The course of readmission in frail older cardiac patients

Aim: The aim of this study is to explore patients' and (in)formal caregivers' perspectives on their role(s) and contributing factors in the course of unplanned hospital readmission of older cardiac patients in the Cardiac Care Bridge (CCB) program. Design: This study is a qualitative multiple case study alongside the CCB randomized trial, based on grounded theory principles. Methods: Five cases within the intervention group, with an unplanned hospital readmission within six months after randomization, were selected. In each case, semi-structured interviews were held with patients (n = 4), informal caregivers (n = 5), physical therapists (n = 4), and community nurses (n = 5) between April and June 2019. Patients' medical records were collected to reconstruct care processes before the readmission. Thematic analysis and the six-step analysis of Strauss & Corbin have been used. Results: Three main themes emerged. Patients experienced acute episodes of physical deterioration before unplanned hospital readmission. The involvement of (in)formal caregivers in adequate observation of patients' health status is vital to prevent rehospitalization (theme 1). Patients and (in)formal caregivers' perception of care needs did not always match, which resulted in hampering care support (theme 2). CCB caregivers experienced difficulties in providing care in some cases, resulting in limited care provision in addition to the existing care services (theme 3). Conclusion: Early detection of deteriorating health status that leads to readmission was often lacking, due to the acuteness of the deterioration. Empowerment of patients and their informal caregivers in the recognition of early signs of deterioration and adequate collaboration between caregivers could support early detection. Patients' care needs and expectations should be prioritized to stimulate participation. Impact: (In)formal caregivers may be able to prevent unplanned hospital readmission of older cardiac patients by ensuring: (1) early detection of health deterioration, (2) empowerment of patient and informal caregivers, and (3) clear understanding of patients' care needs and expectations

Genome-wide association study of regional brain volume suggests involvement of known psychiatry candidate genes, identified new candidates for psychiatric disorders and points to potential modes of their action

Though most psychiatric disorders are highly heritable, it has been hard to identify genetic risk factors involved, which are most likely of small individual effect size. A possible way to aid identification of risk genes is the use of intermediate phenotypes. These are supposed to be closer to the biological substrate(s) of the disorder than psychiatric diagnoses, and therefore less genetically complex. Intermediate phenotypes can be defined e. g. at the level of brain function and of regional brain structure. Both are highly heritable, and regional brain structure is linked to brain function. Within the Brain Imaging Genetics (BIG) study at the Radboud University Nijmegen (Medical Centre) we performed a genome-wide association study (GWAS) in 1000 of the currently 1400 healthy study participants. For all BIG participants, structural MRI brain images were available. Gray and white matter volumes were determined by brain segmentation using SPM software. FSL-FIRST was used to assess volumes of specific brain structures. Genotyping was performed on Affymetrix 6.0 arrays. Results implicate known candidates from earlier GWAS and candidate gene studies in mental disorders in the regulation of regional brain structure. E. g. polymorphisms in CDH13, featuring among the top-findings of GWAS in disorders including ADHD, addiction and schizophrenia, were found associated with amygdala volume. The ADHD candidate gene SNAP25 was found associated with total brain volume. In conclusion, the use of intermediate phenotypes based on (subcortical) brain volumes may shed more light on pathways from genes to diseases, but can also be expected to facilitate gene identification in psychiatric disorders

Identifying Biomarkers in Lymph Node Metastases of Esophageal Adenocarcinoma for Tumor-Targeted Imaging

