The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis ...phenotype.RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10
; Fleischner system HR 1.98, p=2×10
; and 4.4% VRS threshold HR 3.10, p=4×10
). When the scleroderma and Fleischner systems were combined, termed the progressive fibrotic system (C-statistic 0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF. On multivariable analysis, with adjustment for patient age, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77).The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent.
...in the absence of an ideal endpoint such as mortality, the substitution of a validated biomarker for a clinical endpoint (i.e., a surrogate endpoint) that can reliably predict the effect of the ...therapy can significantly improve the efficiency of IPF clinical trials (8-10). ...it is not yet clear how HRCT pattern and extent can help inform management decisions in an individual patient. Kurtosis describes the sharpness of the histogram peak and is inversely proportional to the thickness of the two tails of the histogram. Because lung fibrosis or inflammation causes an increase in the amount of soft tissue in the lung, it will increase mean lung attenuation and thereby decrease the sharpness of the histogram peak (kurtosis) and the degree of leftward skewness of the curve (Figure 1). ...the availability of a noncontrast, volumetric thin high-resolution CT dataset with a CT kernel that does not alter local HU accuracy is essential to accurate feature extraction.
Abstract
Background
The accumulation of deficits model for frailty has been used to develop an electronic health record (EHR) frailty index (eFI) that has been incorporated into British guidelines ...for frailty management. However, there have been limited applications of EHR-based approaches in the United States.
Methods
We constructed an adapted eFI for patients in our Medicare Accountable Care Organization (ACO, N = 12,798) using encounter, diagnosis code, laboratory, medication, and Medicare Annual Wellness Visit (AWV) data from the EHR. We examined the association of the eFI with mortality, health care utilization, and injurious falls.
Results
The overall cohort was 55.7% female, 85.7% white, with a mean age of 74.9 (SD = 7.3) years. In the prior 2 years, 32.1% had AWV data. The eFI could be calculated for 9,013 (70.4%) ACO patients. Of these, 46.5% were classified as prefrail (0.10 < eFI ≤ 0.21) and 40.1% frail (eFI > 0.21). Accounting for age, comorbidity, and prior health care utilization, the eFI independently predicted all-cause mortality, inpatient hospitalizations, emergency department visits, and injurious falls (all p < .001). Having at least one functional deficit captured from the AWV was independently associated with an increased risk of hospitalizations and injurious falls, controlling for other components of the eFI.
Conclusions
Construction of an eFI from the EHR, within the context of a managed care population, is feasible and can help to identify vulnerable older adults. Future work is needed to integrate the eFI with claims-based approaches and test whether it can be used to effectively target interventions tailored to the health needs of frail patients.
Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether ...quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials.
To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations.
Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER Computer-Aided Lung Informatics for Pathology Evaluation and Rating software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria.
In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%.
Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.
BACKGROUND:The HEART Pathway (history, ECG, age, risk factors, and initial troponin) is an accelerated diagnostic protocol designed to identify low-risk emergency department patients with chest pain ...for early discharge without stress testing or angiography. The objective of this study was to determine whether implementation of the HEART Pathway is safe (30-day death and myocardial infarction rate <1% in low-risk patients) and effective (reduces 30-day hospitalizations) in emergency department patients with possible acute coronary syndrome.
METHODS:A prospective pre-post study was conducted at 3 US sites among 8474 adult emergency department patients with possible acute coronary syndrome. Patients included were ≥21 years old, investigated for possible acute coronary syndrome, and had no evidence of ST-segment–elevation myocardial infarction on ECG. Accrual occurred for 12 months before and after HEART Pathway implementation from November 2013 to January 2016. The HEART Pathway accelerated diagnostic protocol was integrated into the electronic health record at each site as an interactive clinical decision support tool. After accelerated diagnostic protocol integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or non-low risk (appropriate for further in-hospital evaluation). The primary safety and effectiveness outcomes, death, and myocardial infarction (MI) and hospitalization rates at 30 days were determined from health records, insurance claims, and death index data.
