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Introduction Despite decreasing consumption by general populations, use of synthetic cannabinoid receptor agonists (SCRAs) persists in some marginalised groups, including those who use other substances. This article explores SCRA consumption in an Australian cannabis treatment sample, comparing those who report ever using SCRAs with those who have never used SCRAs. Methods A questionnaire orally administered in person to a convenience sample of 154 cannabis treatment service clients from New South Wales, Australia (71% male, median age 35) collected information regarding cannabis and SCRA use including motivations, effects and health-related consequences of use, demographics, other substance use and overall health. Demographic profiles and between-group differences were explored. McNemar tests compared effects of SCRA and cannabis. Logistic regression analysis determined predictors of SCRA use. Results Half (53%) reported lifetime SCRA use; 20% reported previous-month use. The SCRA + cannabis group displayed greater polysubstance use and psychological distress. Reduced dependence on cannabis but higher levels of other substance use may predict SCRA use. Although curiosity motivated initial SCRA consumption, perceived psychoactive strength drove continued use. SCRAs appear to induce more negative side-effects than cannabis. Of the SCRA + cannabis group, 27% sought medical assistance for SCRA use. Most (90%) preferred cannabis to SCRAs, citing superior safety, effects and consistency of cannabis. Conclusions Among clients seeking treatment for cannabis use, SCRA use was relatively common, although not a preferred substance. Hazardous substance use and poor mental health characterised SCRA consumers, highlighting the need for continued monitoring by researchers and treatment providers of SCRA consumption in populations who use substances.

Background The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. Methods/Design A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. Discussion This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). Trial registration Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016). Electronic supplementary material The online version of this article (10.1186/s12888-018-1682-2) contains supplementary material, which is available to authorized users.

Objectives Alcohol misuse is a complex systemic problem. The aim of this study was to explore the feasibility of using a transparent and participatory agent-based modelling approach to develop a robust decision support tool to test alcohol policy scenarios before they are implemented in the real world. Methods A consortium of Australia’s leading alcohol experts was engaged to collaboratively develop an agent-based model of alcohol consumption behaviour and related harms. As a case study, four policy scenarios were examined. Results A 19.5 ± 2.5% reduction in acute alcohol-related harms was estimated with the implementation of a 3 a.m. licensed venue closing time plus 1 a.m. lockout; and a 9 ± 2.6% reduction in incidence was estimated with expansion of treatment services to reach 20% of heavy drinkers. Combining the two scenarios produced a 33.3 ± 2.7% reduction in the incidence of acute alcohol-related harms, suggesting a synergistic effect. Conclusions This study demonstrates the feasibility of participatory development of a contextually relevant computer simulation model of alcohol-related harms and highlights the value of the approach in identifying potential policy responses that best leverage limited resources. Electronic supplementary material The online version of this article (doi:10.1007/s00038-017-1041-y) contains supplementary material, which is available to authorized users.

BackgroundThere are no available medications for the management of alcohol dependence for patients with alcoholic liver disease (ALD).AimsTo conduct a multisite, double blind, placebo-controlled, randomised clinical trial of baclofen in the treatment of alcohol dependence, with or without liver disease (trial registration: ClinicalTrials.gov, NCT01711125).MethodPatients (n= 104) were randomised to placebo, baclofen 30 mg/day or 75 mg/day for 12 weeks. Primary outcomes included survival time to lapse (any drinking), relapse (≥5 drinks per day in men and ≥4 in women), and the composite outcome of drinks per drinking day, number of heavy drinking days, and percentage days abstinent.ResultsThere was a significant effect of baclofen (composite groups) on time to lapse (χ2= 6.44,Pd= 0.56) and relapse (χ2= 4.62,Pd= 0.52). A significant treatment effect of baclofen was observed for percentage days abstinent (placebo 43%, baclofen 30 mg 69%, baclofen 75 mg 65%;PConclusionsBaclofen may be an effective treatment option for patients with ALD. However, given the profile of adverse events, the role for this medication might be best limited to specialist services.Declaration of interestNone.

