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Background: Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity. It contributes to the current persistent one-size-fits-all treatment. To replace this treatment by more personalized, precision medicine, new insights are required. We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs., Methods: The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution., Results: Forty seven patients were assessed. FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of -0.25±0.61 L, p ≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p =0.02), and airway resistance. As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters. Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI., Conclusion: FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups. It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations., Competing Interests: Disclosure WHVG received an ERS Fellowship STRTF 2016 and reports a grant from Novartis to the institution for an investigator-initiated trial outside of the submitted work. WV reports grants from GSK, during the conduct of the study, and personal fees from FLUIDDA nv, outside of the submitted work. JDB is the founder and shareholder of FLUIDDA nv, a company that develops and markets part of the technology described in this paper. AC reports a grant from GSK, outside of the submitted work. OSU reports grants from AstraZeneca, GSK, Prosonix, and Edmond Pharma; personal fees from Boehringer Ingelheim, Aerocrine, Napp, Mundipharma, Sandoz, Takeda, Zentiva, and Cipla; and grants and personal fees from Chiesi, outside of the submitted work. CVH reports a grant from FLUIDDA nv, during the conduct of the study and also outside of the submitted work. HAMK reports that his institution has received a per patient fee for participation in the trial reported from FLUIDDA nv. BH, MP, and WDB report no conflicts of interest in this work.

Simple Summary: CAR T-cell therapy has emerged as the new standard of care for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), but real-world outcomes differ across countries. Additionally, real-world data on health-related quality of life (HR-QoL) are scarce but important, as they reflect the direct experience of patients. In the Netherlands, patients can be referred to the CAR-T tumorboard, a national CAR-T expert panel, who decide whether CAR-T is a feasible treatment option. This multicenter study reports on the favorable outcomes, including the HR-QoL, of axicabtagene ciloleucel (axi-cel) for patients with R/R LBCL after ≥2 lines of systemic therapy in the Netherlands. On the other hand, we show that a substantial proportion of patients are still in need of alternative treatments, including improved CAR-T strategies, as they are unfit for or do not respond to axi-cel. Comparing real-world outcomes between cohorts could help to select best practices and further optimize CAR-T treatment. The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020–May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICI) have dramatically changed the landscape of metastatic urothelial carcinoma (UC). However, optimal duration of treatment with ICI in the metastatic setting remains unclear. On the basis of real-world data from the Netherlands of patients treated with pembrolizumab for metastatic UC, we point out that early discontinuation of ICI seems to be reasonable in a subgroup of patients, especially in patients with responding disease (partial or complete response). It is important to draw attention to this topic and to pursue further efforts to evaluate shorter treatment duration for optimizing patient care and outcomes, but also for keeping healthcare affordable. Background: Since there is no clear consensus on optimal treatment duration of PD-(L)1 targeting checkpoint inhibitors in the setting of urothelial cancer (UC) patients, even patients with durable responses are often treated up to 2 years. It is questionable whether this is necessary and whether quality of life improves when treatment is discontinued earlier and restarted when necessary. Methods: We collected available data from locally advanced or metastatic UC patients within the Netherlands between September 2017 and December 2019 treated with first or second-line pembrolizumab, to evaluate treatment duration, reasons for discontinuation, subsequent treatments and survival outcomes. Results: Data were available from 74 patients: 85% (63/74) of patients had a treatment duration of 12 months or shorter, and in seven out of them, treatment was discontinued for another reason than progressive disease. Two patients (3%) had a treatment duration between 12 and 24 months, and eight patients (11%) completed 24 months of treatment. Survival at data cut-off (1 July 2020) with a median follow-up of 35 months was 100% in patients with partial or complete response (6/7 patients) and treatment duration ≤ 12 months, and 100% in patients treated for 24 months. In total, three patients were re-treated with pembrolizumab upon progressive disease during follow-up. Conclusions: In patients who reach partial or complete response during treatment with a PD-(L)1 targeting checkpoint inhibitor, early discontinuation of treatment with pembrolizumab and restart if necessary seems to be reasonable with preserved favorable outcomes. This article should drive further efforts to optimize the treatment duration for patients who respond to treatment with pembrolizumab. [ABSTRACT FROM AUTHOR]

