exercise effects on muscle contractile properties were explored using linear regression analyses. Between-group differences >10% were considered potentially relevant. Pearson correlation (r(p) ) of changes in contractile muscle properties and changes in perceived fatigue was calculated. RESULTS: Twenty two of 30 patients completed baseline and follow-up assessments. Measurements of contractile properties were feasible except for muscle fatigability. We found a potentially relevant between-group difference in the rate of force development favoring the intervention group (1192 N/s, 95% CI = -335; 2739). Change in rate of force development was negatively correlated with change in perceived general (r(p) = -0.54, P = .04) and physical (r(p) = -0.59, P = .02) fatigue. CONCLUSION: Chemotherapy induces a decrease in the rate of force development, which may reflect a larger loss in type II muscle fibers. This may be attenuated with (resistance) exercise. The increase in the rate of force development was related to a decrease in perceived fatigue.

Despite an increased burden from chronic mental health conditions, access to effective mental health services in rural and remote areas is limited, and these services remain spatially undefined. We examine the spatial availability of mental health nurses across local government areas in Australia and identify gaps in mental health service delivery capacity in a finer-grained level than the state/territory data. A spatial distribution of mental health nurses was conducted. We utilized the 2017 National Health Workforce Dataset which was aggregated to LGA level based on the 2018 Australian Bureau Statistics (ABS) Data. The availability of mental health nurses was measured using the full time equivalent (FTE) rates per 100 000 population. We calculated the proportion of LGAs with zero total FTE rates based on remoteness categories. We also compared the mean of total FTE rates based on remoteness categories using analysis of variance. A spatial distribution of mental health nurses was visualized using GIS software for total FTE rates. Our analysis included 544 LGA across Australia, with 24.8% being defined as remote and very remote. The mean total FTE for mental health nurses per 100 000 populations is 56.6 (±132.2) with a median of 17.4 (IQR: 61.8). A wide standard deviation reflects unequal distribution of mental health nurses across LGAs. The availability of total FTE rates for mental health nurses per 100 000 populations is significantly lower in remote and very remote LGAs in comparison with major cities. As many as 35.1% of LGAs across Australia have no FTE for mental health nurses with 46% are remote and very remote. Our study reflects the existing unequal distribution of mental health nurses between metropolitan/urban setting and rural and remote areas. We suggest three broad strategies to address these spatial inequities: improving supply and data information systems; revisiting task-shifting strategies, retraining the existing health workforce to develop skills necessary for mental health care to rural and remote communities; and incorporating the provision of mental health services within expanding innovative delivery models including consumer-led, telemedicine and community-based groups.

Purpose Consumption of the algae spirulina (Arthrospira platensis or maxima) and wakame (Undaria pinnatifida) has been shown to lower LDL cholesterol concentrations in animals and humans, possibly due to the inhibition of intestinal cholesterol absorption. This mechanism, however, has never been investigated in humans. Therefore, we examined in non-hypercholesterolemic men and women the effects of spirulina and wakame consumption on serum markers for intestinal cholesterol absorption. Methods Thirty-five healthy men and women without hypercholesterolemia consumed in a random order daily 4.8 g spirulina, wakame or placebo for 17 days, separated by 14-day washouts. After 17 days, serum cholesterol-standardized campesterol, sitosterol and cholestanol, and lathosterol concentrations were measured as markers for intestinal cholesterol absorption and cholesterol synthesis, respectively. Concentrations of serum total cholesterol, LDL and HDL cholesterol, triacylglycerol, and plasma glucose, and blood pressure were measured as well. Results Compared with placebo, spirulina or wakame did not affect serum cholesterol-standardized campesterol (CI − 0.23 to 0.10 μmol/mmol, P = 0.435 and CI − 0.14 to 0.19 μmol/mmol, P = 0.729, respectively), sitosterol (P = 0.314 and P = 0.112), cholestanol (P = 0.610 and P = 0.809), or lathosterol (P = 0.388 and P = 0.102) concentrations. In addition, serum lipid and plasma glucose concentrations, and blood pressure were not changed. Conclusions Daily consumption of 4.8 g spirulina or wakame for 17 days did not affect plasma markers for intestinal cholesterol absorption or cholesterol synthesis in non-hypercholesterolemic men and women. Serum lipid and glucose concentrations, and blood pressure were also not altered. Electronic supplementary material The online version of this article (10.1007/s00394-019-02073-7) contains supplementary material, which is available to authorized users.

