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Purpose: This prospective study examined the psychometric properties of the adapted Dutch translation of the Short Musculoskeletal Function Assessment (SMFA) questionnaire in patients with isolated unilateral lower fracture (LEF) or upper extremity fracture (UEF). Methods: Patients ( N = 458) completed the SMFA, WHOQOL-BREF, and the RAND-36 at time of diagnosis (i.e. pre-injury status), 1, and 2 weeks post-fracture. Principal axis factoring was performed, and Cronbach's alpha coefficients ( α) and intra-class correlation coefficients (ICC) were calculated. Furthermore, Pearson's product-moment correlations ( r), paired t tests, and standardized response means (SRM) were calculated. Results: A three-factor structure was found: Lower extremity dysfunction, Upper extremity dysfunction, and Daily life consequences. This structure was different for patients with LEF versus UEF. ICCs ranged from .68 to .90, and α varied from .81 to .95. The correlations between the SMFA and, respectively, the RAND-36 and WHOQOL-BREF were small to large depending on the SMFA factor combined with fracture location. Responsiveness was confirmed ( p < .0001; SRM ranging from .28 to 1.71). Conclusions: The SMFA has good psychometric properties in patients with fractures. Patients with UEF and LEF could not be regarded as a homogenous group. The development of separate SMFA modules should be considered. [ABSTRACT FROM AUTHOR]

Background: To optimise the health of pregnant women and their children by evidence-based primary and secondary prevention, more scientific knowledge is needed. To overcome the methodological limitations of many studies on pregnancy and child health, which often use a retrospective design, we established the PRIDE (PRegnancy and Infant DEvelopment) Study.Methods and Results: The PRIDE Study is a large prospective cohort study that aims at including 150 000-200 000 women in early pregnancy to study a broad range of research questions pertaining to pregnancy complications, maternal and child health, and adverse developmental effects in offspring. Women are invited to participate by their prenatal care provider before or at their first prenatal care visit and are asked to fill out web-based questionnaires in gestational weeks 8-10, 17, and 34, as well as biannually throughout childhood. In addition, a food frequency questionnaire and a paternal questionnaire are administered and medical records are consulted. Multiple validation studies will be conducted and paper-and-pencil questionnaires are available for women who cannot or do not want to participate through the Internet. For subgroups of participants, blood and saliva samples for genetic and biochemical analyses are being collected. The pilot phase, which started in July 2011, showed a response rate of 47%. Recruitment will eventually cover all of the Netherlands.Conclusions: We expect that this study, which will be the largest birth cohort in the world so far, will provide new insights in the aetiology of disorders and diseases that originate in pregnancy. The PRIDE Study is open for collaboration. [ABSTRACT FROM AUTHOR]

Objective: OpenSDE is an application that supports structured recording of narrative patient data to enable use of the data in both clinical practice and clinical research. Reliability and accuracy of collected data are essential for subsequent data use. In this study we analyze the uniformity of data entered with OpenSDE. Our objective is to obtain insight into the consensus and differences of recorded data.Methods: Three pediatricians transcribed 20 paper patient records using OpenSDE. The transcribed records were compared and all recorded findings were classified into one of six categories of difference.Results: Of all findings 22% were recorded identically; 17% of the findings were recorded differently (predominantly as free text); 61% was omitted, inferred, or in conflict with the paper record.Conclusion: The results of this study show that recording patient data using structured data entry does not necessarily lead to uniformly structured data. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine trends in incidence and detection of ductal carcinoma in situ (DCIS) of the breast in southern Netherlands in the period 1984–2006 and assess the effect of mass screening. All patients with primary DCIS registered between 1984 and 2006 in the population-based Eindhoven Cancer Registry were included ( n = 1,767). These data were linked to data from the population-based screening programme. The incidence of DCIS of the breast increased from 3/100,000 to almost 34/100,000 person-years in women aged 50–69 years in southern Netherlands since 1984. Mass screening was responsible for this increase. A stable 60% of DCIS was screen-detected. Over 11% of breast cancer patients have DCIS. In conclusion, the incidence of DCIS increased markedly in southern Netherlands with a clear effect of mammography screening since 1992. [ABSTRACT FROM AUTHOR]

