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Objectives: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD., Methods: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop., Results: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating - sum of boxes, clinical dementia rating - global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from -US$66 897 to US$11 896., Conclusions: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Organisation of a screening programme influences programme resilience to a disruption as COVID-19. Due to COVID-19, the Dutch human papillomavirus-based cervical screening programme was temporarily suspended. Afterwards, multiple measures have been taken to catch-up participation. This study aimed to investigate programme resilience by examining the effect of COVID-19 and programme measures taken on participation in cervical screening., Study Design: Observational cohort study., Methods: Data from the national screening registry and Dutch nationwide pathology databank (Palga) were used on invitations and follow-up in 2018/2019 (pre-COVID) and 2020 (COVID). Sending invitations, reminders and self-sampling kits were suspended from March to July 2020. Main outcome measures include distribution of participant characteristics (age, region and screening history), participation rates by age and region, time between invitation and participation (i.e. response time) and self-sampling use per month., Results: Participation rate was significantly lower in 2020 (49.8%) compared to 2018/19 (56.8%, P < 0.001), in all ages and regions. Compared to 2018/19, participation rates decreased most in women invited from January to March 2020 (-6.7%, -9.1% and -10.4%, respectively). From August, participation rates started to recover (difference between -0.8% and -2.7%). Median response time was longer in February and March (2020: 143 and 173 days; 2018/19: 53 and 55 days) and comparable from July onwards (median difference 0-6 days). Self-sampling use was higher in 2020 (16.3%) compared to 2018/19 (7.6%)., Conclusions: The pandemic impacted participation rates in the Dutch cervical screening programme, especially of women invited before the programme pause. Implementation of self-sampling in national cervical screening programmes could increase participation rates and could serve as an alternative screening method in times of exceptional health care circumstances, such as a pandemic. Due to the well-organised programme and measures taken to catch-up participation, the impact of COVID-19 on the screening programme remained small., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Visual attention of young children with autism spectrum disorder (ASD) has been well documented in the literature for the past 20 years. In this study, we developed a Decision Support System (DSS) that uses machine learning (ML) techniques to identify young children with ASD from typically developing (TD) children. Study participants included 26 to 36 months old young children with ASD (n = 61) and TD children (n = 72). The results showed that the proposed DSS achieved up to 87.5% success rate in the early assessment of ASD in young children. Findings suggested that visual attention is a unique, promising biomarker for early assessment of ASD. Study results were discussed, and suggestions for future research were provided., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 ( 89 Zr)-labeled pembrolizumab before PD-1 antibody treatment., Patients and Methods: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89 Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89 Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUV max ) and expressed as geometric mean. Normal organ uptake was calculated as SUV mean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1., Results: Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUV max did not differ between melanoma and NSCLC (4.9 and 6.5, P = 0.49). Tumor 89 Zr-pembrolizumab uptake correlated with tumor response (P trend = 0.014) and progression-free (P = 0.0025) and overall survival (P = 0.026). 89 Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUV mean of 5.8 (standard deviation ±1.8). There was also 89 Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation., Conclusion: 89 Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89 Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation., Competing Interests: Disclosure MJ reports consultancy fees from AstraZeneca (paid to UMCG). JBH reports consultancy roles for Achilles Therapeutics, BioNTech, BMS, GSK, Immunocore, Instil Bio, Molecular Partners, MSD, Merck Serono, Neogene Therapeutics, Novartis, Pfizer, PokeAcel, Roche/Genentech, Sanofi, T-Knife, and Third Rock Ventures and research grants from Amgen, Asher-Bio, BMS, BioNTech, MSD, Novartis, and Neogene Therapeutics (paid to the Netherlands Cancer Institute). WT reports fees from Merck, Sharp, Dohme, and Bristol-Myers-Squibb (paid to UMCG). EGEdV reports an advisory role at Daiichi Sankyo, NSABP, and Sanofi and research funding from Amgen, AstraZeneca, Bayer, Chugai Pharma, Crescendo, CytomX Therapeutics, G1 Therapeutics, Genentech, Nordic Nanovector, Radius Health, Regeneron, Roche, Servier, and Synthon (paid to UMCG). GAPH reports consulting and advisory role at Amgen, Roche, MSD, BMS, Pfizer, Novartis, and Pierre Fabry and research funding from BMS and Seerave (paid to UMCG). TJNH reports consultancy fees (paid to UMCG) from BMS, MSD, Merck, Boehringer, AstraZeneca, and Roche. AJvdW reports an advisory role at Janssen, Takeda, and Boehringer-Ingelheim (paid to UMCG) and research funding from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, and Takeda. MNL-dH reports research funding from Merck, Bayer, and Amgen (paid to UMCG). HJMG reports an advisory role at Eli Lilly, MSD, BMS, and Novartis. All other authors have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

About 25 years ago, concept mapping was introduced in the Netherlands and applied in different fields. A collection of concept mapping projects conducted in the Netherlands was identified, in part in the archive of the Netherlands Institute of Mental Health and Addiction (Trimbos Institute). Some of the 90 identified projects are internationally published. The 90 concept mapping projects reflect the changes in mental health care and can be grouped into 5-year periods and into five typologies. The studies range from conceptualizing the problems of the homeless to the specification of quality indicators for treatment programs for patients with cystic fibrosis. The number of concept mapping projects has varied over time. Growth has been considerable in the last 5 years compared to the previous 5 years. Three case studies are described in detail with 12 characteristics and graphical representations. Concept mapping aligns well with the typical Dutch approach of the "Poldermodel." A broad introduction of concept mapping in European countries in cooperation with other countries, such as the United States and Canada, would strengthen the empirical basis for applying this approach in health care policy, quality, and clinical work., (Copyright © 2016. Published by Elsevier Ltd.)

CD4+ T cells play a critical role in allergic diseases, both in the affected tissue as well as systemically. Our objective was to investigate the in vivo activation state of peripheral blood CD4+ T cells of atopic dermatitis (AD) patients by analyzing gene expression profiles of unstimulated CD4+ T cells. mRNA samples from blood CD4+ T cells, isolated from five AD patients and seven healthy controls (HC), were analyzed using oligonucleotide arrays. Differentially regulated genes were validated by quantitative PCR (Q-PCR) in a larger group of patients with AD, in a group of patients with allergic asthma (AA), and HC subjects. In addition, "typical" T helper type 1 (Th1)- and Th2-related genes were analyzed by Q-PCR. Microarray analysis revealed differential expression of 52 genes in AD patients. Q-PCR confirmed several differentially regulated genes in AD, including CCR10, CRTH2, C-JUN, and NR4A2. Two groups of genes with highly correlating gene expression levels involved in tissue homing and proliferation or apoptosis, respectively, were identified. No marked differences were found in gene expression levels of typical Th1 or Th2 genes in AD or in AA patients. This study demonstrates that peripheral blood, unstimulated CD4+ T cells in AD patients show differentially expressed genes involved in tissue homing, proliferation, and apoptosis. No marked expression differences of "typical" atopy genes were found.