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M Raj Lakshman,
Mamatha Garige,
Maokai A Gong,
Leslie Leckey,
Ravi Varatharajalu,
Robert S Redman,
Devanshi Seth, Paul S Haber,
Kenneth Hirsch,
Richard Amdur,
Ruchi Shah
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ABSTRACT: Chronic alcohol-mediated down-regulation of hepatic ST6Gal1 gene leads to defective glycosylation of lipid-carrying apolipoproteins such as apo E and apo J, resulting in defective VLDL assembly and intracellular lipid and lipoprotein transport, which in turn is responsible for alcoholic hepatosteatosis and ALD. The mechanism of ethanol action involves thedepletion of a unique RNA binding protein that specifically interacts with its 3'-UTR region of ST6Gal1 mRNA resulting in its destabilization and consequent appearance of asialoconjugates as alcohol biomarkers. With respect to ETOH effects on Cardio-Vascular Diseases, we conclude that CYP2E1 and ETOH mediated oxidative stress significantly down regulates not only the hepatic PON1 gene expression, but also serum PON1 and HCTLase activities accompanied by depletion of hepatic GSH, the endogenous antioxidant. These results strongly implicate the susceptibility of PON1 to increased ROS production. In contrast, betaine seems to be both hepatoprotective and atheroprotective by reducing hepatosteatosis and restoring not only liver GSH that quenches free radicals, but also the antiatherogenic PON1 gene expression and activity.
Sub-cellular biochemistry 01/2013; 67:199-233.
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ABSTRACT: Injecting drug users (IDUs), the key risk population for hepatitis C virus (HCV) infection, constitute just a small proportion of HCV treatment clients. This study describes an HCV treatment assessment model developed by an inner-city IDU-targeted primary healthcare (PHC) facility and, using a retrospective clinical audit, documents predictors of successful referrals to a tertiary liver clinic. Between July 2006-December 2010, 479 clients attended the PHC, of whom 353 (74%) were screened for HCV antibody. Sixty percent (212/353) tested positive, of whom 93% (197/212) were screened for HCV-RNA with 73% (143/197) positive. Referrals to a tertiary liver clinic were provided to 96 clients, of whom 68 (71%) attended. Eleven clients commenced antiviral therapy (AVT), with seven achieving sustained virological responses by December 2010. Clients who had not recently injected drugs and those with elevated ALT levels were more likely to attend the referrals, while those not prescribed psychiatric medications were more likely to commence AVT. The relatively high uptake of referrals, the number of individuals commencing AVT and final treatment outcomes are reasonably encouraging, highlighting the potential of targeted PHC services to facilitate reductions in liver disease burden among IDUs.
Journal of substance abuse treatment 08/2012; · 2.90 Impact Factor
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ABSTRACT: BACKGROUND: Low-threshold primary healthcare (PHC) centres targeting injecting drug users (IDUs) are increasingly being created to offer preventative and opportunistic services. However, no data are available on the characteristics of clients who utilise such services, or the effectiveness of these services in facilitating prevention or treatment. METHOD: A retrospective clinical record audit examined the characteristics, service utilisation patterns and referral uptake of 384 clients presenting to a low-threshold PHC service in Sydney, Australia. RESULTS: Of the 384 clients, 85% were IDUs. Sixty-two percent reported also having access to a general medical practitioner (GP), with this group more likely to report taking benzodiazepines or other psychoactive medication. Despite this relatively high level of GP access, only 50% were fully vaccinated against hepatitis B virus (HBV). Testing for blood-borne viral and sexually transmitted infections were the most common reasons for presentation to the PHC. Most (82%) clients made at least one return visit, with an average of 3.5 presentations per client. All clients were offered HBV vaccination where indicated (n=145); and more than half (55%) of referrals to external services were attended. Clients accessing this PHC were younger, more likely to be male and born outside Australia than IDUs attending needle syringe programs (NSPs) in Australia's most populous state, New South Wales. CONCLUSION: Results suggest that this low-threshold PHC service was underutilised and its role as a low-threshold healthcare outlet remains limited. Further research is needed to more clearly delineate the health and economic benefits of this model.
