Isolated tumour microparticles induce endothelial microparticle release in vitro

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Cancer induces a hypercoagulable state, resulting in an increased risk of venous thromboembolism. One of the mechanisms driving this is tissue factor (TF) production by the tumour, released in small lipid bound microparticles. We have previously demonstrated that tumour cell line media-induced procoagulant changes in HUVEC. The aim of this study was to investigate the effect of tumour microparticles and recombinant human TF (rhTF) on the endothelium. Procoagulant microparticles from the PANC-1 cell line were harvested by ultrafiltration. HUVEC were then incubated with these procoagulant microparticles or rhTF. Flow cytometry was used to investigate the effect of endothelial cell surface protein expression and microparticle release. Microparticles but not soluble TF was responsible for the procoagulant activity of cell-free tumour media. We also demonstrated an increase in endothelial microparticle release with exposure to tumour microparticles, with a positive linear relationship observed (R2 = 0.6630 P ≤ 0.0001). rhTF did not induce any of the changes observed with microparticles. Here we demonstrate that procoagulant activity of tumour cell line media is dependent on microparticles, and that exposure of endothelial cells to these microparticles results in an increase in microparticle release from HUVEC. This suggests a mechanism of transfer of procoagulant potential from the cancer to the remote endothelium

The Patient Voice : An analysis of free-text responses from the 2023 National Kidney Patient Experience Survey (Kidney PREM)

The Kidney Patient Reported Experience Measure (Kidney PREM) is facilitated annually by the UK Kidney Association and Kidney Care UK. The Kidney PREM has 39 questions covering 13 themes, and in 2023 was available online only. The end of the survey has a free-text question asking participants to comment on any aspect of their care. “If there is any other aspect of your experience of kidney care that you would like to comment on that has not already been covered, please tell us below”. In 2023, 11,647 people with kidney disease took part, with 4,202 (36% of responses) providing a further comment on their care. The number of individuals responding to Kidney PREM increased slightly from 2022, with the number of respondents leaving a comment increasing by 14.5% in part undoubtedly due to the nature of Kidney PREM being online only. This increase in the number of comments improves understanding of patient experience of kidney care and helps to explain the reasons for changes in theme scores in the national report from the previous year. Additionally, 94.1% of responders gave consent for their comments to be passed back to their kidney centre meaning they can be used to help inform quality improvement. Generally, the profile of responders who left a free-text comment matched that of the national Kidney PREM 2023; however, there was a higher representation in the comments from individuals of a Black ethnic heritage (+1.3%). Compared to Kidney PREM 2022, the profile of responders remained consistent. Comments were mapped to the 13 themes of experience that make up the Kidney PREM survey, as the free-text responses align with them well. How the Kidney Team Treats You received the highest number of related comments (2,283), with 66% of comments under this theme being positive. Comments under this theme focused on positive views about staff, thanking them for their care and dedication, as well as mentioning role-specific staff members positively. Comments containing examples of good experiences of care featured highly. Access to the Kidney Team was the second most common theme (721 comments) to emerge from the comments and was predominantly negative (69%). Respondents commented on wanting to see a consultant more frequently, as well as having appointments scheduled with the dietician, social worker and psychologist. Additionally, respondents mentioned the need for better access to the kidney team outside of dialysis sessions. Environment (649 comments), Scheduling and Planning (546 comments), and Transport (525 comments) received comments from individuals wanting better parking facilities, food to be offered during dialysis sessions and for appointments to be more frequent and better organised with no last-minute cancellations. Appointments via the telephone had mixed reviews with some finding them more convenient and a better use of time, whilst others feel they are less person-centred. Waiting times for transport following dialysis sessions continues to be an issue with individuals having to wait longer than an hour on most occasions. Aspects of care such as Needling, Privacy and Dignity, and Sharing Decisions received fewer comments but should still be considered as important areas of care for improvement. Individuals receiving treatment would like more opportunities to discuss what they would like from their care, needling to be performed by competent members of staff, so as to be less painful and for conversations with consultants and nurses to be conducted in private, with those who identify as female having a separate space to dialyse to maintain dignity. Emerging Themes (494 comments) contain comments which do not align with the Kidney PREM themes, including medication and prescriptions, information about diagnosis or specific treatment issues, and ‘dialysis while on holiday’. This year, in alignment with the Kidney PREM survey, two new themes arose from the free-text responses, Overall Experience and Additional Questions. There were 255 comments (98% positive) about overall experience of care, and 353 comments about additional questions that were asked within the Kidney PREM survey such as whether individuals use Patient Knows Best, language barriers and feedback from last year’s Kidney PREM report. Respondents’ characteristics were also reflected in comments: for instance, younger individuals tended to focus on the Environment and older individuals on How the Kidney Team Treats You and Access to the Kidney Team. Those receiving haemodialysis in-centre or at a satellite unit were more likely to comment about the Environment and Transport, with those not receiving Kidney Replacement Therapy (KRT) or who have received a functioning transplant focused on Scheduling and Planning, and Access to the Kidney Team