During the outbreak of a disease caused by a pathogen with unknown characteristics, the uncertainty of its progression parameters can be reduced by devising methods that, based on rational assumptions, exploit available information to provide actionable insights. In this study, performed a few (~6) weeks into the outbreak of COVID-19 (caused by SARS-CoV-2), one of the most important disease parameters, the average time-to-recovery, was calculated using data publicly available on the internet (daily reported cases of confirmed infections, deaths, and recoveries), and fed into an algorithm that matches confirmed cases with deaths and recoveries. Unmatched cases were adjusted based on the matched cases calculation. The mean time-to-recovery, calculated from all globally reported cases, was found to be 18.01 days (SD 3.31 days) for the matched cases and 18.29 days (SD 2.73 days) taking into consideration the adjusted unmatched cases as well. The proposed method used limited data and provided experimental results in the same region as clinical studies published several months later. This indicates that the proposed method, combined with expert knowledge and informed calculated assumptions, could provide a meaningful calculated average time-to-recovery figure, which can be used as an evidence-based estimation to support containment and mitigation policy decisions, even at the very early stages of an outbreak. [ABSTRACT FROM AUTHOR]

Background Maintaining functional status is among the most important patient-centered outcomes for older adults with cancer. This study investigated the association between comprehensive geriatric assessment (CGA) and progressive disease or decline of IADL-independence 1 year after chemotherapy, overall survival (OS), and premature termination of chemotherapy. CGA-based functional status and quality of life (QOL) 1 year after chemotherapy are also described. Methods This prospective cohort study involved patients aged ≥65 years treated with chemotherapy for any cancer type. CGA and the G8-screening tool were performed before and after the completion of chemotherapy. Analyses were adjusted for tumor type and treatment intent: (a) indolent hematological malignancies, (b) aggressive hematological malignancies, c) solid malignancies treated with curative intent, and (d) solid malignancies treated with palliative intent. Results All 291 included patients lived in The Netherlands; 193 (67.4%) lived fully independent prior to chemotherapy. The median age was 72 years; 164 (56.4%) were male. IADL independence, CGA-based functional status, and QOL were maintained in half of the patients 1 year after chemotherapy. An abnormal G8-score before chemotherapy was a higher risk for progressive disease or a decline of IADL-independence (OR 3.60, 95% CI, 1.98-6.54, P  < .0001), prematurely terminated chemotherapy (OR 2.12, 95% CI, 1.24-3.65, P  = .006), and shorter median OS (HR 1.71, 95% CI, 1.16-2.52, P  = .007). The impact of an abnormal G8-score differed across tumor type (oncological or hematological) and treatment indication (adjuvant or palliative). Conclusion An abnormal G8 score before chemotherapy is associated with progressive disease and functional decline after chemotherapy and shorter median OS, especially in patients with solid malignancies. [ABSTRACT FROM AUTHOR]

Background: People experiencing homelessness often encounter progressive incurable somatic diseases in combination with psychiatric and psychosocial problems, and many need palliative care at the end of their lives. Little is known about how palliative care for this group can be started in good time and provided optimally. The objective of this paper is to give insight into the extent people experiencing homelessness have access to good palliative care. Methods: Qualitative in-depth interviews were held to reconstruct the cases of 19 people experiencing homelessness in the Netherlands. Eight cases concerned persons being in the palliative phase (using the surprise question) and the other 11 cases concerned persons recently died after a period of ill health due to somatic illness. We used purposive sampling until data saturation was reached. The total number of interviews was 52. All interviews were transcribed verbatim and analysed inductively. Results: Three key themes were: 'late access', 'capricious trajectory' and 'complex care'. The first key theme refers to the often delayed start of palliative care, because of the difficulties in recognizing the need for palliative care, the ambivalence of people experiencing homelessness about accepting palliative care, and the lack of facilities with specific expertise in palliative care for them. The second key theme refers to the illness trajectory, which is often capricious because of the challenging behaviour of people experiencing homelessness, an unpredictable disease process and a system not being able to accommodate or meet their needs. The third key theme refers to the complexity of their care with regard to pain and symptom control, psychosocial and spiritual aspects, and the social network. Conclusions: The care for in the palliative phase does not satisfy the core requirements of palliative care since there are bottlenecks regarding timely identification, the social network, and the assessment and management of physical symptoms and psychosocial and spiritual care needs. Education in palliative care of outreach professionals, training staff in shelters in the provision of palliative care, and building a network of palliative care specialists for people experiencing homelessness. [ABSTRACT FROM AUTHOR]

