Clinical School (Austin Health) - Research Publications
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ItemTemporal lobe epilepsy following maintenance electroconvulsive therapyElectrical kindling in the human brain?(WILEY-BLACKWELL, 2016-11)Maintenance electroconvulsive therapy (ECT) is sometimes prescribed for refractory psychiatric conditions. We describe five patients who received maintenance ECT and developed florid temporal epileptiform abnormalities on electroencephalography (EEG) despite no history of epilepsy and normal neuroimaging. All patients had received regular ECT for at least 8 months. Three patients had clinical events consistent with epileptic seizures, and video-EEG monitoring captured electrographic seizures in two patients. After cessation of ECT the EEGs normalized in all patients, and no further clinical seizures occurred. Maintenance ECT may predispose to epilepsy with a seizure focus in the temporal lobe.
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ItemSodium bicarbonate infusion in patients undergoing orthotopic liver transplantation: a single center randomized controlled pilot trial(WILEY-BLACKWELL, 2016-05)BACKGROUND: Liver transplantation-associated acute kidney injury (AKI) carries significant morbidity and mortality. We hypothesized that sodium bicarbonate would reduce the incidence and/or severity of liver transplantation-associated AKI. METHODS: In this double-blinded pilot RCT, adult patients undergoing orthotopic liver transplantation were randomized to an infusion of either 8.4% sodium bicarbonate (0.5 mEq/kg/h for the first hour; 0.15 mEq/kg/h until completion of surgery); (n = 30) or 0.9% sodium chloride (n = 30). PRIMARY OUTCOME: AKI within the first 48 h post-operatively. RESULTS: There were no significant differences between the two treatment groups with regard to baseline characteristics, model for end-stage liver disease and acute physiology and chronic health evaluation (APACHE) II scores, and pre-transplantation renal function. Intra-operative factors were similar for duration of surgery, blood product requirements, crystalloid and colloid volumes infused and requirements for vasoactive therapy. Eleven patients (37%) in the bicarbonate group and 10 patients (33%) in the sodium chloride group developed a post-operative AKI (p = 0.79). Bicarbonate infusion attenuated the degree of immediate post-operative metabolic acidosis; however, this effect dissipated by 48 h. There were no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. CONCLUSIONS: The intra-operative infusion of sodium bicarbonate did not decrease the incidence of AKI in patients following orthotopic liver transplantation.
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ItemThe haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial(WILEY, 2016-04)AIM: The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. METHODS: We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. RESULTS: Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). CONCLUSIONS: I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
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ItemNo Preview AvailableAdvances in ureteroscopy(AME PUBL CO, 2014-09)Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology.
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ItemNo Preview AvailableA multilingual evaluation of current health information on the Internet for the treatments of benign prostatic hyperplasia(ELSEVIER INC, 2014-12)PURPOSE: To compare the quality of current Internet information on benign prostatic hyperplasia (BPH) and its surgical and medical managements across four Western languages and a comparative analysis of website sponsors. BPH Internet information quality is particularly relevant in an era of expanding, minimally invasive and surgical therapies. However, no comprehensive analysis exists. METHODS: World Health Organization Health on the Net (HON) principles may be applied to websites using an automated toolbar function. Using a search engine (www.google.com), 9,000 websites were assessed using keywords related to BPH and its medical and surgical treatment in English, French, German, and Spanish. The first 150 websites in each language had HON principles measured whilst a further analysis of site sponsorship was undertaken. RESULTS: Very few BPH websites had greater than ten per cent HON accredited with significant differences (P<0.001) based on terms used for BPH, its medical and surgical management. Tertiles (thirds) of the first 150 websites returned differences in accredited websites (P<0.0001). English language had most accredited websites. Odds ratios for different terms returning accredited websites also were significantly different across terms (P<0.001). Websites were largely commercially sponsored. CONCLUSIONS: A lack of validation of most BPH sites should be appreciated with discrepancies in quality and number of websites across diseases, languages and also between medical and alternate terms. Physicians should participate in and encourage the development of informative, ethical and reliable health websites on the Internet and direct patients to them.
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ItemAcute Flaccid Paralysis: The New, The Old, and The Preventable(OXFORD UNIV PRESS INC, 2016-01)Acute flaccid paralysis (AFP) has a changing epidemiology with ongoing polio outbreaks and emerging causes such as nonpolio enteroviruses and West Nile virus (WNV). We report a case of AFP from the Horn of Africa that was initially classified as probable polio but subsequently found to be due to WNV.
