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21.

Objective

Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis.

Methods

PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates.

Results

The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use.

Conclusions

Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.  相似文献   
22.

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   
23.

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   
24.

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   
25.
Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.Subject terms: Health policy, Population screening, Cancer screening, Cancer screening  相似文献   
26.
Abstract

Introduction: Student-staff partnerships as a concept to improve medical education have received a growing amount of attention. Such partnerships are collaborations in which students and teachers seek to improve education by each adding their unique contribution to decision-making and implementation processes. Although previous research has demonstrated that students are favourable to this concept, teachers remain hesitant. The present study investigated teachers’ conceptions of student-staff partnerships and of the prerequisites that are necessary to render such partnerships successful and enhance educational quality.

Method: We conducted semi-structured interviews with 14 course coordinators who lead course design teams and also teach in 4 bachelor health programmes, using Bovill and Bulley’s levels of student participation as sensitising concepts during data analysis.

Results: The results pointed to three different conceptions of student-staff partnerships existing among teachers: Teachers teach and students study; teachers teach and value students’ feedback; and teachers and students co-create. The prerequisites for effective co-creation teachers identified were: Teachers must be open to involve students and create dialogues; students must be motivated and have good communication skills; the organisation must be supportive; and teachers should have the final say.

Conclusion: We conclude that teachers’ conceptions are consistent with Bovill and Bulley’s levels of student participation. Under certain conditions, teachers are willing to co-create and reach the highest levels of student participation.  相似文献   
27.

Background

Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.

Methods

Literature available to date concerning the use of FMT to eradicate ARB was reviewed, and the different factors that may have influenced the efficacy of decolonization were evaluated.

Results

Four axes that could have played major roles in the efficacy of FMT were identified: bowel preparation before FMT; donor; dose; and thermal conditioning of faeces. The positive or negative impact of each on the outcome of FMT is discussed.

Conclusion

Although FMT is very efficient for the eradication of Clostridium difficile, the same ‘recipe’ cannot be used for the eradication of ARB. Working together with expert centres may help to improve the efficacy of FMT for this indication, and enable the reduction of in-hospital isolation precautions.  相似文献   
28.
Purpose

Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications.

Methods

Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored.

Results

Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications.

Conclusion

In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors.

Study registration

www.ClinicalTrials.gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.

  相似文献   
29.
Abstract

Thematic analysis is a widely used, yet often misunderstood, method of qualitative data analysis. It is a useful and accessible tool for qualitative researchers, but confusion regarding the method’s philosophical underpinnings and imprecision in how it has been described have complicated its use and acceptance among researchers. In this Guide, we outline what thematic analysis is, positioning it in relation to other methods of qualitative analysis, and describe when it is appropriate to use the method under a variety of epistemological frameworks. We also provide a detailed definition of a theme, as this term is often misapplied. Next, we describe the most commonly used six-step framework for conducting thematic analysis, illustrating each step using examples from our own research. Finally, we discuss advantages and disadvantages of this method and alert researchers to pitfalls to avoid when using thematic analysis. We aim to highlight thematic analysis as a powerful and flexible method of qualitative analysis and to empower researchers at all levels of experience to conduct thematic analysis in rigorous and thoughtful way.  相似文献   
30.
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