BackgroundSelf-reported medical history information is included in many studies. However, data on the validity of Web-based questionnaires assessing medical history are scarce. If proven to be valid, Web-based questionnaires may provide researchers with an efficient means to collect data on this parameter in large populations. ObjectiveThe aim of this study was to assess the validity of a Web-based questionnaire on chronic medical conditions, allergies, and blood pressure readings against obstetric records and data from general practitioners. MethodsSelf-reported questionnaire data were compared with obstetric records for 519 pregnant women participating in the Dutch PRegnancy and Infant DEvelopment (PRIDE) Study from July 2011 through November 2012. These women completed Web-based questionnaires around their first prenatal care visit and in gestational weeks 17 and 34. We calculated kappa statistics (κ) and the observed proportions of positive and negative agreement between the baseline questionnaire and obstetric records for chronic conditions and allergies. In case of inconsistencies between these 2 data sources, medical records from the woman’s general practitioner were consulted as the reference standard. For systolic and diastolic blood pressure, intraclass correlation coefficients (ICCs) were calculated for multiple data points. ResultsAgreement between the baseline questionnaire and the obstetric record was substantial (κ=.61) for any chronic condition and moderate for any allergy (κ=.51). For specific conditions, we found high observed proportions of negative agreement (range 0.88-1.00) and on average moderate observed proportions of positive agreement with a wide range (range 0.19-0.90). Using the reference standard, the sensitivity of the Web-based questionnaire for chronic conditions and allergies was comparable to or even better than the sensitivity of the obstetric records, in particular for migraine (0.90 vs 0.40, P=.02), asthma (0.86 vs 0.61, P=.04), inhalation allergies (0.92 vs 0.74, P=.003), hay fever (0.90 vs 0.64, P=.001), and allergies to animals (0.89 vs 0.53, P=.01). However, some overreporting of allergies was observed in the questionnaire and for some nonsomatic conditions sensitivity of both measurement instruments was low. The ICCs for blood pressure readings ranged between 0.72 and 0.92 with very small mean differences between the 2 methods of data collection. ConclusionsWeb-based questionnaires can be used to validly collect data on many chronic disorders, allergies, and blood pressure readings among pregnant women.

Background: Couples coping with colorectal cancer were monitored during the first year after diagnosis to evaluate the following: (i) levels of patients' and partners' fatigue-hereby comparing their scores to each other and a normative population, (ii) association between patients' and partners' fatigue, (iii) the course of partners' fatigue, and (iv) biopsychosocial predictors of the partners' fatigue, including the patients' level of fatigue.Method: Couples (n = 171) preoperatively completed questions regarding age and sex as well as questionnaires assessing neuroticism and trait anxiety. Questionnaires assessing fatigue, anxiety, and depressive symptoms were measured preoperative (time-0) and 3 (time-1), 6 (time-2), and 12 months (time-3) postoperative. Patients' clinical characteristics were retrieved from the Eindhoven Cancer Registry. Descriptive statistics, correlations, and linear mixed effect models were used.Results: Compared with a normative population, partners' fatigue was similar (p > .05), while patients' fatigue was higher at Time-2 and Time-3 (p values <.001). At each time point, correlations between patients' and partners' fatigue were small (r < .30). Partner's course of fatigue was as follows: 18.2 at time-0, 19.0 at time-1, 19.4 at time-2, and 19.2 at time-3 (p = 0.64). Scoring higher on neuroticism (β = .12) and trait anxiety (β = .23), and more depressive symptoms (β = .30) significantly contributed to higher partners' fatigue.Conclusion: Trait anxiety, neuroticism, and depressive symptoms predicted higher levels of partners' fatigue, while demographic factors, patients' fatigue, and clinical factors did not. Health professionals are advised to be alert for partners with a vulnerable personality and depressive symptoms. If needed, they can for instance refer to a psychologist for treatment. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study aimed to identify the different trajectories of quality of life (QOL) in patients with distal radius fractures (DRF) and ankle fractures (AF). Secondly, it was examined if subgroups could be characterized by sociodemographic, clinical, and psychological variables.Methods: Patients (n = 543) completed the World Health Organization Quality of Life assessment instrument-Bref (WHOQOL-Bref), the pain, coping, and cognitions questionnaire, NEO-five factor inventory (neuroticism and extraversion), and the state-trait anxiety inventory (short version) a few days after fracture (i.e., pre-injury QOL reported). The WHOQOL-Bref was also completed at three, six, and 12 months post-fracture. Latent class trajectory analysis (i.e., regression model) including the Step 3 method was performed in Latent Gold 5.0.Results: The number of classes ranged from three to five for the WHOQOL-Bref facet and the four domains with a total variance explained ranging from 71.6 to 79.4%. Sex was only significant for physical and psychological QOL (p < 0.05), whereas age showed significance for overall, physical, psychological, and environmental QOL (p < 0.05). Type of treatment or fracture type was not significant (p > 0.05). Percentages of chronic comorbidities were 1.8 (i.e., social QOL) to 4.5 (i.e., physical QOL) higher in the lowest compared to the highest QOL classes. Trait anxiety, neuroticism, extraversion, pain catastrophizing, and internal pain locus of control were significantly different between QOL trajectories (p < 0.05).Conclusions: The importance of a biopsychosocial model in trauma care was confirmed. The different courses of QOL after fracture were defined by several sociodemographic and clinical variables as well as psychological characteristics. Based on the identified characteristics, patients at risk for lower QOL may be recognized earlier by health care providers offering opportunities for monitoring and intervention. [ABSTRACT FROM AUTHOR]

• We implemented a high-throughput 384-wells version of the functional FIS assay to screen a large number of PDIOs for compounds that enhance CFTR function. • We found that PDE4 inhibitors are potent CFTR function inducers when residual CFTR function is either present or created by additional compound exposure. • We show that CFTR modulators can be beneficial for CF patients with CFTR mutations that are not eligible for CFTR modulators at present-day. • Our study demonstrates how preclinical studies using PDIOs can be used to initiate drug repurposing efforts, paving the way for patient stratification in the upcoming era of personalized medicine. Preclinical cell-based assays that recapitulate human disease play an important role in drug repurposing. We previously developed a functional forskolin induced swelling (FIS) assay using patient-derived intestinal organoids (PDIOs), allowing functional characterization of CFTR, the gene mutated in people with cystic fibrosis (pwCF). CFTR function-increasing pharmacotherapies have revolutionized treatment for approximately 85% of people with CF who carry the most prevalent F508del- CFTR mutation, but a large unmet need remains to identify new treatments for all pwCF. We used 76 PDIOs not homozygous for F508del- CFTR to test the efficacy of 1400 FDA-approved drugs on improving CFTR function, as measured in FIS assays. The most promising hits were verified in a secondary FIS screen. Based on the results of this secondary screen, we further investigated CFTR elevating function of PDE4 inhibitors and currently existing CFTR modulators. In the primary screen, 30 hits were characterized that elevated CFTR function. In the secondary validation screen, 19 hits were confirmed and categorized in three main drug families: CFTR modulators, PDE4 inhibitors and tyrosine kinase inhibitors. We show that PDE4 inhibitors are potent CFTR function inducers in PDIOs where residual CFTR function is either present, or created by additional compound exposure. Additionally, upon CFTR modulator treatment we show rescue of CF genotypes that are currently not eligible for this therapy. This study exemplifies the feasibility of high-throughput compound screening using PDIOs. We show the potential of repurposing drugs for pwCF carrying non-F508del genotypes that are currently not eligible for therapies. We screened 1400 FDA-approved drugs in CF patient-derived intestinal organoids using the previously established functional FIS assay, and show the potential of repurposing PDE4 inhibitors and CFTR modulators for rare CF genotypes. [ABSTRACT FROM AUTHOR]

