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1.

Background

The majority of patients with gastric or esophago-gastric cancer are at risk for malnutrition. Preoperative malnutrition was shown to increase the incidence of postoperative complications following abdominal surgery. However, it remains unclear if preoperative parenteral nutritional support during neoadjuvant chemotherapy (NACT) may be effective to reduce the rate of postoperative complications in these patients.

Methods/Design

The PERCOG trial is a randomized controlled multicenter observer-blinded trial, investigating if the improvement of the general condition of patients with non-metastasized gastric cancer or cancer of the esophago-gastric junction during NACT by supplemental parenteral nutrition can decrease the postoperative Comprehensive Complication Index (CCI). Statistical analysis of the primary endpoint measure (CCI on postoperative day 30) will be based on the intention-to-treat population. The global level of significance is set at 5% and the sample size (n?=?150) is determined to assure a power of 80%.

Discussion

The results of the PERCOG trial will provide high-level evidence for clinical recommendations regarding the administration of preoperative supportive parenteral nutrition and provide all participating patients the opportunity of an improved treatment.

Trial registration

German Clinical Trials Register, DRKS00009451. Registered on 3 July 2017.
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2.

Background

Intra-operative urinary catheterization frequently causes postoperative catheter related bladder discomfort (CRBD) during recovery. We conducted this study to evaluate the efficacy of tramadol, which with muscarinic receptor antagonist property, as a treatment for CRBD.

Methods

Ninety patients who underwent elective gynecological surgery and complained of CRBD in the (PACU) were randomized into three groups of 30 each. Group A received normal saline, group B 1?mg/kg tramadol, and group C 1.5?mg/kg tramadol. The medication was administered from the Murphy’s dropper with a slow drip, and the severity of CRBD (none, mild, moderate, and severe) and postoperative pain were assessed after 0, 0.5, 1, 2 and 6?h.

Results

The severity of CRBD was reduced in group C compared with that in groups A and B at 1?h, and in groups C and B compared with that in group A at 2?h. The incidence of CRBD was reduced in group C compared with that in groups A and B at 2?h, and in group C compared with that in group A at 6?h. The visual analog scale (VAS) was reduced in group C compared with that in groups A and B at all time intervals. No differences in adverse effects were observed.

Conclusions

Tramadol 1.5?mg/kg was more effective than tramadol 1?mg/kg in treating CRBD and reducing postoperative pain, without significant side effects.

Trial registration

ChiCTR1800016390. Registered on 30 May 2018.
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3.

Objective

The objective of this study is to systematically assess the clinical efficacy of hand-assisted laparoscopic surgery (HALS) and laparoscopic right colectomy (LRC).

Methods

The randomized controlled trials (RCTs) and non-RCTs were collected by searching electronic databases (Pubmed, Embase, and the Cochrane Library). The outcomes included intraoperative outcomes, postoperative outcomes, postoperative morbidity, and oncologic outcomes. Meta-analysis was performed using of RevMan 5.3 software.

Results

A total of five studies involving 438 patients were finally included, with 202 cases in HALS group and 236 cases in LRC group. Results of meta-analysis showed that there was no statistical difference between HALS and LRC in terms of conversion rate, length of hospital stay, reoperation rate, postoperative morbidity, and oncologic outcomes. The operative time was 6.5 min shorter in HALS group; however, it was not a clinically significant difference. Although the incision length was longer in HALS, it did not influence the postoperative recovery.

Conclusions

HALS can be considered an alternative to LRC which combines the advantages of open as well as laparoscopic surgery.
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4.

Background

Pain after major lower limb amputation for peripheral arterial disease (PAD) is a significant problem. A perineural catheter (PNC) can be placed adjacent to the major nerve at the time of amputation with a continuous local anaesthetic infusion given postoperatively to try and reduce pain. Although low-quality observational data suggest that PNC usage reduces postoperative opioid requirements, there are limited data regarding its effect on pain. The aim of PLACEMENT is to explore the feasibility of running an effectiveness trial to assess the impact of a PNC with continuous local anaesthetic infusion, inserted at the time of amputation, on short and medium-term postoperative outcomes.