© 2017 Future Medicine Ltd. Aim: To assess the feasibility of the use of cannabidiol (CBD) for the management of cannabis withdrawal. Patients & methods: Eight participants were admitted to an in-patient detoxification facility for a 7-day open-label trial of CBD. Five participants received 600 mg of CBD and three participants received 1200 mg of CBD. Participants returned for a 28-day follow-up interview. Results & conclusion: CBD was well tolerated by all participants. Five completed the full treatment period and abstinence was maintained by four participants at day 28 follow-up. All those receiving the higher dose completed treatment and achieved abstinence at follow-up. This pilot study suggests that further exploration of CBD as a pharmacological adjunctive therapy for cannabis withdrawal and dependence is warranted. Registration ACTRN1261400024866.

Importance There are no effective medications for treating dependence on cannabis. Objective To examine the safety and efficacy of nabiximols in the treatment of patients with cannabis dependence. Design, Setting, and Participants This parallel double-blind randomized clinical trial comparing nabiximols with placebo in a 12-week, multisite outpatient study recruited participants from February 3, 2016, to June 14, 2017, at 4 outpatient specialist alcohol and drug treatment services in New South Wales, Australia. Participants had cannabis dependence (as defined by theInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and were seeking treatment, were nonresponsive to prior treatment attempts, were 18 to 64 years of age, had no other substance use disorder, had no severe medical or psychiatric conditions, were not pregnant, were not mandated by a court to undergo treatment, and provided informed consent. Results for primary efficacy measures and all secondary outcomes were obtained using a modified intention-to-treat data set. Interventions Participants received 12-week treatment involving weekly clinical reviews, structured counseling, and flexible medication doses—up to 32 sprays daily (tetrahydrocannabinol, 86.4 mg, and cannabidiol, 80 mg), dispensed weekly. Main Outcomes and Measures Primary outcome was self-reported number of days using illicit cannabis during the 12-week period. Other outcomes included alternate cannabis use parameters (periods of abstinence, withdrawal, cravings, and problems), safety parameters (adverse events and aberrant medication use), health status, other substance use, and treatment retention. Results A total of 128 participants (30 women and 98 men; mean [SD] age, 35.0 [10.9] years) were randomized and received at least 1 dose of study medication. Participants had used a mean (SD) of 2.3 (2.1) g of cannabis on a mean (SD) of 25.7 (4.5) days in the past 28 days. Treatment retention was comparable for the 2 groups (placebo, 30 of 67 participants [44.8%]; nabiximols, 30 of 61 participants [49.2%]), and both groups used similar mean (SD) doses (placebo, 18.5 [9.5] sprays daily; nabiximols, 17.6 [9.5] sprays daily, equivalent to a mean [SD] of 47.5 [25.7] mg of tetrahydrocannabinol and 44.0 [23.8] mg of cannabidiol). For the primary end point, the placebo group reported significantly more days using cannabis during the 12 weeks (mean [SD], 53.1 [33.0] days) than the nabiximols group (mean [SD], 35.0 [32.4] days; estimated difference, 18.6 days; 95% CI, 3.5-33.7 days;P = .02). Both groups showed comparable improvements in health status, with no substantial changes in other substance use. Medication was well tolerated with few adverse events. Conclusions and Relevance This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment. Trial Registration anzctr.org.auIdentifier:ACTRN12616000103460