Background: Preferred treatment for resectable oesophageal cancer is surgery with or without neoadjuvant treatment. However, oesophageal surgery has high morbidity and in vulnerable patients with co-morbidity other treatment modalities can be proposed. We examined determinants in decision making for surgery and factors affecting survival in patients with resectable oesophageal cancer in southern Netherlands.Methods: All patients with resectable (T1-3, N0-1, M0-1A) oesophageal cancer (n=849) diagnosed between 2003 and 2010 were selected from the population-based data of the Eindhoven Cancer Registry. Logistic regression analysis and multivariable Cox survival analysis were conducted to examine determinants of surgery and survival.Results: Forty-five percent of the patients underwent surgery. In multivariable survival analysis only surgery, chemoradiation alone and tumour stage influenced overall survival (OS). Patients aged ≥ 70 yrs, a low socioeconomic status (SES), one or more co-morbidities, cT1-tumours, cN1-tumours, a squamous-cell carcinoma, and those with a proximal tumour were significantly less often offered surgical resection. Older patients and patients with cT1 tumours were less likely to receive chemoradiation alone. Patients with clinically positive lymph nodes or a proximal tumour were more likely to receive chemoradiation alone.Conclusion: Treatment modalities including surgery and chemoradiation alone as well as stage of disease were independent predictors of a better OS in patients with potentially resectable oesophageal cancer. Therefore, the decision to perform potentially curative treatment is of crucial importance to improve OS for patients with potentially resectable oesophageal cancer. Although age and SES had no significant influence on overall survival, a higher age and low SES negatively influenced the probability to propose potentially curative treatment. [ABSTRACT FROM AUTHOR]

Background: Home spirometers have been widely implemented in the treatment of people with cystic fibrosis (CF). Frequent spirometry measurements at home could lead to earlier detection of exacerbations. However, previous research indicates that the long-term use of home spirometry is not well maintained by people with CF., Objective: We aimed to gain insight into the long-term uptake of home spirometry in regular multicenter CF care., Methods: Home spirometers combined with a remote monitoring platform were introduced in the treatment of people with CF in 5 Dutch CF centers starting in April 2020. Usage data from April 2020 to December 2022 were analyzed retrospectively. Survival analyses were conducted to assess use consistency over time, and t tests were used to evaluate the impact of increased pulmonary symptoms on home spirometry frequency. The effect of the initiation of a new treatment, Elexacaftor/Tezacaftor/Ivacaftor, on use frequency over time was assessed in a subgroup of participants with repeated measures ANOVA., Results: During the observation period, a total of 604 people with CF were enrolled in the remote monitoring platform and 9930 home spirometry measurements were performed. After the initiation of home spirometry use, the number of users declined rapidly. One year after the initiation, 232 (54.2%) people with CF stopped using home spirometry. During the observation period, 67 (11.1%) users performed more than 20 measurements. Furthermore, the number of consistent home spirometry users decreased over time. After 600 days, only 1% of users had measured their lung function consistently every 31 days. Use frequency slightly increased during periods with increased pulmonary symptoms (ΔMean=0.45, t 497.278 =-4,197; P<.001) and showed an initial rise followed by a decrease after starting treatment with Elexacaftor/Tezacaftor/Ivacaftor (ΔMean=0.45, t 497.278 =-4,197; P<.001)., Conclusions: Consistent uptake of home spirometry in people with CF is low but increases around periods of changing symptoms. A clear strategy for the organization of remote care seemed to improve the long-term uptake of home spirometry. Nevertheless, home spirometry and its intensity are not a goal on their own but should be used as a tool to reach individual goals within local contexts., (©Pia Bertram, Martinus C Oppelaar, Michiel AGE Bannier, Monique HE Reijers, Hester van der Vaart, Renske van der Meer, Josje Altenburg, Lennart Conemans, Bart L Rottier, Marianne Nuijsink, Lara S van den Wijngaart, Peter JFM Merkus, Jolt Roukema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 09.01.2025.)

