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Background: The directional influences between serum sex hormone-binding globulin (SHBG), adiposity and insulin resistance during pubertal growth remain unclear. The aim of this study was to investigate bidirectional associations between SHBG and insulin resistance (HOMA-IR) and adiposity from childhood to early adulthood. Methods: Participants were 396 healthy girls measured at baseline (age 11.2 years) and at 1, 2, 4 and 7.5 years. Serum concentrations of estradiol, testosterone and SHBG were determined by ELISA, glucose and insulin by enzymatic photometry, insulin-like growth factor 1 (IGF-1) by time-resolved fluoroimmunoassays, whole-body fat mass by dual-energy X-ray absorptiometry and HOMA-IR were determined by homeostatic model assessment. The associations were examined using cross-lagged path models. Results: In a cross-lagged path model, SHBG predicted HOMA-IR before menarche β = −0.320 (95% CI: −0.552 to −0.089), P = 0.007, independent of adiposity and IGF-1. After menarche, no directional effect was found between SHBG and insulin resistance or adiposity. Conclusions: Our results suggest that in early puberty, decline in SHBG predicts development of insulin resistance, independent of adiposity. However, after menarche, no directional influences between SHBG, adiposity and insulin resistance were found, suggesting that observational associations between SHBG, adiposity and insulin resistance in pubertal children may be subject to confounding. Further research is needed to understand the underlying mechanisms of the associations between SHBG and cardiometabolic risk markers in peripubertal children.

Background and Aim: The role of preoperative biliary drainage (PBD) before a pylorus-preserving pancreaticoduodenectomy (PPPD) for resectable pancreatic or periampullary malignancy remains unclear. When PBD is clinically warranted, there is limited evidence to guide the choice of fully covered self-expandable metal stents (FCSEMS) or plastic stents in terms of PBD-related complication rates, post-PPPD surgical outcomes, and health care resource utilization. The aim of this study was to compare the efficacy and safety of endoscopic PBD before PPPD with FCSEMS compared with plastic stents in terms of the rate of preoperative, operative, and postoperative adverse events. Our secondary outcome measures included duration of surgery, length of hospitalization, intensive care unit stay, and overall health care resource utilization up to 120 days after PBD. Method(s): We conducted a Victorian multicenter retrospective cohort study that included adult patients who underwent endoscopic PBD before PPPD for one or more of the following indications: cholangitis defined by revised Tokyo guidelines, level of total bilirubin >= 40 mumol/L, expected time to PPPD >= 7 days, or neoadjuvant chemotherapy. Patients were deemed resectable by pancreatic protocol computed tomography or magnetic resonance imaging reviewed at a multidisciplinary discussion. Result(s): A total of 106 patients underwent PBD before PPPD at five Victorian tertiary hospitals from 2010 to 2019. Of these, 32 patients (30.19%) received FCSEMS versus 74 (69.81%) with plastic stents. The mean age was 66.75 +/- 9.79 years, 47.17% of patients were male, and the baseline bilirubin level was 184.91 +/- 113.59 mumol/L. Both FCSEMS and plastic stents effectively reduced bilirubin levels (DELTA140.04 +/- 113.04 mumol/L from baseline), with no difference between the FCSEMS arm and the plastic stents arm (DELTA134.56 +/- 108.35 mumol/L vs DELTA152.19 +/- 123.74 mumol/L; P = 0.47). There was no difference in PBD complication rat