Background and Aims: There is little information with regards to the efficacy of baclofen among alcohol patients concurrently receiving antidepressants (AD). The present study aimed to conduct a secondary analysis of the moderating role of antidepressants in the BacALD trial which evaluated the efficacy of baclofen to reduce alcohol consumption in alcohol dependent patients. Methods: Alcohol dependent patients (N = 104) were treated for 12 weeks with 30 mg/day of baclofen (21 = AD and 15 = no AD), 75 mg baclofen (19 = AD and 16 = no AD) or placebo (17 = AD and 16 = no AD). Patients were included in the trial if they were concurrently receiving anti-depressants upon enrolment but were excluded if they commenced antidepressants 2 months prior to enrolment. Patients were also excluded in the case of concurrent psychotropic medications, active major mental disorder such as bipolar disorder, psychosis, or history of suicide attempt. Predefined primary outcomes included time to lapse (any drinking), relapse (>5 drinks per day in men and >4 in women). Other outcomes included drinks per drinking day, number of heavy drinking days, and percentage days abstinent and frequency of adverse events. Results: For the number of days to first lapse, there was a trend of significance for the interaction baclofen × AD (Log Rank: χ2 = 2.98, P = 0.08, OR: 0.41, 95%CI: 0.15–1.12). For the number of days to relapse, there was a trend of significance for the interaction of baclofen × AD (Log Rank: χ2 = 3.72, P = 0.05, OR: 3.40, 95%CI: 1.01–11.46). Placing significant baseline variables into the models as covariates (tobacco, ALD) weakened these interactions (P's > 0.15). There were no significant effects of ADs on the frequency of adverse events reported (P's > 0.19). Conclusion: Concurrent receipt of ADs commenced more than 2 months prior to baclofen treatment did not negatively impact on drinking outcomes. Future research examining the interaction between commencing ADs during baclofen treatment on alcohol dependent patients is required. Trial Registration: ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01711125","term_id":"NCT01711125"}}NCT01711125, https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01711125","term_id":"NCT01711125"}}NCT01711125

AIMS To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response. DESIGN Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1). SETTING Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia. PARTICIPANTS Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female). MEASUREMENTS Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post-treatment). FINDINGS Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age

Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These include the lack of a current cohesive strategy for treatment and follow-up of mothers and their babies; the uncertain risk of postpartum HBV flares; the lack of randomised trial data on the safety and efficacy of antiviral treatment in pregnancy; the lack of head-to-head studies comparing different antivirals in pregnancy; and the lack of epidemiologic information regarding infection across different populations globally. This position paper provides a comprehensive review of the management of women with HBV infection prior to conception, throughout each stage of pregnancy and postpartum, as well as recommendations and clinical approaches for the follow-up of children born to infected mothers, based on available evidence in the literature and recommendations from international experts. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for most of the chronic infection worldwide.

Baclofen has been shown to reduce alcohol consumption in alcohol-dependent individuals, but there is marked heterogeneity in response. An association between GABBR1 rs29220 and alcohol dependence has been demonstrated previously. The present study evaluated whether the response to baclofen is moderated by a single nucleotide polymorphism (rs29220) in the GABAB receptor subunit 1 gene (GABBR1).Double-blind, placebo-controlled study.Australia.Seventy-two alcohol-dependent men and women receiving 12 weeks of 30 mg/day of baclofen, 75 mg baclofen or placebo.Primary outcomes included time to lapse (any drinking) and relapse (5 drinks per day in men and 4 in women). We also examined alcohol consumption at follow-up (drinks per drinking day, number of heavy drinking days and percentage days abstinent).We observed significant medication × genotype interaction effect for time to relapse (P = 0.049) and a near-significant interaction effect for time to lapse (P = 0.055). For the CC genotype group, the relapse hazard ratio for baclofen versus placebo was 0.32 [95% confidence interval (CI) = 0.14-0.75] and for the G- group it was 1.07 (95% CI = 0.43-2.63). There was also a significant medication × genotype interaction for follow-up alcohol consumption (drinks per drinking day, heavy drinking days and days abstinent) (P = 0.02). Covarying for baseline levels of craving, aspartate aminotransferase and abstinence before enrolment reduced the medication × genotype effect for time to lapse and relapse but not for alcohol consumption at follow-up.The GABBR1 rs29220 polymorphism may influence treatment response and possibly predict adverse effects to baclofen in the treatment of alcohol dependence.