Purpose: Adolescent idiopathic scoliosis (AIS) presents various challenges, including respiratory symptoms that impact pulmonary function. This study aims to explore the feasibility of using a smart shirt for continuous monitoring of lung volumes and heart rate during routine activities in AIS patients., Methods: A single-center exploratory feasibility study was conducted with AIS patients aged 16-22 years with a thoracic curvature of ≥ 30 degrees and absence of respiratory comorbidities. A smart shirt was utilized to continuously monitor cardiopulmonary parameters during mild exercise, which included a standardized walking route with the ascent of multiple stairs., Results: Five participants completed the study. Baseline spirometry measurements showed a range of values for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), and FEV 1 /FVC ratio. During mild exercise, participants exhibited variability in tidal volume, heart rate, breathing rate, and minute ventilation, with increases observed during stair climbing. Breathlessness levels also varied throughout the activity but did not correlate with the measured lung volumes. Overall, the use of the smart shirt for assessing pulmonary function in AIS patients was deemed feasible and well tolerated by participants during the test activities., Conclusion: The study confirms the feasibility of using a smart shirt for continuous measurement of cardiopulmonary parameters in AIS patients during daily activities. Incongruities between spirometry results and perceived dyspnea exists, which questions the nature of the perceived dyspnea. Further research is needed to validate these findings and explore the impact of AIS characteristics on measurement accuracy., (© 2024. The Author(s).)

Background: Portable spirometers are increasingly used to measure lung function at home, but doubts about the accuracy of these devices persist. These doubts stand in the way of the digital transition of chronic respiratory disease care, hence there is a need to address the accuracy of home spirometry in routine care across multiple settings and ages., Objective: This study aimed to assess the accuracy, reproducibility, and responsiveness to the treatment of home spirometry in long-term pediatric and adult cystic fibrosis care., Methods: This retrospective observational study was carried out in 5 Dutch cystic fibrosis centers. Home spirometry outcomes (forced expiratory volume in one second [FEV 1 ], and forced vital capacity [FVC]) for 601 anonymized users were collected during 3 years. For 81 users, data on clinic spirometry and elexacaftor/tezacaftor/ivacaftor (ETI) use were available. Accuracy was assessed using Bland-Altman plots for paired clinic-home measurements on the same day and within 7 days of each other (nearest neighbor). Intratest reproducibility was assessed using the American Thoracic Society/European Respiratory Society repeatability criteria, the coefficient of variation, and spirometry quality grades. Responsiveness was measured by the percentage change in home spirometry outcomes after the start of ETI., Results: Bland-Altman analysis was performed for 86 same-day clinic-home spirometry pairs and for 263 nearest neighbor clinic-home spirometry pairs (n=81). For both sets and for both FEV 1 and FVC, no heteroscedasticity was present and hence the mean bias was expressed as an absolute value. Overall, home spirometry was significantly lower than clinic spirometry (mean ΔFEV 1clinic-home 0.13 L, 95% CI 0.10 to 0.19; mean ΔFVC clinic-home 0.20 L, 95% CI 0.14 to 0.25) and remained lower than clinic spirometry independent of age and experience. One-way ANOVA with post hoc comparisons showed significantly lower differences in clinic-home spirometry in adults than in children (Δmean 0.11, 95% CI -0.20 to -0.01) and teenagers (Δmean 0.14, 95% CI -0.25 to -0.02). For reproducibility analyses, 2669 unique measurement days of 311 individuals were included. Overall, 87.3% (2331/2669) of FEV 1 measurements and 74.3% (1985/2669) of FVC measurements met reproducibility criteria. Kruskal-Wallis with pairwise comparison demonstrated that for both FVC and FEV 1 , coefficient of variation was significantly lower in adults than in children and teenagers. A total of 5104 unique home measurements were graded. Grade E was given to 2435 tests as only one home measurement was performed. Of the remaining 2669 tests, 43.8% (1168/2669) and 43.6% (1163/2669) received grade A and B, respectively. The median percentage change in FEV 1 from baseline after initiation of ETI was 19.2% after 7-14 days and remained stable thereafter (n=33)., Conclusions: Home spirometry is feasible but not equal to clinic spirometry. Home spirometry can confirm whether lung functions remain stable, but the context of measurement and personal trends are more relevant than absolute outcomes., (©Martinus C Oppelaar, Hanneke AC van Helvoort, Michiel AGE Bannier, Monique HE Reijers, Hester van der Vaart, Renske van der Meer, Josje Altenburg, Lennart Conemans, Bart L Rottier, Marianne Nuijsink, Lara S van den Wijngaart, Peter JFM Merkus, Jolt Roukema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.12.2024.)