Background and Aim: The economic burden of decompensated chronic liver disease (CLD) on Australian health care services and its trend over time are not well documented. Our study evaluated the in-hospital health care costs associated with decompensated CLD at Monash Health, the second largest tertiary health care network in Australia. Method(s): Our retrospective database analysis used administrative records, discharge summaries, and cost data captured for all patients admitted to Monash Health with decompensated CLD between January 1, 2009, and December 31, 2018. Patients were identified via International Classification of Diseases, 10th edition (ICD-10) codes for decompensated cirrhosis and cross-referenced with the hospital record.Wecaptured baseline demographic and clinical characteristics and health care resource utilization, including the length of stay, intensive care, and unplanned readmissions. Cost measures were estimated using the Victorian Weighted Inlier Equivalent Separation (WIES) funding data, based on the Australian refined diagnosis-related groups cost weights. No other Medicare costs were included in this analysis. Adescriptive analysis of all study measures was performed, including the 10- year trend of inpatient disease burden attributable to decompensated CLD. Result(s): A total of 1118 adult patients required 1681 acute hospitalizations for decompensated CLD over a 10-year period. The mean age was 58 +/- 13.8 years, and 68% were male. There were 648 patients (57.9%) who died within the study period, at a median of 30 days (IQR, 9-170) from index admission. The overall mean length of stay was 11.5 +/- 5.6 days. A total of 373 patients (22.2%) required intensive care unit (ICU) admission, with a median ICU length of stay of 190 h (IQR, 96-353). Of all admissions, 667 (39.7%) were for ascites, 121 (7.2%) for spontaneous bacterial peritonitis (SBP), 82 (4.9%) for hepatorenal syndrome (HRS), 79 (4.7%) for hepatic encephalopathy, and 34 (2.0%) for a

The burden of chronic Hepatitis B (CHB) infection and associated complications such as hepatocellular carcinoma is growing significantly in Australia due to increased migration from countries with a high prevalence of CHB. Significant barriers to screening and engagement with healthcare persist due to stigma and perceptions associated with CHB within these communities. Our study was a pilot intervention aimed at engaging Afghan, Rohingyan, and Sudanese populations into CHB care through an initial needs assessment. Twenty six patients from Afghan, Rohingyan, and Sudanese communities, identified in the Monash Health CHB database, participated in a combination of survey questionnaires and semi-structured interviews. Language and cultural barriers, lack of HBV knowledge, housing and family reunification priorities associated with new settlement, as well as previous experiences of healthcare engagement were all identified as obstacles to accessing CHB care. Healthcare and health promotion workers should be sensitive to the additional health barriers associated with seeking asylum, as these barriers can take priority over the often asymptomatic and chronic nature of CHB. Communities with high prevalence of CHB require culturally relevant education tools delivered at a community level in order to improve their knowledge.

Background: Minimising unnecessary tests is a global health economic priority with multiple initiatives in place to avoid inappropriate healthcare utilisation(1) and harm. Anti-nuclear antibody (ANA) testing is frequently performed as a diagnostic test for autoimmune conditions, such as systemic lupus erythematosus (SLE) or as a screening test in patients with inflammatory or musculoskeletal symptoms. The value of serial testing in the monitoring of such conditions is unclear and false positive tests can lead to unnecessary further investigation and increased patient anxiety(2) Objectives: To evaluate the frequency of repeated ANA testing as a prelude to Electronic Medical Record (EMR) test alert design in an Australian healthcare network. The primary endpoint was calculation of the total cost associated with repeated testing and whether a longitudinal change in ANA resulted in any new ANA associated rheumatological diagnoses. Our secondary endpoint was the examination of baseline ANA testing behaviours. Method(s): We retrospectively analysed data from a multi-centre tertiary health network in Melbourne, Australia across a 7-year period (19 March 2011 to 23 July 2018). ANA and other autoimmune test results were obtained from the hospital pathology system with a positive ANA cut off set at 1:160. Clinical information was sourced from clinical information systems on patients who had a change in ANA result from negative to positive on repeat testing. The associated cost of repeated ANA testing was calculated based on the baseline cost to the public system. Result(s): A total of 36,715 ANA tests (excluding 980 cancelled same-day requests) were performed in 28,840 patients. Of these, 14,058 (38.3%) were positive with females accounting for 9,265 (65.9%, p<0.001). The most frequent ANA patterns were homogenous (47.4%) and nucleolar (23.3%). ANA titres were as follows; 1:160 (41.4%), 1:320 (15.3%), 1:640 (13.1%) and 1:1280 (29.2%). 7,875 (21.4%) of tests were repeat tests.