Despite large increases in pharmaceutical opioid dependence and related mortality, few studies have focused on the characteristics and treatment experiences of those with pharmaceutical opioid dependence. We describe the formation of a prospective cohort of people receiving treatment for pharmaceutical opioid dependence and describe their baseline characteristics.People who had entered treatment for pharmaceutical opioid dependence (n = 108) were recruited through drug treatment services in New South Wales, Australia. We describe baseline characteristics of those that commenced pharmaceutical opioids for pain or other reasons and conducted a thematic analysis of responses regarding their treatment experience.Mean age was 41 years (SD 11), half were male (48%). Just over half reported lifetime heroin use (57%). Oxycodone (49%) and codeine (29%) were the most common opioids reported. Most (85%) reported past-year problematic pain, 38% reported chronic pain. Half (52%) reported moderate to severe depression symptoms. Most (66%) commenced opioids for pain, and this group were older, less likely to report a previous overdose and less likely to report use of illicit drugs compared to those commencing for other reasons. Five themes related to treatment expectations: (i) stigma; (ii) the restrictive nature of treatment; (iii) knowledge; (iv) pain; and (v) positive experience with buprenorphine.This study describes the complexities in an important emerging treatment population of pharmaceutical opioid-dependent people. Findings highlights that addressing knowledge and perceptions around treatment may be critical to address the rising mortality associated with pharmaceutical opioid dependence.

Introduction: There is clinical impetus to accurately monitor cannabis withdrawal symptoms. In doing this the impact of other drug and mental health comorbidities should be considered.Aims: To report patient demographics, psychiatric and substance use comorbidities and symptoms of cannabis withdrawal in the first 5 days of hospital admission for detoxification.Design: Daily self-reported symptom severity ratings were analysed as functions of gender, secondary drug use and recent mental health history.Setting: Specialised inpatient hospital unit for withdrawal management (detoxification) at a University of Sydney teaching hospital, Sydney, Australia.Participants: Total 193 consecutive patients admitted for routine inpatient cannabis withdrawal management over a 9-month period.Measurements: Patients screened via daily self-reported subjective ratings of cannabis withdrawal.Findings: Average cannabis used per day was 2.6 g. Most patients smoked tobacco daily (91%) and half of the sample (53%) reported other ...

IntroductionMethamphetamine dependence is a growing public health concern. There is currently no pharmacotherapy approved for methamphetamine dependence. Lisdexamfetamine (LDX) dimesylate, used in the treatment of attention-deficit hyperactivity disorder and binge eating disorder, has potential as an agonist therapy for methamphetamine dependence, and possible benefits of reduced risk of aberrant use due to its novel formulation.Methods and analysisA double-blind randomised controlled trial will be used to evaluate the efficacy of LDX in reducing methamphetamine use. The target sample is 180 participants with methamphetamine dependence of ≥2 years, using ≥14 days out of the previous 28, who have previously attempted but not responded to treatment for methamphetamine use. Participants will be randomly assigned to receive either a 15-week intervention consisting of induction (1 week of 150 mg LDX or placebo), maintenance (12 weeks of 250 mg LDX or placebo) and reduction (1 week of 150 mg LDX or placebo and 1 week of 50 mg LDX or placebo). All participants will be given access to four sessions of cognitive–behavioural therapy as treatment as usual and receive a 4-week follow-up appointment. The primary outcomes are efficacy (change from baseline in days of methamphetamine use by self-report for the last 28 days at week 13 and urinalyses confirmation of methamphetamine use) and safety (treatment-related adverse events). Secondary outcomes are total number of days of self-report methamphetamine use over the 12-week active treatment, longest period of abstinence during treatment period, percentage of achieving ≥21 days abstinence, craving, withdrawal, dependence, retention, bloodborne virus transmission risk behaviour, criminal behaviour, as well measures of abuse liability, physical and mental health, other substance use, cognitive performance, psychosocial functioning, treatment retention and satisfaction. Additionally, the study will assess the cost-effectiveness of LDX relative to the placebo control.Ethics and disseminationThe study has been approved by the Human Research Ethics Committee of St. Vincent’s Hospital, Sydney, Australia (HREC/16/SVH/222). Contact the corresponding author for the full trial protocol.Trial registration numberACTRN12617000657325; Pre-results.