Patient Reported Experience of Kidney Care in the UK 2022

Executive Summary This is the seventh annual report of the national Kidney PREM which is a measure of kidney patients’ self-reported experience of the care they receive from kidney centres. It provides people living with kidney disease with the opportunity to feed into serviceimprovement by sharing what matters most to them. Data collection for this report took place for six weeks between 1st October and 11th November 2022. A total of 11,063 valid responses (7,030 online, 4,033 paper) were received, slightly fewer than in previous years. It is noteworthy that 15,210 paper surveys were sent to centres with only 26.5% being returned. Missing data were more common in paper returns. These issues have considerable resource implications. Older people and those receiving haemodialysis were more likely to use paper though the majority in both groups responded online. The proportion of responders aged over 75 (25.1%) was higher than previous years and this group was over-represented in the sample compared to the proportion in this age category in the UK Renal Registry returns for those receiving kidney replacement therapy (KRT). Individuals of Asian ethnic background remain under-represented on the same basis. Transplant recipients were again markedly under-represented (16.8% of returns) whilst those receiving centre and satellite-based haemodialysis (61.1%) were over-represented. The proportion with chronic kidney disease (not receiving KRT) has remained stable at 15.2%. 145 (9%) of these stated that they had chosen conservative management – more than double that in 2021. Overall, a high proportion of participants (27%) said they needed help to complete the survey – especially those over 75, those of Asian ethnic background, and those receiving dialysis. There has been a small increase in the proportion of haemodialysis recipients participating in shared care – though a significant proportion still reported not being asked to participate, especially older respondents (42.2% of those over 75) and those dialysed in-centre rather than in satellites (41.5%). For the first time, participants were asked whether English was their primary spoken language. 1,235 (12.8%) said they had a language other than English. Almost 100 languages were reported, Asian languages being the most prominent. In another first, individuals were given the option to provide the first part of their postcode. 7,998 analysable values (72.3% of all responses) were returned. These data may allow assessment of participant deprivation. Respondents were asked ‘Overall, how much better or worse was your kidney care experience during the last year?’. Though scores for the majority have remained stable, experience seems to have improved slightly amongst those not receiving KRT, whilst for those receiving centreand satellite-based haemodialysis experience seems to have deteriorated. This may reflect a reversal of service changes enforced by the pandemic. In 2020 non-KRT and, to a lesser extent, transplanted individuals experienced reduced outpatient provision and reduced access to specialist nursing, whilst those receiving centre- and satellite-based haemodialysis experienced some benefits, notably changes in transport arrangement. The trends described may reflect a ‘levelling-out’ effect. There was little change from previous years across the 13 Kidney PREM themes. Access to the Renal Team, Privacy & Dignity and Patient Information remain the highest scoring themes and Sharing Decisions About Your Care and Transport continue to be scored poorly. The gains made in the Transport theme in 2020 have dwindled. Scores for Support, Communication and Needling remain just above the lowest two themes, although Support and Needling continue their slight year on year improvement. These low scoring themes also tended to have the widest ranges of centre mean values. There were major differences in some theme scores by treatment modality. Notably scores for Fluid Intake and Diet were markedly low in those not receiving KRT and Sharing Decisions and Privacy & Dignity amongst in centre-based and satellite haemodialysis recipients. Low scores in Communication were largely driven by scores on questions related to communication with GPs and non-healthcare services; in Transport by not being able to leave the haemodialysis unit within 30 minutes of being ready to leave; and in Environment by parking. Scores on How the Renal Team Treats You were generally good though perhaps reduced by low scores on the question of being asked about emotional feelings. Those centres with the lowest theme scores tended to be those with fewest responses. Though there are a number of areas highlighted above in which there is potential for improvement, it is encouraging that the Overall experience question continues to be scored well with only minor differences across modalities

Postprandial plasma amino acid and appetite responses with ingestion of a novel salmon-derived protein peptide in healthy young adults