Background: Psychological distress is highly prevalent among patients with metastatic colorectal cancer. Aims: To perform an economic evaluation of a combined screening and treatment program targeting psychological distress in patients with metastatic colorectal cancer in comparison with usual care. Design: Societal costs were collected alongside a cluster randomized controlled trial for 48 weeks. A total of 349 participants were included. Setting: Participants were recruited from oncology departments at 16 participating hospitals in the Netherlands. Methods: Outcome measures were the Hospital Anxiety and Depression Scale and quality-adjusted life-years. Missing data were imputed using multiple imputation. Uncertainty was estimated using bootstrapping. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty surrounding the cost-effectiveness estimates. Sensitivity analyses were performed to check robustness of results. Results: Between treatment arms, no significant differences were found in Hospital Anxiety and Depression Scale score (mean difference: –0.058; 95% confidence interval: –0.13 to 0.011), quality-adjusted life-years (mean difference: 0.042; 95% confidence interval: –0.015 to 0.099), and societal costs (mean difference: –1152; 95% confidence interval: –5058 to 2214). Cost-effectiveness acceptability curves showed that the probability of cost-effectiveness was 0.64 and 0.74 at willingness-to-pay values of €0 and €10,000 per point improvement on the Hospital Anxiety and Depression Scale, respectively. The probability that the intervention was cost-effective compared to usual care for quality-adjusted life-years was 0.64 and 0.79 at willingness-to-pay values of €0 and €20,000 per quality-adjusted life-year, respectively. Conclusion: The intervention is dominant over usual care, primarily due to lower costs in the intervention group. However, there were no statistically significant differences in clinical effects and the uptake of the intervention was quite low. Therefore, widespread implementation cannot be recommended.

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaffected by the intensified surveillance period. Of the 10 operated patients, 1 (10%) developed diabetes and 7 (70%) pancreatic exocrine insufficiency. The interviews yielded median quality-of-life scores comparable to the general population. Also, after surgery, patients’ attitudes towards surveillance were unchanged (5/10, 50%) or became more positive (4/10, 40%). Although patients were aware of the (sometimes benign) pathological outcome, when asked if surgery had been justified, only 20% (2/10) disagreed, and all would again have chosen to undergo surgery. In conclusion, in individuals at high risk for pancreatic cancer, intensified surveillance temporarily increased cancer worries, without affecting general anxiety or depression. Although pancreatic surgery led to substantial co-morbidity, quality of life was similar to the general population, and surgery did not negatively affect the attitude towards surveillance. Electronic supplementary material The online version of this article (10.1007/s10689-020-00171-8) contains supplementary material, which is available to authorized users.

Background Fluorogenic thrombin generation (TG) assays are commonly used to determine global coagulation phenotype in plasma. Whole blood (WB)-TG assays reach one step closer to physiology by involving the intrinsic blood cells, but erythrocytes cause variable quenching of the fluorescence signals, hampering its routine application.Objective To develop a new assay for continuous WB-TG measurement.Methods In the new WB-TG assay, the erythrocyte-caused distortion of signal was solved by continuously mixing the sample during the measurement. The assay was validated by evaluating the reproducibility and comparing with the paper-based WB-TG assay. Reconstituted human blood and WB from 119 healthy donors was tested to explore the influences of hematocrit and platelet count on TG.Results This novel WB-TG assay showed good reproducibility while being less affected by contact activation compared with the previous paper-based assay. Reconstitution experiments showed that the lag time of TG was shortened by the addition of platelets but not erythrocytes. Increasing hematocrit strongly augmented the peak thrombin, even in the presence of high platelet counts. The lag time and peak of WB-TG of 119 healthy donors were positively related to erythrocyte count after adjusting for age, sex, and oral contraceptive use with multiple linear regression analyses. The reference range and interindividual variation of WB-TG were determined in the healthy cohort.Conclusions A novel WB-TG assay was developed, which is a straightforward tool to measure the involvement of platelets and erythrocytes in TG and may assist the research of blood cell-associated coagulation disorders.

