Reliability of hospital scores for the Cancer Patient Experience Survey: analysis of publicly reported patient survey data

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordOBJECTIVES: To assess the degree to which variations in publicly reported hospital scores arising from the English Cancer Patient Experience Survey (CPES) are subject to chance. DESIGN: Secondary analysis of publically reported data. SETTING: English National Health Service hospitals. PARTICIPANTS: 72 756 patients who were recently treated for cancer in one of 146 hospitals and responded to the 2016 English CPES. MAIN OUTCOME MEASURES: Spearman-Brown reliability of hospital scores on 51 evaluative questions regarding cancer care. RESULTS: Hospitals varied in respondent sample size with a median hospital sample size of 419 responses (range 31-1972). There were some hospitals with generally highly reliable scores across most questions, whereas other hospitals had generally unreliable scores (the median reliability of question scores within individual hospitals varied between 0.11 and 0.86). Similarly, there were some questions with generally high reliability across most hospitals, whereas other questions had generally low reliability. Of the 7377 individual hospital scores publically reported (146 hospitals by 51 questions, minus 69 suppressed scores), only 34% reached a reliability of 0.7, the minimum generally considered to be useful. In order for 80% of the individual hospital scores to reach a reliability of 0.7, some hospitals would require a fourfold increase in number of respondents; although in a few other hospitals sample sizes could be reduced. CONCLUSIONS: The English Patient Experience Survey represents a globally unique source for understanding experience of a patient with cancer; but in its present form, it is not reliable for high stakes comparisons of the performance of different hospitals. Revised sampling strategies and survey questions could help increase the reliability of hospital scores, and thus make the survey fit for use in performance comparisons.Macmillan Cancer SupportCancer Research U

Predictors of postal or online response mode and associations with patient experience and satisfaction in the english cancer patient experience survey

This is the final version. Available on open access from Journal of Medical Internet Research via the DOI in this recordBackground: Patient experience surveys are important tools for improving the quality of cancer services, but the representativeness of responders is a concern. Increasingly, patient surveys that traditionally used postal questionnaires are incorporating an online response option. However, the characteristics and experience ratings of online responders are poorly understood. Objective: We sought to examine predictors of postal or online response mode, and associations with patient experience in the (English) Cancer Patient Experience Survey. Methods: We analyzed data from 71,186 patients with cancer recently treated in National Health Service hospitals who responded to the Cancer Patient Experience Survey 2015. Using logistic regression, we explored patient characteristics associated with greater probability of online response and whether, after adjustment for patient characteristics, the online response was associated with a more or less critical evaluation of cancer care compared to the postal response. Results: Of the 63,134 patients included in the analysis, 4635 (7.34%) responded online. In an adjusted analysis, male (women vs men: odds ratio [OR] 0.50, 95% confidence interval [CI] 0.46-0.54), younger (<55 vs 65-74 years: OR 3.49, 95% CI 3.21-3.80), least deprived (most vs least deprived quintile: OR 0.57, 95% CI 0.51-0.64), and nonwhite (nonwhite vs white ethnic group: OR 1.37, 95% CI 1.24-1.51) patients were more likely to respond online. Compared to postal responders, after adjustment for patient characteristics, online responders had a higher likelihood of reporting an overall satisfied experience of care (OR 1.24, 95% CI 1.16-1.32). For 34 of 49 other items, online responders more frequently reported a less than positive experience of care (8 reached statistical significance), and the associations were positive for the remaining 15 of 49 items (2 reached statistical significance). Conclusions: In the context of a national survey of patients with cancer, online and postal responders tend to differ in their characteristics and rating of satisfaction. Associations between online response and reported experience were generally small and mostly nonsignificant, but with a tendency toward less than positive ratings, although not consistently. Whether the observed associations between response mode and reported experience were causal needs to be examined using experimental survey designs.Macmillan Cancer SupportCancer Research U

Reliability of hospital scores for the Cancer Patient Experience Survey: analysis of publicly reported patient survey data

OBJECTIVES: To assess the degree to which variations in publicly reported hospital scores arising from the English Cancer Patient Experience Survey (CPES) are subject to chance. DESIGN: Secondary analysis of publically reported data. SETTING: English National Health Service hospitals. PARTICIPANTS: 72 756 patients who were recently treated for cancer in one of 146 hospitals and responded to the 2016 English CPES. MAIN OUTCOME MEASURES: Spearman-Brown reliability of hospital scores on 51 evaluative questions regarding cancer care. RESULTS: Hospitals varied in respondent sample size with a median hospital sample size of 419 responses (range 31-1972). There were some hospitals with generally highly reliable scores across most questions, whereas other hospitals had generally unreliable scores (the median reliability of question scores within individual hospitals varied between 0.11 and 0.86). Similarly, there were some questions with generally high reliability across most hospitals, whereas other questions had generally low reliability. Of the 7377 individual hospital scores publically reported (146 hospitals by 51 questions, minus 69 suppressed scores), only 34% reached a reliability of 0.7, the minimum generally considered to be useful. In order for 80% of the individual hospital scores to reach a reliability of 0.7, some hospitals would require a fourfold increase in number of respondents; although in a few other hospitals sample sizes could be reduced. CONCLUSIONS: The English Patient Experience Survey represents a globally unique source for understanding experience of a patient with cancer; but in its present form, it is not reliable for high stakes comparisons of the performance of different hospitals. Revised sampling strategies and survey questions could help increase the reliability of hospital scores, and thus make the survey fit for use in performance comparisons

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

Objective: In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non-BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences. Methods: Ex vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI-determined BML and non-BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony-forming unit–fibroblast (CFU-F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture-expanded CD271+ cells were analyzed for tripotentiality and gene expression. Results: BML regions were associated with greater trabecular bone area and cartilage damage compared with non-BML regions. The proportion of CD45−CD271+ MSCs was higher in BML regions compared with non-BML regions (median difference 5.6-fold; P < 0.001); the CFU-F assay showed a similar trend (median difference 4.3-fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell–derived factor 1 receptor. OA MSCs showed up-regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone. Conclusion: This study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target

Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Differential expression of collectins in human placenta and role in inflammation during spontaneous Labor.

© 2014 Yadav et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Collectins, collagen-containing Ca2+ dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥37 weeks of gestation), undergoing either elective C-section with no labor ('NLc' group, n = 5), or normal vaginal delivery with spontaneous labor ('SLv' group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The 'SLv' group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the 'NLc' group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (p<0.05). In addition, the MMP-9-cleaved form of SP-D (25 kDa) was significantly higher in the placentae of 'SLv' group compared to the 'NLc' group (p = 0.002). Labor associated cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α and MCP-1 showed significant increase (p<0.05) in a dose dependent manner in the placental explants treated with nSP-D and rhSP-D. In conclusion, the study emphasizes that SP-A and SP-D proteins associate with the spontaneous labor and SP-D plausibly contributes to the pro-inflammatory immune milieu of feto-maternal tissues.Funding provided by BT/PR15227/BRB/10/906/2011) Department of Biotechnology (DBT), Government of India http://dbtindia.nic.in/index.asp (TM) and Indian Council of Medical Research (ICMR) Junior Research Fellowship (JRF)/Senior Research Fellowship (SRF), Government of India, www.icmr.nic.in (AKY)

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading