ORCID Profile
0000-0001-7198-0833
Current Organisations
Alfred Health
,
Burnet Institute
,
Monash University
,
National University of Singapore School of Medicine
,
Griffith University Griffith Health
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Health Policy | Sociology | Applied Sociology, Program Evaluation and Social Impact Assessment |
Health Education and Promotion | Public Services Policy Advice and Analysis | Health Policy Evaluation
Publisher: Oxford University Press (OUP)
Date: 02-03-2018
DOI: 10.1093/CID/CIY182
Abstract: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is effective in reducing HIV risk in men who have sex with men (MSM). However, concerns remain that risk compensation in PrEP users may lead to decreased condom use and increased incidence of sexually transmitted infections (STIs). We assessed the impact of PrEP on sexual risk outcomes in MSM. We conducted a systematic review of open-label studies published to August 2017 that reported sexual risk outcomes in the context of daily oral PrEP use in HIV-negative MSM and transgender women. Pooled effect estimates were calculated using random-effects meta-analysis, and a qualitative review and risk of bias assessment were performed. Sixteen observational studies and 1 open-label trial met selection criteria. Eight studies with a total of 4388 participants reported STI prevalence, and 13 studies with a total of 5008 participants reported change in condom use. Pre-exposure prophylaxis use was associated with a significant increase in rectal chlamydia (odds ratio [OR], 1.59 95% confidence interval [CI], 1.19-2.13) and an increase in any STI diagnosis (OR, 1.24 95% CI, .99-1.54). The association of PrEP use with STI diagnoses was stronger in later studies. Most studies showed evidence of an increase in condomless sex among PrEP users. Findings highlight the importance of efforts to minimize STIs among PrEP users and their sexual partners. Monitoring of risk compensation among MSM in the context of PrEP scale-up is needed to assess the impact of PrEP on the sexual health of MSM and to inform preventive strategies.
Publisher: Wiley
Date: 28-06-2021
DOI: 10.1111/DAR.13343
Abstract: Risky drinking frequently remains undiagnosed or untreated, including in hospitalised inpatients. Using the Alcohol Use Disorders Identification Test (AUDIT), we assessed the feasibility of screening for risky drinking and whether screening results aligned with alcohol‐attributable diagnoses in an inpatient population. We conducted a cross‐sectional survey across a tertiary health service in Melbourne, Australia. Researchers collected demographics, AUDIT scores and acceptability from all eligible adult inpatients available on day of survey. Main outcomes were prevalence of risky drinking (AUDIT ≥8), mean AUDIT score and patient acceptability. Identification of risky drinking by the abbreviated ‘AUDIT‐C’ or discharge diagnoses (extracted by data‐linkage with medical records) was compared. Of 473 eligible inpatients, 61% ( n = 289) participated, 22% ( n = 103) were unavailable and 17% ( n = 81) declined. Median age was 64 years (IQR = 48, 76) 54% ( n = 157) were male. Mean AUDIT score was 4.4 (SD = 5.5). Risky drinking prevalence was 20% ( n = 57), 2% ( n = 7) had scores suggestive of dependence (AUDIT ≥20, a subset of risky drinkers). Odds of risky drinking were reduced in females (OR 0.19, 95% CI 0.09, 0.41 P 0.001) and participants ≥70 years (OR 0.22, 95% CI 0.07, 0.71 P = 0.01). Alcohol‐attributable diagnoses did not consistently align with risky drinking, with half of inpatients with wholly attributable diagnoses classified as low risk. Most inpatients considered screening acceptable (89%, n = 256). Pre‐admission risky drinking was evident in one‐fifth of hospital inpatients, but alcohol‐attributable diagnoses were unreliable proxy measures of risky drinking. Screening in‐patients with the AUDIT was acceptable to inpatients and can be feasibly implemented in an Australian tertiary hospital setting.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2018
Publisher: Wiley
Date: 25-03-2019
DOI: 10.1111/APT.15210
Abstract: Global targets to eliminate hepatitis C (HCV) might be met by sustained treatment uptake. To describe factors facilitating HCV treatment uptake and potential challenges to sustaining treatment levels after universal access to direct-acting anti-virals (DAA) across Australia. We analysed national Pharmaceutical Benefits Scheme data to determine the number of DAA prescriptions commenced before and after universal access from March 2016 to June 2017. We inferred facilitators and barriers to treatment uptake, and challenges that will prevent local and global jurisdictions reaching elimination targets. In 2016, 32 877 in iduals (14% of people living with HCV in Australia) commenced HCV DAA treatment, and 34 952 (15%) in iduals commenced treatment in the first year of universal access. Treatment uptake peaked at 13 109 DAA commencements per quarter immediately after universal access, but more than halved (to 5320 in 2017 Q2) within 12 months. General practitioners have written 24% of all prescriptions but with a significantly increased proportion over time (9% in 2016 Q1 to 37% in 2017 Q2). In contrast, hepatology or infectious diseases specialists have written a declining share from 74% to 38% during the same period. General practitioners provided a greater proportion (47%) of care in regional/remote areas than major cities. Broad treatment access led to rapid initial increases in treatment uptake, but this uptake has not been sustained. Our results suggest achieving global elimination targets requires more than treatment availability: people with HCV need easy access to testing and linkage to care in community settings employing a erse prescriber base.
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0041-0101(01)00268-9
Abstract: Symptoms of envenomation by the New-Guinean small-eyed snake Micropechis ikaheka (Elapidae) include peripheral neurotoxicity and myotoxicity. We have now purified to homogeneity a long-chain neurotoxin, mikatoxin, from M. ikaheka venom by successive gel filtration and reverse-phase chromatography. Electrospray ionization mass spectrometry showed mikatoxin to be a homogenous peptide of MW 7775.6. Mikatoxin was devoid of any phospholipase A(2) activity associated with the crude venom and did not exhibit any intrinsic anticholinesterase activity. In the chick biventer cervicis muscle, it produced an irreversible, concentration-dependent block of responses to exogenously applied acetylcholine and carbachol as well as twitches evoked by nerve, but not by direct muscle stimulation. Moreover, mikatoxin, like alpha-bungarotoxin and erabutoxin-b, did not show significant fade response to train-of-four stimulation of the mouse phrenic nerve-hemi diaphragm muscle. It also failed to block ganglionic transmission in the guinea pig ileum and muscarinic responses in the rat anococcygeus muscle. Our study provides strong evidence for the presence of a neurotoxin (mikatoxin) in M. ikaheka venom that produces neuromuscular blockade in skeletal muscle attributable to selective and irreversible antagonism of postsynaptic nicotinic acetylcholine receptors of the neuromuscular junction and likely contributes to the peripheral neurotoxicity observed in M. ikaheka envenomation.
Publisher: AMPCo
Date: 04-2016
DOI: 10.5694/MJA16.00167
Publisher: Wiley
Date: 02-04-2023
DOI: 10.1111/ADD.16189
Abstract: Few studies of the impacts of the coronavirus disease 2019 (COVID‐19) public health measures on drug markets and drug use patterns have used longitudinal data. We aimed to examine whether COVID‐19 measures were associated with increases in meth hetamine price, decreases in meth hetamine use frequency and subsequent changes in secondary outcomes of other drug use frequency in metropolitan Melbourne and regional Victoria. Longitudinal analysis framework was used from a longitudinal cohort of people who use meth hetamine. Victoria state, Australia. One hundred eighty‐five VMAX study participants who reported a meth hetamine purchase after the onset of the pandemic were used for the price paid analysis. Meth hetamine or other drug use frequency analysis was performed using 277 participants who used meth hetamine during the pandemic or in the year before the pandemic. Price paid per gram of meth hetamine derived from the most recent purchase price and most recent purchase quantity. Frequency of meth hetamine and other drug use measured as the average number of days per week used in the last month. Compared with pre‐COVID‐19 period, meth hetamine prices increased by AUD351.63 ( P value .001) and by AUD456.51 ( P value .001) in Melbourne and regional Victoria, respectively, during the period in which the most intense public health measures were implemented in Victoria. Although prices decreased after harder restrictions were lifted (by AUD232.84, P value .001 and AUD263.68, P value .001, in Melbourne and regional Victoria, respectively), they remained higher than pre‐COVID‐19 levels. A complementary 76% decrease was observed in relation to meth hetamine use frequency in regional Victoria ( P value = 0.006) that was not offset by any changes in the frequency of use of other drugs such as alcohol, tobacco or other illicit drugs. COVID‐19 public health measures in Victoria state, Australia, appear to have been associated with major price changes in the meth hetamine market and decreased frequency of use of the drug.
Publisher: American Chemical Society (ACS)
Date: 25-11-2006
DOI: 10.1021/BI0516024
Abstract: Agonist-binding kinetics to the nicotinic acetylcholine receptor (AChR) from Torpedo californica were measured using sequential-mixing stopped-flow fluorescence methods to determine the contribution of each in idual site to agonist-induced opening and desensitization. Timed dansyl-C6-choline (DC6C) binding followed by its dissociation upon mixing with high, competing agonist concentrations revealed four kinetic components: an initial, fast fluorescence decay, followed by a transient increase, and then two characteristic decays that reflect dissociation from the desensitized agonist sites. The transient increase resulted from DC6C binding to the open-channel based on its prevention by proadifen, a noncompetitive antagonist. Further characterization of DC6C channel binding by the inhibition of [3H]phencyclidine binding and by equilibrium measurements of DC6C fluorescence yielded KD values of 2-4 microM for the desensitized AChR and approximately 600 microM for the closed state. At this site, DC6C displayed a strongly blue-shifted emission spectrum, higher intrinsic fluorescence, and weaker energy transfer from tryptophans than when bound to either agonist site. The initial, fast fluorescence decay was assigned to DC6C dissociation from the alphadelta site of the AChR in its closed conformation, on the basis of inhibition with the site-selective antagonists d-tubocurarine and alpha-conotoxin MI. Fast decay litude data indicated an apparent affinity of 0.9 microM for the closed-state alphadelta site the closed-state alphagamma-site affinity is inferred to be near 100 microM. These values and the known affinities for the desensitized conformation show that the alphagamma site drives AChR desensitization to a approximately 40-fold greater extent than the alphadelta site, undergoes energetically larger conformational changes, and is the primary determinant of agonist potency.
