Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital

BACKGROUND: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. METHOD: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. RESULTS: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. CONCLUSION: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program

“<i>I do it because they do it</i>”:social-neutralisation in information security practices of Saudi medical interns

Successful implementation of information security policies (ISP) and IT controls play an important role in safeguarding patient privacy in healthcare organizations. Our study investigates the factors that lead to healthcare practitioners' neutralisation of ISPs, leading to non-compliance. The study adopted a qualitative approach and conducted a series of semi-structured interviews with medical interns and hospital IT department managers and staff in an academic hospital in Saudi Arabia. The study's findings revealed that the MIs imitate their peers' actions and employ similar justifications when violating ISP dictates. Moreover, MI team superiors' (seniors) ISP non-compliance influence MIs tendency to invoke neutralisation techniques. We found that the trust between the medical team members is an essential social facilitator that motivates MIs to invoke neutralisation techniques to justify violating ISP policies and controls. These findings add new insights that help us to understand the relationship between the social context and neutralisation theory in triggering ISP non-compliance

Reverse Engineering the Yeast RNR1 Transcriptional Control System

Transcription is controlled by multi-protein complexes binding to short non-coding regions of genomic DNA. These complexes interact combinatorially. A major goal of modern biology is to provide simple models that predict this complex behavior. The yeast gene RNR1 is transcribed periodically during the cell cycle. Here, we present a pilot study to demonstrate a new method of deciphering the logic behind transcriptional regulation. We took regular samples from cell cycle synchronized cultures of Saccharomyces cerevisiae and extracted nuclear protein. We tested these samples to measure the amount of protein that bound to seven different 16 base pair sequences of DNA that have been previously identified as protein binding locations in the promoter of the RNR1 gene. These tests were performed using surface plasmon resonance. We found that the surface plasmon resonance signals showed significant variation throughout the cell cycle. We correlated the protein binding data with previously published mRNA expression data and interpreted this to show that transcription requires protein bound to a particular site and either five different sites or one additional sites. We conclude that this demonstrates the feasibility of this approach to decipher the combinatorial logic of transcription

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported. We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected. The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated

Pseudotumoural soft tissue lesions of the hand and wrist: a pictorial review

Mimickers of soft tissue tumours in the hand and wrist are more frequent than true neoplastic lesions. Pseudotumours belong to a large and heterogeneous group of disorders, varying from normal anatomical variants, cystic lesions, post-traumatic lesions, skin lesions, inflammatory and infectious lesions, non-neoplastic vascular lesions, metabolic disorders (crystal deposition disease and amyloidosis) and miscellaneous disorders. Although the imaging approach to pseudotumoural lesions is often very similar to the approach to “true” soft tissue tumoral counterparts, further management of these lesions is different. Biopsy should be performed only in doubtful cases, when the diagnosis is unclear. Therefore, the radiologist plays a pivotal role in the diagnosis of these lesions. Awareness of the normal anatomy and existence and common imaging presentation of these diseases, in combination with relevant clinical findings (clinical history, age, location and skin changes), enables the radiologist to make the correct diagnosis in most cases, thereby limiting the need for invasive procedures

Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation

Analysis of Endocytic Pathways in Drosophila Cells Reveals a Conserved Role for GBF1 in Internalization via GEECs

In mammalian cells, endocytosis of the fluid phase and glycosylphosphatidylinositol-anchored proteins (GPI-APs) forms GEECs (GPI-AP enriched early endosomal compartments) via an Arf1- and Cdc42-mediated, dynamin independent mechanism. Here we use four different fluorescently labeled probes and several markers in combination with quantitative kinetic assays, RNA interference and high resolution imaging to delineate major endocytic routes in Drosophila cultured cells. We find that the hallmarks of the pinocytic GEEC pathway are conserved in Drosophila and identify garz, the fly ortholog of the GTP exchange factor GBF1, as a novel component of this pathway. Live confocal and TIRF imaging reveals that a fraction of GBF1 GFP dynamically associates with ABD RFP (a sensor for activated Arf1 present on nascent pinosomes). Correspondingly, a GTP exchange mutant of GBF1 has altered ABD RFP localization in the evanescent field and is impaired in fluid phase uptake. Furthermore, GBF1 activation is required for the GEEC pathway even in the presence of Brefeldin A, implying that, like Arf1, it has a role in endocytosis that is separable from its role in secretion

Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility

A Survey of Bayesian Statistical Approaches for Big Data

The modern era is characterised as an era of information or Big Data. This has motivated a huge literature on new methods for extracting information and insights from these data. A natural question is how these approaches differ from those that were available prior to the advent of Big Data. We present a review of published studies that present Bayesian statistical approaches specifically for Big Data and discuss the reported and perceived benefits of these approaches. We conclude by addressing the question of whether focusing only on improving computational algorithms and infrastructure will be enough to face the challenges of Big Data