A comparison of the effects of oral vs. intravenous hydration on subclinical acute kidney injury: a protocol of a randomised controlled trial

Background: Optimal treatment for established renal failure is living donor kidney transplantation. However this pathway exposes healthy individuals to significant reduction in nephron mass via major surgical procedure. Laparoscopic donor nephrectomy is now the most common method for live donor transplantation, reducing both donor post-operative pain and recovery time. However this procedure exposes kidneys to additional haemodynamic stresses. It has been suggested that donor hydration—particularly the use of preoperative intravenous fluids—may counteract these stresses, reducing subclinical acute kidney injury and ultimately improving long-term renal function. This may be important in both preservation of donor renal function and recipient graft longevity. Methods/Design: A prospective single-centre single-blinded randomized controlled trial will be carried out to determine the effects of donor preoperative intravenous fluids. The primary outcome is donor subclinical acute kidney injury (defined as plasma NGAL, >153 ng/ml) on day 1 postoperatively. Secondary outcomes include intraoperative haemodynamics, recipient subclinical acute kidney injury, perioperative complications and donor sleep quality. Donors will be randomised into two groups: the intervention group will receive active pre-hydration consisting of three litres of intravenous Hartmann’s solution between midnight and 8 am before morning kidney donation, while the control group will not receive this. Both groups will receive unlimited oral fluids until midnight, as is routine. Plasma NGAL will be measured at pre-specified perioperative time points, intraoperative haemodynamic data will be collected using non-invasive cardiac output monitoring and clinical notes will be used to obtain demographic and clinical data. The researcher will be blinded to the donor fluid hydration status. Blinded statistical analysis will be performed on an intention-to-treat basis. A prospective power calculation estimates a required sample size of 86 patients. Discussion: This study will provide important data, as there is currently little evidence about the use of donor preoperative fluids in laparoscopic nephrectomy. It is hoped that the results obtained will guide future clinical practice

Renal function, uraemia and early arteriovenous fistula failure

Background Guidance varies regarding the optimal timing of arteriovenous fistula (AVF) creation. The aim of this study was to evaluate the association between uraemia, haemodialysis and early AVF failure. Methods Immunoblotting and cell proliferation assays were performed on vascular smooth muscle cells (VSM) cells isolated from long saphenous vein samples to evaluate the cells’ ability to proliferate when stimulated with uraemic (post-dialysis) and hyperuraemic (pre-dialysis) serum. Clinical data was collected prospectively for 569 consecutive radiocephalic (RCF) and brachiocephalic (BCF) fistulae. The primary outcome was AVF failure at 6 weeks. Dialysis status (haemodialysis (HD); pre-dialysis (Pre-D)), eGFR and serum urea were evaluated to determine if they affected early AVF failure. Results Human VSM cells demonstrated increased capacity to proliferate when stimulated with hyperuraemic serum. There was no significant difference in early failure rate of either RCF or BCF depending on dialysis status (pre-D RCF 31.4% (n = 188); pre-D BCF 22.4% (n = 165); HD RCF 29.3% (n = 99); HD BCF 25.9% (n = 116); p = 0.34). There was no difference in mean eGFR between those patients with early AVF failure and those without (11.2+/-0.2 ml/min/1.73 m2 vs. 11.6+/-0.4 ml/min/1.73 m2; p = 0.47). Uraemia was associated with early AVF failure (serum urea: 35.0+/-0.7 mg/dl vs. 26.6+/-0.3 mg/dl (p &lt; 0.001)). Conclusions We present the first in vivo evidence of an association between adverse early AVF outcomes and uraemia. This is supported mechanistically by in vitro work demonstrating a pro-mitogenic effect of hyperuraemic serum. We hypothesise that uraemia-driven upregulation of VSM cell proliferation at the site of surgical insult in contributes to higher early AVF failure rates.</p

Immediate access arteriovenous grafts versus tunnelled central venous catheters: study protocol for a randomised controlled trial

Background Autologous arteriovenous fistulae (AVF) are the optimal form of vascular access for haemodialysis. AVFs typically require 6 to 8 weeks to “mature” from the time of surgery before they can be cannulated. Patients with end-stage renal disease needing urgent vascular access therefore traditionally require insertion of a tunnelled central venous catheter (TCVC). TCVCs are associated with high infection rates and central venous stenosis. Early cannulation synthetic arteriovenous grafts (ecAVG) provide a novel alternative to TCVCs, permitting rapid access to the bloodstream and immediate needling for haemodialysis. Published rates of infection in small series are low. The aim of this study is to compare whether TCVC ± AVF or ecAVG ± AVF provide a better strategy for managing patients requiring immediate vascular access for haemodialysis. Methods/design This is a prospective randomised controlled trial comparing the strategy of TCVC ± AVF to ecAVG ± AVF. Patients requiring urgent vascular access will receive a study information sheet and written consent will be obtained. Patients will be randomised to receive either: (i) TCVC (and native AVF if this is anatomically possible) or (ii) ecAVG (± AVF). 118 patients will be recruited. The primary outcome is systemic bacteraemia at 6 months. Secondary outcomes include culture-proven bacteraemia rates at 1 year and 2 years; primary and secondary patency rates at 3, 6, 12 and 24 months; stenoses; re-intervention rates; re-admission rate; mortality and quality of life. Additionally, treatment delays, impact on service provision and cost-effectiveness will be evaluated. Discussion This is the first randomised controlled trial comparing TCVC to ecAVG for patients requiring urgent vascular access for haemodialysis. The complications of TCVC are considered an unfortunate necessity in patients requiring urgent haemodialysis who do not have autologous vascular access. If this study demonstrates that ecAVGs provide a safe and practical alternative to TCVC, this could instigate a paradigm shift in nephrology thinking and access planning.</p