Publisher: Wiley
Date: 15-03-2013
Publisher: Wiley
Date: 09-02-2020
DOI: 10.1111/BPH.14954
Publisher: Springer Science and Business Media LLC
Date: 16-05-2016
Publisher: Springer Science and Business Media LLC
Date: 18-03-2022
DOI: 10.1186/S12889-022-12907-5
Abstract: Hepatitis B is a chronic viral infection, a leading cause of primary liver cancer and identified as a major public health priority by the World Health Organization. Despite a high proportion of people in Australia who have been diagnosed with hepatitis B, significant gaps remain in health care access and in accurate knowledge about hepatitis B. Most people with hepatitis B in Australia were born in China, where the infection has an intergenerational impact with significant social implications resulting from the infection. Understanding how people of Chinese ethnicity with hepatitis B understand and respond to hepatitis B is imperative for reducing morbidity, mortality, and the personal and social impact of the infection. Qualitative semi-structured interviews with people with hepatitis B of Chinese ethnicity recruited through a specialist service identified the advice people with hepatitis B thought was important enough to inform the experience of people newly diagnosed with hepatitis B. A thematic analysis of the data privileged the lived experience of participants and their personal, rather than clinical, explanations of the virus. Hepatitis B infection had psychological and physical consequences that were informed by cultural norms, and to which people had responded to with significant behavioural change. Despite this cohort being engaged with specialist clinical services with access to the most recent, comprehensive, and expert information, much of the advice people with hepatitis B identified as important for living with hepatitis B was not based on biomedical understandings. Key suggestions from people with hepatitis B were to form sustainable clinical relationships, develop emotional resilience, make dietary changes, regulate energy, and issues related to disclosure. The study highlights conflicts between biomedical and public health explanations and the lived experience of hepatitis B among people of Chinese ethnicity in Australia. Beliefs about hepatitis B are embedded within cultural understandings of health that can conflict with bio-medical explanations of the infection. Acknowledging these perspectives provides for insightful communication between health services and their clients, and the development of nuanced models of care informed by the experience of people with hepatitis B.
Publisher: Elsevier BV
Date: 02-2014
Publisher: Elsevier BV
Date: 04-2004
Publisher: Wiley
Date: 27-09-2019
DOI: 10.1111/JGH.14457
Abstract: Viral hepatitis affects more than 320 million people globally, leading to significant morbidity and mortality due to liver failure and hepatocellular carcinoma (HCC). More than 248 million people (3.2% globally) are chronically infected with hepatitis B virus (HBV), and an estimated 80 million people (1.1% globally) are chronically infected with hepatitis C virus (HCV). In 2015, more than 700 000 deaths were directly attributable to HBV, and nearly 500 000 deaths were attributable to HCV infection 2-5% of HBV-infected people develop HCC per annum irrespective of the presence of cirrhosis, whereas 1-5% HCV-infected people with advanced fibrosis develop HCC per annum. The rapidly escalating global mortality related to HBV and HCV related viral hepatitis to be the 7th leading cause of death worldwide in 2013, from 10th leading cause in 1990. Australia, New Zealand, and Pacific Island Countries and Territories fall within the World Health Organization Western Pacific Region, which has a high prevalence of viral hepatitis and related morbidity, particularly HBV. Remarkably, in this region, HBV-related mortality is greater than for tuberculosis, HIV infection, and malaria combined. The region provides a unique contrast in viral hepatitis prevalence, health system resources, and approaches taken to achieve World Health Organization global elimination targets for HBV and HCV infection. This review highlights the latest evidence in viral hepatitis epidemiology and explores the health resources available to combat viral hepatitis, focusing on the major challenges and critical needs to achieve elimination in Australia, New Zealand, and Pacific Island Countries and Territories.
Publisher: IATED
Date: 03-2016
Publisher: Wiley
Date: 21-08-2012
DOI: 10.1111/J.1440-1746.2012.07148.X
Abstract: Unexplained liver injury including fibrosis and portal hypertension has rarely been reported among patients with HIV in the absence of co-infection with hepatitis B (HBV) or hepatitis C (HCV). We describe a series of HIV mono-infected patients with evidence of non-cirrhotic portal hypertension. HIV-infected patients with evidence of portal hypertension who were anti-HBV and anti-HCV negative and HBV and HCV RNA polymerase chain reaction (PCR) negative were identified from patients managed by the Victorian statewide HIV referral service located at The Alfred Hospital, Melbourne. Portal hypertension was defined as either radiological or endoscopic evidence of varices, portal vein flow obstruction, or elevated hepatic venous pressure gradient (HPVG). Five patients were found to have portal hypertension. These patients were male, aged 41 to 65 years, with known duration of HIV infection between 11 to 25 years. All had been treated with antiretroviral therapy, including didanosine. Tests for metabolic, autoimmune, and hereditary causes of liver disease failed to establish an etiology for the liver injury. All had radiological or endoscopic findings of varices, and four patients had radiological features of portal vein obstruction or flow reversal. Only one patient underwent HPVG measurement, which was elevated. Non-invasive fibrosis assessment revealed increased liver stiffness in three (out of four) patients, and no cirrhotic features were found on those who underwent liver biopsy. To our knowledge, this is the largest published series of non-cirrhotic portal hypertension in HIV mono-infected patients in Australia. Further research is needed to understand what relationship, if any, HIV or its treatments might have on liver injury over time.
