Functioning and health in patients with cancer on home-parenteral nutrition: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Malnutrition is a common problem in patients with cancer. One possible strategy to prevent malnutrition and further deterioration is to administer home-parenteral nutrition (HPN). While the effect on survival is still not clear, HPN presumably improves functioning and quality of life. Thus, patients' experiences concerning functioning and quality of life need to be considered when deciding on the provision of HPN. Currently used quality of life measures hardly reflect patients' perspectives and experiences. The objective of our study was to investigate the perspectives of patients with cancer on their experience of functioning and health in relation to HPN in order to get an item pool to develop a comprehensive measure to assess the impact of HPN in this population.</p> <p>Methods</p> <p>We conducted a series of qualitative semi-structured interviews. The interviews were analysed to identify categories of the International Classification of Functioning, Disability and Health (ICF) addressed by patients' statements. Patients were consecutively included in the study until an additional patient did not yield any new information.</p> <p>Results</p> <p>We extracted 94 different ICF-categories from 16 interviews representing patient-relevant aspects of functioning and health (32 categories from the ICF component 'Body Functions', 10 from 'Body Structures', 32 from 'Activities & Participation', 18 from 'Environmental Factors'). About 8% of the concepts derived from the interviews could not be linked to specific ICF categories because they were either too general, disease-specific or pertained to 'Personal Factors'. Patients referred to 22 different aspects of functioning improving due to HPN; mainly activities of daily living, mobility, sleep and emotional functions.</p> <p>Conclusions</p> <p>The ICF proved to be a satisfactory framework to standardize the response of patients with cancer on HPN. For most aspects reported by the patients, a matching concept and ICF category could be found. The development of categories of the component 'Personal Factors' should be promoted to close the existing gap when analyzing interviews using the ICF. The identification and standardization of concepts derived from individual interviews was the first step towards creating new measures based on patients' preferences and experiences which both catch the most relevant aspects of functioning and are sensitive enough to monitor change associated to an intervention such as HPN in a vulnerable population with cancer.</p

The ICF forms a useful framework for classifying individual patient goals in post-acute rehabilitation

OBJECTIVE: Timely goal setting in close collaboration with the patient is essential to successful rehabilitation. We therefore sought to identify goals of patients in early post-acute rehabilitation as predictors of improved functioning. DESIGN: We conducted a prospective multi-centre cohort study in 5 early post-acute rehabilitation facilities. PATIENTS: Patients with musculoskeletal, cardiopulmonary and neurological conditions were recruited between May 2005 and August 2008. METHODS: A semi-structured questionnaire was used to identify patient goals and to assess improvement in overall functioning. Patients' goals were coded according to the International Classification of Functioning, Disability and Health (ICF). By means of a mixed effects model we examined the association between goal attainment and improved functioning. RESULTS: A total of 116 patients gave 546 statements, of which 426 were linked to 74 ICF categories, which were assigned to the existing comprehensive post-acute ICF Core Sets. Improvements in walking, recreation and leisure, pain, and transfer were the most frequently reported goals. In multivariable analysis patients' goal attainment was not a predictor for improved overall functioning. CONCLUSION: The ICF can be used to identify and structure patients' goals. Patients' perspective should be considered in the rehabilitation process

Silentium! Run-Analyse-Eradicate the Noise out of the DB/OS Stack

When multiple tenants compete for resources, database performance tends to suffer. Yet there are scenarios where guaranteed sub-millisecond latencies are crucial, such as in real-time data processing, IoT devices, or when operating in safety-critical environments. In this paper, we study how to make query latencies deterministic in the face of noise (whether caused by other tenants or unrelated operating system tasks). We perform controlled experiments with an in-memory database engine in a multi-tenant setting, where we successively eradicate noisy interference from within the system software stack, to the point where the engine runs close to bare-metal on the underlying hardware. We show that we can achieve query latencies comparable to the database engine running as the sole tenant, but without noticeably impacting the workload of competing tenants. We discuss these results in the context of ongoing efforts to build custom operating systems for database workloads, and point out that for certain use cases, the margin for improvement is rather narrow. In fact, for scenarios like ours, existing operating systems might just be good enough, provided that they are expertly configured. We then critically discuss these findings in the light of a broader family of database systems (e.g. including disk-based), and how to extend the approach of this paper accordingly

Patterns of healthcare seeking among people reporting chronic conditions in rural sub-Saharan Africa: findings from a population-based study in Burkina Faso.

OBJECTIVE: Non-communicable diseases are rapidly becoming one of the leading causes of morbidity and mortality in sub-Saharan Africa. Yet, little is known about patterns of healthcare seeking among people with chronic conditions in these settings. We aimed to explore determinants of healthcare seeking among people who reported at least one chronic condition in rural Burkina Faso. METHODS: Data were drawn from a cross-sectional population-based survey conducted across 24 districts on 52 562 individuals from March to June 2017. We used multinomial logistic regression to assess factors associated with seeking care at a formal provider (facility-based care) or at an informal provider (home and traditional treatment) compared to no care. RESULTS: 1124 individuals (2% of all respondents) reported at least one chronic condition. Among those, 22.8% reported formal care use, 10.6% informal care use, and 66.6% no care. The presence of other household members reporting a chronic condition (RRR = 0.57, 95%-CI [0.39, 0.82]) was negatively associated with seeking formal care. Wealthier households (RRR = 2.14, 95%-CI [1.26, 3.64]), perceived illness severity (RRR = 3.23, 95%-CI [2.22, 4.70]) and suffering from major chronic conditions (RRR = 1.54, 95%-CI [1.13, 2.11]) were positively associated with seeking formal care. CONCLUSION: Only a minority of individuals with chronic conditions sought formal care, with important differences due to socio-economic status. Policies and interventions aimed at increasing the availability and affordability of services for early detection and management in peripheral settings should be prioritised

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Effects of Weight Loss on Glutathione Peroxidase 3 Serum Concentrations and Adipose Tissue Expression in Human Obesity

Background/Aims: Altered expression and circulating levels of glutathione peroxidase 3 (GPX3) have been observed in obesity and type 2 diabetes (T2D) across species. Here, we investigate whether GPX3 serum concentrations and adipose tissue (AT) GPX3 mRNA expression are related to obesity and weight loss. Methods: GPX3 serum concentration was measured in 630 individuals, including a subgroup (n = 293) for which omental and subcutaneous (SC) GPX3 mRNA expression has been analyzed. GPX3 analyses include three interventions: 6 months after bariatric surgery (n = 80) or combined exercise/hypocaloric diet (n = 20) or two-step bariatric surgery (n = 24) studies. Results: Bariatric surgery-induced weight loss (–25.8 ± 8.4%), but not a moderate weight reduction of –8.8 ± 6.5% was associated with significantly reduced GPX3 serum concentrations. GPX3 mRNA is significantly higher expressed in AT from individuals with normal glucose metabolism compared to T2D patients. SC AT GPX3 expression is significantly higher in lean compared to obese as well as in insulin-sensitive compared insulin-resistant individuals with obesity. Weight loss after bariatric surgery causes a significant increase in SC AT GPX3 expression. AT GPX3 expression significantly correlates with age, BMI, fat distribution, insulin sensitivity (only SC AT), but not with circulating GPX3. Conclusion: Our data support the notion that SC AT GPX3 expression is associated with obesity, fat distribution and related to whole body insulin resistance

EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation

<p>Abstract</p> <p>Background</p> <p>Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed <it>EFS </it>(<it>embryonal Fyn-associated substrate</it>) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated <it>EFS </it>promoter region CpG island in tumor classification and metastatic progression.</p> <p>Methods</p> <p><it>EFS </it>methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients.</p> <p>Results</p> <p>Analysis of 16 UM showed full methylation of the <it>EFS </it>CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with <it>EFS </it>methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with <it>EFS </it>methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of <it>EFS </it>mRNA expression with <it>EFS </it>methylation in UM. We further found that <it>EFS </it>methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. <it>EFS </it>methylation always affects both alleles in normal and tumor samples.</p> <p>Conclusions</p> <p>Biallelic <it>EFS </it>methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The <it>EFS </it>methylation of a UM may depend on which type of precursor cell the tumor originated from.</p

Multifactorial Regulation of a Hox Target Gene

Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior–posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo

Patients' functioning as predictor of nursing workload in acute hospital units providing rehabilitation care: a multi-centre cohort study

<p>Abstract</p> <p>Background</p> <p>Management decisions regarding quality and quantity of nurse staffing have important consequences for hospital budgets. Furthermore, these management decisions must address the nursing care requirements of the particular patients within an organizational unit. In order to determine optimal nurse staffing needs, the extent of nursing workload must first be known. Nursing workload is largely a function of the composite of the patients' individual health status, particularly with respect to functioning status, individual need for nursing care, and severity of symptoms. The International Classification of Functioning, Disability and Health (ICF) and the derived subsets, the so-called ICF Core Sets, are a standardized approach to describe patients' functioning status. The objectives of this study were to (1) examine the association between patients' functioning, as encoded by categories of the Acute ICF Core Sets, and nursing workload in patients in the acute care situation, (2) compare the variance in nursing workload explained by the ICF Core Set categories and with the Barthel Index, and (3) validate the Acute ICF Core Sets by their ability to predict nursing workload.</p> <p>Methods</p> <p>Patients' functioning at admission was assessed using the respective Acute ICF Core Set and the Barthel Index, whereas nursing workload data was collected using an established instrument. Associations between dependent and independent variables were modelled using linear regression. Variable selection was carried out using penalized regression.</p> <p>Results</p> <p>In patients with neurological and cardiopulmonary conditions, selected ICF categories and the Barthel Index Score explained the same variance in nursing workload (44% in neurological conditions, 35% in cardiopulmonary conditions), whereas ICF was slightly superior to Barthel Index Score for musculoskeletal conditions (20% versus 16%).</p> <p>Conclusions</p> <p>A substantial fraction of the variance in nursing workload in patients with rehabilitation needs in the acute hospital could be predicted by selected categories of the Acute ICF Core Sets, or by the Barthel Index score. Incorporating ICF Core Set-based data in nursing management decisions, particularly staffing decisions, may be beneficial.</p