Methods/design

Fifty patients undergoing a major lower limb amputation (below or above the knee) for PAD will be recruited from two centres. Patients will be randomised in a 1:1 ratio to receive standard postoperative analgesia, with or without insertion of a PNC and local anaesthetic infusion for the first 5 postoperative days. Outcome data will be captured for the first 5 days, including pain scores (primary outcome, captured three times a day), opioid use, nausea or vomiting, itching, dizziness and complications. Patients will be contacted 2 and 6 months after surgery to assess quality of life, phantom limb pain, chronic stump pain and total healthcare costs. Semi-structured interviews will be conducted with at least 10 patients (dependent on saturation of analytic themes on preliminary coding) purposefully sampled to achieve variation in site and study arm. Interviews will explore patients’ perception of post-amputation pain and its treatment, and experience of study processes. Semi-structured interviews with 5–10 health professionals will explore feasibility, fidelity, and acceptability of the study. Data from this pilot will be used to assess feasibility of, and estimate parameters to calculate the sample size for an effectiveness trial. Full ethical approval has been granted (Wales Research Ethics Committee 3 reference number 16/WA/0353).

Discussion

PLACEMENT will be the first study to explore the feasibility of running an effectiveness trial on PNC usage for postoperative pain in amputees, and provide parameters to calculate the appropriate sample size for this study.

Trial registration

ISRCTN.com, ISRCTN85710690. Registered on 21 October 2016.European Clinical Trials Database (EudraCT), 2016-003544-37. Registered on 24 August 2016.
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5.

Background

There has been an increased drive towards Evidence Based Policing in recent years. Unlike in other public sector services, such as health and education, randomised controlled trials in the police setting are relatively rare. This paper discusses some of the methodological and practical challenges of conducting a randomised controlled trial in the police setting in the UK, based on our experience of the Connect trial. This pragmatic, cluster-randomised controlled trial investigated the effectiveness of a face-to-face training intervention for frontline officers in comparison to routine training. The primary outcome was the number of incidents which resulted in a police response reported to North Yorkshire Police control room in a 1-month period up to 6 months after delivery of training.

Main text

The methodological and practical challenges that we experienced whilst conducting the Connect trial are discussed under six headings: establishing the unit of randomisation; population of interest and sample size; co-production of evidence; time frame; outcomes; and organisational issues.

Conclusion

Recommendations on the conduct of future randomised controlled trials in the police setting are made. To understand the context in which research is undertaken, collaboration between police and academia is needed and police officers should be embedded within trial management groups. Engagement with police data analysts to understand what data is available and facilitate obtaining trial data is also recommended. Police forces may wish to review their IT systems and recording practices. Pragmatic trials are encouraged and time frames need to allow for trial set-up and obtaining relevant ethical approvals.

Trial registration

ISRCTN Registry, ID: ISRCTN11685602. Retrospectively registered on 13 May 2016.
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6.

Background

Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation.

Methods/design

We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV1) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV1 z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome.

Discussion

The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIV-infected children live and where HIV-associated CLD is highly prevalent.

Trial registration

ClinicalTrials.gov, NCT02426112. Registered on 21 April 2015.
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7.

Objective

This study examined the differences of psychological strains between Chinese and American college students and discussed how strains may influence individuals’ suicidal ideation and depression.

Participants/methods

A total of 539 college students (298 from China and 241 from the U.S.) were recruited in March 2016 to complete the survey study. Multiple linear regressions were used in data analysis.

Results

Students in America had higher scores on depression and stress than students in China, while students in China rated higher on suicidal ideation than students in America. In contrast of students in America facing more coping strains, students in China were confronting more value strains in their life.

Conclusion

The cross-cultural variations in the effect of psychological strains have been substantiated in current study, indicating that understanding the psychological strains in different cultural contexts is necessary for the early intervention and prevention in college aged populations.
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8.

Background

Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified.

Methods

We used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012.

Results

We detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period.

Conclusions

This is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.
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9.

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (1H & 13C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.
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10.

Context

Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

Objective

To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

Design

Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

Setting

Referral practice and research center.

Participants

60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

Main outcome measures

Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

Results

CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

Conclusion

A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.
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11.

Background

Preoperative anxiety is common in pediatric patients. When dexmedetomidine is used alone for sedation as premedication, children tend to awaken when separated from their parents, and body movements occur during invasive procedures. We tested the hypothesis that the combination of dexmedetomidine and ketamine may be a useful premedication to alleviate preoperative anxiety and improve cooperation during intravenous cannulation in pediatric patients, while producing minimal adverse events.

Methods

A total of 135 children, aged 2–5 years and American Society of Anesthesiologists status I–II, scheduled for eye surgery were randomly allocated to receive intranasal dexmedetomidine 2.5 μg/kg (group D), oral ketamine 3 mg/kg and intranasal dexmedetomidine 2 μg/kg (group DK), or oral ketamine 6 mg/kg (group K) 30 min before surgery. Sedation state was evaluated every 10 min after premedication and emotional state was assessed during separation from their parents and peripheral intravenous cannulation. Adverse events were recorded for 24 h postoperatively. The primary endpoint was the rate of successful intravenous cannulation.