Publisher: Wiley
Date: 06-11-2019
DOI: 10.1111/JVH.13020
Abstract: Hepatitis C virus contributes to substantial and growing mortality and morbidity. Fortunately, the advent of highly effective interferon-free direct-acting antiviral (DAA) medications and new diagnostic tests has the potential to dramatically alter the epidemiologic trajectory of hepatitis C, particularly for "hard-to-reach" populations. Treatment advances and cure will also likely alter the in idual experience of living with hepatitis C. However, it is not yet known in what capacity. This paper provides an overview of the population-level impact of DAA treatment, highlighting the need to further our understanding of the impact of treatment on behaviour, health and wellbeing through lived experience and more sensitive patient-reported outcome measures.
Publisher: Springer Netherlands
Date: 2017
Publisher: International Union of Crystallography (IUCr)
Date: 28-09-2002
DOI: 10.1107/S0907444902011022
Abstract: Bucain is a three-finger toxin, structurally homologous to snake-venom muscarinic toxins, from the venom of the Malayan krait Bungarus candidus. These proteins have molecular masses of approximately 6000-8000 Da and encompass the potent curaremimetic neurotoxins which confer lethality to Elapidae and Hydrophidae venoms. Bucain was crystallized in two crystal forms by the hanging-drop vapour-diffusion technique in 0.1 M sodium citrate pH 5.6, 15% PEG 4000 and 0.15 M ammonium acetate. Form I crystals belong to the monoclinic system space group C2, with unit-cell parameters a = 93.73, b = 49.02, c = 74.09 A, beta = 111.32 degrees, and diffract to a nominal resolution of 1.61 A. Form II crystals also belong to the space group C2, with unit-cell parameters a = 165.04, b = 49.44, c = 127.60 A, beta = 125.55 degrees, and diffract to a nominal resolution of 2.78 A. The self-rotation function indicates the presence of four and eight molecules in the crystallographic asymmetric unit of the form I and form II crystals, respectively. Attempts to solve these structures by molecular-replacement methods have not been successful and a heavy-atom derivative search has been initiated.
Publisher: Oxford University Press (OUP)
Date: 02-08-2016
DOI: 10.1093/JAC/DKW285
Abstract: Antimicrobial stewardship teams play an important role in assisting with the optimization of antimicrobial use in acute care settings. We aimed to determine whether a rapid review by a multidisciplinary antimicrobial stewardship team would improve the timeliness of optimal antimicrobial therapy for patients with positive blood cultures. This prospective randomized controlled trial was undertaken in two Australian hospitals. Patients received either standard care (a clinical microbiologist, registrar or laboratory scientist communicating the positive blood culture by phone to the treating doctor) or intervention (standard care plus rapid review by a multidisciplinary antimicrobial stewardship team). Outcomes included time to appropriate and/or active antimicrobial therapy and in-hospital mortality. The trial was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12614000258651). A total of 160 patients were enrolled in this study: 81 in the standard care arm and 79 in the intervention arm. Patients in the intervention arm were commenced earlier on active (HR 8.02, 95% CI: 2.15-29.91) and appropriate antimicrobials (HR 1.95, 95% CI: 1.13-3.38), with a higher proportion of patients allocated to the intervention arm receiving active therapy at 48 h (96% versus 82%) and appropriate therapy at 72 h (70% versus 54%). The majority of patients where the blood culture was a contaminant were not started on antimicrobial therapy, and there were no significant differences in time to cessation of antimicrobial therapy. Antimicrobial stewardship team review of patients with pathogenic positive blood cultures improved the time to both active and appropriate antimicrobial therapy.
Publisher: Informa UK Limited
Date: 28-09-2017
Publisher: Springer Science and Business Media LLC
Date: 18-01-2016
DOI: 10.1007/S10461-015-1281-X
Abstract: We performed a systematic review to estimate the proportion of men who have sex with men (MSM) in Asia who are bisexual and compare prevalence of HIV and sexual risk between men who have sex with men and women (MSMW) and men who have sex with men only (MSMO). Forty-eight articles based on 55 unique s les were identified from nine countries in Asia. Bisexual behaviour was common among MSM (pooled prevalence 32.8 %). Prevalence of HIV (pooled OR 0.90 95 % CI 0.77-1.05), recent syphilis infection (pooled OR 0.99 95 % CI 0.93-1.06) and unprotected anal intercourse (pooled OR 0.80 95 % CI 0.57-1.11) were similar between MSMW and MSMO, but heterogeneity was high. MSMW had lower odds of reporting a prior HIV test than MSMO (OR 0.82 95 % CI 0.70-0.95 p = 0.01, I(2) = 0 %). Targeted interventions are needed to increase uptake of HIV testing among MSMW. Increased reporting of disaggregated data in surveillance and research will help improve understanding of risk in MSMW and inform targeted interventions.
Publisher: Informa UK Limited
Date: 04-05-2018
DOI: 10.1080/14787210.2018.1471355
Abstract: Broad availability of direct-acting antiviral therapy for hepatitis C virus (HCV) raises the possibility that HCV prevalence and incidence can be reduced through scaling-up treatment, leading to the elimination of HCV. High rates of linkage to HIV care among HIV-infected gay and bisexual men may facilitate high uptake of HCV treatment, possibly making HCV elimination more achievable in this group. Areas covered: This review covers HCV elimination in HIV-infected gay and bisexual men, including epidemiology, spontaneous clearance and long term sequelae in the absence of direct-acting antiviral therapy direct-acting antiviral therapy uptake and effectiveness in this group HCV reinfection following successful treatment and areas for further research. Expert commentary: Early data from the direct-acting antiviral era suggest that treatment uptake is increasing among HIV infected GBM, and SVR rates are very promising. However, in order to sustain current treatment rates, additional interventions at the behavioral, physician, and structural levels may be required to increase HCV diagnosis, including prompt detection of HCV reinfection. Timely consideration of these issues is required to maximize the population-level impact of HCV direct-acting antiviral therapy. Potential HCV transmissions from HIV-uninfected GBM, across international borders, and from those who are not GBM also warrant consideration.