The International journal on drug policy 07/2012; · 2.54 Impact Factor
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ABSTRACT: Despite a safe, effective vaccine, hepatitis B virus (HBV) vaccination coverage remains low among people who inject drugs (PWID). Characteristics of participants screened for a trial investigating the efficacy of financial incentives in increasing vaccination completion among PWID were examined to inform targeting of vaccination programs. Recruitment occurred at two health services in inner-city Sydney that target PWID. HBV status was confirmed via serological testing, and questionnaires elicited demographic, drug use, and HBV risk data. Multinomial logistic regression was utilized to determine variables independently associated with HBV status. Of 172 participants, 64% were susceptible, 17% exposed (HBV core antibody-positive), and 19% demonstrated evidence of prior vaccination (HBV surface antibody ≥ 10 mIU/ml). Compared with exposed participants, susceptible participants were significantly more likely to be aged less than 35 years and significantly less likely to be receiving current opioid substitution therapy (OST) and to test hepatitis C antibody-positive. In comparison to vaccinated participants, susceptible participants were significantly more likely to be male and significantly less likely to report daily or more frequent injecting, current OST, and prior awareness of HBV vaccine. HBV vaccination uptake could potentially be increased by targeting younger, less frequent injectors, particularly young men. In addition to expanding vaccination through OST, targeting "at risk" youth who are likely to have missed adolescent catch-up programs may be an important strategy to increase coverage. The lack of an association between incarceration and vaccination also suggests increasing vaccination uptake and completion in adult and juvenile correctional facilities may also be important.
Journal of Urban Health 06/2012; 89(5):769-78. · 2.13 Impact Factor
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Addiction 05/2012; 107(7):1361-2. · 4.31 Impact Factor
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ABSTRACT: Cannabis is one of the most widely used illicit drugs worldwide. However, while the rates of cannabis dependence and treatment increase, there remains no medications approved for this use. Due to its sedative effects and low abuse liability, the typical antipsychotic pericyazine has been utilized in some parts of Australia for the treatment of cannabis dependence. We aimed to provide documentation of preliminary outcomes and acceptability of pericyazine treatment in a small sample. A naturalistic case series study was conducted in which 21 patients were enrolled for a 4-week course of pericyazine (up to 8 × 2.5 mg tablets daily) and weekly medical review. Levels of cannabis use were reported and side effects with electrocardiography and blood tests were monitored. Measures of dependence severity, depression, anxiety, and insomnia were taken at baseline and follow-up utilizing validated psychometric tools. Significant reductions in cannabis use, depression, anxiety, and insomnia severity occurred across time. Pericyazine appeared to be well tolerated and easily administered in the community clinics. The results provide some preliminary evidence that low-dose short-term pericyazine may be an acceptable mode of treatment in this population. Given the open-label nature of the design, we cannot conclude that pharmacotherapy was uniquely responsible for the treatment effect. Nonetheless, low-dose pericyazine may be a potentially effective approach to the treatment of cannabis dependence, and further evaluation via a randomized placebo-controlled trial is warranted.
Substance Abuse. 03/2012; 2012(3):1-5.
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ABSTRACT: At an international level, there are calls for a greater focus on women and harm reduction in recognition that female drug users have a unique set of issues that are not routinely assessed in drug treatment programs.
To assess the pregnancy history, current pregnancy risk and contraceptive use of nonpregnant women attending opioid treatment programs (OTPs).
This study involved a structured questionnaire survey of 204 women attending outpatient OTP services within the Sydney South West Area Health Service.
Two hundred and four women of 302 (67.5%) enroled in OTPs at the time completed surveys. Key findings were high pregnancy rates, with 28.9% of women reporting six or more pregnancies, high rates of adverse pregnancy outcomes (miscarriage, termination and stillbirth) compared with national data and poor uptake of contraception, with only 54.7% of sexually active women not wanting to get pregnant using a method. Women expressed diverse preferences for the type and location of women's health services they felt would meet their needs.
Women in OTP clinics have unaddressed reproductive health issues, particularly around contraception. Addressing these will potentially minimise the risk of material deprivation and social exclusion in these women and improve their well-being through greater control and choice over their fertility. Current women's health service provision in OTP programs involves referral to external services, but an integrated model of care may best address the unmet contraceptive needs of these women.