This study assessed postprandial plasma aminoacidemia, glycemia, insulinemia and appetite responses to ingestion of a novel salmon-derived protein peptide (Salmon PP) compared with milk protein isolate (Milk PI). In a randomised, participant-blind crossover design, eleven healthy adults (M = 5, F = 6; mean ± sd age: 22 ± 3 years; BMI: 24 ± 3 kg/m2) ingested 0·3 g/kg/body mass of Salmon PP or Milk PI. Arterialised blood samples were collected whilst fasted and over a 240-min postprandial period. Appetite sensations were measured via visual analogue scales. An ad libitum buffet-style test meal was administered after each trial. The incremental AUC (iAUC) plasma essential amino acid (EAA) response was similar between Salmon PP and Milk PI. The iAUC plasma leucine response was significantly greater following Milk PI ingestion (P &lt; 0·001), whereas temporal and iAUC plasma total amino acid (P = 0·001), non-essential amino acid (P = 0·002), glycine (P = 0·0025) and hydroxyproline (P &lt; 0·001) responses were greater following Salmon PP ingestion. Plasma insulin increased similarly above post-absorptive values following Salmon PP and Milk PI ingestion, whilst plasma glucose was largely unaltered. Indices of appetite were similarly altered following Salmon PP and Milk PI ingestion, and total energy and macronutrient intake during the ad libitum meal was similar between Salmon PP and Milk PI. The postprandial plasma EAA, glycine, proline and hydroxyproline response to Salmon PP ingestion suggest this novel protein source could support muscle and possibly connective tissue adaptive remodelling, which warrants further investigation, particularly as the plasma leucine response to Salmon PP ingestion was inferior to Milk PI.</p

Interventions for treating urinary incontinence after stroke in adults

Background Urinary incontinence can affect 40% to 60% of people admitted to hospital after a stroke, with 25% still having problems when discharged from hospital and 15% remaining incontinent after one year. This is an update of a review published in 2005 and updated in 2008. Objectives To assess the effects of interventions for treating urinary incontinence after stroke in adults at least one‐month post‐stroke. Search methods We searched the Cochrane Incontinence and Cochrane Stroke Specialised Registers (searched 30 October 2017 and 1 November 2017 respectively), which contain trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearched journals and conference proceedings. Selection criteria We included randomised or quasi‐randomised controlled trials. Data collection and analysis Two review authors independently undertook data extraction, risk of bias assessment and implemented GRADE. Main results We included 20 trials (reporting 21 comparisons) with 1338 participants. Data for prespecified outcomes were not available except where reported below. Intervention versus no intervention/usual care Behavioural interventions: Low‐quality evidence suggests behavioural interventions may reduce the mean number of incontinent episodes in 24 hours (mean difference (MD) –1.00, 95% confidence interval (CI) –2.74 to 0.74; 1 trial; 18 participants; P = 0.26). Further, low‐quality evidence from two trials suggests that behavioural interventions may make little or no difference to quality of life (SMD ‐0.99, 95% CI ‐2.83 to 0.86; 55 participants). Specialised professional input interventions: One trial of moderate‐quality suggested structured assessment and management by continence nurse practitioners probably made little or no difference to the number of people continent three months after treatment (risk ratio (RR) 1.28, 95% CI 0.81 to 2.02; 121 participants; equivalent to an increase from 354 to 453 per 1000, 95% CI 287 to 715). Complementary therapy: Five trials assessed complementary therapy using traditional acupuncture, electroacupuncture and ginger‐salt‐partitioned moxibustion plus routine acupuncture. Low‐quality evidence from five trials suggested that complementary therapy may increase the number of participants continent after treatment; participants in the treatment group were three times more likely to be continent (RR 2.82, 95% CI 1.57 to 5.07; 524 participants; equivalent to an increase from 193 to 544 per 1000, 95% CI 303 to 978). Adverse events were reported narratively in one study of electroacupuncture, reporting on bruising and postacupuncture abdominal pain in the intervention group. Physical therapy: Two trials reporting three comparisons suggest that physical therapy using transcutaneous electrical nerve stimulation (TENS) may reduce the mean number of incontinent episodes in 24 hours (MD –4.76, 95% CI –8.10 to –1.41; 142 participants; low‐quality evidence). One trial of TENS reporting two comparisons found that the intervention probably improves overall functional ability (MD 8.97, 95% CI 1.27 to 16.68; 81 participants; moderate‐quality evidence). Intervention versus placebo Physical therapy: One trial of physical therapy suggests TPTNS may make little or no difference to the number of participants continent after treatment (RR 0.75, 95% CI 0.19 to 3.04; 54 participants) or number of incontinent episodes (MD –1.10, 95% CI –3.99 to 1.79; 39 participants). One trial suggested improvement in the TPTNS group at 26‐weeks (OR 0.04, 95% CI 0.004 to 0.41) but there was no evidence of a difference in perceived bladder condition at six weeks (OR 2.33, 95% CI 0.63 to 8.65) or 12 weeks (OR 1.22, 95% CI 0.29 to 5.17). Data from one trial provided no evidence that TPTNS made a difference to quality of life measured with the ICIQLUTSqol (MD 3.90, 95% CI –4.25 to 12.05; 30 participants). Minor adverse events, such as minor skin irritation and ankle cramping, were reported in one study. Pharmacotherapy interventions: There was no evidence from one study that oestrogen therapy made a difference to the mean number of incontinent episodes per week in mild incontinence (paired samples, MD –1.71, 95% CI –3.51 to 0.09) or severe incontinence (paired samples, MD –6.40, 95% CI –9.47 to –3.33). One study reported no adverse events. Specific intervention versus another intervention Behavioural interventions: One trial comparing a behavioural intervention (timed voiding) with a pharmacotherapy intervention (oxybutynin) contained no useable data. Complementary therapy: One trial comparing different acupuncture needles and depth of needle insertion to assess the effect on incontinence reported that, after four courses of treatment, 78.1% participants in the elongated needle group had no incontinent episodes versus 40% in the filiform needle group (57 participants). This trial was assessed as unclear or high for all types of bias apart from incomplete outcome data. Combined intervention versus single intervention One trial compared a combined intervention (sensory motor biofeedback plus timed prompted voiding) against a single intervention (timed voiding). The combined intervention may make little or no difference to the number of participants continent after treatment (RR 0.55, 95% CI 0.06 to 5.21; 23 participants; equivalent to a decrease from 167 to 92 per 1000, 95% CI 10 to 868) or to the number of incontinent episodes (MD 2.20, 95% CI 0.12 to 4.28; 23 participants). Specific intervention versus attention control Physical therapy interventions: One study found TPTNS may make little or no difference to the number of participants continent after treatment compared to an attention control group undertaking stretching exercises (RR 1.33, 95% CI 0.38 to 4.72; 24 participants; equivalent to an increase from 250 to 333 per 1000, 95% CI 95 to 1000). Authors' conclusions There is insufficient evidence to guide continence care of adults in the rehabilitative phase after stroke. As few trials tested the same intervention, conclusions are drawn from few, usually small, trials. CIs were wide, making it difficult to ascertain if there were clinically important differences. Only four trials had adequate allocation concealment and many were limited by poor reporting, making it impossible to judge the extent to which they were prone to bias. More appropriately powered, multicentre trials of interventions are required to provide robust evidence for interventions to improve urinary incontinence after stroke

