Comparison of Image Registration Based Measures of Regional Lung Ventilation from Dynamic Spiral CT with Xe-CT

Purpose: Regional lung volume change as a function of lung inflation serves as an index of parenchymal and airway status as well as an index of regional ventilation and can be used to detect pathologic changes over time. In this article, we propose a new regional measure of lung mechanics --- the specific air volume change by corrected Jacobian. Methods: 4DCT and Xe-CT data sets from four adult sheep are used in this study. Nonlinear, 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration. Approximately 200 annotated anatomical points are used as landmarks to evaluate registration accuracy. Three different registration-based measures of regional lung mechanics are derived and compared: the specific air volume change calculated from the Jacobian (SAJ); the specific air volume change calculated by the corrected Jacobian (SACJ); and the specific air volume change by intensity change (SAI). Results: After registration, the mean registration error is on the order of 1 mm. For cubical ROIs in cubes with size 20 mm $\times$ 20 mm $\times$ 20 mm, the SAJ and SACJ measures show significantly higher correlation (linear regression, average $r^2=0.75$ and $r^2=0.82$) with the Xe-CT based measure of specific ventilation (sV) than the SAI measure. For ROIs in slabs along the ventral-dorsal vertical direction with size of 150 mm $\times$ 8 mm $\times$ 40 mm, the SAJ, SACJ, and SAI all show high correlation (linear regression, average $r^2=0.88$, $r^2=0.92$ and $r^2=0.87$) with the Xe-CT based sV without significant differences when comparing between the three methods. Conclusion: Given a deformation field by an image registration algorithm, significant differences between the SAJ, SACJ, and SAI measures were found at a regional level compared to the Xe-CT sV in four sheep that were studied

Organisational interventions to reduce length of stay in hospital: a rapid evidence assessment

This is the final version of the report. Available from the publisher via the DOI in this record.BACKGROUND: Available evidence on effective interventions to reduce length of stay in hospital is wide-ranging and complex, with underlying factors including those acting at the health system, organisational and patient levels, and the interface between these. There is a need to better understand the diverse literature on reducing the length of hospital stay. OBJECTIVES: This study sought to (i) describe the nature of interventions that have been used to reduce length of stay in acute care hospitals; (ii) identify the factors that are known to influence length of stay; and (iii) assess the impact of interventions on patient outcomes, service outcomes and costs. DATA SOURCES: We searched MEDLINE (Ovid), EMBASE, the Health Management Information Consortium and System for Information on Grey Literature in Europe for the period January 1995 to January 2013 with no limitation of publication type. METHODS: We conducted a rapid evidence synthesis of the peer-reviewed literature on organisational interventions set in or initiated from acute hospitals. We considered evidence published between 2003 and 2013. Data were analysed drawing on the principles of narrative synthesis. We also carried out interviews with eight NHS managers and clinical leads in four sites in England. Results: A total of 53 studies met our inclusion criteria, including 19 systematic reviews and 34 primary studies. Although the overall evidence base was varied and frequently lacked a robust study design, we identified a range of interventions that showed potential to reduce length of stay. These were multidisciplinary team working, for example some forms of organised stroke care; improved discharge planning; early supported discharge programmes; and care pathways. Nursing-led inpatient units were associated with improved outcomes but, if anything, increased length of stay. Factors influencing the impact of interventions on length of stay included contextual factors and the population targeted. The evidence was mixed with regard to the extent to which interventions seeking to reduce length of stay were associated with cost savings. LIMITATIONS: We only considered assessments of interventions which provided a quantitative estimate of the impact of the given organisational intervention on length of hospital stay. There was a general lack of robust evidence and poor reporting, weakening the conclusions that can be drawn from the review. CONCLUSIONS: The design and implementation of an intervention seeking to reduce (directly or indirectly) the length of stay in hospital should be informed by local context and needs. This involves understanding how the intervention is seeking to change processes and behaviours that are anticipated, based on the available evidence, to achieve desired outcomes (‘theory of change’). It will also involve assessing the organisational structures and processes that will need to be put in place to ensure that staff who are expected to deliver the intervention are appropriately prepared and supported. With regard to future research, greater attention should be given to the theoretical underpinning of the design, implementation and evaluation of interventions or programmes. There is a need for further research using appropriate methodology to assess the effectiveness of different types of interventions in different settings. Different evaluation approaches may be useful, and closer relationships between researchers and NHS organisations would enable more formative evaluation. Full economic costing should be undertaken where possible, including considering the cost implications for the wider local health economyThe National Institute for Health Research Health Services and Delivery Research programme

Risk assessment for hospital admission in patients with COPD; a multi-centre UK prospective observational study.

In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs. The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand). We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay. Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD. Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales. The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES). In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up. Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD. For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD). The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD. The SPPB can aid in clinical decision making and when prioritising healthcare resources

Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya

Background In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function. Methods Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child’s immunisation booklet containing records of birth weight and serial weights in the first year. Results 2373 children participated, 52% girls, median age (IQR), 10 years (8–13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms ‘wheeze in the last 12 months’; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and ‘trouble breathing’ 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027. Conclusion These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa

Antagonism of Host Antiviral Responses by Kaposi's Sarcoma-Associated Herpesvirus Tegument Protein ORF45

Virus infection of a cell generally evokes an immune response by the host to defeat the intruder in its effort. Many viruses have developed an array of strategies to evade or antagonize host antiviral responses. Kaposi's sarcoma-associated herpesvirus (KSHV) is demonstrated in this report to be able to prevent activation of host antiviral defense mechanisms upon infection. Cells infected with wild-type KSHV were permissive for superinfection with vesicular stomatitis virus (VSV), suggesting that KSHV virions fail to induce host antiviral responses. We previously showed that ORF45, a KSHV immediate-early protein as well as a tegument protein of virions, interacts with IRF-7 and inhibits virus-mediated type I interferon induction by blocking IRF-7 phosphorylation and nuclear translocation (Zhu et al., Proc. Natl. Acad. Sci. USA. 99:5573-5578, 2002). Here, using an ORF45-null recombinant virus, we demonstrate a profound role of ORF45 in inhibiting host antiviral responses. Infection of cells with an ORF45-null mutant recombinant KSHV (BAC-stop45) triggered an immune response that resisted VSV super-infection, concomitantly associated with appreciable increases in transcription of type I IFN and downstream anti-viral effector genes. Gain-of-function analysis showed that ectopic expression of ORF45 in human fibroblast cells by a lentivirus vector decreased the antiviral responses of the cells. shRNA-mediated silencing of IRF-7, that predominantly regulates both the early and late phase induction of type I IFNs, clearly indicated its critical contribution to the innate antiviral responses generated against incoming KSHV particles. Thus ORF45 through its targeting of the crucial IRF-7 regulated type I IFN antiviral responses significantly contributes to the KSHV survival immediately following a primary infection allowing for progression onto subsequent stages in its life-cycle

Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study

Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Health Data Research UKFunder: NIHR Cambridge Comprehensive Biomedical Research CentreFunder: NIHR Nottingham BRC respiratory themeObjectives: Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors. Design: Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II–IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up. Setting: Five UK centres interested in COPD. Participants: Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks. Interventions: Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima–media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test. Primary and secondary outcome measures: New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality. Results: Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728). Conclusion: Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD. Trial registration number: ID 11101