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51.

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Methods and results

The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.

Conclusion

The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.  相似文献   
52.

Background

Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)–related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients.

Methods

We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients.

Results

A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17–26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab,?cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications.

Conclusion

In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population.Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.  相似文献   
53.

Background

Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy.

Methods

One-hundred implantable cardioverter-defibrillator patients with structural heart disease who underwent VT ablation were included. Propensity score-matched patients with recurrent VT treated with medical therapy were identified from a prospective registry of approximately 7000 de novo implantable cardioverter-defibrillator patients. Outcomes and costs were ascertained using health administrative databases.

Results

Among patients who underwent VT ablation, the cumulative rates of VA-related hospitalizations were lower in the 2 years after their ablation procedure compared with the year before (rate ratio, 0.3; 95% confidence interval [CI], 0.22-0.43). Rates of CV-related hospitalization and hospitalization because of VA post index date were similar between the VT ablation and medical therapy groups (hazard ratio [HR], 0.94; 95% CI, 0.57-1.54 and HR, 1.04; 95% CI, 0.57-1.91, respectively). Health care costs in the VT ablation patients were not increased post-ablation compared with the medical management group. The risk of all-cause mortality was lower among patients in the VT ablation group relative to the medical therapy group (HR, 0.64; 95% CI, 0.4-0.99).

Conclusions

Patients who underwent VT ablation experienced a significant reduction in their rate of VA-related hospitalizations. Patients treated with VT ablation had similar rates of CV-related hospitalization compared with those treated with medical therapy without increased health care-related costs.  相似文献   
54.

Background and aim

Given the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP).

Methods and results

We performed a systematic search of all available RCTs conducted up to October 2018 in the following databases: PubMed, Scopus, and Cochrane. RCTs that investigated the effect of folate on CRP were included in the present study. Data were combined with the use of generic inverse-variance random-effects models. Statistical heterogeneity between studies was evaluated using Cochran's Q-test. Ten RCTs (1179 subjects) were included in the present meta-analysis. Pooled analysis results showed that folate supplementation significantly lowered the serum CRP level (weighted mean difference (WMD): ?0.685 mg/l, 95% CI: ?1.053, ?0.318, p < 0.001). However, heterogeneity was significant (I2 = 96.7%, p = 0.000). Stratified analyses indicated that sex, intervention period, and type of study population were sources of heterogeneity. Following analysis, results revealed that the greatest impact was observed in women (WMD: ?0.967 mg/l, 95% CI: ?1.101, ?0.833, p = 0.000), patients with type 2 diabetes mellitus (WMD: ?1.764 mg/l, 95% CI: ?2.002, ?1.526, p = 0.000), and intervention period less than 12 weeks (WMD: ?0.742 mg/l, 95% CI: ?0.834, ?0.650, p = 0.000).

Conclusion

This meta-analysis suggested that folic acid supplementation could significantly lower the serum CRP level. Folic acid leads to greater CRP lowering effect in women, patients with T2DM, and those with less than 12-week intervention.  相似文献   
55.

Context

Goals-of-care discussions are associated with improved end-of-life care for patients and therefore may be used as a process measure in quality improvement, research, and reimbursement programs.

Objectives

To examine three methods to assess occurrence of a goals-of-care discussion—patient report, clinician report, and documentation in the electronic health record (EHR)—at a clinic visit for seriously ill patients and determine whether each method is associated with patient-reported receipt of goal-concordant care.

Methods

We conducted a secondary analysis of a multicenter cluster-randomized trial, with 494 patients and 124 clinicians caring for them. Self-reported surveys collected from patients and clinicians two weeks after a clinic visit assessed occurrence of a goals-of-care discussion. Documentation of a goals-of-care discussion was abstracted from the EHR. Patient-reported receipt of goal-concordant care was assessed by survey two weeks after the visit.

Results

Fifty-two percent of patients reported occurrence of a goals-of-care discussion at the clinic visit; clinicians reported occurrence of a discussion at 66% of visits. EHR documentation occurred in 42% of visits (P < 0.001 for each compared with other two). Patients who reported occurrence of a goals-of-care discussion at the visit were more likely to report receipt of goal-concordant care than patients who reported no discussion (β 0.441, 95% CI 0.190–0.692; P = 0.001). Neither occurrence of a discussion by clinician report nor by EHR documentation was associated with goal-concordant care.

Conclusion

Different approaches to assess goals-of-care discussions give differing results, yet each may have advantages. Patient report is most likely to correlate with patient-reported receipt of goal-concordant care.  相似文献   
56.

Background

The International Agency for Research on Cancer (IARC) has recently classified glyphosate as a Group 2A ‘probably carcinogenic to humans’. Due to this carcinogenic classification and resulting international debate, there is an increased demand for studies evaluating human health effects from glyphosate exposures. There is currently limited information on human exposures to glyphosate and a paucity of data regarding glyphosate's biological half-life in humans.

Objective

This study aims to estimate the human half-life of glyphosate from human urine samples collected from amenity horticulture workers using glyphosate based pesticide products.