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.BCP.2004.10.018
Abstract: A new family of weak K(+) channel toxins (designated kappa-KTx) with a novel "bi-helical" scaffold has recently been characterized from Heterometrus fulvipes (Scorpionidae) venom. Based on the presence of the minimum functional dyad (Y5 and K19), kappa-hefutoxin-1 (kappa-KTx1.1) was investigated and found to block Kv 1.2 (IC(50) approximately 40 microM) and Kv 1.3 (IC(50) approximately 150 microM) channels. In the present study, kappa-KTx1.3, that shares approximately 60% identity with kappa-hefutoxin 1, has been isolated from Heterometrus spinifer venom. Interestingly, despite the presence of the functional dyad (Y5 and K19), kappa-KTx1.3 failed to reproduce the K(+) channel blocking activity of kappa-hefutoxin-1. Since the dyad lysine in kappa-KTx1.3 was flanked by another lysine (K20), it was hypothesized that this additional positive charge could hinder the critical electrostatic interactions known to occur between the dyad lysine and the Kv 1 channel selectivity filter. Hence, mutants of kappa-KTx1.3, substituting K20 with a neutral (K20A) or a negatively (K20E) or another positively (K20R) charged amino acid were synthesized. kappa-KTx1.3 K20E, in congruence with kappa-hefutoxin 1 with respect to subtype selectivity and affinity, produced blockade of Kv 1.2 (IC(50) = 36.8+/-4.9 microM) and Kv 1.3 (IC(50)=53.7+/-6.7 microM) but not Kv 1.1 channels. kappa-KTx1.3 K20A produced blockade of both Kv 1.2 (IC(50) = 36.9+/-4.9 microM) and Kv 1.3 (IC(50)=115.7+/-7.3 microM) and in addition, acquired affinity for Kv 1.1 channels (IC(50) =1 10.7+/-7.7 microM). kappa-KTx1.3 K20R failed to produce any blockade on the channel subtypes tested. These data suggest that the presence of an additional charged residue in a position adjacent to the dyad lysine impedes the functional block of Kv 1 channels produced by kappa-KTx1.3.
Publisher: AMPCo
Date: 23-01-2012
DOI: 10.5694/MJA11.11026
Abstract: Murray Valley encephalitis virus (MVEV) is a mosquito-borne virus that is found across Australia, Papua New Guinea and Irian Jaya. MVEV is endemic to northern Australia and causes occasional outbreaks across south-eastern Australia. 2011 saw a dramatic increase in MVEV activity in endemic regions and the re-emergence of MVEV in south-eastern Australia. This followed significant regional flooding and increased numbers of the main mosquito vector, Culex annulirostris, and was evident from the widespread seroconversion of sentinel chickens, fatalities among horses and several cases in humans, resulting in at least three deaths. The last major outbreak in Australia was in 1974, during which 58 cases were identified and the mortality rate was about 20%. With the potential for a further outbreak of MVEV in the 2011-2012 summer and following autumn, we highlight the importance of this disease, its clinical characteristics and radiological and laboratory features. We present a suspected but unproven case of MVEV infection to illustrate some of the challenges in clinical management. It remains difficult to establish an early diagnosis of MVEV infection, and there is a lack of proven therapeutic options.
Publisher: Wiley
Date: 10-06-2019
DOI: 10.1111/LIV.14152
Abstract: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in people who inject drugs (PWID). A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models. The search identified 8075 references 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76). Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.
Publisher: Wiley
Date: 28-08-2018
DOI: 10.1111/JVH.12975
Abstract: Modelling suggests that more frequent screening of people who inject drugs (PWID) and an improved care cascade are required to achieve the WHO hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030. We determined the testing frequencies (2-yearly, annually, 6-monthly and 3-monthly) and retention in care required among PWID to achieve the HCV incidence reduction target through treatment as prevention in low (25%), medium (50%) and high (75%) chronic HCV prevalence settings. Mathematical modelling of HCV transmission among PWID, capturing testing, treatment and other features of the care cascade were employed. In low-prevalence settings, 2-yearly antibody testing of PWID was estimated to reach the elimination target by 2027-2030 depending on retention in care, with annual testing reducing the time by up to 3 years. In medium-prevalence settings, if close to 90% testing coverage were achieved, then annual antibody testing of PWID would be sufficient. If testing coverage were lower (80%), 6-monthly antibody testing with at least 70% retention in care or annual HCV RNA/cAg testing would be required. In high-prevalence settings, even 3-monthly HCV RNA/cAg testing of PWID was unable to achieve the incidence reduction target. Thus, for geographical areas or subpopulations with high prevalence, WHO incidence targets are unlikely to be met without 3-monthly RNA/cAg testing accompanied by other prevention measures. Novel testing strategies, such as rapid point-of-care antibody testing or replacing antibody testing with RNA/cAg tests as a screening tool, can provide additional population-level impacts to compensate for imperfect follow-up or testing coverage.