INTRODUCTION: Tumor-targeted imaging is a promising technique for the detection of lymph node metastases (LNM) and primary tumors. It remains unclear which biomarker is the most suitable target to distinguish malignant from healthy tissue in esophageal adenocarcinoma (EAC). OBJECTIVE: We performed an immunohistochemistry study to identify viable tumor markers for tumor-targeted imaging of EAC. METHODS: We used samples from 72 patients with EAC to determine the immunohistochemical expression of ten potential tumor biomarkers for EAC (carbonic anhydrase IX [CA-IX], carcinoembryonic antigen [CEA], hepatic growth factor receptor, epidermal growth factor receptor, epithelial membrane antigen [EMA], epithelial cell adhesion molecule [EpCAM], human epidermal growth factor receptor 2 [HER-2], urokinase plasminogen activator receptor, vascular endothelial growth factor-A [VEGF-A], and VEGF receptor 2). Immunohistochemistry was performed on tissue microarrays of LNM (n = 48), primary EACs (n = 62), fibrotic tissues (n = 11), nonmalignant lymph nodes (n = 24), and normal esophageal and gastric tissues (n = 40). Tumor marker staining was scored on intensity and percentage of positive cells. RESULTS: EMA and EpCAM showed strong expression in LNM (> 95%) and primary EACs (> 95%). Significant expression was also observed for LNM and EAC using VEGF-A (85 and 92%), CEA (68 and 54%), and CA-IX (4 and 34%). The other tumor biomarkers showed expression of 0-15% for LNM and primary EAC. Except for VEGF-A, nonmalignant lymph node staining was scored as slight or absent. CONCLUSIONS: High expression rates and correlation between LNM in EAC combined with low expression rates in healthy lymph nodes and esophagus tissues were observed for EpCAM and CEA, meaning these are promising targets for tumor-targeted imaging approaches for lymph nodes in patients with EAC

Dutch GP healthcare consumption in COVID-19 heterogeneous regions:An interregional time-series approach in 2020-2021

Background Many countries observed a sharp decline in the use of general practice services after the outbreak of the COVID-19 pandemic. However, research has not yet considered how changes in healthcare consumption varied among regions with the same restrictive measures but different COVID-19 prevalence.Aim To investigate how the COVID-19 pandemic affected healthcare consumption in Dutch general practice during 2020 and 2021, among regions with known heterogeneity in COVID-19 prevalence, from a pre-pandemic baseline in 2019.Design Population-based cohort study using electronic health records.Setting Dutch general practices involved in regional research networks.MethodsInterrupted time-series analysis of changes in healthcare consumption from before to during the pandemic. Descriptive statistics on the number of potential COVID-19 related contacts, reason for contact and type of contact.Results The study covered 3 627 597 contacts (425 639 patients), 3 532 693 contacts (433 340 patients), and 4 134 636 contacts (434 872 patients) in 2019, 2020, and 2021, respectively. Time-series analysis revealed a significant decrease in healthcare consumption after the outbreak of the pandemic. Despite interregional heterogeneity in COVID-19 prevalence, healthcare consumption decreased comparably over time in the three regions, before rebounding to a level significantly higher than baseline in 2021. Physical consultations transitioned to phone or digital over time.Conclusions Healthcare consumption decreased irrespective of the regional prevalence of COVID-19 from the start of the pandemic, with the Delta variant triggering a further decrease. Overall, changes in care consumption appeared to reflect contextual factors and societal restrictions rather than infection rates

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

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Application of stochastic programming to reduce uncertainties in quality-based supply planning of slaughterhouses

To match products of different quality with end market preferences under supply uncertainty, it is crucial to integrate product quality information in logistics decision making. We present a case of this integration in a meat processing company that faces uncertainty in delivered livestock quality. We develop a stochastic programming model that exploits historical product quality delivery data to produce slaughterhouse allocation plans with reduced levels of uncertainty in received livestock quality. The allocation plans generated by this model fulfil demand for multiple quality features at separate slaughterhouses under prescribed service levels while minimizing transportation costs. We test the model on real world problem instances generated from a data set provided by an industrial partner. Results show that historical farmer delivery data can be used to reduce uncertainty in quality of animals to be delivered to slaughterhouses

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R2* pixel maps were produced for each tumour and at each time point and changes in R2* induced by carbogen were determined. There was a mean reduction in R2* of 6.4% (P=0.003) for DU145 xenografts and 5.8% (P=0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R2* during carbogen inhalation with a mean reduction of 21.6% (P=0.0005). Decreases in prostate tumour R2* in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae