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Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
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The study of brain function using MRI relies on acquisition techniques that are sensitive to different aspects of the hemodynamic response contiguous to areas of neuronal activity. For this purpose different contrasts such as arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional MRI techniques have been developed to investigate cerebral blood flow (CBF) and blood oxygenation, respectively. Analysis of such data typically proceeds by separate, linear modeling of the appropriate CBF or BOLD time courses. In this work an approach is developed that provides simultaneous inference on hemodynamic changes via a nonlinear physiological model of ASL data acquired at multiple echo times. Importantly, this includes a significant contribution by changes in the static magnetization, M, to the ASL signal. Inference is carried out in a Bayesian framework. This is able to extract, from dual-echo ASL data, probabilistic estimates of percentage changes of CBF, R(2) (*), and the static magnetization, M. This approach provides increased sensitivity in inferring CBF changes and reduced contamination in inferring BOLD changes when compared with general linear model approaches on single-echo ASL data. We also consider how the static magnetization, M, might be related to changes in CBV by assuming the same mechanism for water exchange as in vascular space occupancy.  相似文献   
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Toby O. Smith   《Physiotherapy》2006,92(3):135-145
Pretibial lacerations and lower limb wounds are referred to plastic surgery teams for split skin graft surgery. Traditionally, these patients have been immobilised on bedrest following surgery. More recently, patients have commenced ambulation earlier to avoid medical complications and facilitate discharge. The objective of this literature review was to determine when such patients should begin walking. A literature search was undertaken using the electronic databases AMED, Cinahl, Embase, Medline (via Ovid), PEDro and Pubmed. Clinical trials using human subjects, written in English, were included. Seventeen (of 1137) papers met the inclusion criteria and were reviewed. The literature suggested that patients should begin walking immediately or at the earliest possible opportunity after lower limb skin graft surgery. Although the literature advocated early ambulation, the evidence base presented with a number of recurrent methodological limitations, including small sample sizes, lack of a control sample, and limited follow-up. Accordingly, further research employing large, well-designed, randomised controlled trials is recommended. It will then be possible to understand with greater certainty when patients should begin walking after lower extremity split skin graft surgery.  相似文献   
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OBJECTIVE: To determine the age at which infants achieve velopharyngeal closure during vocalization. DESIGN: Longitudinal with repeated measures. SETTING: Laboratory. PARTICIPANTS: Six healthy infants were studied monthly from ages 2 to 6 months while they interacted with a parent and an investigator. MAIN OUTCOME MEASURES: The presence or absence of velopharyngeal closure, as determined by sensing ram pressure at the anterior nares. RESULTS: The velopharynx was open for windups, whimpers, and laughs, and it was closed for cries, screams, and raspberries, regardless of age. The frequency with which the velopharynx closed during syllable utterances increased significantly with age. CONCLUSIONS: Velopharyngeal closure for speech-like utterance increases with age, but is not complete and is still undergoing development at 6 months of age. Velopharyngeal closure during infancy may be influenced by pressure demands of the utterance; however, support for this speculation is stronger for other types of utterances than it is for speech-like utterances. The method used in this study holds promise for evaluating infants with suspected velopharyngeal impairment.  相似文献   
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STUDY OBJECTIVES: Use of fast track has been shown to improve the emergency department flow of less urgent patients. It has been speculated, however, that this could negatively affect the care of urgent patients. The objective of this study was to determine whether a dedicated fast track for less urgent patients [Canadian Triage and Acuity scale category 4/5 (CTAS 4/5)] affected (1) the time to assessment for urgent patients (CTAS 3), (2) the length of stay for less urgent patients (CTAS 4 and 5), and (3) the left-without-being-seen rate. METHODS: In June 2003, fast track was opened in our emergency department from 13:00 to 19:00 h. A before-after intervention comparison analysis was completed for 1 week in Aug 2002 and the same week in Aug 2003. Data collected included (1) time to assessment of CTAS 3 patients, (2) the length of stay for CTAS 4/5 patients, and (3) percentage of patients who left without being seen. RESULTS: A total of 368 patients were reviewed for 2002 and 380 patients were reviewed for 2003. Median time to assessment of CTAS 3 patients presenting from 13:00 to 19:00 h was reduced from 66 min (Interquartile range: 40, 94 min) in 2002 to 60 min (IQR: 38, 108 min) after fast track was open in 2003 (P = 0.95). Median length of stay of CTAS 4 and 5 patients was reduced from 170 min (IQR: 111, 256 min) to 110 min (IQR: 69, 185 min) (P < 0.001). The overall left-without-being-seen rate decreased from 5% (20/368) to 2% (9/380). CONCLUSION: A dedicated fast track for CTAS 4/5 patients can reduce the length of stay and the left-without-being-seen rate with no impact on CTAS 3 patients seen in the main emergency department.  相似文献   
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