Background: Remote care usefulness and climate change co-benefits should be addressed simultaneously to incentivize political action., Objectives: To assess the changes in healthcare consumption, lung function and greenhouse gas (GHG) emissions during the COVID-19 pandemic in Dutch cystic fibrosis (CF) care., Design: Retrospective multicentre observational study in five Dutch CF centres., Methods: Eighty-one participants were included. Healthcare consumption was described alongside the COVID-19 Stringency Index (2019-2022). Travel related GHG emissions were calculated for every clinic visit. Changes in percentage predicted Forced Expiratory Volume in one second (ppFEV1) were assessed using a paired-samples T -test., Results: Healthcare consumption patterns followed COVID-19 public health measure stringency but returned back to the "old normal". Emission of 5.450, 3 kg of carbon dioxide equivalents were avoided while quality of care was relatively preserved. ppFEV1 declined as expected ( Δ Means 3.69%, 95%CI 2.11-5.28)., Conclusion: Remote monitoring of lung function and symptoms and teleconsultations in CF can reduce GHG emissions while maintaining quality of care. As health sectors constitute a large share of national climate change footprints, digital health can partly alleviate this burden by reducing private travel., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Oppelaar, Bannier, Reijers, van der Vaart, van der Meer, Altenburg, Conemans, Rottier, Nuijsink, van den Wijngaart, Merkus and Roukema.)

Background: The current literature inadequately addresses the extent to which remote monitoring should be integrated into care models for chronic respiratory diseases (CRDs)., Objective: This study examined a remote monitoring program (RMP) in cystic fibrosis (CF) by exploring experiences, future perspectives, and use behavior over 3 years, with the aim of developing future directions for remote monitoring in CRDs., Methods: This was a mixed methods, multicenter, observational study in 5 Dutch CF centers following a sequential explanatory design. Self-designed questionnaires using the technology acceptance model were sent out to people with CF who had a minimum of 12 months of experience with the RMP and local health care professionals (HCPs). Questionnaire outcomes were used to inform semistructured interviews with HCPs and people with CF. Qualitative findings were reported following the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. Anonymous data on use frequency of all people with CF were analyzed., Results: Between the second quarter of 2020 and the end of 2022, a total of 608 people with CF were enrolled in the program, and a total of 9418 lung function tests and 2631 symptom surveys were conducted. In total, 65% (24/37) of HCPs and 89% (72/81) of people with CF responded to the questionnaire, and 7 HCPs and 12 people with CF participated in semistructured interviews. Both people with CF and HCPs were positive about remote monitoring in CF care and found the RMP a good addition to daily care (people with CF: 44/72, 61%; HCPs: 21/24, 88%). Benefits ranged from supporting individual patients to reducing health care consumption. The most valued monitoring tool was home spirometry by both people with CF (66/72, 92%) and HCPs (22/24, 92%). Downsides included the potential to lose sight of patients and negative psychosocial effects, as 17% (12/72) of people with CF experienced some form of stress due to the RMP. A large majority of people with CF (59/72, 82%) and HCPs (22/24, 92%) wanted to keep using the RMP in future, with 79% (19/24) of HCPs and 75% (54/72) of people with CF looking forward to more replacement of in-person care with digital care during periods of well-being. Future perspectives for the RMP were centered on creating hybrid care models, personalizing remote care, and balancing individual benefits with monitoring burden., Conclusions: Remote monitoring has considerable potential in supporting people with CF and HCPs within the CF care model. We identified 4 practice-based future directions for remote monitoring in CF and CRD care. The strategies, ranging from patient driven to prediction driven, can help clinicians, researchers, and policy makers navigate the rapidly changing digital health field, integrate remote monitoring into local care models, and align remote care with patient and clinician needs., (©Martinus C Oppelaar, Yvette Emond, Michiel A G E Bannier, Monique H E Reijers, Hester van der Vaart, Renske van der Meer, Josje Altenburg, Lennart Conemans, Bart L Rottier, Marianne Nuijsink, Lara S van den Wijngaart, Peter J F M Merkus, Maud Heinen, Jolt Roukema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.08.2024.)

Limited data on the clinical management of drug-drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Purpose: To determine whether maternal depressive symptoms at multiple time points during pregnancy are associated with infant wheezing in the first 2 years of life to assess etiologically relevant time windows., Methods: We included Dutch women participating in the PRIDE Study with delivery in 2013-2019. Maternal depressive symptoms were assessed with the Hospital Anxiety and Depression Scale and Edinburgh Depression Scale at enrollment and in gestational weeks 17 and 34. The International Study of Asthma and Allergies in Childhood questionnaire was used to assess infant wheezing biannually postpartum. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with modified Poisson regression., Results: Among 5294 pregnancies included, maternal depressive symptoms in gestational weeks 15-22 was associated with any wheezing in the first 2 years of life (RR 1.36, 95% CI 1.04-1.78) and with current wheezing at 12 (RR 1.29, 95% CI 1.03-1.61) and 18 months (RR 1.33, 1.04-1.69). Depressive symptoms in gestational weeks 32-35 seemed to be associated with any wheezing reported at two years (RR 1.27, 95% CI 0.96-1.69) and current wheezing at 12 months (RR 1.28, 95% CI 1.02-1.60). Four trajectories of depressive symptoms were identified. Only the trajectory with increasing symptoms throughout pregnancy seemed to be associated with infant wheezing (RR 1.36, 95% CI 0.97-1.89)., Conclusions: Maternal depressive symptoms in mid- and late pregnancy may be associated with development of infant wheezing, particularly those with onset in the second half of pregnancy. Research is needed to identify biological pathways and associations with more objective, long-term respiratory morbidity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Merkus reports financial support was provided by Lung Foundation Netherlands., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: We highlight the recent advances in home monitoring of patients with asthma, and show that these advances converge towards the implementation of digital twin systems., Recent Findings: Connected devices for asthma are increasingly numerous, reliable and effective: new electronic monitoring devices extend to nebulizers and spacers, are able to assess the quality of the inhalation technique, and to identify asthma attack triggers when they include a geolocation function; environmental data can be acquired from databases and refined by wearable air quality sensors; smartwatches are better validated. Connected devices are increasingly integrated into global monitoring systems. At the same time, machine learning techniques open up the possibility of using the large amount of data collected to obtain a holistic assessment of asthma patients, and social robots and virtual assistants can help patients in the daily management of their asthma., Summary: Advances in the internet of things, machine learning techniques and digital patient support tools for asthma are paving the way for a new era of research on digital twins in asthma., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (≥6 years) with ≥1 Phe508del mutation and a minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real-life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV 1 , BMI, and adverse events at initiation and 1, 3, 6, and 12 months after starting ETI. The number of exacerbations was recorded in the 12 months before and the 12 months after ETI treatment. Patients eligible for compassionate use had a FEV 1 <40% predicted. Wilcoxon signed-rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12 months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1 month. Mean absolute increase of FEV 1 was 11.8/13.7% (p ≤ .001) and BMI was 0.49/1.87 kg/m 2 (p < .001-0.02) after 1/12 months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long-term effects of treatment with ETI in patients with severe CF lung disease in a real-life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Rationale: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC)., Methods: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed-effect models and multivariable logistic regression to estimate the association of FIS with long-term forced expiratory volume in 1 s % predicted (FEV 1 pp) decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC., Results: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV 1 pp decline of 0.32% (95% CI 0.11-0.54%; p=0.004) per 1000-point change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR 0.18, 95% CI 0.07-0.46; p<0.001), CF-related liver disease (adjusted OR 0.18, 95% CI 0.06-0.54; p=0.002) and diabetes (adjusted OR 0.34, 95% CI 0.12-0.97; p=0.044). These associations were absent for SCC., Conclusion: This study exemplifies the prognostic value of a patient-derived organoid-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences., Competing Interests: Conflict of interest: J.M. Beekman reports personal fees from Vertex Pharmaceuticals, Proteostasis