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ItemThe impact of fluid intervention on complications and length of hospital stay after pancreaticoduodenectomy (Whipple's procedure)(BIOMED CENTRAL LTD, 2014-05-14)BACKGROUND: There is limited information on the impact on perioperative fluid intervention on complications and length of hospital stay following pancreaticoduodenectomy. Therefore, we conducted a detailed analysis of fluid intervention in patients undergoing pancreaticoduodenectomy at a university teaching hospital to test the hypothesis that a restrictive intravenous fluid regime and/or a neutral or negative cumulative fluid balance, would impact on perioperative complications and length of hospital stay. METHODS: We retrospectively obtained demographic, operative details, detailed fluid prescription, complications and outcomes data for 150 consecutive patients undergoing pancreaticoduodenectomy in a university teaching hospital. Prognostic predictors for length of hospital stay and complications were determined. RESULTS: One hundred and fifty consecutive patients undergoing pancreaticoduodenectomy were evaluated between 2006 and 2012. The majority of patients were, middle-aged, overweight and ASA class III. Postoperative complications were frequent and occurred in 86 patients (57%). The majority of complications were graded as Clavien-Dindo Class 2 and 3. Postoperative pancreatic fistula occurred in 13 patients (9%), and delayed gastric emptying occurred in 25 patients (17%). Other postoperative surgical complications included sepsis (22%), bile leak (4%), and postoperative bleeding (2%). Serious medical complications included pulmonary edema (6%), myocardial infarction (8%), cardiac arrhythmias (13%), respiratory failure (8%), and renal failure (7%). Patients with complications received a higher median volume of intravenous therapy and had higher cumulative positive fluid balances. Postoperative length of stay was significantly longer in patients with complications (median 25 days vs. 10 days; p < 0.001). After adjustment for covariates, a fluid balance of less than 1 litre on postoperative day 1 and surgeon caseloads were associated with the development of complications. CONCLUSIONS: In the context of pancreaticoduodenectomy, restrictive perioperative fluid intervention and negative cumulative fluid balance were associated with fewer complications and shorter length of hospital stay. These findings provide good opportunities to evaluate strategies aimed at improving perioperative care.
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ItemNurse-Led Intervention to Improve Knowledge of Medications in Survivors of Stroke or Transient Ischemic Attack: A Cluster Randomized Controlled Trial(FRONTIERS MEDIA SA, 2016-11-18)INTRODUCTION: Limited evidence exists on effective interventions to improve knowledge of preventive medications in patients with chronic diseases, such as stroke. We investigated the effectiveness of a nurse-led intervention, where a component was to improve knowledge of prevention medications, in patients with stroke or transient ischemic attack (TIA). METHODS: Prospective sub-study of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management, a randomized controlled trial of risk factor management. We recruited patients aged ≥18 years and hospitalized for stroke/TIA. The intervention comprised an individualized management program, involving nurse-led education, and management plan with medical specialist oversight. The outcome, participants' knowledge of secondary prevention medications at 12 months, was assessed using questionnaires. A score of ≥5 was considered as good knowledge. Effectiveness of the intervention on knowledge of medications was determined using logistic regression. RESULTS: Between May 2014 and January 2015, 142 consecutive participants from the main trial were included in this sub-study, 64 to usual care and 78 to the intervention (median age 68.9 years, 68% males, and 79% ischemic stroke). In multivariable analyses, we found no significant difference between intervention groups in knowledge of medications. Factors independently associated with good knowledge (score ≥5) at 12 months included higher socioeconomic position (OR 4.79, 95% CI 1.76, 13.07), greater functional ability (OR 1.69, 95% CI 1.17, 2.45), being married/living with a partner (OR 3.12, 95% CI 1.10, 8.87), and using instructions on pill bottle/package as an administration aid (OR 4.82, 95% CI 1.76, 13.22). Being aged ≥65 years was associated with poorer knowledge of medications (OR 0.24, 95% CI 0.08, 0.71), while knowledge was worse among those taking three medications (OR 0.15, 95% CI 0.03, 0.66) or ≥4 medications (OR 0.09, 95% CI 0.02, 0.44), when compared to participants taking fewer (≤2) prevention medications. CONCLUSION: There was no evidence that the nurse-led intervention was effective for improving knowledge of secondary prevention medications in patients with stroke/TIA at 12 months. However, older patients and those taking more medications should be particularly targeted for more intensive education. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12688000166370).
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ItemAssessment of Liver Remnant Using ICG Clearance Intraoperatively during Vascular Exclusion: Early Experience with the ALIIVE Technique.(Hindawi Limited, 2015)Background. The most significant risk following major hepatectomy is postoperative liver insufficiency. Current preoperative assessment of the future liver remnant relies upon assumptions which may not be valid in the setting of advanced resection strategies. This paper reports the feasibility of the ALIIVE technique which assesses the liver remnant with ICG clearance intraoperatively during vascular exclusion. Methods. 10 patients undergoing planned major liver resection (hemihepatectomy or greater) were recruited. Routine preoperative assessment included CT and standardized volumetry. ICG clearance was measured noninvasively using a finger spectrophotometer at various time points including following parenchymal transection during inflow and outflow occlusion before vascular division, the ALIIVE step. Results. There were one case of mortality and three cases of posthepatectomy liver failure. The patient who died had the lowest ALIIVE ICG clearance (7.1%/min versus 14.4 ± 4.9). Routine preoperative CT and standardized volumetry did not predict outcome. Discussion/Conclusion. The novel ALIIVE technique is feasible and assesses actual future liver remnant function before the point of no return during major hepatectomy. This technique may be useful as a check step to offer a margin of safety to prevent posthepatectomy liver failure and death. Further confirmatory studies are required to determine a safety cutoff level.
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ItemPD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC(PUBLIC LIBRARY SCIENCE, 2016-04-22)INTRODUCTION: Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC. METHODS: A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression. RESULTS: Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36-0.94, p = 0.031; HR 0.46, 95%CI 0.26-0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50-0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%). CONCLUSION: PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.