Publications

BACKGROUND

Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy.

METHODS

ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593.

FINDINGS

ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group.

INTERPRETATION

In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.

FUNDING

NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.

PURPOSE

This study describes the impact of an open-access, case-based global health ethics workshop and describes the breadth of dilemmas faced by students to inform future interventions.

METHODS

Eighty-two medical students who undertook electives at 16 international sites between 2012 and 2015 received web-based surveys at three time points, incorporating quantitative and free-text probes of knowledge, skills, and attitudes related to global health clinical ethics dilemmas. Sixty students (73%) completed the pre-workshop survey, 38 (46%) completed the post-workshop survey, and 43 (52%) completed the post-trip survey.

RESULTS

Analysis demonstrated improvement following the workshop in self-rated preparedness to manage ethical dilemmas abroad, identify ways to prepare for dilemmas, engage support persons, and manage related emotions (all comparisons, p < 0.001). Participants described 245 anticipated or actual dilemmas, comprising nine domains. Nearly one-third of the dilemmas that were experienced involved the student as an active participant. Only 21% of respondents experiencing a dilemma discussed the dilemma with a local support person.

CONCLUSIONS

This analysis describes an ethics curriculum that prepares students to face ethical dilemmas during international clinical rotations. It broadens the representation of the dilemmas that students face, and highlights areas for curricular focus and optimization of on-site and post-trip student support resources.

BACKGROUND

Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of both tissue injury and infection. Urine NGAL levels strongly predict acute kidney injury and mortality in patients with cirrhosis, but ascites NGAL is not well characterized. We hypothesized that ascites NGAL level is a marker of spontaneous bacterial peritonitis (SBP) and mortality risk in patients with cirrhosis.

METHODS

Hospitalized patients with cirrhosis and ascites undergoing diagnostic paracentesis were prospectively enrolled and followed until death or discharge. Patients with secondary peritonitis, prior transplantation, or active colitis were excluded. NGAL was measured in the ascites and serum. Ascites NGAL level was evaluated as a marker of SBP (defined as ascites absolute neutrophil count > 250 cells/mm) and predictor of in-patient mortality.

RESULTS

A total of 146 patients were enrolled, and of these, 29 patients (20%) had SBP. Baseline characteristics were similar between subjects with and without SBP. Median (IQR) ascites NGAL was significantly higher in patients with SBP compared to those without SBP (221.3 [145.9-392.9] vs. 139.2 [73.9-237.2], p < 0.01). Sixteen (11%) patients died in the hospital. In the final multivariable model, ascites NGAL (OR 1.02 per 10 units, p < 0.01) remained predictive of in-hospital mortality, controlling for SBP (OR 9.76, p < 0.01) and MELD (OR 1.11, p = 0.01). In ROC analysis, ascites NGAL had an AUC of 0.79 for inhospital mortality, and the final model including ascites NGAL, MELD, and SBP had an AUC of 0.94.

CONCLUSIONS

Ascites NGAL level may be a biomarker of peritonitis in hospitalized patient with cirrhosis and an independent predictor of short-term in-hospital mortality, even controlling for SBP and MELD.