Therapeutics, Eloxx Pharmaceuticals, Teva Pharmaceutical Industries and Galapagos, outside the submitted work; in addition, J.M. Beekman has a patent related to the FIS-assay with royalties paid. C.K. van der Ent reports grants from GSK, Nutricia, TEVA, Gilead, Vertex, ProQR, Proteostasis, Galapagos NV and Eloxx, outside the submitted work; in addition, C.K. van der Ent has a patent 10006904 with royalties paid. G.H. Koppelman reports grants from Lung Foundation of the Netherlands, Vertex Pharmaceuticals, UBBO EMMIUS foundation, GSK, TEVA the Netherlands, TETRI Foundation and European Union (H2020), outside the submitted work; and has participated in advisory board meetings for GSK and PURE-IMS outside the submitted work (money paid to institution). P. van Mourik reports financial compensation (money to institution) from Vertex for participation in a webinar, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: The COVID-19 pandemic has boosted the use of forced expiratory volume in 1 second (FEV 1 ) telemonitoring in pediatric asthma, but a consensus on its most efficient and effective implementation is still lacking. To find answers, it is important to study how such an intervention is perceived, experienced, and used by both patients and health care professionals (HCPs)., Objective: The aim of this study was to provide perspectives on how FEV 1 home monitoring should be used in pediatric asthma., Methods: This is a qualitative, multicenter, prospective, observational study which included patients with asthma aged 6-16 and HCPs. Primary outcomes were results of 2 surveys that were sent to all participants at study start and after 3-4 months. Secondary outcomes consisted of FEV 1 device usage during 4 months after receiving the FEV 1 device., Results: A total of 39 participants (26 patients and 13 HCPs) were included in this study. Survey response rates were 97% (38/39) at the start and 87% (34/39) at the end of the study. Both patients and HCPs were receptive toward online FEV 1 home monitoring and found it contributive to asthma control, self-management, and disease perception. The main concerns were about reliability of the FEV 1 device and validity of home-performed lung function maneuvers. FEV 1 devices were used with a median frequency of 7.5 (IQR 3.3-25.5) during the 4-month study period., Conclusions: Patients and HCPs are receptive toward online FEV 1 home monitoring. Frequency of measurements varied largely among individuals, yet perceived benefits remained similar. This emphasizes that online FEV 1 home monitoring strategies should be used as a means to reach individual goals, rather than being a goal on their own., (©Martinus C Oppelaar, Lara S van den Wijngaart, Peter J F M Merkus, Ellen A Croonen, Cindy A C Hugen, Marianne L Brouwer, Annemie L M Boehmer, Jolt Roukema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.10.2021.)

Background: The natural food supplements curcumin and genistein, and the drug ivacaftor were found effective as CFTR potentiators in the organoids of individuals carrying a S1251N gating mutation, possibly in a synergistic fashion. Based on these in vitro findings, we evaluated the clinical efficacy of a treatment with curcumin, genistein and ivacaftor, in different combinations., Methods: In three multi-center trials people with CF carrying the S1251N mutation were treated for 8 weeks with curcumin+genistein, ivacaftor and ivacaftor+genistein. We evaluated change in lung function, sweat chloride concentration, CFQ-r, BMI and fecal elastase to determine the clinical effect. We evaluated the pharmacokinetic properties of the compounds by evaluating the concentration in plasma collected after treatment and the effect of the same plasma on the intestinal organoids., Results: A clear clinical effect of treatment with ivacaftor was observed, evidenced by a significant improvement in clinical parameters. In contrast we observed no clear clinical effect of curcumin and/or genistein, except for a small but significant reduction in sweat chloride and airway resistance. Plasma concentrations of the food supplements were low, as was the response of the organoids to this plasma., Conclusions: We observed a clear clinical effect of treatment with ivacaftor, which is in line with the high responsiveness of the intestinal organoids to this drug. No clear clinical effect was observed of the treatment with curcumin and/or genistein, the low plasma concentration of these compounds emphasizes that pharmacokinetic properties of a compound have to be considered when in vitro experiments are performed., Competing Interests: Declaration of Competing Interest J.M.B. and C.K.v.d.E are inventors on a patent application related to these findings. GHK reports research funding from the Lung Foundation of the Netherlands, GSK, Ubbo Emmius Foundation, Vertex, TEVA the Netherlands, TETRI Foundation, outside the submitted work and participation in advisory boards from GSK and PureIMS, outside the submitted work., (Copyright © 2020. Published by Elsevier B.V.)