Background and Aim: Entecavir (ETV) and tenofovir (TDF) are potent antiviral therapies for chronic hepatitis B (CHB). Data remain limited on the long-term (> 48 weeks) efficacy and safety of ETV and TDF in patients with CHB managed in a tertiary care setting, particularly treatmentexperienced and cirrhotic patients. We evaluated the long-term safety and efficacy of ETV and TDF in a large heterogeneous cohort of initial and treatment-experienced patients with CHB. Method(s): We conducted a multicenter retrospective cohort study of patients with CHB aged >= 18 years who received either ETV or TDF for >= 6 months. Patients were treated at seven tertiary health care networks across Melbourne, Australia, between January 2007 and January 2017. The primary end-points were undetectable hepatitis B virus (HBV)-DNA suppression (viral load [VL] of < 15 IU/mL) and alanine aminotransferase (ALT) normalization (American Association for the Study of Liver Diseases criteria). The rate of HBeAg and HBsAg loss/seroconversion, adverse events (AEs), and clinical outcomes, such as hepatocellular carcinoma and hepatic decompensation, were also evaluated. Result(s): Of the 1093 patients in the cohort, 68.89% were male, and the mean age was 48.28 +/- 13.18 years. At baseline, 28.73% were cirrhotic, and 30.28% were treatment-experienced. Baseline mean HBV-DNA VL was 4.63 +/- 2.14 log10 IU/mL. A total of 779 patients (71.27%) received ETV and 314 (28.73%) received TDF, with median treatment durations of 37 (IQR, 20-56) and 24.5 (IQR, 15-31) months, respectively. In the ETV group, 34% were HBeAg seropositive, and in the TDF group, 42.52% were. The Kaplan-Meier curve estimated probability of complete HBV-DNA suppression on ETV or TDF was 42.82% at 10 months, 69.57% at 20 months, and 83.31% at 30 months. Multivariate Cox regression analysis of the entire cohort identified baseline cirrhosis (hazard ratio [HR], 0.54; 95% CI, 0.32-0.91; P = 0.02) as an independent negative predictor for HBV-DNA s

We demonstrate that using a broadband, first order, and coherent pump laser enables effective and efficient forward-pumped distributed Raman amplification for long-haul transmission systems, thanks to the simultaneous suppression of ASE noise and RIN-related penalty. We show in both experiments and simulation that this scheme extends the reach of 10 × 120 Gb/s DP-QPSK WDM transmission by a minimum of 50%, compared with low RIN Bi-doped fibre laser and other commercially available pump lasers. Moreover, it requires very low forward pump power, and maintains uniform/symmetric signal power distribution which allows effective nonlinearity compensation.

Introduction: Immunotherapy is an increasingly important component of care in the management of several advanced malignancies, including metastatic melanoma and non-small cell lung cancer. Immune-mediated adverse events to therapy involving the gastrointestinal tract have been described, namely, autoimmune colitis and hepatitis. We aimed to evaluate the incidence, risk factors, and management of the gastrointestinal-related autoimmune side effects of checkpoint inhibitor therapy. Method(s): We conducted a retrospective audit of the files of all patients who received checkpoint inhibitor therapy at a major tertiary referral center from January 1, 2015, to June 1, 2017. We focused on the cytotoxic T-lym-phocyte-associated antigen 4 (CTLA-4) inhibitor ipilimumab and the programmed cell death 1 (PD-1) inhibitors nivolumab and pembrolizumab. We analyzed the data in two groups: patients who developed any autoimmune complications while being treated with checkpoint inhibitor therapy and patients who did not. We assessed for differences in pre-existing autoimmune comorbidities and liver function test results over a 16-week period from commencement of their therapy. We then performed an in-depth review of the management of the patients who developed autoimmune colitis and hepatitis. Result(s): We identified 56 patients receiving checkpoint inhibitor ther-apy, of whom 45 patients (80.4%) received nivolumab, seven (12.5%) received ipilimumab, and one (1.8%) received pembrolizumab. Three patients received both nivolumab and ipilimumab (5.4%). A total of 14/56 patients (33%) developed an autoimmune-related side effect. Of these 14 patients, four (28.6%) developed autoimmune colitis and one (7.1%) developed autoimmune hepatitis. The other common autoim-mune complications were hyperthyroidism (2, 14.3%), pneumonitis (2, 14.3%), and hypophysitis (2, 14.3%). There was no statistically significant difference between the two groups at baseline with respect to age, sex, or ethnicity. B