BACKGROUND: This study aims to report on the design of a model to determine the cost-effectiveness of prevention and treatment of early psychosis (PsyMod) and to estimate ten-year cost-effectiveness and budget impact of interventions targeting individuals with ultra-high risk (UHR) of developing psychosis or with first episode psychosis (FEP).METHODS: PsyMod was built in parallel with the development of a new standard of care for treatment of early psychosis in the Netherlands. PsyMod is a state-transition cohort simulation model and considers six health states, namely ultra-high risk of psychosis (UHR), FEP, post-FEP, no-UHR, recovery/remission, and death. Results are expressed as total healthcare costs, QALYs, incremental cost-effectiveness ratio (ICER), and budget impact.RESULTS: PsyMod was used to extrapolate budget impact and cost-effectiveness of cognitive behavioural therapy for preventing FEP for individuals at UHR of psychosis (CBTuhr) compared to care as usual. CBTuhr resulted in a per-patient increase of 0.06 QALYs and a per patient cost reduction of €654 (dominant ICER) with a reduction in 5-year healthcare costs of €1,002,166.CONCLUSIONS: PsyMod can be used to examine cost-effectiveness and budget impact of interventions targeting prevention and treatment of FEP and is freely available for academic purposes upon request by the authors.

Background: Coronary artery disease (CAD) will increasingly determine outcome in the aging adult congenital heart disease (CHD) population. We aimed to determine sex-specific incidence of CAD in adult CHD patients throughout adulthood, compared to the general population. Methods and results: We followed 11,723 adult CHD patients (median age 33 years; 49% male; 57% mild, 34% moderate, 9% severe CHD) from the Dutch CONCOR registry, and two age-sex-matched persons per patient from the general population for first CAD event in national registers (period 2002–2012). Incidence rates were estimated using smoothed hazard functions. CAD risk during follow-up, stratified by CHD severity, was compared using proportional subdistribution hazards regression. In ACHD patients, 103 CAD events (43 women) occurred over 60,456 person-years. Rates per 1000person-years increased from 0.3(95% confidence interval: 0.1–0.6) at age 20 to 5.8(3.7–8.9) at 70 years in female, and from 0.5(0.3–1.0) to 7.8(5.1–11.8) in male patients. Compared to the general population, relative risk was 12.0(2.5–56.3) in women and 4.6(1.7–12.1) in men aged 20 years. Relative risk declined with age, remaining significant up to age ~65 years in women and ~50 years in men. In patients with mild, moderate and severe CHD, CAD risk was 1.3(0.9–1.9), 1.6(1.0–2.5) and 2.9(1.3–6.9) times increased compared to the general population, respectively. Conclusions: We found increased CAD risk in adult CHD patients, with greater relative risk at younger age, in women and those with more severe CHD. These results underline the importance of screening for and treatment of CAD risk factors in these patients.

