Search

Abstract Objectives To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV). Materials and methods Patients diagnosed with cT1 RCC during 2014–2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV 50). Trends over time in nephron‐sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV. Results Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron‐sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron‐sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high‐volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%). Conclusion HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron‐sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high‐volume hospitals.

Background: Apathy is reported after subthalamic nucleus deep brain stimulation (STN DBS) and associated with a decreased quality of life in Parkinson's disease (PD) patients. Recent studies hypothesized that the location of active DBS contact point relative to the STN subdivisions (motor, associative and limbic) could be related to an increase of apathy. Methods: 22 PD-patients that underwent STN DBS between January 2019 and February 2020 were divided in an apathy and non-apathy group using the change in the Starkstein Apathy Scale (SAS) after six months of DBS. For both groups the location of DBS electrodes was determined based on 7T MRI subthalamic network analysis, enabling visualization of the subdivisions and their projections relative to the active contact point. MDS-UPDRS III scores were included to evaluate DBS effect. Results: In six patients a post-DBS increase in apathy score was assessed, versus 16 non-apathy patients. Network analysis showed that active contacts in apathy patients were more often positioned in or close to the area within the STN with high density of surrounding projections to associative cortex areas than in non-apathy patients; 63% apathy versus 42% (P = 0.02). The density of surrounding motor projections was lower in the group with increased apathy (18%) than in the group without increased apathy (38%, P = 0.01). Motor UPDRS improvement for the apathy group was 39% and for the non-apathy group 58% (n.s.) Conclusion: This new approach in patient-specific subthalamic 7T MRI network analysis visualized an anatomical connectivity substrate for apathy in DBS, with active electrode contacts predominantly in the associative STN.

Immunoglobulin G (IgG) antibodies are a critical component of the adaptive immune system, binding to and neutralizing pathogens and other foreign substances. Recent advances in molecular antibody biology and structural protein engineering enabled the modification of IgG antibodies to enhance their therapeutic potential. This review summarizes recent progress in both natural and engineered structural modifications of IgG antibodies, including allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor binding optimization. We discuss the functional consequences of these modifications to highlight their potential for therapeutical applications.

Objectives The aim of this multicentre COVID-PREDICT study (a nationwide observational cohort study that aims to better understand clinical course of COVID-19 and to predict which COVID-19 patients should receive which treatment and which type of care) was to determine the association between atrial fibrillation (AF) and mortality, intensive care unit (ICU) admission, complications and discharge destination in hospitalised COVID-19 patients.Setting Data from a historical cohort study in eight hospitals (both academic and non-academic) in the Netherlands between January 2020 and July 2021 were used in this study.Participants 3064 hospitalised COVID-19 patients >18 years old.Primary and secondary outcome measures The primary outcome was the incidence of new-onset AF during hospitalisation. Secondary outcomes were the association between new-onset AF (vs prevalent or non-AF) and mortality, ICU admissions, complications and discharge destination, performed by univariable and multivariable logistic regression analyses.Results Of the 3064 included patients (60.6% men, median age: 65 years, IQR 55–75 years), 72 (2.3%) patients had prevalent AF and 164 (5.4%) patients developed new-onset AF during hospitalisation. Compared with patients without AF, patients with new-onset AF had a higher incidence of death (adjusted OR (aOR) 1.71, 95% CI 1.17 to 2.59) an ICU admission (aOR 5.45, 95% CI 3.90 to 7.61). Mortality was non-significantly different between patients with prevalent AF and those with new-onset AF (aOR 0.97, 95% CI 0.53 to 1.76). However, new-onset AF was associated with a higher incidence of ICU admission and complications compared with prevalent AF (OR 6.34, 95% CI 2.95 to 13.63, OR 3.04, 95% CI 1.67 to 5.55, respectively).Conclusion New-onset AF was associated with an increased incidence of death, ICU admission, complications and a lower chance to be discharged home. These effects were far less pronounced in patients with prevalent AF. Therefore, new-onset AF seems to represent a marker of disease severity, rather than a cause of adverse outcomes.

Age-friendly gemeenschappen waarin burgers van alle leeftijden prettig samenleven en voor elkaar zorgen, met professionals en vrijwilligers als ondersteuning, is het toekomstbeeld. Afgelopen drie jaar zette Nederland op grote schaal in op het ontwikkelen van lokale netwerken rondom het vraagstuk van de ouder wordende samenleving. Echter, wat werkt om deze gemeenschappen te laten groeien en bloeien? In een participatief actieonderzoek leerden we samen met betrokkenen van 110 lokale netwerken in Nederland die experimenteerden over de werkzame mechanismen van deze lokale netwerken. Belangrijke mechanismen zijn: 1) denken vanuit een eco-systeem benadering; 2) wicked skills van betrokkenen; 3) proces-gestuurd met brede mix aan perspectieven en krachten; 4) faciliteren om samen te leren, en 5) senioren als gelijkwaardige (gespreks)partner. Deze studie laat zien dat met name het samenwerken tussen professionals en senioren uitdagend is in netwerken. Bewustzijn van de moreel-existentiële aspecten van samenwerken is hierin van belang, net als de vaardigheden om hier ruimte voor te maken in de dagelijkse praktijk en de bereidheid om hier samen over te leren.