Australian and New Zealand Journal of Obstetrics and Gynaecology 02/2012; 52(2):146-50. · 1.24 Impact Factor
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ABSTRACT: Background. There is a paucity of research in Australia on the characteristics of women in treatment for illicit substance use in pregnancy and the health outcomes of their neonates. Aims. To determine the clinical features and outcomes of high-risk, marginalized women seeking treatment for illicit substance use in pregnancy and their neonates. Methods. 139 women with a history of substance abuse/dependence engaged with a perinatal drug health service in Sydney, Australia. Maternal (demographic, drug use, psychological, physical, obstetric, and antenatal care) and neonatal characteristics (delivery, early health outcomes) were examined. Results. Compared to national figures, pregnant women attending a specialist perinatal and family drug health service were more likely to report being Australian born, Aboriginal or Torres Strait Islander, younger, unemployed, and multiparous. Opiates were the primary drug of concern (81.3%). Pregnancy complications were common (61.9%). Neonates were more likely to be preterm, have low birth weight, and be admitted to special care nursery. NAS was the most prevalent birth complication (69.8%) and almost half required pharmacotherapy. Conclusion. Mother-infant dyads affected by substance use in pregnancy are at significant risk. There is a need to review clinical models of care and examine the longer-term impacts on infant development.
Obstetrics and Gynecology International 01/2012; 2012:867265.
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Drug and Alcohol Review 12/2011; 31(1):114-5; author reply 116-7. · 1.55 Impact Factor
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Maryam Alavi,
Jason Grebely,
Gail V Matthews,
Kathy Petoumenos,
Barbara Yeung,
Carolyn Day,
Andrew R Lloyd,
Ingrid Van Beek,
John M Kaldor,
Margaret Hellard,
Gregory J Dore, Paul S Haber
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ABSTRACT: Pegylated interferon (PEG-IFN) treatment for hepatitis C virus (HCV) infection has neuropsychiatric side effects. Data on the effect of HCV treatment on mental health among injecting drug users (IDUs) are limited. We assessed mental health during treatment of recently acquired HCV, within a predominantly IDU population.
Participants with HCV received PEG-IFN-α-2a (180 µg/week) for 24 weeks; HCV/HIV received PEG-IFN with ribavirin. Depression was assessed using the Mini-International Neuropsychiatric Interview (MINI). Logistic regression was used to identify factors associated with depression at enrolment and during treatment. Also, the effect of depression prior to and during treatment on sustained virological response (SVR) was assessed.
Of 163 participants, 111 received treatment (HCV, n = 74; HCV/HIV, n = 37), with 76% ever reporting IDU. At enrolment, 16% had depression (n = 25). In adjusted analysis, depression at enrolment occurred less often in participants full-/part-time employed (adjusted odds ratio [AOR] 0.23; 95% confidence interval [CI]: 0.06, 0.82, P = 0.023) and more often in recent IDUs (AOR 3.04; 95% CI: 1.19, 7.72, P = 0.019). During treatment, 35% (n = 31) developed new-onset depression. In adjusted analysis, poorer social functioning (higher score) was associated with new-onset depression (score ≤ 9 vs score ≥ 17; OR 5.69; 95% CI: 1.61, 20.14, P = 0.007). SVR was similar among participants with and without depression at enrolment (60% vs 61%, P = 0.951) and in those with and without new-onset depression (74% vs 63%, P = 0.293).
Although depression at enrolment and during treatment was common among participants with recent HCV, neither influenced SVR. Participants with poor social functioning may be most at risk of developing depression during HCV therapy.
Journal of Gastroenterology and Hepatology 12/2011; 27(5):957-65. · 2.87 Impact Factor
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The Medical journal of Australia 10/2011; 195(7):371-2. · 2.81 Impact Factor
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ABSTRACT: Case-management is a client-centred intervention to improve the coordination and continuity of delivery of services for people with complex needs. This service has been incorporated into opioid treatment programs in various ways. This study was undertaken to compare two case-management models, termed individual case-management (ICM) and team-based case-management (TBCM). This study aims to describe the new TBCM and client attitudes to, and acceptance of, this model compared with ICM.
Clients from two opioid treatment programs, one implementing ICM and one implementing the TBCM, were recruited to undertake a self-complete survey examining satisfaction with case-management during dosing hours over 7 months. Surveys took approximately 10 min to complete.
One hundred and sixty-three clients were surveyed (62 ICM, 101 TBCM). Clients were demographically similar, but differed in terms of treatment and drug use characteristics. Significantly higher ratings of case-management were reported from TBCM compared with ICM clients for help with opiate use (P < 0.001), other drug use (P < 0.001), mental health (P < 0.001), accommodation (P = 0.023), relationships/parenting (P = 0.003) and physical health (P = 0.002) and clinic services in terms of fairness and consistency, safety, respect, staff quality and confidentiality (P < 0.001). Compared with ICM clients, TBCM clients were more likely to report ease of access to case-management (P < 0.001), wait significantly less time to see a case-manager (38% vs. 7% seen same day) and 93% and 47% of clients, respectively, reported satisfaction with treatment (P < 0.001).