Aims The aim of the present study was to assess the association between dental implant stability and peripheral blood cell composition and levels of coagulation factors in patients treated with alveolar ridge preservation with platelet-rich fibrin (PRF) and bovine bone substitute. Materials and methods Fifty patients were included between 2015 and 2017. PRF was prepared from autologous blood, in which blood cells and coagulation factor levels were measured. PRF and bovine bone were placed in the socket, followed by closure with PRF membrane. Implants were placed 14 (+/- 2.5) weeks postextraction. The implant stability quotient was measured at t = 0, t = 10 days, t = 7 weeks, and t = 17 weeks by resonance frequency analysis. Results Erythrocyte count was inversely associated with PRF membrane length, but not with implant stability. Conversely, platelet count did not correlate with membrane size but inversely correlated with implant stability at 7 and 17 weeks. In addition, implant stability was directly correlated with levels FXIII (t = 0, p

Background and Aims Patients with cirrhosis have a rebalanced hemostasis, often with normal or elevated thrombin-generating (TG) capacity in plasma. Whole blood (WB) TG allows faster determination and, importantly, includes the influence of all circulating blood cells. We aimed to study the TG profile of patients with cirrhosis in WB and in platelet poor plasma.Methods Thrombin-generating capacity in WB and plasma were assessed with a near-patient WB-TG assay and the calibrated automated thrombinography assay, respectively. TG assays were tested in presence and absence of thrombomodulin. Conventional coagulation tests were also performed.Results Thirty-four patients with cirrhosis and twenty-two controls were analyzed. Compared with controls, patients had substantially deranged results in conventional coagulation tests. Comparable WB-TG capacity (endogenous thrombin potential until peak, ETPp) but significantly lower peak thrombin were found in patients, and these results persisted when thrombomodulin was present. TG of the patients was more resistant to thrombomodulin than controls in both WB and plasma, although the inhibitory effect of thrombomodulin was drastically weaker in WB than in plasma. The peak of WB-TG in patients correlated moderately with their hematocrit and platelet count. Significant correlations were found between TG results in WB and plasma.Conclusions The WB-TG assay shows a normal to hypocoagulable state in patients with cirrhosis with a decreased anticoagulant activity of TM compared to plasma-TG. The clinical value of this assay needs further validation.

We determined whether progression-free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell-free DNA (cfDNA) from 164 postmenopausal women with ER-positive, HER2-negative MBC refractory to a non-steroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013-004120-11) was characterised for 10 relevant breast cancer genes by next generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N=102) showed longer median PFS of 5.7 months (P=0.006) and OS of 124.8 months (P=0.008) than patients with high ctDNA load (N=62) (4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with

The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigen-presenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS.

Valid health economic models are essential to inform the adoption and reimbursement of therapies for diabetes mellitus. Often existing health economic models are applied in other countries and settings than those where they were developed. This practice requires assessing the transferability of a model developed from one setting to another. We evaluate the transferability of the MICADO model, developed for the Dutch 2007 setting, in two different settings using a range of adjustment steps. MICADO predicts micro- and macrovascular events at the population level.MICADO simulation results were compared to observed events in an Italian 2000-2015 cohort (Casale Monferrato Survey [CMS]) and in a Dutch 2008-2019 (Hoorn Diabetes Care Center [DCS]) cohort after adjusting the demographic characteristics. Additional adjustments were performed to: (1) risk factors prevalence at baseline, (2) prevalence of complications, and (3) all-cause mortality risks by age and sex. Model validity was assessed by mean average percentage error (MAPE) of cumulative incidences over 10 years of follow-up, where lower values mean better accuracy.For mortality, MAPE was lower for CMS compared to DCS (0.38 vs. 0.70 following demographic adjustment) and adjustment step 3 improved it to 0.20 in CMS, whereas step 2 showed best results in DCS (0.65). MAPE for heart failure and stroke in DCS were 0.11 and 0.22, respectively, while for CMS was 0.42 and 0.41.The transferability of the MICADO model varied by event and per cohort. Additional adjustments improved prediction of events for MICADO. To ensure a valid model in a new setting it is imperative to assess the impact of adjustments in terms of model accuracy, even when this involves the same country, but a new time period.