Background and Aims: Cirrhosis associated immune dysfunction (CAID) contributes to the high morbidity and mortality from infections in individuals with cirrhosis. CAID has deficiency not only in quantity of immune cells, but also in quality that cannot simply be explained by portal hypertension and splenic sequestration. Malnutrition may be partly responsible for this immune dysfunction. QuantiFERON-monitor (QFM, Qiagen, USA) is a novel immune function assay that measures IFN-gamma production following dual stimulation of both the innate and adaptive immune systems. We aimed to identify whether immune dysfunction in cirrhotics is associated with malnutrition. Method(s): We prospectively measured QFM in 81 cirrhotic patients awaiting liver transplantation at our centre as part of the first clinical trials assessing QFM before and after transplantation. Low QFM is suggestive of immunosuppression. Patients also had nutritional assessments including the subjective global assessment (SGA) and handgrip strength (HGS). SGA scoring is (A) well nourished, (B) mild/moderately malnourished, and (C) severely malnourished. HGS was assessed in kg. Groups were compared using multivariate linear regression. Result(s): 57/81 male and median age 54yo. The most common aetiology was HCV (n = 35) and 29 had hepatocellular carcinoma (HCC). The median QFM decreased as malnutrition increased, with 211 IU/mL in SGA A (n = 26, 32.1%), 137 IU/mL in B (n = 41, 50.6%) and 26.6 IU/mL in C (n = 14, 17.3%). On univariate analysis, both SGA (p = 0.009) and HGS (p = 0.02) were significantly associated with QFM, along with MELD score (p = 0.0001). On multivariate analysis, severe malnutrition (SGA C) was an independent predictor of immune function (p = 0.03). Multivariate analysis of QFM Conclusion(s): Severe malnutrition (SGA C) plays a significant role in the immunosuppressed status of patients with cirrhosis, even after taking into account the severity of liver disease. Improving nutritional statu

Research has been slow to leverage digitalised medical records as a data resource. Our study assessed patient acceptability of opt-out consent for secondary use of digital patient data. A questionnaire was distributed to patients in multiple languages and with an interpreter. Of 919 completed surveys, 33% were of non-English speaking background, 15% self-reported cognitive impairment and 3% were refugees. Opt-out consent was accepted in this diverse population; 87% of participants approved, or were indifferent to opt-out consent. Gender, employment and cognition status were not significant determinants of acceptability.Copyright © 2018 Royal Australasian College of Physicians.

Background and Aim: Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease with no proven effective medical therapy. Several randomized controlled trials have investigated the safety and efficacy of either high- or low-dose ursodeoxycholic acid (UDCA) compared with placebo as a potential treatment strategy, with conflicting results. The aim of this meta-analysis was to determine the efficacy and safety of high-dose (>15 mg/kg/day) versus low-dose (<= 15 mg/kg/day)UDCAin treating PSC. Method(s): We searched the Cochrane Library, MEDLINE, Embase, and the Web of Science for eligible studies comparing high- or low-dose UDCA in adult patients with PSC from 1990 to 2017. The primary end points evaluated were patient mortality, liver transplantation, clinical symptoms (fatigue and/or pruritus), serum biochemistry, progression of liver histology, and adverse events. The Mantel-Haenszel method was used to estimate the pooled risk ratios for binary outcomes, and Cohen's weighted mean difference for continuous outcomes. Heterogeneity was measured using the chi-squared test. Result(s): Fourteen studies (12 randomized controlled trials and two phase 3 studies) with 883 patients were included. Eight studies investigated low doses (10-15 mg/kg/day), four studies assessed high doses (17-30 mg/kg/ day), and two studies used both high- and low-doseUDCAin parallel. There were no significant differences between high- and low-dose UDCA with respect to mortality (relative risk [RR], 1.08; 95% CI, 0.35-3.29), progression of liver histology (RR, 0.27; 95% CI, 0.03-2.7), and adverse events (RR, 0.55; 95% CI, 0.09-3.38). There were no significant differences between high-dose UDCA and placebo with respect to mortality (RR, 0.98; 95% CI, 0.36-2.65), treatment failure (RR, 1.15; 95% CI, 0.96-2.24), adverse events (RR, 1.08; 95% CI, 0.96-2.24), cholangiographic deterioration (RR, 0.59; 95% CI, 0.27-1.30), clinical symptoms (fatigue and/or pruritus) (RR, 5; 95% CI, 0.26

Background and Aim: Cirrhosis-associated immune dysfunction (CAID) contributes to the high morbidity and mortality from infections in individuals with cirrhosis. CAID has deficiency not only in quantity of immune cells but also in quality, which cannot simply be explained by portal hypertension and splenic sequestration. Malnutrition is highly prevalent in those with cirrhosis and may be partly responsible for this immune dysfunction. QuantiFERON-monitor (QFM; Qiagen, USA) is a novel immune function assay that measures IFN-gamma production following dual stimulation of both the innate and adaptive immune systems. We aimed to identify whether immune dysfunction in cirrhosis is associated with malnutrition. Method(s): We prospectively measured QFM in 81 cirrhotic patients awaiting liver transplantation at our center as part of the first clinical trials assessing QFM before and after transplantation. Low QFM is suggestive of immunosuppression. Nutritional assessment and measures of muscle function were conducted at the time of QFM measurement to determine the degree of malnutrition and sarcopenia in cirrhotic patients. Nutritional status, as determined by subjective global assessment (SGA), classified patients as "A" (well nourished), "B" (moderately malnourished), or "C" (severely malnourished). Handgrip strength was used as a measure of functional muscle strength and was assessed in kilograms. Groups were compared using the Kruskal-Wallis test and multivariate linear regression with backward regression. Result(s): Of the 81 patients, 57 (70%) were male, and patients had a median age of 54 years. The most common etiology was hepatitis C virus (n = 35), and 29 had hepatocellular carcinoma. Median MELD score was 20, and Child-Pugh score was 10. Fifty-five patients (68%) were malnourished (SGA B + C). The median QFM decreased as malnutrition increased: 211 IU/mL in SGA A (n = 26, 32.1%), 137 IU/mL in SGA B (n = 41, 50.6%), and 26.6 IU/mL in SGA C (n = 14, 17.3%). On univ

Introduction: Poor-quality bowel preparation has been reported in 20- 30% of colonoscopies. This is associated with significant cost and inconvenience to patients, clinicians, and the healthcare system. The patient barriers to achieving optimal pre-colonoscopy bowel preparation remain poorly characterized. Method(s): A random consecutive sample of day procedure patients attending Monash Health for a colonoscopy was invited to participate in an anonymous survey before sedation between February and May 2017. The surveys were self-administered. Demographic data and a qualitative assessment of the patient experience with bowel preparation were captured. Result(s): A total of 71 patients completed the survey, and 4.69% reported failure to complete the bowel preparation. Only 23.44% self-reported their last bowel effluent as clear. Patients reported the following components of bowel preparation as difficult to understand or follow: management of preparation-associated nausea (32.83%), how to flavor the preparation (26.56%), and when or whether to stop regular medications (12.5%). Patients reported limited understanding of the following components: when to resume medications (25%), when to restart a normal diet (18.75%), and when to return to work (17.18%). Among the patients, 78.13% owned a smartphone and 68% reported feeling comfortable or proficient at using smartphone apps. Patient preference for the mode of delivery of future instructions regarding bowel preparation were 60% for a mobile app, 38% for paper, and 2% for a phone call. Conclusion(s): Novel educational interventions to address patient-related factors for poor bowel preparation are urgently required to improve the diagnostic and therapeutic utility of colonoscopy examination. This is the first study to report a high rate of smartphone ownership among patients undergoing a colonoscopy at a day procedure unit, with high patient acceptability of a smartphone app to aid colonoscopy preparation.