Publisher: International Union of Crystallography (IUCr)
Date: 21-02-2003
DOI: 10.1107/S0907444903001094
Abstract: Candoxin, a novel three-finger toxin from Bungarus candidus, is a reversible antagonist of muscle (alphabetagammadelta) but a poorly reversible antagonist of neuronal alpha7 nicotinic acetylcholine receptors. It has a molecular weight of 7344 Da, with 66 amino-acid residues including ten half-cystines. The fifth disulfide bridge is located at the tip of loop I (Cys6-Cys11) instead of in loop II as found in other alpha-neurotoxins. Interestingly, candoxin lacks the segment cyclized by the fifth disulfide bridge at the tip of the middle loop of long-chain neurotoxins, which was reported to be critical for binding to alpha7 receptors. As a first step to determining its three-dimensional structure, candoxin was crystallized by the hanging-drop vapour-diffusion technique in conditions around 1.5 M sodium chloride, 10%(v/v) ethanol. The crystals formed belonged to the hexagonal system, space group P6(2)22, with unit-cell parameters a = 54.88, b = 54.88, c = 75.54 A, alpha = beta = 90, gamma = 120 degrees, and diffract to a resolution of 1.80 A. The crystallographic asymmetric unit contains one molecule of candoxin, with an estimated solvent content of 44.6%. Attempts to solve these structures by molecular-replacement methods have not been successful and a heavy-atom derivative search has been initiated.
Publisher: Elsevier BV
Date: 2002
DOI: 10.1016/S0006-2952(01)00854-1
Abstract: The sting of the black scorpion Heterometrus spinifer, which can cause intense localized pain, has not been reported to produce lethal cardiovascular complications, which are well known to result from scorpion envenomation as a consequence of a massive release of catecholamines. Therefore, we have undertaken a biochemical and pharmacological characterization of the venom of H. spinifer. Pharmacologically, the venom (0.125 microL/mL) produced a marked, reversible contracture in the chick biventer cervicis muscle that was blocked by d-tubocurarine (2 microM) but not by tetrodotoxin (5 microM) and omega-conotoxin GVIA (3 microM). The anticholinesterase neostigmine (1 microM) potentiated the contracture by 5.3-fold. An ultra-filtrate fraction of MW 3000 did not. In the rat anococcygeus muscle, the venom produced a contractile response that was partially (37.4 +/- 1.6%) blocked by atropine (5 microM) phentolamine (5 microM) blocked the remaining response. Tetrodotoxin (5 microM) did not block the contractile response of the venom on the anococcygeus muscle. Electrospray ionization-mass spectrometry/mass spectrometry confirmed the presence of high concentrations of acetylcholine (79.8 +/- 1.7 microM) and norepinephrine (146.7 +/- 19.8 microM) in H. spinifer venom, which can fully account for the observed cholinergic and adrenergic effects. In contrast to scorpion venoms that selectively target neuronal ion channels in mediating transmitter release, our data show that H. spinifer venom does not possess such activity, which likely explains the apparent lack of lethality of black scorpion envenomation.
Publisher: Elsevier BV
Date: 11-2020
Publisher: BMJ
Date: 12-04-2016
DOI: 10.1136/GUTJNL-2016-311504
Abstract: The WHO's draft HCV elimination targets propose an 80% reduction in incidence and a 65% reduction in HCV-related deaths by 2030. We estimate the treatment scale-up required and cost-effectiveness of reaching these targets among injecting drug use (IDU)-acquired infections using Australian disease estimates. A mathematical model of HCV transmission, liver disease progression and treatment among current and former people who inject drugs (PWID). Treatment scale-up and the most efficient allocation to priority groups (PWID or patients with advanced liver disease) were determined total healthcare and treatment costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) compared with inaction were calculated. 5662 (95% CI 5202 to 6901) courses per year (30/1000 IDU-acquired infections) were required, prioritised to patients with advanced liver disease, to reach the mortality target. 4725 (3278-8420) courses per year (59/1000 PWID) were required, prioritised to PWID, to reach the incidence target this also achieved the mortality target, but to avoid clinically unacceptable HCV-related deaths an additional 5564 (1959-6917) treatments per year (30/1000 IDU-acquired infections) were required for 5 years for patients with advanced liver disease. Achieving both targets in this way cost $A4.6 ($A4.2-$A4.9) billion more than inaction, but gained 184 000 (119 000-417 000) QALYs, giving an ICER of $A25 121 ($A11 062-$A39 036) per QALY gained. Achieving WHO elimination targets with treatment scale-up is likely to be cost-effective, based on Australian HCV burden and demographics. Reducing incidence should be a priority to achieve both WHO elimination goals in the long-term.
Publisher: Wiley
Date: 05-2019
DOI: 10.1002/JIA2.25288
Publisher: BMJ
Date: 26-03-2015
Publisher: Wiley
Date: 10-05-2022
DOI: 10.1111/APT.16953
Abstract: Conventional healthcare models struggle to engage those at risk of hepatitis C virus (HCV) infection. This international study evaluated point-of-care (PoC) HCV RNA diagnostic outreach and direct-acting antiviral (DAA) treatment for in iduals receiving opioid agonist therapy (OAT) in community pharmacies. We assessed the effectiveness of a roving nurse-led pathway offering PoC HCV RNA testing to OAT clients in community pharmacies relative to conventional care. Pharmacies in Scotland, Wales, and Australia were randomised to provide PoC HCV RNA testing or conventional referral. Pharmacists directed OAT clients to on-site nurses (intervention) or local clinics (control). Infected participants were treated with DAAs, alongside OAT. Primary outcome was the number of participants with sustained virologic response at 12 weeks (SVR) and analysed using mixed effects logistic regression in the intention-to-treat (ITT) population. Forty pharmacies were randomised. The ITT population contained 1410 OAT clients. In the conventional arm (n = 648), 62 (10%) agreed to testing, 17 (27%) were tested, 6 (35%) were positive and 5 (83%) initiated treatment. In the intervention arm (n = 762), 148 (19%) agreed to testing, 144 (97%) were tested, 23 (16%) were positive and 22 (96%) initiated treatment. SVR was obtained by 2 (40% conventional) and 18 (82% intervention). Intervention arm participants had higher odds of testing, OR 16.95 (7.07-40.64, p < 0.001) treatment, OR 4.29 (1.43-12.92, p = 0.010) and SVR, OR 8.64 (1.82-40.91, p = 0.007). Nurse-led PoC diagnosis in pharmacies made HCV care more accessible for OAT clients relative to conventional care. However, strategies to improve testing uptake are required. NCT03935906.
Publisher: American Chemical Society (ACS)
Date: 18-05-2016
DOI: 10.1021/ACS.BIOCHEM.6B00139
Abstract: Peptide toxins from scorpion venoms constitute the largest group of toxins that target the voltage-gated potassium channel (Kv). Spinoxin (SPX) isolated from the venom of scorpion Heterometrus spinifer is a 34-residue peptide neurotoxin cross-linked by four disulfide bridges. SPX is a potent inhibitor of Kv1.3 potassium channels (IC50 = 63 nM), which are considered to be valid molecular targets in the diagnostics and therapy of various autoimmune disorders and cancers. Here we synthesized 25 analogues of SPX and analyzed the role of each amino acid in SPX using alanine scanning to study its structure-function relationships. All synthetic analogues showed similar disulfide bond pairings and secondary structures as native SPX. Alanine replacements at Lys(23), Asn(26), and Lys(30) resulted in loss of activity against Kv1.3 potassium channels, whereas replacements at Arg(7), Met(14), Lys(27), and Tyr(32) also largely reduced inhibitory activity. These results suggest that the side chains of these amino acids in SPX play an important role in its interaction with Kv1.3 channels. In particular, Lys(23) appears to be a key residue that underpins Kv1.3 channel inhibition. Of these seven amino acid residues, four are basic amino acids, suggesting that the positive electrostatic potential on the surface of SPX is likely required for high affinity interaction with Kv1.3 channels. This study provides insight into the structure-function relationships of SPX with implications for the rational design of new lead compounds targeting potassium channels with high potency.
Publisher: Wiley
Date: 04-2018
DOI: 10.1002/JIA2.25051
Publisher: SAGE Publications
Date: 09-2021
Publisher: Elsevier BV
Date: 03-2003
DOI: 10.1016/S0041-0101(02)00388-4
Abstract: Non-conventional toxins constitute a poorly characterized class of three-finger toxins isolated exclusively from Elapidae venoms. These toxins are monomers of 62-68 amino acid residues and contain five disulfide bridges. However, unlike alpha/kappa-neurotoxins and kappa-neurotoxins which have the fifth disulfide bridge in their middle loop (loop II), the fifth disulfide bridge in non-conventional toxins is located in loop I (N-terminus loop). Overall, non-conventional toxins share approximately 28-42% identity with other three-finger toxins including alpha-neurotoxins, alpha/kappa-neurotoxins and kappa-neurotoxins. Recent structural studies have revealed that non-conventional toxins also display the typical three-finger motif. Non-conventional toxins are typically characterized by a lower order of toxicity (LD(50) approximately 5-80 mg/kg) in contrast to prototype alpha-neurotoxins (LD(50) approximately 0.04-0.3 mg/kg) and hence they are also referred to as 'weak toxins'. Further, it is generally assumed that non-conventional toxins target muscle (alpha(2)beta gamma delta) receptors with low affinities several orders of magnitude lower than alpha-neurotoxins and alpha/kappa-neurotoxins. However, it is now known that some non-conventional toxins also antagonize neuronal alpha 7 nicotinic acetylcholine receptors. Hence, non-conventional toxins are not a functionally homogeneous group and other, yet unknown, molecular targets for this class of snake venom toxins may exist. Non-conventional toxins may therefore be a useful source of ligands with novel biological activity targeting the plethora of neuronal nicotinic receptors as well as other physiological processes.
Publisher: Elsevier BV
Date: 08-2008
Publisher: Wiley
Date: 10-04-2001
DOI: 10.1016/S0014-5793(01)02342-0
Abstract: Alpha-toxins from scorpion venoms prolong the action potential of excitable cells by blocking sodium channel inactivation. We have purified bukatoxin, an alpha-toxin from scorpion (Buthus martensi Karsch) venom, to homogeneity. Bukatoxin produced marked relaxant responses in the carbachol-precontracted rat anococcygeus muscle (ACM), which were mediated through the L-arginine-nitric oxide synthase-nitric oxide pathway, consequent to a neuronal release of nitric oxide. Based on the presence of proline residues in the flanking segments of protein-protein interaction sites, we predicted the site between (52)PP(56) to be the potential interaction site of bukatoxin. A homology model of bukatoxin indicated the presence of this site on the surface. Buka11, a synthetic peptide designed based on this predicted site, produced a concentration-dependent nitric oxide-mediated relaxant response in ACM. Using alanine-substituted peptides, we have shown the importance (53)DKV(55) flanked by proline residues in the functional site of bukatoxin.
