Which patients are assessed by lung cancer nurse specialists? A national lung cancer audit study of over 128,000 patients across England

Background: Lung cancer nurse specialists (LCNS) are integral to the multidisciplinary clinical team, providing personalised physical and psycho-social interventions, and care management for people with lung cancer. The National Institute of Health and Care Excellence (NICE) recommend that all patients have access to a LCNS. We conducted a national study assessing whether there is variation in access to and timing of LCNS assessment. Methods: The National Cancer Action Team’s LCNS workforce census in England was linked with patient and hospital Trust data from the English National Lung Cancer Audit. Multivariate logistic regression was used to assess features associated with LCNS assessment. Results: 128,124 lung cancer patients were seen from 2007 to 2011. LCNS assessment confirmation was ‘yes’ in 62%, ‘no’ in 6% and ‘missing’ in 32%. Where (in clinic versus ward) and when (before versus after diagnosis) patients were assessed by a LCNS also varied. Older patients with poor performance status, early cancer stage, and comorbidities were less likely to be assessed; there was no difference with sex or socioeconomic group. Patients receiving any anti-cancer treatment were more likely to be assessed. Assessment was lower in Trusts with high annual patient numbers (odds ratio = 0.58, 95% confidence interval 0.37–0.91) and where LCNS caseload > 250 (0.69, 0.41–1.16, although not statistically significant), but increased where workload was conducted mostly by band 8 nurses (2.22, 1.22–4.02). Conclusion: LCNS assessment varied by patient and Trust features, which may indicate unmet need for some patients. The current workforce needs to expand as well as retain experienced LCNSs

Are working practices of lung cancer nurse specialists associated with variation in peoples' receipt of anticancer therapy?

OBJECTIVES: Treatment choices for people with lung cancer may be influenced by contact and engagement with lung cancer nurse specialists (LCNSs). We investigated how service factors, LCNS workload, and LCNS working practices may influence the receipt of anticancer treatment. MATERIALS AND METHODS: English National Lung Cancer Audit data and inpatient Hospital Episode Statistics for 109,079 people with lung cancer surviving 30 days from diagnosis were linked along with LCNS workforce census data and a bespoke nationwide LCNS survey. Multinomial logistic regression was used to determine adjusted relative risk ratios (RRRs) for receipt of anticancer therapies associated with LCNS assessment, LCNS workforce composition, caseload, LCNS reported working practices, treatment facilities at the patients' attending hospitals, and the size of the lung cancer service. RESULTS: Assessment by an LCNS was the strongest independent predictor for receipt of anticancer therapy, with early LCNS assessments being particularly associated with greater receipt of surgery (RRR 1.85, 95%CI 1.63-2.11). For people we considered clinically suitable for surgery, receipt was 55%. Large LCNS caseloads were associated with decreased receipt of surgery among suitable patients (RRR 0.71, 95%CI 0.51-0.97) for caseloads >250 compared to ≤150. Reported LCNS working practices were associated with receipt of surgery, particularly provision of psychological support (RRR 1.60, 95%CI 1.02-2.51) and social support (RRR 1.56, 95%CI 1.07-2.28). CONCLUSION: LCNS assessment, workload, and working practices are associated with the likelihood of patients receiving anticancer therapy. Enabling and supporting LCNSs to undertake key case management interventions offers an opportunity to improve treatment uptake and reduce the apparent gap in receipt of surgery for those suitable

Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36-54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351-727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia

Interpreting outcome following foot surgery in people with rheumatoid arthritis

BACKGROUND: Foot surgery is common in RA but the current lack of understanding of how patients interpret outcomes inhibits evaluation of procedures in clinical and research settings. This study aimed to explore which factors are important to people with RA when they evaluate the outcome of foot and ankle surgery. METHODS AND RESULTS: Semi structured interviews with 11 RA participants who had mixed experiences of foot surgery were conducted and analysed using thematic analysis. Responses showed that while participants interpreted surgical outcome in respect to a multitude of factors, five major themes emerged: functional ability, participation, appearance of feet and footwear, surgeons' opinion, and pain. Participants interpreted levels of physical function in light of other aspects of their disease, reflecting on relative change from their preoperative state more than absolute levels of ability. Appearance was important to almost all participants: physical appearance, foot shape, and footwear were closely interlinked, yet participants saw these as distinct concepts and frequently entered into a defensive repertoire, feeling the need to justify that their perception of outcome was not about cosmesis. Surgeons' post-operative evaluation of the procedure was highly influential and made a lasting impression, irrespective of how the outcome compared to the participants' initial goals. Whilst pain was important to almost all participants, it had the greatest impact upon them when it interfered with their ability to undertake valued activities. CONCLUSIONS: People with RA interpret the outcome of foot surgery using multiple interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than anticipated. These factors can help clinicians in discussing surgical options in patients

High Density Lipoprotein (HDL) Promotes Glucose Uptake in Adipocytes and Glycogen Synthesis in Muscle Cells

Background: High density lipoprotein (HDL) was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. Methods and Results: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1- [ 3 H]-2deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI) in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3) phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK) a were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-a were diminished in SR-BI knock-down 3T3-L1 cells. Conclusions: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells throug

Human Endometrial CD98 Is Essential for Blastocyst Adhesion

BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease