Reference levels for short duration signals used in Auditory Brainstem Response testing: An overview in the New Zealand context.

The Auditory Brainstem Response (ABR) is an electrophysiological response used for objective hearing testing. A sound is played in the ear to stimulate nerves in the brain, and the nerve activity is then measured. The technique is particularly important for testing the hearing of infants and children as the process is relatively automatic. In New Zealand, the sounds delivered by ABR devices are calibrated to different levels than devices used in most places around the world. This is because New Zealand uses a non-standard calibration reference while other regions around the world are increasingly using a standardised calibration reference, published in ISO 389. The different references mean that hearing test results and their interpretation will also differ from those performed overseas, and are not able to be easily compared to published data. No set of reference levels are objectively right or wrong. The purpose of standardisation is to offer a common approach in order to avoid differences in sound levels across regions and across transducers like insert earphones and bone conductors in widespread use. Only with standardisation can valid comparisons be made in routine clinical as well as research activities. However, it is worth adding that in addition to reference levels being non-standard in New Zealand, the research from which they were derived has not been fully published and we believe the values contain an unexplained anomaly. Further compounding this issue, the techniques used to calibrate ABR devices are also non-standard, which has resulted in hitherto unrecognised errors. The New Zealand reference levels are sufficiently different from the standardised reference levels to cause real-world human and financial implications. For example, the higher levels used with insert earphones can cause an apparent reduction in the severity of a hearing loss, and thus differences in the way a hearing aid might be set up for anyone diagnosed with a hearing loss. Given that standardised reference levels are available via ISO 389, and given that following this standard would enable alignment of clinical and research activities in New Zealand and internationally (and alignment within New Zealand across transducers and stimuli), the rationale for continuing with non-standard calibration referencesis unclear. To resolve these problems, we recommend that New Zealand adopts the standardised reference levels in ISO 389, and the associated techniques for calibration of ABR devices

Endoscopy management algorithms: role of cyanoacrylate glue injection and self-expanding metal stents in acute variceal haemorrhage

Mortality from acute variceal bleeding (AVB) has improved markedly over the last 2–3 decades due to increased specialisation and standardisation of medical and endoscopic practice culminating in the production of consensus guidance based on expert opinion. Nonetheless, despite greater exposure, training and endoscopic practices, 30-day mortality still remains high at around 30%. This is a reflection of the high morbidity with liver disease, and limited endoscopic experience and/or endoscopic techniques used by the majority of general endoscopists. Clinical necessity defines our drive for further endoscopic innovation to improve ‘best practice’ and, therefore, clinical outcomes accordingly. Sclerotherpy, variceal band ligation and/or rescue balloon tamponade have been entrenched in most treatment algorithms over the decades. However, in recent years and albeit limited to specialised liver centres, cyanoacrylate glue injection therapy (for oesophageal and gastric varices), and the placement of a self-expanding metallic stent for oesophageal varices have begun to offer improved endoscopic care in experienced hands. Yet even in specialised centres, their application is sporadic and operator dependent. Here, we discuss the evidence of these newer endoscopic approaches, and hope to propose their inclusion in endoscopic therapy algorithms for ‘best practice’ management of AVB in all appropriately supported endoscopy units

Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer-assisted digital image analysis (DIA) of Sirius Red-stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively-transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty-two patients were analyzed. The median HVPG was 8mmHg (interquartile range [IQR]: 5-10). Portal hypertension (HVPG ≥6<10mmHg) was present in 30 (69.8%), and HVPG ≥10mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.75-23.25). Median Child-Pugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.3-12.4) versus 23% in stage 6 (IQR 17-33.7, P<0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically-significant portal hypertension (HVPG ≥10mmHg, odds ratio: 1.085, confidence interval: 1.004-1.172, P=0.040). A CPA of 14% was the best cut-off value for clinically-significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event-free survival was significantly shorter in patients with CSPH or with a CPA value ≥14%, or with a combination of both. Conclusion: In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing "early" from "late" severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG ≥10mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The rfh cirrhosis Gfr

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis leading to significant differences between "true" and calculated glomerular filtration rate (GFR). We compared the performance of MDRD-4, MDRD-6 and CKD-EPI with "true" GFR and the impact of this difference on MELD calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulas. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. "True" GFR (mGFR) was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the MDRD formula. Subsequently, a corrected MELD was calculated and was compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the measured GFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis respectively. A difference>20 ml/min/1.73m(2) between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation derived (R(2) =74·6%) was: GFR=45·9x(creatinine(-0) ·(836) )x(urea(-0) ·(229) )x(INR(-0) ·(113) )x(age(0) ·(129) )x(sodium(0) ·(972) )x1·236(if male)x0·92(if moderate/severe ascites). The model was a good fit and showed the greatest accuracy compared to that of existing formulae. CONCLUSION: We developed and validated a new accurate model for GFR assessment in cirrhosis, the RFH cirrhosis GFR, using readily available variables. This remains to be tested and incorporated in prognostic scores in patients with cirrhosis

Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity

OBJECTIVES: We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. METHODS: We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. RESULTS: 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). CONCLUSIONS: Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode

Digital image analysis of collagen assessment of progression of fibrosis in recurrent HCV after liver transplantation

