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Abstract Background Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) have become the current standard-of-care for advanced cancers. This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE), including endocrinopathy. Case presentation A 63-year-old woman was diagnosed with a non-small cell lung carcinoma of the right superior lobe, cT3N2M0. She developed thyrotoxicosis followed by hypothyroidism induced by consolidation immunotherapy with durvalumab (anti-PD-L1). Analysis of the human leukocyte antigen (HLA) region showed HLA-DR4 (susceptible) and DR13 (protective). The possible mechanisms are subsequently discussed in detail. Conclusions The case of a patient with thyroiditis associated with the PD-L1 inhibitor durvalumab is described, highlighting the need for proactive monitoring of thyroid hormone levels. Identifying biomarkers associated with an increased risk of ICI-induced side effects (such as HLA) is of interest for better patient selection, optimal management and improved understanding of the mechanisms involved.

Abstract Background Several changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development. Methods Narrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation. Results General practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented. Conclusions Independent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

Abstract Background Urinary tract infections (UTIs) are common, especially among women. Antibiotics are commonly used to treat UTIs, but might not always be necessary, for example in the case of uncomplicated UTIs such as cystitis. Shared decision making (SDM) could reduce the risk of unnecessary antibiotic prescriptions for uncomplicated cystitis. We investigated the current management and the use of SDM for uncomplicated cystitis in primary care. Methods We performed a qualitative semi-structured interview study among 23 women with a history of cystitis, 12 general practitioner (GP) assistants, and 12 GPs in the Netherlands from July to October 2020. All interviews were individually performed by telephone. The data were analyzed through the use of using open and axial coding. Results The GP assistants managed the initial diagnostics and treatment of uncomplicated cystitis in all general practices. Usually, antibiotics were considered the standard treatment of cystitis. In most general practices, SDM was not used in the treatment of uncomplicated cystitis, mainly because of a lack of time. Women reported that they valued being involved in the treatment decision-making process, but they were not always involved. Further, both GP assistants and GPs indicated that SDM would improve the care pathway of uncomplicated UTIs. Conclusion In our study, SDM was infrequently used to help women with uncomplicated cystitis. To reduce the use of antibiotics for uncomplicated UTIs, a tailored intervention is needed to implement SDM for the treatment of uncomplicated cystitis in primary care.

Helium is the second most abundant element in the universe, and at low temperatures it becomes a quantum crystal with exotic physical properties such as second sound, superfluidity, and giant plasticity. Here authors prepare 2D solid helium at room temperature through diamond lattice confinement.

IntroductionUne collaboration efficace et soutenue entre cliniciens et professionnels en santé publique peut améliorer la santé des individus et la santé de la population. Le concept de santé publique clinique favorise cette collaboration entre médecine clinique et santé publique et permet de relever des défis complexes en matière de santé.Dans ce commentaire, nous décrivons le concept de santé publique clinique, les types de problèmes complexes qui nécessitent une collaboration entre les professionnels responsables de la santé des individus et ceux responsables de la santé de la population, de même que les obstacles à la santé publique clinique et les applications de la santé publique clinique qui ont émergé pendant la pandémie de COVID-19. ArgumentaireIl existe une complémentarité entre la médecine clinique, qui est axée sur la santé des individus, et la santé publique, qui est axée sur la promotion et la protection de la santé des populations. Une collaboration entre ces deux disciplines est nécessaire pour résoudre les problèmes de santé complexes. Pour ce faire, toutefois, il convient de s’attaquer aux obstacles relatifs aux disciplines, ainsi qu’aux obstacles culturels et financiers qui empêchent une collaboration accrue et durable en la matière. Les succès récents, particulièrement durant la pandémie de COVID-19, constituent un modèle de collaboration de ce type entre cliniciens et praticiens en santé publique. ConclusionUne approche en matière de santé publique qui favorise une collaboration permanente entre cliniciens et professionnels en santé publique pour lutter contre des menaces sanitaires complexes aura plus d’impact que la somme de ses parties.

