Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT

Background Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. Objectives To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. Design This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. Participants Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. Interventions Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. Main outcome measures The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. Results Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. Limitations The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. Conclusions The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy

Mass spectrometric investigations to obtain the first direct comparisons of endogenous breath and blood volatile organic compound concentrations in healthy volunteers

Volatile organic compounds (VOCs) in breath could be clinically useful for the early detection and diagnosis of diseases, physiological disorders and therapeutic monitoring. However, it is crucial to compare the reliability and precision of breath measurements with those from blood if endogenous VOCs on breath are to be used as biomarkers. Few studies have been undertaken to investigate this, none of which relate to endogenous VOCs in freely breathing subjects. Here we establish the reliability and precision of breath measurements to determine endogenous VOC concentrations in comparison to blood measurements in order to assess the viability of using breath measurements for potential diagnostic and screening purposes. Acetone and isoprene concentration levels in the breath, radial arterial blood and peripheral venous blood and in vivo arterial blood/breath ratios for freely breathing subjects have been determined using mass spectrometric techniques. Mean (range) breath concentrations in parts per billion by volume are 1090 (515-2335) for acetone and 465 (308-702) for isoprene. The mean (range) blood concentrations are: for acetone in radial arterial blood 26 (10-73) μmol/l and in peripheral venous blood 18 (9-39) μmol/l; for isoprene in radial arterial blood 6.8 (3.7-11) μmol/l and in peripheral venous blood 14 (5.5-30) μmol/l. Arterial blood/breath ratios mean (range) are 580 (320-860) for acetone and 0.38 (0.19-0.58) for isoprene. An important finding is that the coefficients of repeatability as a percentage of mean are less than 30% in breath but greater than 70% in blood. This study suggests that breath VOC measurements could provide a more consistent measure for investigating underlying physiological function or pathology than single blood measurements. © 2009 Elsevier B.V. All rights reserved

Long Covid stigma: estimating burden and validating scale in a UK-based sample

BACKGROUND: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability. This study aimed to develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma. METHODS: Data from the follow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling was used. Thirteen questions on stigma were designed to develop the LCSS capturing three domains–enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated. RESULTS: 966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70–0.86, internalised 0.75–0.84, anticipated 0.58–0.87, and model fit was good. The prevalence of experiencing stigma at least ‘sometimes’ and ‘often/always’ was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without. CONCLUSION: This study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid

LVAD HRQoL conceptual framework.

Conceptual framework based on clusters and statements within identifying key domains and items that are important to LVAD recipients.</p

S1 Protocol -

(PDF)</p

S1 Data -

(XLSX)</p

Frequency points rating map.

Points map showing which statements recipients thought frequently reflected their experiences. Scoring for Frequency: 1 = Never; 2 = Sometimes; 3 = Frequently; 4 = All of the time. (TIF)</p

Average rating scores pattern match by cluster.

Average cluster scores are shown at the top and bottom of the ladder. Clusters are positioned on the vertical axis and vertical lines represent each rating variable. Horizontal lines join the cluster scores within each rating variable for comparison. This shows the relative importance of clusters for recipients.</p

Bridging values for statements.

Bridging values for statements.</p

Importance point rating map.

Points map showing which statements were considered important by LVAD recipients. Scoring Importance: 1 = Not important; 2 = Important; 3 = Very important. (TIF)</p