RESULTS:Preimplementation and postimplementation cohorts included 3713 and 4761 patients, respectively. The HEART Pathway identified 30.7% as low risk; 0.4% of these patients experienced death or MI within 30 days. Hospitalization at 30 days was reduced by 6% in the postimplementation versus preimplementation cohort (55.6% versus 61.6%; adjusted odds ratio, 0.79; 95% CI, 0.71–0.87). During the index visit, more MIs were detected in the postimplementation cohort (6.6% versus 5.7%; adjusted odds ratio, 1.36; 95% CI, 1.12–1.65). Rates of death or MI during follow-up were similar (1.1% versus 1.3%; adjusted odds ratio, 0.88; 95% CI, 0.58–1.33).
CONCLUSIONS:HEART Pathway implementation was associated with decreased hospitalizations, increased identification of index visit MIs, and a very low death and MI rate among low-risk patients. These findings support use of the HEART Pathway to identify low-risk patients who can be safely discharged without stress testing or angiography.
CLINICAL TRIAL REGISTRATION:URLhttp://www.clinicaltrials.gov. Unique identifierNCT02056964.
Computer-based computed tomography (CT) analysis can provide objective quantitation of disease in idiopathic pulmonary fibrosis (IPF). A computer algorithm, CALIPER, was compared with conventional CT ...and pulmonary function measures of disease severity for mortality prediction.CT and pulmonary function variables (forced expiratory volume in 1 s, forced vital capacity, diffusion capacity of the lung for carbon monoxide, transfer coefficient of the lung for carbon monoxide and composite physiologic index (CPI)) of 283 consecutive patients with a multidisciplinary diagnosis of IPF were evaluated against mortality. Visual and CALIPER CT features included total extent of interstitial lung disease, honeycombing, reticular pattern, ground glass opacities and emphysema. In addition, CALIPER scored pulmonary vessel volume (PVV) while traction bronchiectasis and consolidation were only scored visually. A combination of mortality predictors was compared with the Gender, Age, Physiology model.On univariate analyses, all visual and CALIPER-derived interstitial features and functional indices were predictive of mortality to a 0.01 level of significance. On multivariate analysis, visual CT parameters were discarded. Independent predictors of mortality were CPI (hazard ratio (95% CI) 1.05 (1.02-1.07), p<0.001) and two CALIPER parameters: PVV (1.23 (1.08-1.40), p=0.001) and honeycombing (1.18 (1.06-1.32), p=0.002). A three-group staging system derived from this model was powerfully predictive of mortality (2.23 (1.85-2.69), p<0.0001).CALIPER-derived parameters, in particular PVV, are more accurate prognostically than traditional visual CT scores. Quantitative tools such as CALIPER have the potential to improve staging systems in IPF.
CLL cell trafficking between blood and tissue compartments is an integral part of the disease process. Idelalisib, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor causes rapid lymph node ...shrinkage, along with an increase in lymphocytosis, prior to inducing objective responses in CLL patients. This characteristic activity presumably is due to CLL cell redistribution from tissues into the blood, but the underlying mechanisms are not fully understood. We therefore analyzed idelalisib effects on CLL cell adhesion to endothelial and bone marrow stromal cells (EC, BMSC). We found that idelalisib inhibited CLL cell adhesion to EC and BMSC under static and shear flow conditions. TNFα-induced VCAM-1 (CD106) expression in supporting layers increased CLL cell adhesion and accentuated the inhibitory effect of idelalisib. Co-culture with EC and BMSC also protected CLL from undergoing apoptosis, and this EC- and BMSC-mediated protection was antagonized by idelalisib. Furthermore, we demonstrate that CLL cell adhesion to EC and VLA-4 (CD49d) resulted in the phosphorylation of Akt, which was sensitive to inhibition by idelalisib. These findings demonstrate that idelalisib interferes with integrin-mediated CLL cell adhesion to EC and BMSC, providing a novel mechanism to explain idelalisib-induced redistribution of CLL cells from tissues into the blood.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The worldwide spread of invasive Aedes mosquitoes and arboviral disease, have renewed the pressure for effective and sustainable urban mosquito control. We report on the success of a model we are ...confident will usher in a new era of urban mosquito control. The key innovation is the mobilization of neighbors guided by scientific advisors, an approach we termed Citizen Action through Science (Citizen AcTS). This approach was tested in a NE US town of approximately 1,000 residential yards infested with the invasive Asian tiger mosquito, Aedes albopictus, a major nuisance arboviral vector. We report a highly significant reduction in biting pressure that was maintained over time, and establish the thresholds needed for success. The Citizen AcTS model rejects the top-down approach consistently associated with intervention failures. Instead, it works through respectful exchanges among scientists and residents that lead to trust and individual 'buy-in' and transferring program ownership to the community.