IntroductionEffective, sustained collaboration between clinical and public health professionals can lead to improved individual and population health. The concept of clinical public health promotes collaboration between clinical medicine and public health to address complex, real­world health challenges.In this commentary, we describe the concept of clinical public health, the types of complex problems that require collaboration between individual and population health, and the barriers towards and applications of clinical public health that have become evident during the COVID­19 pandemic. RationaleThe focus of clinical medicine on the health of individuals and the aims of public health to promote and protect the health of populations are complementary. Interdisciplinary collaborations at both levels of health interventions are needed to address complex health problems. However, there is a need to address the disciplinary, cultural and financial barriers to achieving greater and sustained collaboration. Recent successes, particularly during the COVID­19 pandemic, provide a model for such collaboration between clinicians and public health practitioners ConclusionA public health approach that fosters ongoing collaboration between clinical and public health professionals in the face of complex health threats will have greater impact than the sum of the parts.

Abstract Background In people and dogs, torasemide has higher bioavailability, longer half‐life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited. Objective To assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin‐angiotensin‐aldosterone system (RAAS). Animals Six clinically healthy adult European shorthair cats. Methods Randomized 4‐period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model. Results Mean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half‐life was 12.9 hours. Urine output significantly increased after torasemide administration (P

BackgroundPatients with rheumatic diseases are known to experience drug-related problems at various times during their treatment. As these problems can negatively influence patients’ health, they should be prevented or resolved as soon as possible, for which patients might benefit from additional support. Telehealth has the potential to continuously provide information and offers the possibility to easily contact a health care provider in order to support patients with medication use. Knowledge of factors influencing the patient’s preference for telehealth channels can improve the actual use of telehealth channels. ObjectiveThis study aims to identify factors that influence the preferences of patients with rheumatic diseases regarding telehealth channels for support with medication use. MethodsA qualitative study with face-to-face interviews was performed among patients with an inflammatory rheumatic disease in the Netherlands. A total of 4 telehealth channels were used: a frequently asked questions page, a digital human, an app for SMS text messaging with health care providers, and an app for video-calling with health care providers. Using a semistructured interview guide based on domains of the Capability, Opportunity, Motivation, and Behavior (COM-B) model, participants were questioned about (1) their general opinion on the 4 telehealth channels, (2) factors influencing preference for individual telehealth channels, and (3) factors influencing preference for individual telehealth channels in relation to the other available channels. Interviews were recorded, transcribed, and categorically analyzed. ResultsA total of 15 patients were interviewed (female: n=8, 53%; male: n=7, 47%; mean age 55, SD 16.8 years; median treatment duration of 41, IQR 12-106 months). The following 3 categories of factors influencing patient preference regarding telehealth channels were identified: (1) problem-related factors included problems needing a visual check, problems specifically related to the patient, and urgency of the problem; (2) patient-related factors included personal communication preference and patient characteristics; and (3) channel-related factors included familiarity with the telehealth channel, direct communication with a health care provider, methods of searching, and conversation history. ConclusionsPreference for telehealth channels is influenced by factors related to the problem experienced, the patient experiencing the problem, and telehealth channel characteristics. As the preference for telehealth channels varies between these categories, multiple telehealth channels should be offered to enable patients to tailor the support with their medication use to their needs.

We investigate the ultrafast response of crystalline Ge2Sb2Te5 nanoparticles (NPs) below the phase transformation threshold fluence. The observed rapid change of the optical response and the presence of coherent optical phonons are consistent with the relaxation dynamics in bulk Ge2Sb2Te5 films and, more importantly, occur within the same ultrafast timescales. We conclude that the benefit of the lower energy consumption of memories based on Ge-Sb-Te (GST) NPs aggregates, demonstrated by Casarin et al. (2018), occurs with no disadvantage, as the read/write speed can be as fast as in bulk GSTs.

