Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

© 2017 The Author(s). Background: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. Results: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001). Conclusion: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD. Trial registration:ClinicalTrials.govregistration number NCT01351792(registration date May 10, 2011), ClinicalTrials.govregistration number NCT00848406(registration date February 19, 2009), ClinicalTrials.govregistration number NCT00807469(registration date December 11, 2008)

Integration and continuity of primary care: polyclinics and alternatives - a patient-centred analysis of how organisation constrains care co-ordination

Background An ageing population, the increasing specialisation of clinical services and diverse health-care provider ownership make the co-ordination and continuity of complex care increasingly problematic. The way in which the provision of complex health care is co-ordinated produces – or fails to produce – six forms of continuity of care (cross-sectional, longitudinal, flexible, access, informational and relational). Care co-ordination is accomplished by a combination of activities by patients themselves; provider organisations; care networks co-ordinating the separate provider organisations; and overall health-system governance. This research examines how far organisational integration might promote care co-ordination at the clinical level. Objectives To examine (1) what differences the organisational integration of primary care makes, compared with network governance, to horizontal and vertical co-ordination of care; (2) what difference provider ownership (corporate, partnership, public) makes; (3) how much scope either structure allows for managerial discretion and ‘performance’; (4) differences between networked and hierarchical governance regarding the continuity and integration of primary care; and (5) the implications of the above for managerial practice in primary care. Methods Multiple-methods design combining (1) the assembly of an analytic framework by non-systematic review; (2) a framework analysis of patients’ experiences of the continuities of care; (3) a systematic comparison of organisational case studies made in the same study sites; (4) a cross-country comparison of care co-ordination mechanisms found in our NHS study sites with those in publicly owned and managed Swedish polyclinics; and (5) the analysis and synthesis of data using an ‘inside-out’ analytic strategy. Study sites included professional partnership, corporate and publicly owned and managed primary care providers, and different configurations of organisational integration or separation of community health services, mental health services, social services and acute inpatient care. Results Starting from data about patients’ experiences of the co-ordination or under-co-ordination of care, we identified five care co-ordination mechanisms present in both the integrated organisations and the care networks; four main obstacles to care co-ordination within the integrated organisations, of which two were also present in the care networks; seven main obstacles to care co-ordination that were specific to the care networks; and nine care co-ordination mechanisms present in the integrated organisations. Taking everything into consideration, integrated organisations appeared more favourable to producing continuities of care than did care networks. Network structures demonstrated more flexibility in adding services for small care groups temporarily, but the expansion of integrated organisations had advantages when adding new services on a longer term and a larger scale. Ownership differences affected the range of services to which patients had direct access; primary care doctors’ managerial responsibilities (relevant to care co-ordination because of their impact on general practitioner workload); and the scope for doctors to develop special interests. We found little difference between integrated organisations and care networks in terms of managerial discretion and performance. Conclusions On balance, an integrated organisation seems more likely to favour the development of care co-ordination and, therefore, continuities of care than a system of care networks. At least four different variants of ownership and management of organisationally integrated primary care providers are practicable in NHS-like settings. Future research is therefore required, above all to evaluate comparatively the different techniques for coordinating patient discharge across the triple interface between hospitals, general practices and community health services; and to discover what effects increasing the scale and scope of general practice activities will have on continuity of care

The FOAM study : Is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial

This is an investigator initiated trial, VU medical center Amsterdam is the sponsor, contact information: prof. CJM de Groot, Department of Obstetrics and Gynaecology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands, Tel: + 31-204444444. This study is funded by ZonMw, a Dutch organization for Health Research and Development, project number 837001504. ZonMW gives financial support for the whole project. IQ Medical Ventures provides the ExEm FOAM® kits. The funding bodies have no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript.Peer reviewedPublisher PD

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial

Funding Information: The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foamVR kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Peer reviewedPublisher PD

Towards reducing variations in infant mortality and morbidity : a population-based approach

Background: Our aims were (1) to improve understanding of regional variation in early-life mortality rates and the UK’s poor performance in international comparisons; and (2) to identify the extent to which late and moderately preterm (LMPT) birth contributes to early childhood mortality and morbidity. Objective: To undertake a programme of linked population-based research studies to work towards reducing variations in infant mortality and morbidity rates. Design: Two interlinked streams: (1) a detailed analysis of national and regional data sets and (2) establishment of cohorts of LMPT babies and term-born control babies. Setting: Cohorts were drawn from the geographically defined areas of Leicestershire and Nottinghamshire, and analyses were carried out at the University of Leicester. Data sources: For stream 1, national data were obtained from four sources: the Office for National Statistics, NHS Numbers for Babies, Centre for Maternal and Child Enquiries and East Midlands and South Yorkshire Congenital Anomalies Register. For stream 2, prospective data were collected for 1130 LMPT babies and 1255 term-born control babies. Main outcome measures: Detailed analysis of stillbirth and early childhood mortality rates with a particular focus on factors leading to biased or unfair comparison; review of clinical, health economic and developmental outcomes over the first 2 years of life for LMPT and term-born babies. Results: The deprivation gap in neonatal mortality has widened over time, despite government efforts to reduce it. Stillbirth rates are twice as high in the most deprived as in the least deprived decile. Approximately 70% of all infant deaths are the result of either preterm birth or a major congenital abnormality, and these are heavily influenced by mothers’ exposure to deprivation. Births at < 24 weeks’ gestation constitute only 1% of all births, but account for 20% of infant mortality. Classification of birth status for these babies varies widely across England. Risk of LMPT birth is greatest in the most deprived groups within society. Compared with term-born peers, LMPT babies are at an increased risk of neonatal morbidity, neonatal unit admission and poorer long-term health and developmental outcomes. Cognitive and socioemotional development problems confer the greatest long-term burden, with the risk being amplified by socioeconomic factors. During the first 24 months of life each child born LMPT generates approximately £3500 of additional health and societal costs. Conclusions: Health professionals should be cautious in reviewing unadjusted early-life mortality rates, particularly when these relate to individual trusts. When more sophisticated analysis is not possible, babies of < 24 weeks’ gestation should be excluded. Neonatal services should review the care they offer to babies born LMPT to ensure that it is appropriate to their needs. The risk of adverse outcome is low in LMPT children. However, the risk appears higher for some types of antenatal problems and when the mother is from a deprived background

Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference −1.2%, 95% CI: −3.4% to 1.5%; P¼ 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18–41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies—management based on HyfoSy results versus HSG results—the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference −1.2%; 95% CI: −3.4% to 1.5%). For the procedures itself, HyFoSy cost e136 and HSG e280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were e3307 for the HyFoSy strategy and e3427 for the HSG strategy (mean difference e−119; 95% CI: e−125 to e−114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was e10 042, meaning that by using HyFoSy instead of HSG we would save e10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting—and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746

The effects of integrated care: a systematic review of UK and international evidence

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725

Getting More Out of Less - A Quantitative Serological Screening Tool for Simultaneous Detection of Multiple Influenza A Hemagglutinin-Types in Chickens

Current avian influenza surveillance in poultry primarily targets subtypes of interest for the veterinary sector (H5, H7). However, as virological and serological evidence suggest, surveillance of additional subtypes is important for public health as well as for the poultry industry. Therefore, we developed a protein microarray enabling simultaneous identification of antibodies directed against different HA-types of influenza A viruses in chickens. The assay successfully discriminated negative from experimentally and naturally infected, seropositive chickens. Sensitivity and specificity depended on the cut-off level used but ranged from 84.4% to 100% and 100%, respectively, for a cut off level of =1:40, showing minimal cross reactivity. As this testing platform is also validated for the use in humans, it constitutes a surveillance tool that can be applied in human-animal interface studies