Introduction: Decompensated cirrhosis is a major health-care issue associated with increased morbidity and mortality and reduced quality of life. The Delphi panel of quality indicators (QIs) for cirrhosis care was derived in 2010. We investigated the impact on clinical outcomes of adherence to these QIs for ascites, variceal hemorrhage, and hepatic encephalopathy (HE). Method(s): From 2011 to 2016, 197 patients were admitted to Monash Health, a tertiary referral center, with their first hepatic decompensation. We assessed adherence to the QIs and the association of adherence with 30-day readmission, death within 90 days of index admission, and length of stay (LOS). Multivariate logistic regression analysis was used to assess the association between QI adherence and clinical outcomes. Result(s): Therewere no significant differences in age and sex among the three groups at baseline. Patients presenting with HE had significantly higher Model for End-stage Liver Disease (MELD) and MELD-Na scores compared with those presenting with ascites or variceal hemorrhage (P < 0.001) (Table 1). The main etiology of liver disease for the pooled cohort was alcohol use (67.01%) and hepatitis C (29.44%). The overall mean +/- SD length of admission was 8.90 +/- 9.79 days. Rates of adherence to the QIs are shown in Table 2, with a lower rate of adherence to QIs of care for HE compared with ascites or variceal hemorrhage, which did not reach statistical significance (P = 0.53). Adherence to general care QIs, such as documentation of MELD score and hepatitis A/B status, was low. The independent predictors of 90-day mortality for all patients with decompensated cirrhosis (Table 3) included overall adherence rate to all QIs (odds ratio [OR], 0.95; P = 0.001) and MELD score (OR, 1.12; P < 0.001). No QIs significantly predicted 30-day readmission rate or LOS. Conclusion(s): Our study found a low rate of adherence to QIs of care for HE and general care. We found that overall adherence to the D

Spinally projecting neurons in the rostral ventrolateral medulla (RVLM) play a critical role in the generation of vasomotor sympathetic tone and are thought to receive convergent input from neurons at every level of the neuraxis; the factors that determine their ongoing activity remain unresolved. In this study we use a genetically restricted viral tracing strategy to definitively map their spatially diffuse connectome. We infected bulbospinal RVLM neurons with a recombinant rabies variant that drives reporter expression in monosynaptically connected input neurons and mapped their distribution using an MRI-based volumetric atlas and a novel image alignment and visualization tool that efficiently translates the positions of neurons captured in conventional photomicrographs to Cartesian coordinates. We identified prominent inputs from well-established neurohumoral and viscero-sympathetic sensory actuators, medullary autonomic and respiratory subnuclei, and supramedullary autonomic nuclei. The majority of inputs lay within the brainstem (88-94%), and included putative respiratory neurons in the pre-Bötzinger Complex and post-inspiratory complex that are therefore likely to underlie respiratory-sympathetic coupling. We also discovered a substantial and previously unrecognized input from the region immediately ventral to nucleus prepositus hypoglossi. In contrast, RVLM sympathetic premotor neurons were only sparsely innervated by suprapontine structures including the paraventricular nucleus, lateral hypothalamus, periaqueductal gray, and superior colliculus, and we found almost no evidence of direct inputs from the cortex or amygdala. Our approach can be used to quantify, standardize and share complete neuroanatomical datasets, and therefore provides researchers with a platform for presentation, analysis and independent reanalysis of connectomic data.

The study aimed to assess whether aerobic exercise (AEx) training and a fibre-enriched diet can reduce hepatic fat content (HFC) and increase glycaemic control in pre-diabetic patients with non-alcoholic fatty liver disease (NAFLD). Six-hundred-and-three patients from seven clinics in Yangpu district, Shanghai, China were recruited. Of them 115 individuals aged 50–65-year fulfilled the inclusion criteria (NAFLD with impaired fasting glucose or impaired glucose tolerance) and were randomly assigned into exercise (AEx n = 29), diet (Diet n = 28), exercise plus diet (AED n = 29), or no-intervention (NI n = 29) groups. Progressive supervised AEx training (60–75% VO2max intensity) was given 2–3 times/week in 30–60 min/sessions, and the diet intervention was provided as lunch with 38% carbohydrate and diet fibre of 12 g/day for 8.6-month. HFC was assessed by 1H MRS. We found that HFC was significantly reduced in the AEx (−24.4%), diet (−23.2%), and AED (−47.9%) groups by contrast to the 20.9% increase in the NI group (p = 0.001 for all) after intervention. However, only AED group significantly decreased HbA1c (−4.4%, p = 0.01) compared with the NI group (−0.6%). Aerobic exercise training combined with fibre-enriched diet can reduce HFC more effectively than either exercise or increased fibre-intake alone in pre-diabetic patients with NAFLD.

info:eu-repo/semantics/nonPublished

[This corrects the article DOI: 10.1155/2015/932934.].