To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response.Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1).Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia.Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female).Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA24 weeks post-treatment).Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR.People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy.

Aim To compare the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence. Design A double-blind, placebo-controlled trial. Setting Three treatment centres in Australia. Participants A total of 169 alcohol dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day) or placebo for 12 weeks. Intervention All subjects were offered manualized compliance therapy, a brief intervention that targets problems that may affect treatment compliance such as ambivalence and misperceptions about medication. Measurements Time to the first drink, time to first relapse, drinks per drinking day and cumulative abstinence. Findings In intention-to-treat analyses, there were no differences between groups on outcome measures of drinking, craving or biochemical markers. Similarly, analyses of the 94 subjects that completed the study in full and demonstrated 80% compliance, revealed no significant treatment effects. Differential treatment effects were identified after stratification according to scores on the Alcohol Dependence Scale (ADS) and Depression Anxiety and Stress Scale (DASS). A significant beneficial treatment effect on time to first relapse was revealed for subjects with ‘no depression’ allocated to naltrexone (n = 56; P

We explored the involvement of cell types, cytokines and lipid peroxidation in a rat dietary model of fibrosing steatohepatitis.Male rats were fed a high fat diet deficient in methionine and choline (MCD) for up to 17 weeks. Whole liver, hepatocytes and non-parenchymal cells were analysed for reduced glutathione (GSH) levels, products of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), liver injury, and fibrosis.MCD diet-fed rats developed hepatic steatosis at week 2 and focal necroinflammatory change by week 5, while pericellular fibrosis evolved and progressed between weeks 12 and 17. Collagen alpha(1)(1) gene expression was upregulated by week 5 and increased fivefold by week 17. Stellate cells were the unique source of collagen gene expression. TIMP-1 and -2 were increased at week 12. Livers of MCD diet-fed rats exhibited lowered levels of GSH and elevated TBARS. Hepatocytes were the source of lipid peroxidation, and mRNA levels for TGFbeta1 were increased only in this cell type.The MCD model of 'fibrosing steatohepatitis' replicates the histologic features of human steatohepatitis, and the sequence of steatosis, inflammatory cell injury and fibrogenesis. The temporal sequence is consistent with a concept for involvement of oxidative injury in inflammatory recruitment and pathogenesis of hepatic fibrogenesis.

Patients often complain of indigestion, but what do they mean? Indigestion is an old English word that means lack of adequate digestion, but patients and doctors interpret this in different ways. Many patients mean heartburn or acid regurgitation, the classic symptoms of gastro-oesophageal reflux disease. Some describe belching, abdominal rumblings, or even bad breath as indigestion. Others mean pain localised to the epigastrium or a non-painful discomfort in the upper abdomen which may be described as fullness, bloating, or an inability to finish a normal meal (early satiety). Dyspepsia is best restricted to mean pain or discomfort centred in the upper abdomen. #### Major structural causes of dyspepsia Overlap of subgroups of dyspepsia based on symptoms in patients with documented functional dyspepsia There are many causes of dyspepsia, but at least two thirds of patients have no structural or biochemical explanation for their symptoms. It has been suggested that dyspepsia can be subdivided based on groups (or clusters) of symptoms. However, subgroups have not proved to be of value in identifying the underlying cause of dyspepsia and overlap considerably. Some patients report having troublesome burping associated with abdominal bloating or discomfort that is transiently relieved by bringing up the wind. These patients have aerophagy, and repeated swallowing of air may be obvious during the consultation. History taking is key to identifying the likely cause of dyspepsia. ### Gastro-oesophageal reflux disease It is important and practical to distinguish gastro-oesophageal reflux disease (GORD) from dyspepsia. Frequent heartburn is a cardinal symptom of GORD; acid reflux causes a retrosternal or epigastric burning feeling that characteristically radiates up towards the throat, is relieved transiently by antacids, and is precipitated by a meal or by lying down. #### Uncommon causes of upper abdominal pain or discomfort that may be confused with dyspepsia

We aimed to determine if changes in the patterns of upper gastrointestinal diseases at endoscopy have occurred over the past decade. Retrospectively, 917 consecutive patients were selected based on upper endoscopy between June 1 and August 31, in 1990 (n = 217), 1994 (n = 270), and 1998 (n = 430). Demographic, clinical, endoscopic, and histological information were extracted from the medical records on a standardized case record form. Over the eight-year period, follow-up of peptic ulcer (15%, 5%, and 5%, respectively, in 1990, 1994, and 1998, df = 2, P < 0.001), bleeding (22%, 14%, and 13%, P = 0.008), and nausea/vomiting (15%, 16%, and 10%, df = 2, P = 0.003) had become less frequent, but reflux (21%, 19%, and 34%, df = 2, P < 0.001) and dyspepsia (24%, 43%, and 32%, df = 2, P < 0.001) more frequent indications for upper endoscopy. The prevalence of peptic ulcer disease decreased (22%, 15%, and 13%, df = 2, P = 0.025), but the prevalence of reflux esophagitis increased significantly (29%, 30%, and 39%, df = 2, P = 0.010). The prevalence of both the use of nonsteroidal antiinflammatory drugs (NSAIDs) (18%, 20%, and 11%, respectively, in 1990, 1994, and 1998, df = 2, P = 0.004) and H. pylori infection (39% in 1994 and 30% in 1998, df = 1, P = 0.032) decreased. Overall, NSAID use was independently associated with gastric ulcers (OR = 2.39, 95% CI 1.21–4.73, χ2 = 6.31, df = 1, P = 0.012), but not esophagitis. H. pylori infection was independently associated with duodenal ulcers (OR = 4.74, 95% CI 2.30–9.77, χ2 = 17.8, df = 1, P < 0.001), histologically chronic (OR = 166.8, 95% CI 76.1–365.4, χ2 = 313.0, df = 1, P < 0.001) and active (OR = 30.1, 95% CI 17.0–53.5, χ2 = 189.7, df = 1, P < 0.001) gastritis and lymphoid aggregates (OR = 5.49, 95% CI 3.02–9.97, χ2 = 36.3, df = 1, P < 0.001). In conclusion, the prevalence of peptic ulcer disease appears to have been decreasing, whereas reflux esophagitis has been increasing over the past decade in Western Sydney. The decreased use of NSAIDs and decline of H. pylori infection have likely both contributed to the reduction of peptic ulcer disease, but the increase in reflux esophagitis remains to be fully explained.

The pathogenesis of functional dyspepsia remains poorly understood. There is increasing evidence pointing to a predominant role of gastroduodenal visceral hypersensitivity in the pathogenesis, where patients have abnormally reduced gastric and small intestinal sensory thresholds. Motor abnormalities observed in subgroups of patients include delayed gastric emptying, antral hypomotility, gastric dysrhythmias, abnormal gastrointestinal reflexes and small intestinal dysmotility, but these may be secondary pheno nena. The central nervous system modifies peripheral visceral afferent pathways and, hente, psychological factors may possibly alter symptom status. Other putative mechanisms include Helicobacter pylori gastritis and gastric acid hypersecretion or sensitivity, but the role of these remain controversial.