Contains fulltext : 251573.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The Dutch Surgical Aneurysm Audit (DSAA) initiative was established in 2013 to monitor and improve nationwide outcomes of aortic aneurysm surgery. The objective of this study was to examine whether outcomes of surgery for intact abdominal aortic aneurysms (iAAA) have improved over time. METHODS: Patients who underwent primary repair of an iAAA by standard endovascular (EVAR) or open surgical repair (OSR) between 2014 and 2019 were selected from the DSAA for inclusion. The primary outcome was peri-operative mortality trend per year, stratified by OSR and EVAR. Secondary outcomes were trends per year in major complications, textbook outcome (TbO), and characteristics of treated patients. The trends per year were evaluated and reported in odds ratios per year. RESULTS: In this study, 11 624 patients (74.8%) underwent EVAR and 3 908 patients (25.2%) underwent OSR. For EVAR, after adjustment for confounding factors, there was no improvement in peri-operative mortality (aOR [adjusted odds ratio] 1.06, 95% CI 0.94 - 1.20), while major complications decreased (2014: 10.1%, 2019: 7.0%; aOR 0.91, 95% CI 0.88 - 0.95) and the TbO rate increased (2014: 68.1%, 2019: 80.9%; aOR 1.13, 95% CI 1.10 - 1.16). For OSR, the peri-operative mortality decreased (2014: 6.1%, 2019: 4.6%; aOR 0.89, 95% CI 0.82 - 0.98), as well as major complications (2014: 28.6%, 2019: 23.3%; aOR 0.95, 95% CI 0.91 - 0.99). Furthermore, the proportion of TbO increased (2014: 49.1%, 2019: 58.3%; aOR 1.05, 95% CI 1.01 - 1.10). In both the EVAR and OSR group, the proportion of patients with cardiac comorbidity increased. CONCLUSION: Since the establishment of this nationwide quality improvement initiative (DSAA), all outcomes of iAAA repair following EVAR and OSR have improved, except for peri-operative mortality following EVAR which remained unchanged.

Aims Heart failure is the main threat to long-term health in adults with transposition of the great arteries (TGA) corrected by an atrial switch operation (AtrSO). Current guidelines refrain from recommending heart failure medication in TGA-AtrSO, as there is insufficient data to support the hypothesis that it is beneficial. Medication is therefore prescribed based on personal judgements. We aimed to evaluate medication use in TGA-AtrSO patients and examine the association of use of renin–angiotensin–aldosterone system (RAAS) inhibitors and β-blockers with long-term survival. Methods and results We identified 150 TGA-AtrSO patients [median age 30 years (interquartile range 25–35), 63% male] included in the CONCOR registry from five tertiary medical centres with subsequent linkage to the Dutch Dispensed Drug Register for the years 2006–2014. Use of RAAS inhibitors, β-blockers, and diuretics increased with age, from, respectively, 21% [95% confidence interval (CI) 14–40], 12% (95% CI 7–21), and 3% (95% CI 2–7) at age 25, to 49% (95% CI 38–60), 51% (95% CI 38–63), and 41% (95% CI 29–54) at age 45. Time-varying Cox marginal structural models that adjusted for confounding medication showed a lower mortality risk with use of RAAS inhibitors and β-blockers in symptomatic patients [hazard ratio (HR) = 0.13 (95% CI 0.03–0.73); P = 0.020 and HR = 0.12 (95% CI 0.02–0.17); P = 0.019, respectively]. However, in the overall cohort, no benefit of RAAS inhibitors and β-blockers was seen [HR = 0.93 (95% CI 0.24–3.63); P = 0.92 and HR = 0.98 (0.23–4.17); P = 0.98, respectively]. Conclusion The use of heart failure medication is high in TGA-AtrSO patients, although evidence of its benefit is limited. This study showed lower risk of mortality with use of RAAS inhibitors and β-blockers in symptomatic patients only. These findings can direct future guidelines, supporting use of RAAS inhibitors and β-blockers in symptomatic, but not asymptomatic patients.