BackgroundCommunity-acquired pneumonia (CAP) represents a major health burden worldwide. Dysregulation of the immune response plays an important role in adverse outcomes in patients with CAP.MethodsWe analyzed peripheral blood mononuclear cells by 36-color spectral flow cytometry in adult patients hospitalized for CAP (n=40), matched control subjects (n=31), and patients hospitalized for COVID-19 (n=35).ResultsWe identified 86 immune cell metaclusters, 19 of which (22.1%) were differentially abundant in patients with CAP versus matched controls. The most notable differences involved classical monocyte metaclusters, which were more abundant in CAP and displayed phenotypic alterations reminiscent of immunosuppression, increased susceptibility to apoptosis, and enhanced expression of chemokine receptors. Expression profiles on classical monocytes, driven by CCR7 and CXCR5, divided patients with CAP into two clusters with a distinct inflammatory response and disease course. The peripheral immune response in patients with CAP was highly similar to that in patients with COVID-19, but increased CCR7 expression on classical monocytes was only present in CAP.ConclusionCAP is associated with profound cellular changes in blood that mainly relate to classical monocytes and largely overlap with the immune response detected in COVID-19.

The Jahn–Teller effect (JTE) is central to the understanding of the physical and chemical properties of a broad variety of molecules and materials. Whereas the manifestations of the JTE in stationary properties of matter are relatively well studied, the study of JTE-induced dynamics is still in its infancy, largely owing to its ultrafast and non-adiabatic nature. For example, the time scales reported for the distortion of CH 4 + from the initial T d geometry to a nominal C 2 v relaxed structure range from 1.85 fs over 10 ± 2 fs to 20 ± 7 fs. Here, by combining element-specific attosecond transient-absorption spectroscopy and quantum-dynamics simulations, we show that the initial electronic relaxation occurs within 5 fs and that the subsequent nuclear dynamics are dominated by the Q2 scissoring and Q1 symmetric stretching modes, which dephase in 41 ± 10 fs and 13 ± 3 fs, respectively. Significant structural relaxation is found to take place only along the e-symmetry Q2 mode. These results demonstrate that CH 4 + created by ionization of CH 4 is best thought of as a highly fluxional species that possesses a long-time-averaged vibrational distribution centered around a D 2 d structure. The methods demonstrated in our work provide guidelines for the understanding of Jahn–Teller driven non-adiabatic dynamics in other more complex systems.

Smart city projects rely upon dynamic and complex multi-stakeholder collaboration. This collaboration can be challenging. In this study, we use an instrumental lens and argue that tools can help public professionals in dealing with smart governance challenges. Building upon smart governance and collaborative governance models, we conceptualize smart governance as a toolbox. Based on our “smart governance toolbox”, we assess the variety of tools available for professionals to initiate and support multi-stakeholder collaboration by reviewing academic and grey literature. This review results in the identification of a broad range of tools that research and practice have developed. However, we also demonstrate that certain parts of the ‘smart governance toolbox’ remain almost empty: there are few tools for assessing the smart collaborative governance context, facilitating the collaborative structure, tackling technology issues, and measuring outcomes of smart city practices. Future design research should focus on developing instruments needed to make the smart governance toolbox complete.

Abstract Background Clinical practice guidelines recommend to inform female cancer patients about their infertility risks due to cancer treatment. Unfortunately, it seems that guideline adherence is suboptimal. In order to improve quality of integrated female oncofertility care, a systematic assessment of current practice is necessary. Methods A multicenter cross‐sectional survey study in which a set of systematically developed quality indicators was processed, was conducted among female cancer patients (diagnosed in 2016/2017). These indicators represented all domains in oncofertility care; risk communication, referral, counseling, and decision‐making. Indicator scores were calculated, and determinants were assessed by multilevel multivariate analyses. Results One hundred twenty‐one out of 344 female cancer patients participated. Eight out of 11 indicators scored below 90% adherence. Of all patients, 72.7% was informed about their infertility, 51.2% was offered a referral, with 18.8% all aspects were discussed in counseling, and 35.5% received written and/or digital information. Patient's age, strength of wish to conceive, time before cancer treatment, and type of healthcare provider significantly influenced the scores of three indicators. Conclusions Current quality of female oncofertility care is far from optimal. Therefore, improvement is needed. To achieve this, improvement strategies that are tailored to the identified determinants and to guideline‐specific barriers should be developed.

Background: Enhancing the application of shared decision-making (SDM) is critical for integrating patient preferences in breast cancer treatment choices. We investigated the effect of an adapted multilevel SDM implementation program in breast cancer care. Methods: Breast cancer patients qualifying for (neo)adjuvant systemic treatment were included in a multicenter before–after study. Consultations were audio recorded between June 2018 and July 2019 and analyzed using the five-item Observing Patient Involvement in Decision-Making (OPTION-5) instrument to score SDM application by clinicians. The Shared Decision-Making Questionnaire (SDM-Q-9) was used to rate patients’ perceived SDM level. Consultation duration, decision types, number of options discussed and consultations per patient were monitored. Regression analysis was used to investigate the correlated variables and program components. Results: Mean OPTION-5 scores increased from 33.9 (n = 63) before implementation to 54.3 (n = 49) after implementation (p < 0.001). The SDM-Q-9 scores did not change: 91.1 (n = 51) at baseline versus 88.9 (n = 23) after implementation (p = 0.81). Without increasing consultation time, clinicians discussed more options after implementation. The regression analysis showed that exposure to the implementation program, redistribution of tasks and discussing feedback from consultations was associated with a higher level of SDM. Conclusion: The multilevel program helped clinicians achieve clinically relevant improvement in SDM, especially when it is tailored to (individuals in) teams and includes (e-)training, discussing feedback on consultations and redistribution of tasks.