Results

The rate of successful venous cannulation was 47% with dexmedetomidine alone, 68% with ketamine alone, and 80% with combined premedication (P?=?0.006). The rate of satisfactory separation from parents was not different among groups. The incidence of adverse events was higher in group K compared with the other two groups (postoperative vomiting, P?=?0.0041; respiratory-related complications during the perioperative period, P?=?0.0032; and postoperative psychological/psychiatric adverse events, P?=?0.0152).

Conclusion

The combination of intranasal dexmedetomidine 2 μg/kg and oral ketamine 3 mg/kg produces satisfactory separation from parents and more successful venous cannulation, allowing children to smoothly accept induction of general anesthesia.

Trial registration

Chinese Clinical Trial Register (Unique identifier: ChiCTR-TRC-14004475, Date of registration: 2 April 2014).
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12.

Background

Amyotrophic Lateral Sclerosis (ALS) is a rapid progressive neurodegenerative disease, characterized by a selective loss of motor neurons, brain stem and spinal cord which leads to deterioration of motor abilities. Devices that promote interaction with tasks on computers can enhance performance and lead to greater independence and utilization of technology.

Objective

To evaluate performance on a computer task in individuals with ALS using three different commonly used non-immersive devices.

Method

Thirty individuals with ALS (18 men and 12 women, mean age 59?years, range 44–74?years) with a mean score of 26, (minimum score of 14 and maximum 41) on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and 30 healthy controls matched for age and gender, participated. All participants were randomly divided into three groups, each using a different device system (motion tracking, finger motion control or touchscreen) to perform three task phases (acquisition, retention and transfer).

Results

Both the ALS and control group (CG) showed better performance on the computer task when using the touchscreen device, but there was limited transfer of performance onto the task performed on the Finger Motion control or motion tracking. However, we found that using the motion tracking device led to transfer of performance to the touchscreen.

Conclusion

This study presents novel and important findings when selecting interaction devices for individuals with ALS to access technology by demonstrating immediate performance benefits of using a touchscreen device, such as improvement of motor skills. There were possible transferable skills obtained when using virtual systems which may allow flexibility and enable individuals to maintain performance overtime.

Trial registration

Registration name: Virtual Task in Amyotrophic Lateral Sclerosis; Registration number: NCT03113630; retrospectively registered on 04/13/2017. Date of enrolment of the first participant to the trial: 02/02/2016.
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13.

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.
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14.

Background

Duloxetine, Etoricoxib and opioid are of the commonly administered drugs in Lumbar laminectomy. The aim of this study is to assess the effect of perioperative use of Duloxetine in combination with Etoricoxib on postoperative pain and opioid requirements.

Methods

One hundred twenty patients with ASA physical status were enrolled with age between 18 and 70 years. Patients were divided randomly into four groups of 30 patients: group P received placebo, group E received etoricoxib 120 mg, group D received duloxetine 60 mg and group D/E received duloxetine 60 mg capsules and etoricoxib 120 mg; 1 h before surgery and 24 h after.

Results

Neither Duloxetine nor etoricoxib individually had effect on pain with movement, while their combination revealed a significant reduction in pain scores over the entire postoperative period at rest and on movement. Etoricoxib showed a significant decrease in pain at all times at rest when compared with group P, while it showed significant pain decrease only at 0, 2 and 4 h when compared with group D. On the other hand duloxetine alone showed significant decrease in pain at rest at 24 h and 48 h when compared with group P. ConcerningMorphine requirement after 24 h.; it wassignificantly lower in the D/E group in comparison with groups P, E and D. It should be noted also that there was a significant decrease morphine requirement in both groups E and D.

Conclusion

The perioperative administration of the combination of etoricoxib and duloxetine improved analgesia and reduced opioid consumption without significant side effects.

Trial registration

ISRCTN48329522. 17 June 2017
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15.

Background

The objective of this study was to assess the effect of a web-based audit and feedback (A&F) intervention with outreach visits to support decision-making by multidisciplinary teams.

Methods

We performed a multicentre cluster-randomized trial within the field of comprehensive cardiac rehabilitation (CR) in the Netherlands. Our participants were multidisciplinary teams in Dutch CR centres who were enrolled in the study between July 2012 and December 2013 and received the intervention for at least 1 year. The intervention included web-based A&F with feedback on clinical performance, facilities for goal setting and action planning, and educational outreach visits. Teams were randomized either to receive feedback that was limited to psychosocial rehabilitation (study group A) or to physical rehabilitation (study group B). The main outcome measure was the difference in performance between study groups in 11 care processes and six patient outcomes, measured at patient level. Secondary outcomes included effects on guideline concordance for the four main CR therapies.