A Growth Study on Phenylketonurics

Data from forty-eight medical records of phenylketonuria children under treatment were investigated to determine if growth, as measured by stature, was normal; and to determine if the state of control or the age at beginning of treatment had an effect on growth. Mean intakes of phenylalanine, protein, and calories were obtained on the nutritional data only if the simultaneous serum phenylalanine was equal to or less than 6 milligrams per cent. These means were grouped according to the age of the children into 7 groups (0 The height at beginning of treatment and the last measured height was compared with established norms of the Brush Foundation Study. To determine whether the state of control or age of beginning treatment were factors in growth, the children were divided into groups according to (1) age dietary treatment was instituted (equal to or less than six months and over six months), and (2) state of control. Good” control for this part of the study was having serum phenylalanine levels equal to or less than 4 milligrams per cent 75 percent of the time, and poor control, those having levels over 4 milligrams per cent 75 per cent of the time. The mean height of the parents compared favorably with the mean height for the white American male and female. At beginning of treatment the children were approximately half an inch shorter than estimated norms but at their last measured height they were 1,40 inches shorter. When the last recorded heights of the phenylketonuric children were analyzed considering time of beginning of treatment and state of control during treatment, there was no significant difference between the groups. The mean phenylalanine intake ranged from 227 to 488 milligrams each day. On a pound basis Group 1 consumed 19.3 milligrams per pound, with a gradual decrease to a low of 9.7 milligrams per pound in the 73 to 108 month age group. Protein intakes ranged from 20.8 grams a day for Group 1 to 45.7 grams each day for Group 7. The protein intake of the youngest group was above that recommended by the National Research Council, Groups 2, 3, 4, and 6 intakes were only slightly above the recommendations, Groups 5 and 7 had a somewhat lower intake than recommended. Mean caloric intake ranged from 611l to 1817 calories each day, increasing with increasing age. Calorie intake in Group 1 was 53.6 calories per pound of body weight. This was slightly higher than the recommended allowances. All other groups had mean calorie intakes less than those the National Research Council recommends. It was concluded that treated phenylketonuric children are significantly shorter than established norms but that age at beginning of treatment and control during treatment had no influence on the last heights of the children

Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort

Background: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment. Objectives: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing. Study design: Chronically infected, treatment-naïve, HCV genotype 1 patients (n = 146) attending NHS Greater Glasgow and Clyde clinics were investigated for RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A region was amplified by nested polymerase chain reaction. The 1.4 kb amplified product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43, 54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms. Results: Overall, 23.29% (34/146) of patients had an RAV or polymorphism detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70% (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four patients had dual combinations of mutations (T54S + V36L; T54S + V55A and 2 patients with T54S + Q80K). Conclusions: Q80K was the most prevalent baseline polymorphism detected in the Scottish cohort. Simeprevir treatment is not recommended in patients infected with the Q80K genotype 1a variant. This highlights the need for baseline sequencing prior to administration of this drug in this population

Optimising vascular access in incident haemodialysis patients

Arteriovenous fistula (AVF) are widely considered to be the optimal form of vascular access for haemodialysis incurring fewer complications, superior patency, better dialysis quality and a lower mortality than tunnelled central venous catheters (TCVCs). The use of TCVCs is associated with a six-fold increase in the risk of systemic sepsis, long-term morbidity from central vein stenosis and a higher risk of cardiovascular and all-cause mortality compared to AVF. Despite the relative success of strategies such as “Fistula First” and the best practice target in England and Wales (with simultaneous improvement in prevalent autologous access use) there has been no associated improvement in incident vascular access rates. The importance of “getting it right from the start” cannot be overemphasized. Patients who start dialysis via a line are more likely to remain with a line. Data from the UK Renal Registry indicate that 59.8% of patients starting on a TCVC remain dialysing via a TCVC at 3 months and >40% still have their TCVC after 1 year. The legacy of poor early vascular access decision-making remains with the patient throughout their life on dialysis. This thesis sought to evaluate methods for improving vascular access within the incident patient cohort. A multifaceted approach was taken to address several key themes: 1. TCVC complications and central vein stenosis: avoiding problems for the future. 2. Predicting maturation in incident dialysis patients. 3. Promoting maturation: strategies to optimise maturation. 4. Right access, right patient, right time: individualised, patient-centred care. 5. ‘Crashlanders’: managing patients who present without prior warning. The emphasis of this work was directed towards finding pragmatic, patient-focussed solutions to clinically relevant problems. The dogma of “Fistula First at all costs” is challenged