Opportunistic assessment of sarcopenia on CT examinations is becoming increasingly common. This study aimed to determine relationships between CT-measured skeletal muscle size and attenuation with ...1-year risk of mortality in older adults enrolled in a Medicare Shared Savings Program (MSSP).
Relationships between skeletal muscle metrics and all-cause mortality were determined in 436 participants (52% women, mean age 75 years) who had abdominopelvic CT examinations. On CT images, skeletal muscles were segmented at the level of L3 using two methods: (a) all muscles with a threshold of -29 to +150 Hounsfield units (HU), using a dedicated segmentation software, (b) left psoas muscle using a free-hand region of interest tool on a clinical workstation. Muscle cross-sectional area (CSA) and muscle attenuation were measured. Cox regression models were fit to determine the associations between muscle metrics and mortality, adjusting for age, sex, race, smoking status, cancer diagnosis, and Charlson comorbidity index.
Within 1 year of follow-up, 20.6% (90/436) participants died. In the fully-adjusted model, higher muscle index and muscle attenuation were associated with lower risk of mortality. A one-unit standard deviation (SD) increase was associated with a HR = 0.69 (95% CI = 0.49, 0.96; p = .03) for total muscle index, HR = 0.67 (95% CI = 0.49, 0.90; p < .01) for psoas muscle index, HR = 0.54 (95% CI = 0.40, 0.74; p < .01) for total muscle attenuation, and HR = 0.79 (95% CI = 0.66, 0.95; p = .01) for psoas muscle attenuation.
In older adults, higher skeletal muscle index and muscle attenuation on abdominopelvic CT examinations were associated with better survival, after adjusting for multiple risk factors.
Objectives
To determine whether computer-based CT quantitation of change can improve on visual change quantification of parenchymal features in IPF.
Methods
Sixty-six IPF patients with serial CT ...imaging (6-24 months apart) had CT features scored visually and with a computer software tool: ground glass opacity, reticulation and honeycombing (all three variables summed as interstitial lung disease extent ILD) and emphysema. Pulmonary vessel volume (PVV) was estimated by computer only. Relationships between changes in CT features and forced vital capacity (FVC) were examined using univariate and multivariate linear regression analyses.
Results
On univariate analysis, changes in computer variables demonstrated stronger linkages to FVC change than changes in visual scores (CALIPER ILD:R
2
=0.53,
p
<0.0001; Visual ILD:R
2
=0.16,
p
=0.001). PVV increase correlated most strongly with relative FVC change (R
2
=0.57). When PVV constituents (vessel size and location) were examined, an increase in middle zone vessels linked most strongly to FVC decline (R
2
=0.57) and was independent of baseline disease severity (characterised by CT fibrosis extent, FVC, or DLco).
Conclusions
An increase in PVV, specifically an increase in middle zone lung vessels, was the strongest CT determinant of FVC decline in IPF and was independent of baseline disease severity.
Key Points
•
Computer analysis improves on visual CT scoring in evaluating deterioration on CT
•
Increasing pulmonary vessel volume is the strongest CT predictor of functional deterioration
•
Increasing pulmonary vessel volume predicts functional decline independent of baseline disease severity
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