Results

Data from 18 centres (14,847 patients) were analysed, of which 12 centres (9353 patients) were assigned to group A and six (5494 patients) to group B. During the intervention, a total of 233 quality improvement goals was identified by participating teams, of which 49 (21%) were achieved during the study period. Except for a modest improvement in data completeness (4.5% improvement per year; 95% CI 0.65 to 8.36), we found no effect of our intervention on any of our primary or secondary outcome measures.

Conclusions

Within a multidisciplinary setting, our web-based A&F intervention engaged teams to define local performance improvement goals but failed to support them in actually completing the improvement actions that were needed to achieve those goals. Future research should focus on improving the actionability of feedback on clinical performance and on addressing the socio-technical perspective of the implementation process.

Trial registration

NTR3251
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16.
17.

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.
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18.

Background

Multiorifice catheters have been shown to provide superior analgesia and significantly reduce local anesthetic consumption compared with end-hole catheters in epidural studies. This prospective, blinded, randomized study tested the hypothesis that, in continuous femoral nerve block (CFNB) under ultrasound guidance, multiorifice catheter would reduce local anesthetic consumption at 24?h compared with end-hole catheter.

Methods

Eighty adult patients (aged ≥18?years) scheduled to undergo primary total knee arthroplasty under a combination of CFNB, sciatic nerve block and general anesthesia were randomized to CFNB using either a 3-pair micro-hole (Contiplex, BRAUN®, 20G - 400?mm) or an end-hole (Silverstim VYGON®, 20G - 500?mm) catheter. Once the femoral catheter was sited, a bolus of 20?mL lidocaine 1% was injected. An electronic pump then delivered an automated 5?mL bolus of ropivacaine 0.2% hourly, with 10?mL self-administered patient controlled analgesia boluses.

Results

There was no inter-group difference in either median number of ropivacaine boluses on demand during the first 24?h (4(2–7) vs. 4(2–8) in six-hole and end-hole groups, respectively; P?=?0.832) or median ropivacaine consumption at 48?h (365(295–418) vs. 387(323–466); P?=?0.452).No significant differences were recorded between the groups at 24?h regarding median average verbal rate pain scale (2(0–3) vs. 2(0–4); P?=?0.486) or morphine consumption (0(0–20) vs. 0(0–20); P?=?0.749). Quadriceps muscle strength declined to 7% (0–20) and 10% (0–28) in the six-hole and end-hole groups, respectively, at 24?h after surgery (P?=?0.733).

Conclusions

In this superiority trial, catheter orifice configuration did not influence the effectiveness of CFNB in this setting: quality of analgesia was similar, with no reduction in either local anesthetic or morphine consumption, and equivalent postoperative quadriceps weakness.

Trial registration

Retrospectively registered at (NCT03376178). Date: 21 November 2017.
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19.

Background

The evidence on the use of the oral dimethyl-fumarate after the discontinuation of treatment with natalizumab in people with Multiple Sclerosis is still little. Natalizumab discontinuation may induce the recurrence or rebound of the clinical and neuroradiological disease activity. Currently no therapeutic approach has been established to abolish disease reactivation and rebound after natalizumab interruption.

Case Presentation

We describe a case of a 21-year-old woman affected from a highly active relapsing-remitting Multiple Sclerosis who developed a clinical and radiological rebound 5 months after the last infusion of natalizumab, while she was being treated with dimethyl-fumarate 240 mg twice daily. She had received a bridge “therapy” with Cyclophosphamide before staring dimethyl-fumarate.

Conclusion

We report on this case to stimulate further research to establish whether new current and future drugs available for multiple sclerosis are able to halt the disease rebound after the natalizumab interruption.
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20.

Background

Pseudomyxoma peritonei is a rare condition consisting of mucinous ascites, most commonly arising from mucinous tumors of the appendix and occasionally from the ovary. Very rarely mucinous implants arise in the retroperitoneum without any intra-peritoneal involvement. This has been termed as pseudomyxoma extraperitonei.

Case presentation

We report a case of a 57 year old man who developed pseudomyxoma extraperitonei, 35 years after undergoing an appendicectomy for a perforated appendix.

Conclusions

Pseudomyxoma extraperitonei has been previously reported, however we report the longest incubation period of 35 years for this condition.
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