Background Both aspiration and stent retriever thrombectomy are safe and effective in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation. Little is known on the outcomes of these techniques in patients with basilar artery occlusion. This study aimed to compare clinical, technical, and safety outcomes of aspiration and stent retriever thrombectomy as first‐line treatment for basilar artery occlusion in the BASICS (Basilar artery International Cooperation Study) trial. Methods For this post hoc analysis of the BASICS trial, all patients with a basilar artery occlusion who received endovascular treatment with either direct aspiration or stent retriever thrombectomy as first‐line approach were included. When both techniques were registered as first choice, patients were considered to have been treated with stent retriever. The primary outcome was favorable functional outcome, defined as a modified Rankin scale score of 0–3 at 90 days follow‐up, and analyzed using binary logistic regression analysis. Secondary outcomes included the modified Rankin scale score at 90 days (ranging from 0 to 6), procedure duration, mortality at 90 days, and symptomatic intracranial hemorrhage. Secondary outcomes were analyzed using binary, linear, or ordinal regression analyses. All analyses were adjusted for predefined variables. Results Among 158 BASICS patients treated with endovascular treatment,127 were treated with either stent retriever (N=67, 53%), or aspiration (N=60, 47%) as the first‐line treatment modality. We observed no significant difference in favorable functional outcome between patients treated with aspiration and stent retriever thrombectomy as first modality (adjusted odds ratio, 1.80; [95% CI, 0.68–4.76]). Also modified Rankin scale score at 90 days (adjusted common odds ratio, 0.62; [95% CI, 0.30–1.27]) and incidence of symptomatic intracranial hemorrhage (adjusted odds ratio, 0.61; [95% CI, 0.08–4.76]) showed no significant differences between both techniques. Procedure time was shorter with a median of 32 versus 47 minutes (26%; 95% CI, −42 to −6) and mortality rates at 90 days were lower (adjusted odds ratio, 0.36; [95% CI: 0.13–1.00]) in the direct aspiration group. Conclusions This study shows no difference in favorable functional outcome in patients with a basilar artery occlusion treated with direct aspiration compared with patients treated with stent retriever thrombectomy within the BASICS trial, despite a shorter procedure time and lower mortality rate at 90 days.

Background and purpose: Whether or not to resurface the patella during primary total knee arthroplasty (TKA) remains controversial. We aimed to investigate the association between patellar resurfacing and patient-reported outcome measure (PROM) improvement 1 year postoperatively in terms of physical functioning and pain following TKA. Patients and methods: We performed an observational study using the Dutch Arthroplasty Register on prospectively collected PROM data (n = 17,224, years 2014–2019). Preoperative and 1-year PROM pain scores (NRS at rest; during activity) and physical functioning scores (KOOS-PS, OKS) were examined. Stratification was performed for cruciate-retaining (CR) and posterior-stabilized (PS) and for the 4 most frequently used TKA implants in the Netherlands (Nexgen, Genesis II, PFC/Sigma, Vanguard) using multivariable linear regression adjusting for age, ASA classification, preoperative general health (EQ VAS), and preoperative PROMs. Results: 4,525 resurfaced and 12,699 unresurfaced patellae in TKA were analyzed. Overall, no significant difference in 1-year PROM improvement was found between the 2 groups. In CR TKAs, resurfacing resulted in less improvement in KOOS-PS and OKS (adjusted difference between groups (B) –1.68, 95% confidence interval (CI) –2.86 to –0.50 and B –0.94, CI –1.57 to –0.31. Fewer improvements for patellar resurfacing in TKA were found for the Genesis TKA on NRS pain at rest (B –0.23, CI–0.40 to –0.06) and Oxford knee score (B –1.61, CI –2.24 to –0.98). Conclusion: No significant differences were found in 1-year improvement of physical functioning and pain between TKA with resurfaced and unresurfaced patellae.

Background: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume. Materials and Methods: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICVcore and TBVcore. Associations between the core volume, ICVcore, TBVcore, and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy. Results: In 200 patients, the median core volume was 13 (5–41) mL. Median ICV and TBV were 1377 (1283–1456) mL and 1108 (1020–1197) mL. Median ICVcore and TBVcore were 0.9 (0.4–2.8)% and 1.7 (0.5–3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33–0.69]), ICVcore (acOR per IQR 0.50 [95%CI 0.35–0.69]), and TBVcore (acOR per IQR 0.41 95%CI 0.33–0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICVcore, and the TBVcore. Conclusion: Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.