Patient Reported Experience of Kidney Care in the UK 2021

Headline findings • 12,416 people with kidney disease, from all 68 treating centres in the UK, took part in Kidney PREM this year, largely online. • Overall experience of kidney care continues to be rated highly, with many patients who provided a written comment thanking staff for their commitment and efforts. • For four in five participants, overall experience of kidney care stayed the same or was better during the last year of COVID-19. People with a transplant and those with CKD are more likely than those receiving dialysis to report a worse experience of kidney care over the last year. • Privacy and Dignity, Patient Information and Access to the Renal Team continue to be high scoring and are the most consistent regardless of treatment. • Experience of Communication between members of the renal unit team and people with kidney disease was scored far higher than communication between members of the renal team and GPs. • Patient reported experience of Sharing Decisions About Your Care is particularly low scoring, with greater variability in experience between centres and across treatment types. More than half of those on haemodialysis have not been invited to take part in tasks of haemodialysis care, or do not know if they have. • Broadly half of those receiving in-centre or in-satellite haemodialysis say that staff always Needle their fistula or graft with as little pain as possible; this remains a low scoring area with considerable range between centres. • People receiving peritoneal dialysis and home haemodialysis report improved experience of Support from the renal unit team with treatment this year, compared to those receiving in-centre haemodialysis. Support in general continues to be a low scoring theme, notably lower than in 2019. • Experience of Advice on Fluid Intake scores higher than Advice on Diet, and both are rated higher by those receiving dialysis than people with CKD or in receipt of a transplant. • People receiving peritoneal dialysis report improved experience of Tests, with results being returned more quickly; this has worsened for those with a transplant and remains relatively low for people receiving in-centre haemodialysis. Half of respondents do not always understand their test results. • Patient reported experience of Transport continues to be scored better compared to scores in 2019. As in previous years, Transport is one of the lowest scoring aspects of kidney care experience. • People with CKD report relatively poorer experiences than people on kidney replacement therapy; the median (middle) score awarded for overall experience decreased to 6.0 from 7.0 in 2020 and remains there this year