The integration of rapid qualitative research in clinical trials: reflections from the ward-based goal-directed fluid therapy (GDFT) in acute pancreatitis feasibility trial.

BACKGROUND: There has been an increase in the integration of qualitative studies in randomised controlled trials. The purpose of this article is to reflect on our experience of carrying out a rapid qualitative study during a feasibility trial of goal-directed fluid therapy (GDFT) in patients with acute pancreatitis, including our sharing of emerging findings and the use of these findings by the trial team. METHODS: The study was designed as a rapid feedback evaluation and combined interviews with staff and patients who took part in the trial. FINDINGS: The rapid qualitative study pointed to common problems in trial recruitment among multiple sites, where lack of engagement of clinical teams across sites might impact negatively on patient recruitment. The article describes how the use of rapid feedback loops can be used as the trial is ongoing to inform changes in implementation. It also covers the potential challenges of working rapidly and collaborative with the trial team. CONCLUSIONS: Rapid feedback evaluations can be used to generate findings across all stages of trial design and delivery. Additional research is required to explore the implementation of this research design in other settings and trial designs.

Effect of post-operative goal-directed fluid therapy (GDFT) on organ function after orthotopic liver transplantation: Secondary outcome analysis of the COLT randomised control trial.

BACKGROUND: Goal-directed fluid therapy (GDFT) has been shown to reduce the complications following a variety of major surgical procedures, possibly mediated by improved organ perfusion and function. We have shown that it is feasible to randomise patients to GDFT or standard fluid management following liver transplant in the cardiac-output optimisation following liver transplantation (COLT) trial. The current study compares end organ function in patients from the COLT trial who received GDFT in comparison to those receiving standard care (SC) following liver transplant. METHODS: Adult patients with liver cirrhosis undergoing liver transplantation were randomised to GDFT or SC for the first 12 h following surgery as detailed in a published trial protocol. GDFT protocol was based on stroke volume (SV) optimisation using 250 ml crystalloid boluses. Total fluid administration and time to extubation were recorded. Hourly SV and cardiac output (CO) readings were recorded from the non-invasive cardiac output monitoring (NICOM) device in both groups. Pulmonary function was assessed by arterial blood gas (ABG) and ventilatory parameters. Lung injury was assessed using PaO2:FiO2 ratios and calculated pulmonary compliance. The KDIGO score was used for determining acute kidney injury. Renal and liver graft function were assessed during the post-operative period and at 3 months and 1-year. RESULTS: 60 patients were randomised to GDFT (n = 30) or SC (n = 30). All patients completed the 12 h intervention period. GDFT group received a significantly higher total volume of fluid during the 12 h trial intervention period (GDFT 5317 (2335) vs. SC 3807 (1345) ml, p = 0.003); in particular crystalloids (GDFT 3968 (2073) vs. SC 2510 (1027) ml, p = 0.002). There was no evidence of significant difference between the groups in SV or CO during the assessment periods. Time to extubation, PaO2: FIO2 ratios, pulmonary compliance, ventilatory or blood gas measurements were similar in both groups. There was a significant rise in serum creatinine from baseline (77 µmol/L) compared to first (87 µmol/L, p = 0.039) and second (107 µmol/L, p = 0.001) post-operative days. There was no difference between GDFT and SC in the highest KDIGO scores for the first 7 days post-LT. At 1-year follow-up, there was no difference in need for renal replacement therapy or graft function. CONCLUSIONS: In this randomised trial of fluid therapy post liver transplant, GDFT was associated with an increased volume of crystalloids administered but did not alter early post-operative pulmonary or renal function when compared with standard care.

Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) represent a vulnerable group with multiple risk factors that are associated with poor outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite established susceptibility to infectious complications and the importance of humoral immunity in protection against SARS-CoV-2, few studies have investigated the humoral immune response to SARS-CoV-2 within this population. Here, we evaluate the seroprevalence of SARS-CoV-2 in patients awaiting renal transplantation and determine whether seroconverted patients with ESKD have durable and functional neutralizing activity against SARS-CoV-2. METHODS: Serum samples were obtained from 164 patients with ESKD by August 2020. Humoral immune responses were evaluated by SARS-CoV-2 spike S1 subunit and nucleoprotein semiquantitative enzyme-linked immunosorbent assay (ELISA) and SARS-CoV-2 spike pseudotype neutralization assay. RESULTS: All patients with ESKD with reverse-transcriptase polymerase chain reaction (RT-PCR)-confirmed infection (n = 17) except for 1 individual seroconverted against SARS-CoV-2. Overall seroprevalence (anti-S1 and/or anti-N IgG) was 36% and was higher in patients on hemodialysis (44.2%). A total of 35.6% of individuals who seroconverted were asymptomatic. Seroconversion in the absence of a neutralizing antibody (nAb) titer was observed in 12 patients, all of whom were asymptomatic. Repeat measurements at a median of 93 days from baseline sampling revealed that most individuals retained detectable responses although a significant drop in S1, N and nAb titers was observed. CONCLUSION: Patients with ESKD, including those who develop asymptomatic disease, routinely seroconvert and produce detectable nAb titers against SARS-CoV-2. Although IgG levels wane over time, the neutralizing antibodies remain detectable in most patients, suggesting some level of protection is likely maintained, particularly in those who originally develop stronger responses.

Presentation, course, and outcome of postneonatal presentations of vein of Galen malformation: a large, single-institution case series.

AIM: To describe presentation, clinical course, and outcome in postneonatal presentations of vein of Galen malformation (VGM). METHOD: Children older than 28 days presenting with VGM (from 2006-2016) were included. Notes/scans were reviewed. Outcome was dichotomized into 'good' or 'poor' using the Recovery and Recurrence Questionnaire. Logistic regression was performed to explore relationships between clinico-radiological features and outcome. RESULTS: Thirty-one children (18 males, 13 females) were included, presenting at a median age of 9.6 months (range 1.2mo-11y 7mo), most commonly with macrocrania (n=24) and prominent facial veins (n=9). Seven had evidence of cardiac failure. VGM morphology was choroidal in 19. Hydrocephalus (n=24) and loss of white matter volume (n=15) were the most common imaging abnormalities. Twenty-nine patients underwent glue embolization (median two per child). Angiographic shunt closure was achieved in 21 out of 28 survivors. Three children died of intracranial haemorrhage (1y, 6y, and 30d after embolization). Ten patients underwent neurosurgical procedures; to treat haemorrhage in four, and hydrocephalus in the rest. Outcome was categorized as good in 20 out of 28 survivors, but this was not predictable on the basis of the variables listed above. INTERPRETATION: Postneonatally presenting VGM has distinctive clinico-radiological features, attributable to venous hypertension. Endovascular treatment is associated with good outcomes, but more specific prognostic prediction was not possible within this cohort. WHAT THIS PAPER ADDS: Clinical and radiological features in older children with vein of Galen malformation relate to venous hypertension. Outcome is good in most cases with endovascular therapy. Mortality is low but is related to intracranial haemorrhage.