Since the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, including several members of the sialic acid-binding receptor (SIGLEC) family. Here, we demonstrate that interaction between tumor cell-expressed sialic acids and SIGLEC-5/14 on neutrophils inhibits antibody-dependent cellular cytotoxicity (ADCC). We observed that conjugate formation and trogocytosis, both essential processes for neutrophil ADCC, were limited by the sialic acid-SIGLEC-5/14 interaction. During neutrophil-tumor cell conjugate formation, we found that inhibition of the interaction between tumor-expressed sialic acids and SIGLEC-5/14 on neutrophils increased the CD11b/CD18 high affinity conformation. By dynamic acoustic force measurement, the binding between tumor cells and neutrophils was assessed. The interaction between SIGLEC-5/14 and the sialic acids was shown to inhibit the CD11b/CD18-regulated binding between neutrophils and antibody-opsonized tumor cells. Moreover, the interaction between sialic acids and SIGLEC-5/14-consequently hindered trogocytosis and tumor cell killing. In summary, our results provide evidence that the sialic acid-SIGLEC-5/14 interaction is an additional target for innate checkpoint blockade in the tumor microenvironment.

Evolution of magnetic resonance imaging (MRI) findings in horses with sagittal groove disease (SGD) of the proximal phalanx is relatively sparsely described. This retrospective, descriptive, longitudinal study describes the findings of sequential low-field MRI fetlock examinations in horses with SGD of the proximal phalanx using a classification system. Twenty-nine horses were included, predominantly warmbloods used for show jumping (79%). For 29 limbs re-examined during the initial rehabilitation period, classification remained constant (n = 18), increased (n = 2), decreased (n = 7), and fluctuated (n = 2). Notably, two limbs with initial classification 4b (bone oedema-like signal with subchondral microfissure) and one with 4c (bone oedema-like signal with subchondral demineralisation) progressed to classification 5 (incomplete macrofissure/fracture), highlighting their potential as prodromal or imminent fissure pathology. Following conservative (n = 28) and surgical (n = 1) treatment, 86% of the horses re-entered full training and competition with a mean ± sd recovery time of 9.4 ± 4.4 months. In total, 20% of horses in the study subsequently presented for repeat MRI due to recurrent lameness after resuming full work, with classification that was the same (n = 2), increased (n = 2), or decreased (n = 2) compared with the last scan. This study underscores the variability in progression of SGD MRI findings, emphasising the need for further larger-scale research into patterns of progression.

Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.

Abstract Background Unintentional changes to patients’ medicine regimens and drug non-adherence are discovered by medication reconciliation. High numbers of outpatient visits and medication reconciliation being time-consuming, make it challenging to perform medication reconciliation for all outpatients. Therefore, we aimed to get insight into the proportion of outpatient visits in which information obtained with medication reconciliation led to additional drug-related actions. Methods In October and November 2018, we performed a cross-sectional observational study at the rheumatology outpatient clinic. Based on a standardized data collection form, outpatient visits were observed by a pharmacy technician trained to observe and report all drug-related actions made by the rheumatologist. Afterwards, the nine observed rheumatologists and an expert panel, consisting of two rheumatologists and two pharmacists, were individually asked which drug information reported on the drug list composed by medication reconciliation was required to perform the drug-related actions. The four members of the expert panel discussed until consensus was reached about their assessment of the required information. Subsequently, a researcher determined if the required information was available in digital sources: electronic medical record (electronic prescribing system plus physician’s medical notes) or Dutch Nationwide Medication Record System. Results Of the 114 selected patients, 83 (73%) patients were included. If both digital drug sources were available, patient’s input during medication reconciliation resulted in additional information to perform drug-related actions according to the rheumatologist in 0% of the visits and according to the expert panel in 14%. If there was only access to the electronic medical record, the proportions were 8 and 29%, respectively. Patient’s input was especially required for starting a new drug and discussing drug-related problems. Conclusions If rheumatologists only had access to the electronic medical record, in 1 out of 3 visits the patient provided additional information during medication reconciliation which was required to perform a drug-related action. When rheumatologists had access to two digital sources, patient’s additional input during medication reconciliation was at most 14%. As the added value of patient’s input was highest when rheumatologists prescribe a new drug and/or discuss a drug-related problem, it may be considered that rheumatologists only perform medication reconciliation during the visit when performing one of these actions.