Aim: This cross-sectional study aimed to map the functional profile of individuals with dyskinetic cerebral palsy (CP), to determine interrelationships between the functional classification systems, and to investigate the relationship of functional abilities with dystonia and choreoathetosis severity.Methods: Fifty-five children (<15y) and young people (15-22y) (30 males, 25 females; mean age 14y 6mo, standard deviation 4y 1mo) with dyskinetic CP were assessed using the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), Eating and Drinking Ability Classification System (EDACS), and Viking Speech Scale (VSS), as well as the Dyskinesia Impairment Scale.Results: Over 50 per cent of the participants exhibited the highest limitation levels in GMFCS, MACS, and VSS. Better functional abilities were seen in EDACS and CFCS. Moderate to excellent interrelationship was found among the classification scales. All scales had significant correlation (rs =0.65 - 0.81) with dystonia severity except for CFCS in the young people group. Finally, only MACS (rs =0.40) and EDACS (rs =0.55) in the young people group demonstrated significant correlation with choreoathetosis severity.Interpretation: The need for inclusion of speech, eating, and drinking in the functional assessment of dyskinetic CP is highlighted. The study further supports the strategy of managing dystonia in particular at a younger age followed by choreoathetosis in a later stage. [ABSTRACT FROM AUTHOR]

Background: Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. Methods and Findings: The average annual disease burden was computed for the period 2007–2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911–9961) and influenza (8670 DALYs/year; 95% UI: 8468–8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the National Immunisation Programme. The average disease burden per individual varied from 0.2 (95% UI: 0.1–0.4) DALYs per 100 infections for giardiasis, to 5081 and 3581 (95% UI: 3540–3611) DALYs per 100 infections for rabies and variant Creutzfeldt-Jakob disease, respectively. Conclusions: For guiding and supporting public health policy decisions regarding the prioritisation of interventions and preventive measures, estimates of disease burden and the comparison of burden between diseases can be informative. Although the collection of disease-specific parameters and estimation of incidence is a process subject to continuous improvement, the current study established a baseline for assessing the impact of future public health initiatives. [ABSTRACT FROM AUTHOR]

Little is known about the time span of progression from high-grade cervical intraepithelial neoplasia (CIN2/3) to invasive cervical cancer. Estimation of this duration from longitudinal studies is not permitted, as CIN2/3 should be treated when detected. Cross-sectional data on the age-specific incidence of detected CIN2/3 and cervical cancer cases are readily available in national registries, but these data are difficult to interpret because neither the moment of lesion development nor the onset of invasive cancer is observed. We developed a statistical model for estimating the duration of time between CIN2/3 and preclinical cancer using Dutch national registries for the years 2000–2005. Human papillomavirus (HPV) genotype data were used to separate CIN2/3 and cancer incidences to obtain estimates for HPV-16-positive and HPV-16-negative lesions. The median time from CIN2/3 to cancer was estimated to be 23.5 years (95% confidence interval: 20.8, 26.6), and 1.6% of the lesions progressed to cancer within 10 years. The median duration for HPV-16-positive lesions was similar, but 2.4% of the HPV-16-positive lesions progressed to cancer within 10 years, as compared with 0.6% for HPV-16-negative lesions. Estimated durations of time to cancer are essential for reassessment of the optimal screening interval in light of vaccination and novel screening tests. [ABSTRACT FROM PUBLISHER]

Introduction: Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline. Methods: Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, <100 CD4 cells/mm3, or AIDS) among therapy-naïve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process. Results: All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm3 for 1984–1995 [n = 111], 1996–2002 [n = 139], and 2003–2007 seroconverters [n = 356], respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm3 for 1984–1995 seroconverters and 308 cells/mm3 for 2003–2007 seroconverters (difference in slope, p = 0.045). Conclusion: Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996. [ABSTRACT FROM AUTHOR]