Background Australians born in countries where hepatitis B infection is endemic are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. However, a program of screening, surveillance and treatment of chronic hepatitis B (CHB) in high risk populations could significantly reduce disease progression and death related to end-stage liver disease and HCC. Consequently we are implementing the B Positive pilot project, aiming to optimise the management of CHB in at-risk populations in south-west Sydney. Program participants receive routine care, enhanced disease surveillance or specialist referral, according to their stage of CHB infection, level of viral load and extent of liver injury. In this paper we examine the program's potential impact on health services utilisation in the study area. Methods Estimated numbers of CHB infections were derived from Australian Bureau of Statistics data and applying estimates of HBV prevalence rates from migrants' countries of birth. These figures were entered into a Markov model of disease progression, constructing a hypothetical cohort of Asian-born adults with CHB infection. We calculated the number of participants in different CHB disease states and estimated the numbers of GP and specialist consultations and liver ultrasound examinations the cohort would require annually over the life of the program. Results Assuming a 25% participation rate among the 5,800 local residents estimated to have chronic hepatitis B infection, approximately 750 people would require routine follow up, 260 enhanced disease surveillance and 210 specialist care during the first year after recruitment is completed. This translates into 5 additional appointments per year for each local GP, 25 for each specialist and 420 additional liver ultrasound examinations. Conclusions While the program will not greatly affect the volume of local GP consultations, it will lead to a significant increase in demand for specialist services. New models of CHB care may be required to aid program implementation and up scaling the program will need to factor in additional demands on health care utilisation in areas of high hepatitis B sero-prevalence.

Background: Helicobacter pylori ( H. pylori ) is a cause of chronic gastritis and maybe responsible for functional dyspepsia in a subset of patients. Many risk factors, such as alcohol consumption and smoking, may contribute to the colonization and infection of H. pylori in humans. However, studies on the relationship between H. pylori infection and drinking or smoking have produced conflicting results. Objective: The aim of this study was to examine whether consumption of alcohol or smoking is associated with active H. pylori infection in functional dyspepsia patients. Methods: H. pylori infection was confirmed by CLOtest and histology on at least two biopsies. Active chronic gastritis was diagnosed using the updated Sydney system. In addition to gender and age, information on drinking and smoking habits was collected using a standard questionnaire. Functional dyspepsia was diagnosed according to the Rome II diagnostic criteria. Results: H. pylori infection was positive in 27.3% of the 139 functional dyspepsia patients. Both age and gender were not significantly associated with H. pylori infection. A multiple logistic model found that alcohol consumption (OR = 9.05, 95% CI: 1.05–77.98) and pathology (active gastritis) (OR = 595.39, 95% CI: 81.43–4353.33) were associated with H. pylori infection. Active gastritis was associated with alcohol consumption (OR = 2.89, 95% CI: 1.03–8.02), smoking (OR = 2.72, 95% CI: 1.22–6.05) and age (OR = 1.03, 95% CI: 1.01–1.06). Conclusions: In patients with functional dyspepsia, there is no significant association between active H. pylori infection and smoking. However, alcohol consumption appears to be associated with H. pylori infection.

The mechanistic significance of oxidative stress to fibrogenesis in the methionine and choline-deficient (MCD) diet-induced model of steatohepatitis was evaluated by antioxidant intervention, using either vitamin E or L-2-oxothiazolidine-4-carboxylate (OTC), a cysteine precursor that promotes glutathione synthesis. Significant depletion of hepatic reduced glutathione (GSH) and elevation of thiobarbituric acid reactive substances (TBARS) occurred from week 3 in association with hepatic injury in mice fed the MCD diet. Hepatic stellate cell (HSC) activation and increased collagen alpha(1)(I) mRNA expression, together with morphologic fibrosis were evident from week 5. Vitamin E repleted GSH, reduced TBARS, steatosis, inflammation, HSC activation and collagen alpha(1)(I) mRNA expression, and ameliorated fibrosis. Vitamin E did not effect the expression of either profibrogenic cytokines (transforming growth factor-beta 1, connective tissue growth factor) or matrix remodeling enzymes (tissue inhibitor of metalloproteinase-1 and -2, matrix metalloproteinase-2 and -13). Despite repletion of hepatic GSH in OTC-supplemented mice, the initial benefit in the reduction of hepatic TBARS and inhibition of collagen alpha(1)(I) mRNA expression at week 5, failed to protect these mice from hepatic injury or fibrosis at later time points. Oxidative stress or products of lipid peroxidation mediate HSC activation and collagen gene expression directly in the MCD model of steatohepatitis. Vitamin E but not glutathione augmentation can interrupt this pathogenic process.