Abstract Background Results of ACL reconstruction are influenced by both patient and surgical variables. Until now a significant amount of studies have focused on the influence of surgical technique on primary outcome, often leaving patient variables untouched. This study investigates the combined influence of patient and surgical variables through multivariate analysis. Methods Single-center retrospective cohort study. All patients who underwent primary ACL hamstring reconstruction within a 5-year period were included. Patient characteristics (gender, age, height, weight, BMI at time of surgery) and surgical variables (surgical technique, concomitant knee injury, graft diameter, type of femoral and tibial fixation) were collected. Patients were asked about Tegner Activity Scale (TAS), complications and revision surgery. Multivariate logistic regression was used to study risk factors. First graft failure and potential risk factors (patient and surgical) were univariately assessed. Risk factors with a p-value ≤ 0.05 were included in the multivariate model. Results Six hundred forty-seven primary ACL hamstring reconstructions were included. There were 41 graft failures (failure rate 6.3%). Patient gender, age, height and preoperative TAS had a significant influence on the risk of failure in the univariate analysis. The multivariate analyses showed that age and sex remained significant independent risk factors. Patients with a failed ACL reconstruction were younger (24.3 vs 29.4 years, OR 0.937), with women at a lower risk for failure of their ACL reconstruction (90.2% males vs 9.8% females, female OR 0.123). ACL graft diameter and other surgical variables aren’t confounders for graft failure. Conclusion This study shows that patient variables seem to have a larger influence on the failure rate of ACL hamstring reconstructive surgery than surgical variables. Identification of the right patient variables can help us make more informed decisions for our patients and create patient-specific treatment protocols. Young men’s higher risk of failure suggests that these patients may benefit from a different reconstruction technique, such as use of a patellar tendon or combined ligament augmentation. Level of evidence Retrospective cohort III.

Abstract Background Adoption of a personal health record (PHR) depends on its usability and perceived usefulness. Therefore, we aimed to assess the usability and perceived usefulness of an online PHR used for medication reconciliation and to assess the association between patient-, clinical-, hospital-, and ICT-related factors and the usability and perceived usefulness at both the in- and outpatient clinics. Methods A multicenter cross-sectional study was conducted with patients with either an outpatient visit (rheumatology ward) or planned admission in the hospital (cardiology, neurology, internal medicine or pulmonary wards). All patients received an invitation to update their medication list in the PHR 2 weeks prior to their appointment. One month after the hospital visit, PHR-users were asked to rate usability (using the System Usability Scale (SUS)) and perceived usefulness on a 5-point Likert scale. The usability and perceived usefulness were classified according to the adjective rating scale of Bangor et al. The usability was furthermore dichotomized in the categories: low (SUS between 0 and 51) and good (SUS 51–100) usability. Associations between patient-, clinical-, hospital-, and ICT-related factors and the usability and perceived usefulness were analysed. Results 255 of the 743 invited PHR-users completed the questionnaire. 78% inpatients and 83% outpatients indicated that usability of the PHR was good. There were no significant association between patient-, clinical-, hospital-, and ICT-related factors and the usability of the PHR. The majority of the patients (57% inpatients and 67% outpatients) classified perceived usefulness of the PHR as good, excellent, or best imaginable. Outpatients who also used the PHR for other drug related purposes reported a higher perceived usefulness (adjusted odds ratio 20.0; 95% confidence interval 2.36–170). Besides that, there was no significant association between patient-, clinical-, hospital-, and ICT-related factors and the perceived usefulness of the PHR. Conclusions The majority of the patients indicated that the PHR for medication reconciliation was useful and easy to use, but there is still room for improvement. To improve the intervention, further research should explore patients’ barriers and facilitators of using a PHR for medication reconciliation.