Background & Aims: Histological assessment of fibrosis progression is currently performed by staging systems which are not continuous quantitative measurements. We aimed at assessing a quantitative measurement of fibrosis collagen proportionate area (CPA), to evaluate fibrosis progression and compare it to Ishak stage progression. Methods: We studied a consecutive cohort of 155 patients with recurrent HCV hepatitis after liver transplantation (LT), who had liver biopsies at one year and were subsequently evaluated for progression of fibrosis using CPA and Ishak staging, and correlated with clinical decompensation. The upper quartile of distribution of fibrosis rates (difference in CPA or Ishak stage between paired biopsies) defined fast fibrosers. Results: Patients had 610 biopsies and a median follow-up of 116 (18-252) months. Decompensation occurred in 29 (18%) patients. Median Ishak stage progression rate was 0.42 units/year: (24 (15%) fast fibrosers). Median CPA fibrosis progression rate was 0.71%/year (36 (23%) fast fibrosers). Clinical decompensation was independently associated by Cox regression only with CPA (p = 0.007), with AUROCs of 0.81 (95% CI 0.71-0.91) compared to 0.68 (95% CI 0.56-0.81) for Ishak stage. Fast fibrosis defined by CPA progression was independently associated with histological de novo hepatitis (OR: 3.77), older donor age (OR: 1.03) and non-use/discontinuation of azathioprine before 1 year post-LT (OR: 3.85), whereas when defined by Ishak progression, fast fibrosers was only associated with histological de novo hepatitis. Conclusions: CPA fibrosis progression rate is a better predictor of clinical outcome than progression by Ishak stage. Histological de novo hepatitis, older donor age and non-use/discontinuation of azathioprine are associated with rapid fibrosis progression in recurrent HCV chronic hepatitis after liver transplantation. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma (HCC) in patients within Milan criteria.

Background: Increased preoperative inflammation scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and inflammation-based index (IBI) have been related to post-transplant HCC recurrence. We evaluated the association between inflammation-based scores (NLR, PLR, IBI) and post-LT HCC recurrence as well as tumour necrosis after transarterial embolisation. Methods: 150 consecutive patients that were transplanted for HCC within the Milan criteria between 1996-2010 were included; data regarding inflammatory markers, patient and tumour characteristics were analyzed. Results: NLR, PLR and IBI were not significantly associated with post-LT HCC recurrence or worse overall survival. Increased NLR and PLR were associated with complete tumour necrosis in the subset of patients that received preoperative transarterial embolization (P<0.05). Cox regression analysis revealed that absence of neo-adjuvant transarterial therapy (OR=4.33, 95%CI 1.28-14.64; P=0.02) and no fulfilment of the Milan criteria in the explanted liver (OR=3.34, 95%CI 1.08-10.35; P=0.04) were independently associated with post-LT HCC recurrence. Conclusion: Inflammation-based scores did not predict HCC recurrence post-LT in our group of patients. NLR and PLR were associated with better response to TAE, as this was recorded histologically in the explanted liver. Histological fulfilment of the Milan criteria and absence of neo-adjuvant transarterial treatment were significantly associated with post-LT HCC recurrence. Liver Transpl , 2014. © 2014 AASLD

Adverse events among Ontario home care clients associated with emergency room visit or hospitalization: a retrospective cohort study

Background: Home care (HC) is a critical component of the ongoing restructuring of healthcare in Canada. It impacts three dimensions of healthcare delivery: primary healthcare, chronic disease management, and aging at home strategies. The purpose of our study is to investigate a significant safety dimension of HC, the occurrence of adverse events and their related outcomes. The study reports on the incidence of HC adverse events, the magnitude of the events, the types of events that occur, and the consequences experienced by HC clients in the province of Ontario. Methods: A retrospective cohort design was used, utilizing comprehensive secondary databases available for Ontario HC clients from the years 2008 and 2009. The data were derived from the Canadian Home Care Reporting System, the Hospital Discharge Abstract Database, the National Ambulatory Care Reporting System, the Ontario Mental Health Reporting System, and the Continuing Care Reporting System. Descriptive analysis was used to identify the type and frequency of the adverse events recorded and the consequences of the events. Logistic regression analysis was used to examine the association between the events and their consequences. Results: The study found that the incident rate for adverse events for the HC clients included in the cohort was 13%. The most frequent adverse events identified in the databases were injurious falls, injuries from other than a fall, and medication-related incidents. With respect to outcomes, we determined that an injurious fall was associated with a significant increase in the odds of a client requiring long-term-care facility admission and of client death. We further determined that three types of events, delirium, sepsis, and medication-related incidents were associated directly with an increase in the odds of client death. Conclusions: Our study concludes that 13% of clients in homecare experience an adverse event annually. We also determined that an injurious fall was the most frequent of the adverse events and was associated with increased admission to long-term care or death. We recommend the use of tools that are presently available in Canada, such as the Resident Assessment Instrument and its Clinical Assessment Protocols, for assessing and mitigating the risk of an adverse event occurring.This work was supported by the Canadian Patient Safety Institute; Canadian Institutes of Health Research (CIHR) (Institutes of Health Services and Policy Research, Aging, Circulatory and Respiratory Health and Musculoskeletal Health and Arthritis); the Change Foundation; and the Canadian Health Services Research Foundation (grant number HC-10-05 Doran-Blais