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Objectives: Timely detection and diagnosis of dementia are beneficial for providing appropriate, anticipatory care and preventing acute situations. However, initiating diagnostic testing is a complex and dynamic process that requires general practitioners (GPs) to balance competing priorities. Previously identified barriers, such as a lack of time, knowledge, and resources, may not fully represent the challenges involved in this process. Therefore, this study aimed to examine GPs' more implicit considerations on starting the diagnostic trajectory for dementia. Methods: A qualitative study was conducted using semi‐structured interviews with 14 Dutch GPs who were purposively selected through maximum variation sampling. The interview transcripts were inductively analyzed in multiple rounds by a multidisciplinary research team using thematic analysis. Results: GPs' considerations on starting the diagnostic trajectory for dementia can be summarized in three main themes that are interconnected: (1) 'the presumed patient's willingness', that is, facing a dilemma of wanting to respect patient autonomy in cases of denial or an absence of a diagnostic request, while at the same time identifying a problem and feeling the urgency to act; (2) 'the GP's attempt not to harm', that is, balancing between not wanting to harm the patient and/or relatives with the burdensome label of dementia and with the possible negative consequences of a late diagnosis; and (3) 'time, trust, and interprofessional collaboration influence timeliness of diagnostic work‐up', that is, time available for consultations, time as a diagnostic factor, GP's diagnostic confidence, and trustful physician–patient relationship. Conclusions: This study revealed that important ethical dilemmas regarding patient autonomy and the principle of doing no harm lie behind practical GP barriers to initiating diagnostic testing for dementia. Time, trust, and interprofessional collaboration were found to facilitate GPs in determining the right decision and timing with each individual patient and their relatives. Future research could explore the value of diagnostic decision aids that explicitly involve patients and their relatives in this balancing act. [ABSTRACT FROM AUTHOR]

The effect of cold-rolling on the microstructure and molten salt corrosion behaviour of 316L alloy was investigated. Corrosion tests were performed in FLiNaK salt at 600 °C for 300 h. The present results indicate that cold-rolling leads to enhanced corrosion in molten salt despite its beneficial effect on the alloys mechanical properties. It is shown that the corrosion resistance of cold-rolled 316L alloy is largely governed by the presence of high-angle grain boundaries (HAGBs) and geometrically-necessary dislocations (GNDs). Exacerbated corrosion is thus directly related to the increased prevalence of grain boundaries and dislocations within the microstructure.

The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort – all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort (h2 = 0.10, 95% CI 0.00–0.69) and stronger evidence in the second cohort (h2 = 0.56, 95% CI 0.23–0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort (h2serotype = 0.07, 95% CI 0.04–0.14 and h2GPSC = 0.06, 95% CI 0.03–0.13) and the second cohort (h2serotype = 0.11, 95% CI 0.05–0.21 and h2GPSC = 0.20, 95% CI 0.12–0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10-9) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations.

Streptococcus suis is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for S. suis infection. We created Tn-Seq libraries in a virulent S. suis strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in ex vivo models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in S. suis pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.

Objective To evaluate the perceived quality of follow-up telephone consultations (TCs) from the perspective of patients and healthcare professionals (HCPs) of multiple medical disciplines during the COVID-19 pandemic.Design A qualitative study using semi-structured interviews and reflexive thematic analysis.Setting Seven medical disciplines (general dermatology, dermato-oncology, head and neck oncology, internal medicine, medical oncology, gynaecological oncology and surgical oncology) at a large university hospital in the Netherlands.Participants Patients who received and HCPs who provided TCs as a substitute for outpatient follow-up appointments during the COVID-19 pandemic.Results Eighty-two patients and 58 HCPs were interviewed. Predominantly, patients and HCPs were satisfied with the quality of care by TCs. They regarded TCs as efficient, accessible and of acceptable quality, provided there was an established patient-HCP relationship, medical complaints were absent and physical examination was not indicated. However, most patients were worried about the accuracy of their health assessment in the absence of physical examination and non-verbal communication. Both patients and HCPs wish to use TCs in the future alternatively with face-to-face consultations.Conclusion This study concludes that TCs seem a valuable contribution to the context of follow-up care and could partially replace face-to-face consultations. TCs can be performed in stable, chronic patients with whom a doctor-patient relationship has already been established. Face-to-face consultations are considered more appropriate in the case of new patients, challenging or emotionally charged consultations and when clinically relevant physical examination is indicated. Due to the context-dependent nature of experiences of patients and HCPs, TCs should be used with an individually customised approach based on patient and disease specifics, in which shared decision-making plays an extensive role. Before major implementation is considered, sufficient data on the safety regarding missed diagnoses or cancer recurrences should be assembled first.

BackgroundAs the number of cancer survivors is increasing, it is important to be able to offer exercise and physical activity (PA)–promoting interventions that are both effective and reasonably accessible. Internet-based interventions are typically less expensive and more accessible alternatives to on-site supervised interventions. Currently, little is known about the characteristics of nonparticipants in PA promotion trials in the cancer survivorship setting, both in general and specifically in trials using internet-supported interventions. ObjectiveThis study aims to gain insight into the characteristics associated with nonparticipation in a blended internet-based supported intervention trial to promote PA. MethodsBreast and prostate cancer survivors, 3-36 months after primary curative treatment, were invited to participate in the PABLO trial; this trial compared an internet-based intervention to enhance PA levels, with or without additional support from a physical therapist, to usual care. Participants and nonparticipants were asked to complete a comprehensive questionnaire assessing sociodemographics, fatigue, and health-related quality of life. Baseline data for participants and nonparticipants were compared using the independent Student t test and chi-square test. ResultsThe inclusion rate in the trial was 11.03% (137/1242). Of the nonparticipants, 13.95% (154/1104) completed the questionnaire. Participants were more highly educated (P=.04), had a paid job less often (P=.03), and were on sick leave more often (P=.03). They reported less PA per week, both moderate (P=.03) and vigorous (P

Since no uniform treatment protocol for pancreatic irreversible electroporation (IRE) exists, the heterogeneity throughout literature complicates the comparison of results. To reach agreement among experts, a consensus study was performed. Eleven experts, recruited according to predefined criteria regarding previous IRE publications, participated anonymously in three rounds of questionnaires according to a modified Delphi technique. Consensus was defined as having reached ≥80% agreement. Response rates were 100, 64, and 64% in rounds 1 to 3, respectively; consensus was reached in 93%. Pancreatic IRE should be considered for stage III pancreatic cancer and inoperable recurrent disease after previous local treatment. Absolute contraindications are ventricular arrhythmias, implantable stimulation devices, congestive heart failure NYHA class 4, and severe ascites. The inter-electrode distance should be 10 to 20 mm and the exposure length should be 15 mm. After 10 test pulses, 90 treatment pulses of 1,500 V/cm should be delivered continuously, with a 90-µs pulse length. The first postprocedural contrast-enhanced computed tomography should take place 1 month post-IRE, and then every 3 months. This article provides expert recommendations regarding patient selection, procedure, and follow-up for IRE treatment in pancreatic malignancies through a modified Delphi consensus study. Future studies should define the maximum tumor diameter, response evaluation criteria, and the optimal number of preoperative FOLFIRINOX cycles. [ABSTRACT FROM AUTHOR]

Simple Summary: Image-guided tumor ablation has become an indispensable part of oncological care, with an increasing demand and need for novel implements to optimize treatment outcomes. The purpose of this pictorial essay was to illustrate the added value of intra-arterial contrast administration during CT-guided liver tumor ablation procedures. Eight clinical cases from three tertiary referral institutions demonstrate the ability to improve the conspicuity of the target liver tumor(s) and identify surrounding critical vascular structures, promptly detect 'vanished' and/or additional tumors, differentiate local tumor progression from non-enhancing scar tissue, and instantly detect and respond to iatrogenic hemorrhagic events. In conclusion, although at the cost of adding a minor but safe intervention, the use of an intra-arterial-administered contrast agent during a CT-guided thermal ablation procedure is a potential quality-improving real-time image-guiding method and should therefore be embedded in (inter)national standards of practice. With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect 'vanished' and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice. [ABSTRACT FROM AUTHOR]

Simple Summary: For patients diagnosed with metastatic colorectal cancer, having colorectal liver metastases along with metastases in other organs may be deemed a contraindication for local treatment with curative intent. This observational study investigates whether administering local treatment to all metastatic sites could enhance overall survival rates. A total of 941 patients were included, among whom were 60 patients with metastases in both the liver and other organ(s). Our findings reveal that although patients with both liver and extrahepatic metastases exhibited lower survival rates compared to those with solely liver metastases, a survival plateau emerged after approximately 6.2 years. This implies that comprehensive local treatment of all metastatic sites might confer benefits for long-term survival. These insights could impact decision making regarding the scope of local treatment for patients with colorectal cancer that have metastases in multiple organs. Background: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites. Methods: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS). Results: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029–2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017–3.841, p = 0.041). Conclusions: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis of the hand can lead to pain, stiffness, and deformation, and thus to functional disability. The purpose of this study was to compare short-term clinical outcomes of 2 silicone proximal interphalangeal (PIP) joint implants, NeuFlex and Integra, in patients with primary osteoarthritis. Methods: We included 72 PIP joints, of which 40 were replaced by a NeuFlex implant and 32 by an Integra implant. The average follow-up was 12 months for the Integra group and 16 months for the NeuFlex group. Results: There was no change in active flexion preoperatively and postoperatively. Extension lag and Disabilities of the Arm, Shoulder, and Hand score decreased substantially in both groups, whereas grip strength and Patient-Specific Functional Scale (PSFS) score increased. All patients were satisfied. Between groups, there was a significant difference in the PSFS score, in favor of the Integra group. Conclusions: Both implants have excellent results, but more research is needed with more patients to prevent bias and to determine the long-term outcome of these implants. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a causative agent of meningitis and bacteremia. In a combined pathogen and host GWAS, Lees et al. find that host genetic variation is associated with both susceptibility and severity of pneumococcal meningitis, and specific bacterial genetic variation associated with susceptibility.