Methods

Full void urine spot samples were collected over a period of approximately 24?h for eight work tasks involving seven workers. The elimination time and estimation of the half-life of glyphosate using three different measurement metrics: the unadjusted glyphosate concentrations, creatinine corrected concentrations and by using Urinary Excretion Rates (UER) (μg L?1, μmol/mol creatinine and UER μg L?1) was calculated by summary and linear interpolation using regression analysis.

Results

This study estimates the human biological half-life of glyphosate as approximately 5 ½, 10 and 7 ¼ hours for unadjusted samples, creatinine corrected concentrations and by using UER (μg L?1, μmol/mol creatinine, UER μg L?1), respectively. The approximated glyphosate half-life calculations seem to have less variability when using the UER compared to the other measuring metrics.

Conclusion

This study provides new information on the elimination rate of glyphosate and an approximate biological half-life range for humans. This information can help optimise the design of sampling strategies, as well as assisting in the interpretation of results for human biomonitoring studies involving this active ingredient. The data could also contribute to the development or refinement of Physiologically Based PharmacoKinetic (PBPK) models for glyphosate.  相似文献   
57.
ABSTRACT

Each year, over 600 youth under the age of 25 experience literal homelessness in Austin, Texas. Of these youth, 76% have a history of involvement with foster care or the juvenile justice system—far exceeding the rates of system involvement observed among homeless youth in other large communities in the United States (approximately 54%; Voices of Youth Count, 2017). Recently, Austin was selected by the U.S. Department of Housing & Urban Development as one of ten communities nationwide to participate in the Youth Homelessness Demonstration Program (YHDP), a federal initiative designed to effectively end youth homelessness by 2020. Youth with lived experience are central players in the development and implementation of Austin's response to the youth homelessness crisis. A group of twelve of these youth (the “Austin Youth Collective to End Youth Homelessness,” or AYC) serve as key decision-making partners within the Austin YHDP team. Representatives of the AYC are deeply involved at every level of the community planning process, from the development of youth-centric housing options to system redesign efforts to ensure that youth do not exit the foster care or juvenile justice systems to homelessness. The article provides an overview of the development and contributions of the AYC—including their programmatic recommendations and advocacy work—as well as key recommendations for communities looking to leverage youth voice at the systems level.  相似文献   
58.

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Materials and methods

The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.

Results

In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).

Conclusions

We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.  相似文献   
59.

Objective

To assess a 6-month nutritional and physical activity intervention program on the nutritional status of overweight or obese and not very active 8-14 years old children by means of a controlled pre-post design (ACTIVA’T program).

Method

Pre-post study in 8-14 years old overweight or obese and low active children from Vilafranca del Penedès (Barcelona, Spain) randomized in control group (n = 51, 47.1% girls, nutritional intervention and ≤3 h/wk physical activity) and ACTIVA’T group (n = 45, 37.8% girls, nutritional and physical activity ≥5 h/wk intervention). Body mass index, waist/height index, and diet quality by means of KIDMED test at the beginning and at the end of the program were assessed. During the intervention, each participant was accompanied by a relative (father or mother) who performed the same activities as the children.

Results

Dietary recommendations have positively changed the habits of both ACTIVA’T and control group. The reversion in the prevalence of overweight and obesity was 93.8% and 58.6%, respectively, in the ACTIVA’T group, compared to 25.0% and 35.8% in the control group. Abdominal obesity was decreased from 42.2% to 17.8% in the ACTIVA’T group and from 47.1% to 27.5% in the control group.

Conclusions

The program ACTIVA’T (nutritional education and physical activity promotion) improves the quality of diet and reverses the prevalence of overweight and obesity in the underactive child population.  相似文献   
60.

Introduction

There are limited randomized data comparing radical cystectomy (RC) with bladder-sparing tri-modality therapy (TMT) in the treatment of muscle-invasive bladder cancer (MIBC). Both strategies are thought to have similar survival outcomes with different morbidity profiles. We compare the effectiveness of TMT and RC using decision-analytic modeling and the endpoint of quality-adjusted life years (QALYs).

Patients and Methods

Using a Markov model, we simulated the lifetime outcomes after TMT versus RC ± neoadjuvant chemotherapy for 67-year-old patients with clinical stage T2-T4aN0M0 MIBC. Model probabilities and utilities were extracted from the literature. The incremental effectiveness was reported in QALYs and sensitivity analyses were performed.

Results

For all patients with MIBC, although the model showed identical survival, TMT was the most effective strategy with an incremental gain of 0.59 QALYs over RC (7.83 vs. 7.24 QALYs, respectively). When limiting the model to favorable, contemporary cohorts in both the TMT and RC strategies, TMT remained more effective with an incremental gain of 1.61 QALYs (9.37 vs. 7.76 QALYs, respectively). One-way sensitivity analyses demonstrated the model was sensitive to the quality of life parameters (ie, the utilities) for RC and TMT. When testing the 95% confidence interval of the RC utility parameter the model demonstrated an incremental gain with TMT from ?0.54 to 4.23 QALYs. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 63% of model iterations.

Conclusions

This modeling study found that treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of QALYs relative to RC.  相似文献   
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