These initial data indicate client acceptance and satisfaction with the TBCM model. Further evaluation of the model, including cost-effectiveness, is warranted.
Drug and Alcohol Review 09/2011; 31(4):499-506. · 1.55 Impact Factor
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ABSTRACT: Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and physiological/cell signaling pathways include fibrinolysis, osteopontin, transforming growth factor-β-SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non-alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.
Journal of Gastroenterology and Hepatology 07/2011; 26(7):1089-105. · 2.87 Impact Factor
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Australian and New Zealand Journal of Public Health 06/2011; 35(3):294-5. · 1.20 Impact Factor
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ABSTRACT: Barriers to entering addiction medicine (AM) have led to a persisting workforce shortage. To address this problem, the Chapter of Addiction Medicine (AChAM) was formed in 2001 as a subdivision of the Royal Australasian College of Physicians (RACP). Through consultation, AChAM has identified the scope of practice and offered fellowship to suitable established practitioners. The Chapter successfully applied to the Australian Government for recognition of AM as a medical specialty, which was finalized in November 2009. Specialist reimbursement item numbers were incorporated into that decision process and commence operating in November 2010. AChAM has designed and implemented a training scheme using a model similar to that of the RACP internal medicine training program. This comprises 3 years of basic general medical training post internship followed by 3 years of discipline-specific supervised training. The training is broadly based, with experience in both ambulatory care and inpatient care, and including physical health as well as mental health. Assessment is continuous and competency based. There is no exit examination. The overriding clinical approach rests upon the harm minimization framework consistent with long-established national drug policy in Australia and favors evidence-based treatment.
Substance Abuse 04/2011; 32(2):115-9. · 1.33 Impact Factor
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ABSTRACT: Injecting drug users (IDUs) experience numerous health problems, but report barriers to utilising general practitioners (GPs). A nurse-led Harm Minimisation-based Primary Healthcare (HMPH) service for IDUs was established within a needle and syringe program in inner-city Sydney with Area Health Service medical support and clinical governance. This paper aimed to describe the HMPH service, review service utilisation and assess nurses' perceptions of their work with IDUs. A review of the most recent 200 clinic files was undertaken. Service utilisation, GP and other health service use and access were extracted and analysed using SPSS. A semi-structured qualitative interview with clinic nurses regarding their experience working with IDUs and local GPs was conducted and analysed. Since its inception in mid-2006, the service has been utilised by 417 clients. Of the most recent 200 files, blood-borne virus and sexually transmitted infection screening were the primary reason for presentation (64.5%). At least one follow-up visit was attended by 90% of clients. A total of 62% of clients reported consulting a GP in the last 12 months. The service provided 102 referrals. Nurses believed that IDUs tend to utilise GPs ineffectively and that self-care is a low priority, but that they can support IDUs to overcome some barriers to GPs and facilitate access. Targeted primary health care services led by nurses with focussed medical support and co-located with needle and syringe programs can fill an important gap in delivering and facilitating health care to IDUs.
Australian Journal of Primary Health 01/2011; 17(1):10-5. · 0.50 Impact Factor
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ABSTRACT: Objective. This paper reports the findings comparing the obstetrical health, antenatal care, and psychosocial characteristics of pregnant women with a known history of substance dependence (n = 41) and a comparison group of pregnant women attending a general antenatal clinic (n = 47). Method. Face-to-face interviews were used to assess obstetrical health, antenatal care, physical and mental functioning, substance use, and exposure to violence. Results. The substance-dependent group had more difficulty accessing antenatal care and reported more obstetrical health complications during pregnancy. Women in the substance-dependent group were more likely to report not wanting to become pregnant and were less likely to report using birth control at the time of conception. Conclusions. The profile of pregnant women (in specialised antenatal care for substance dependence) is one of severe disadvantage and poor health. The challenge is to develop and resource innovative and effective multisectoral systems to educate women and provide effective care for both women and infants.
International Journal of Pediatrics 01/2011; 2011:729237.
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Jason Grebely,
Gail V Matthews,
Margaret Hellard,
David Shaw,
Ingrid van Beek,
Kathy Petoumenos,
Maryam Alavi,
Barbara Yeung, Paul S Haber,
Andrew R Lloyd,
John M Kaldor,
Gregory J Dore
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ABSTRACT: Adherence to HCV therapy impacts sustained virological response (SVR) but there are limited data on adherence, particularly among injecting drug users (IDUs). We assessed 80/80 adherence (≥80% of PEG-IFN doses, ≥80% treatment), on-treatment adherence, and treatment completion in a study of treatment of recent HCV infection (ATAHC).
Participants with HCV received pegylated interferon (PEG-IFN) alfa-2a (180μg/week, n=74) and those with HCV/HIV received PEG-IFN alfa-2a with ribavirin (n=35), for a planned 24 weeks. Logistic regression analyses were used to identify predictors of PEG-IFN 80/80 adherence.
A total of 109 out of 163 patients received treatment (HCV, n=74; HCV/HIV, n=35), with 75% ever reporting IDU. The proportion with 80/80 PEG-IFN adherence was 82% (n=89). During treatment, 14% missed ≥1 dose (on-treatment adherence=99%). Completion of 0-4, 5-19, 20-23, and all 24 weeks of PEG-IFN therapy occurred in 10% (n=11), 14% (n=15), 6% (n=7) and 70% (n=76) of cases, respectively. Participants with no tertiary education were less likely to have 80/80 PEG-IFN adherence (AOR 0.29, p=0.045). IDU prior to or during treatment did not impact 80/80 PEG-IFN adherence. SVR was higher among those patients with ≥80/80 PEG-IFN adherence (67% vs. 35%, p=0.007), but similar among those with and without missed doses during therapy (73% vs. 60%, p=0.309). SVR in those patients discontinuing therapy between 0-4, 5-19, 20-23, and 24 weeks was 9%, 33%, 43%, and 76%, respectively (p<0.001).
High adherence to treatment for recent HCV was observed, irrespective of IDU prior to, or during, therapy. Sub-optimal PEG-IFN exposure was mainly driven by early treatment discontinuation rather than missed doses during therapy.
Journal of Hepatology 11/2010; 55(1):76-85. · 9.26 Impact Factor
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ABSTRACT: To assess which baseline characteristics of patients predict response to treatment with acamprosate (ACAMP) and naltrexone (NTX) in alcohol dependence.
Outcome data from a 12-week randomized controlled trial of NTX, ACAMP and placebo for alcohol dependence were analysed by multiple logistic regression analyses to determine the predictive effects of gender and the baseline measures of dependence severity, craving, depression, anxiety and readiness to change in addition to NTX and ACAMP treatment. Moderators of the effect of each medication on outcomes were also examined.
Relapse was predicted by the interaction terms of ACAMP and alcohol dependence severity, NTX and depression as well as NTX and the readiness to change measure Taking Steps. Abstinence was similarly predicted by the interaction term ACAMP and alcohol dependence severity.
The efficacy of NTX and ACAMP in reducing relapse or lapse is influenced by different clinical characteristics.
Alcohol and Alcoholism 10/2010; 45(6):520-6. · 2.95 Impact Factor
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ABSTRACT: To evaluate the assessment and treatment outcomes of a prison hepatitis service.
A retrospective, observational cohort study of prison inmates who attended hepatitis clinics from 1996 to 2005 at correctional centres in New South Wales.
Inmates who attended the clinics, including a nested case-control series of patients who received antiviral treatment and age- and sex-matched patients who did not receive treatment.
Demographic and clinical characteristics of patients who attended the service; correlates of selection for antiviral treatment; and clinical and virological outcomes of treatment.
Of the 1043 inmates who attended the clinics, 851 were men (82%) and 994 (95%) were referred for HCV infection; the mean age for this group was 33 years (range, 18-74 years). In the case-control series (185 treated and 186 untreated patients), selection for treatment was not biased by culturally and linguistically diverse background, current methadone treatment or psychiatric status. In the treated group, 76 of 138 genotyped patients had a genotype that is predictive of favourable treatment response, and a small minority of those with available liver biopsy results had established cirrhosis (7/119 patients). Of treated patients for whom complete follow-up data were available, 55% achieved sustained virological response and 100% adhered to therapy. In addition, treatment episodes were not especially complicated.
Although the prison population has high rates of injecting drug use and poor mental health, imprisonment offers an opportunity for assessment and treatment of chronic HCV infection.
The Medical journal of Australia 05/2010; 192(9):496-500. · 2.81 Impact Factor