Autistic Traits, STEM, and Medicine: Autism Spectrum Quotient Scores Predict Medical Students’ Career Specialty Preferences

There is a higher than chance representation of autistic people and people with elevated autistic traits in Science, Technology, Engineering and Mathematics (STEM) industries. Medical students, despite studying a STEM subject, have lower autistic traits than other STEM students. Medicine is heterogenous, covering technique-oriented specialties (e.g., surgery) with little patient interaction, person-oriented specialties (e.g., pediatrics), and general practice. We present an online survey in which 502 UK university students (medicine, n = 344; STEM, n = 94; non-STEM, n = 64) reported their study area and career aspirations and completed the Autism Spectrum Quotient (AQ), a quantitative self-report measure of autistic traits. Our main findings were that medical students had significantly lower AQ scores than other STEM ( p &lt; .001, d = 0.614) and non-STEM students ( p &lt; .001, d = 0.874), and that medical students aiming to pursue technique-focused career paths had significantly higher AQ scores than medical students aiming to pursue person-oriented career paths ( p = .009, d = 0.318). Each of these effects remained statistically significant after adjusting for alpha inflation. The findings of this study corroborate those of previous research reporting a link between autism and STEM; they also provide evidence that autistic traits are a predictor of medical students’ career ambitions, with those students with high AQ scores being more likely to pursue technique-focused (as opposed to person-focused) roles. This may be informative for developing and optimizing the strengths of individuals with differing levels of autistic traits. </jats:p

Prominent misinformation interventions reduce misperceptions but increase scepticism.

Current interventions to combat misinformation, including fact-checking, media literacy tips and media coverage of misinformation, may have unintended consequences for democracy. We propose that these interventions may increase scepticism towards all information, including accurate information. Across three online survey experiments in three diverse countries (the United States, Poland and Hong Kong; total n = 6,127), we tested the negative spillover effects of existing strategies and compared them with three alternative interventions against misinformation. We examined how exposure to fact-checking, media literacy tips and media coverage of misinformation affects individuals perception of both factual and false information, as well as their trust in key democratic institutions. Our results show that while all interventions successfully reduce belief in false information, they also negatively impact the credibility of factual information. This highlights the need for further improved strategies that minimize the harms and maximize the benefits of interventions against misinformation

Long-term functional patency and cost-effectiveness of arteriovenous fistula creation under regional anesthesia: a randomized controlled trial

BACKGROUND:Regional anesthesia improves short-term blood flow through arteriovenous fistulas (AVFs). We previously demonstrated that, compared with local anesthesia, regional anesthesia improves primary AVF patency at 3 months. METHODS:To study the effects of regional versus local anesthesia on longer-term AVF patency, we performed an observer-blinded randomized controlled trial at three university hospitals in Glasgow, United Kingdom. We randomly assigned 126 patients undergoing primary radiocephalic or brachiocephalic AVF creation to receive regional anesthesia (brachial plexus block; 0.5% L-bupivacaine and 1.5% lidocaine with epinephrine) or local anesthesia (0.5% L-bupivacaine and 1% lidocaine). This report includes findings on primary, functional, and secondary patency at 12 months; reinterventions; and additional access procedures (primary outcome measures were previously reported). We analyzed data by intention to treat, and also performed cost-effectiveness analyses. RESULTS:At 12 months, we found higher primary patency among patients receiving regional versus local anesthesia (50 of 63 [79%] versus 37 of 63 [59%] patients; odds ratio [OR], 2.7; 95% confidence interval [95% CI], 1.6 to 3.8; P=0.02) as well as higher functional patency (43 of 63 [68%] versus 31 of 63 [49%] patients; OR, 2.1; 95% CI, 1.5 to 2.7; P=0.008). In 12 months, 21 revisional procedures, 53 new AVFs, and 50 temporary dialysis catheters were required. Regional anesthesia resulted in net savings of £195.10 (US$237.36) per patient at 1 year, and an incremental cost-effectiveness ratio of approximately £12,900 (US$15,694.20) per quality-adjusted life years over a 5-year time horizon. Results were robust after extensive sensitivity and scenario analyses. CONCLUSIONS:Compared with local anesthesia, regional anesthesia significantly improved both primary and functional AVF patency at 1 year and is cost-effective. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Local Anaesthesia versus Regional Block for Arteriovenous Fistulae, NCT01706354