Objectives:. The surprise question, “Would I be surprised if this patient died in the next 12 months?” is a tool to identify patients at high risk of death in the next year. Especially in the situation of an ICU admission, it is important to recognize patients who could and could not have the benefits of an intensive treatment in the ICU department. Design and Setting:. A single-center, prospective, observational cohort study was conducted between April 2013 and April 2018, in ICU Gelre hospitals, location Apeldoorn. Patients:. A total of 3,140 patients were included (57% male) with a mean age of 63.5 years. Seven-hundred thirteen patients (23%) died within 1 year. Interventions:. The physician answered three different surprise question’s with either “yes” or “no”: “I expect that the patient is going to survive the ICU admission” (surprise question 1), “I expect that the patient is going to survive the hospital stay” (surprise question 2), and “I expect that the patient is going to survive one year after ICU admission” (surprise question 3). We tested positive and negative predicted values of the surprise questions, the mean accuracy of the surprise questions, and kappa statistics. Measurements and Main Results:. The positive and negative predictive values of the surprise questions for ICU admission, hospital admission, and 1-year survival were, respectively, 64%/94%, 59%/92%, and 60%/86%. Accordingly, the mean accuracy and kappa statistics were 93% (95% CI, 92–94%), κ equals to 0.43, 89% (95% CI, 88–90%), κ equals to 0.40, and 81% (95% CI, 80–82%), κ equals to 0.43. Conclusions:. The frequently overlooked simple and cheap surprise question is probably an useful tool to evaluate the prognosis of acutely admitted critically ill patients.

Abstract Background Streptococcus pneumoniae is a commensal of the human upper respiratory tract and a major cause of morbidity and mortality worldwide. This paper presents the distribution of serotypes and antimicrobial resistance in commensal S. pneumoniae strains cultured from healthy carriers older than four years of age in nine European countries. Methods Nasal swabs from healthy persons (age between 4 and 107 years old) were obtained by general practitioners from each country from November 2010 to August 2011. Swabs were cultured for S. pneumoniae using a standardized protocol. Antibiotic resistance was determined for isolated S. pneumoniae by broth microdilution. Capsular sequencing typing was used to identify serotypes, followed by serotype-specific PCR assays in case of ambiguous results. Results Thirty-two thousand one hundred sixty-one nasal swabs were collected from which 937 S. pneumoniae were isolated. A large variation in serotype distribution and antimicrobial resistant serotypes across the participating countries was observed. Pneumococcal vaccination was associated with a higher risk of pneumococcal colonization and antimicrobial resistance independently of country and vaccine used, either conjugate vaccine or PPV 23). Conclusions Serotype 11A was the most common in carriage followed by serotypes 23A and 19A. The serotypes showing the highest resistance to penicillin were 14 followed by 19A. Serotype 15A showed the highest proportion of multidrug resistance.

Abstract Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3 cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3 cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion If thermal ablation proves to be non-inferior in treating lesions ≤3 cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration NCT03088150, January 11th 2017.

The aim of this study was to assess primary tumor sidedness of colorectal cancer (CRC), rat sarcoma viral oncogene homolog (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and microsatellite instability (MSI) status as prognostic factors predicting complications, survival outcomes, and local tumor progression (LTP) following surgery and thermal ablation in patients with colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study included 520 patients, 774 procedures, and 2101 tumors undergoing local treatment (resection and/or thermal ablation) from 2000 to 2021. Outcomes following local treatment were analyzed for primary tumor sidedness of CRC, RAS, and BRAF mutations and MSI status. The Kaplan–Meier method was used to estimate local tumor progression-free survival (LTPFS), local control (LC), distant progression-free survival (DPFS), and overall survival (OS). Uni- and multivariable analyses were performed based on Cox proportional hazards model. The chi-square test was used to analyze complications. Complications (p = 0.485), OS (p = 0.252), LTPFS (p = 0.939), and LC (p = 0.423) was not associated with tumor-sidedness. Compared to right-sided colon cancer (CC) (reference HR 1.000), DPFS was superior for left-sided CC and rectal cancer (p = 0.018) with an HR for left-sided CC of 0.742 (95% CI, 0.596–0.923) and for RC of 0.760 (95% CI, 0.597–0.966). Regarding RAS mutations, no significant difference was found in OS (p = 0.116). DPFS (p = 0.001), LTPFS (p = 0.039), and LC (p = 0.025) were significantly lower in the RAS mutation group. Though no difference in LTPFS was found between RAS wildtype and RAS mutated CRLM following resection (p = 0.532), LTPFS was worse for RAS mutated tumors compared to RAS wildtype following thermal ablation (p = 0.037). OS was significantly lower in the BRAF mutation group (p < 0.001) and in the MSI group (p < 0.001) following local treatment, while both did not affect DPFS, LTPFS, and LC. This AmCORE based study suggests the necessity of wider margins to reduce LTP rates in patients with RAS mutated CRLM, especially for thermal ablation. Upfront knowledge regarding molecular biomarkers may contribute to improved oncological outcomes.