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/JVH.12741
Abstract: Inadequate response to injecting drug use (IDU) is a significant problem the world over. Low levels of funding, political inaction, poor levels of health service coverage, high prevalence and incidence of IDU-related blood-borne viruses (BBVs) and ongoing stigmatization/marginalization affect people who inject drugs (PWID) regardless of the income status of the country they reside in. These barriers and system failings are, however, exacerbated in low and middle-income countries (LMICs), meaning that the potential consequences of inaction are more pressing. In this narrative review, we describe the levels of IDU and IDU-specific BBV prevalence in LMICs levels of harm reduction implementation the consequences of late or insufficient response, the shortcomings of data collection and dissemination and the barriers to effective LMIC harm reduction implementation. We also exemplify cases where IDU-related harms and BBV epidemics have been successfully curtailed in LMICs, showing that effective response, despite the barriers, is possible. In conclusion, we suggest four key priorities on the basis of the review: confirming the presence or absence of IDU in LMICs, improving the collection and dissemination of national IDU-specific data, increasing the level of harm reduction programme implementation in LMICs, and increasing both national and international advocacy for PWID and attendant public health interventions.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.DRUGPO.2017.07.006
Abstract: Modelling suggests that achieving the World Health Organization's elimination targets for hepatitis C virus (HCV) is possible by scaling up use of direct-acting antiviral (DAA) therapy. However, poor linkage to health services and retention in care presents a major barrier, in particular among people who inject drugs (PWID). We identify and assess the cost-effectiveness of additional health system interventions required to achieve HCV elimination targets in Australia, a setting where all people living with HCV have access to DAA therapy. We used a dynamic HCV transmission and liver-disease progression mathematical model among current and former PWID, capturing testing, treatment and other features of the care cascade. Interventions tested were: availability of point-of-care RNA testing increased testing of PWID using biomarkers in place of liver stiffness measurement and scaling up primary care treatment delivery. The projected treatment uptake in Australia reduced the number of people living with HCV from approximately 230,000 in 2015 to approximately 24,000 by 2030 and reduced incidence by 45%. However, the majority (74%) of remaining infections were undiagnosed and among PWID. Scaling up primary care treatment delivery and using biomarkers in place of liver stiffness measurement only reduced incidence by a further 1% but saved AU$32 million by 2030, with no change to health outcomes. Additionally replacing HCV antibody testing with point-of-care RNA testing increased healthcare cost savings to AU$62 million, increased incidence reduction to 64% and gained 11,000 quality-adjusted life years, but critically, additional screening of PWID was required to achieve HCV elimination targets. Even with unlimited and unrestricted access to HCV DAA treatment, interventions to improve the HCV cascade of care and target PWID will be required to achieve elimination targets.
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/JGH.13223
Abstract: Reducing the burden of hepatitis C virus (HCV) related liver disease will require treating people who inject drugs (PWID), the group at most risk of infection and transmission. We determine the cost-effectiveness of treating PWID with interferon-free direct-acting antiviral therapy in Australia. Using a deterministic model of HCV treatment and liver disease progression, including a fixed rate of re-infection, the expected healthcare costs and quality-adjusted life years (QALYs) of a cohort of newly HCV-infected PWID were calculated for: no treatment treatment after initial infection ("early-treatment") and treatment prior to developing compensated cirrhosis ("late-treatment"). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. Late-treatment was cost-effective compared to no treatment, with a discounted average gain of 2.98 (95%confidence interval 2.88-5.22) QALYs per person for an additional cost of $15,132 ($11,246-18,922), giving an ICER of $5078 ($2847-5295) per QALY gained. Compared to late-treatment, early-treatment gained a further discounted average of 2.27 (0.58-4.80) QALYs per person for $38,794 ($34,789-41,367), giving an ICER of $17,090 ($2847-63,282), which was cost-effective in approximately 90% of Monte-Carlo uncertainty simulations. For every 100 newly HCV-infected PWID, there were an estimated 40 (39-56) eventual liver-related deaths without treatment, compared to 7 (6-11) and 8 (7-13) with early-treatment and late-treatment available respectively. Treating HCV-infected PWID with new therapies is cost-effective and could prevent a significant number of liver-related deaths. Although late-treatment was the most cost-effective option, the cost per QALY gained for early-treatment compared to late-treatment is likely to be below unofficial Australian willingness to pay thresholds.
Publisher: AMPCo
Date: 03-2013
DOI: 10.5694/MJA12.10556
Abstract: To examine increased notifications of hepatitis C virus (HCV) in men who have sex with men (MSM) infected with HIV in Victoria, and evaluate HCV transmission risk factors other than injecting drug use. Case series through retrospective review of all HCV cases in Victoria from 1 April 2010 to 30 June 2011, with clinical and laboratory data examined in likely MSM to identify a co-infected cohort. Patients with newly acquired HCV with HIV co-infection were invited to complete a questionnaire exploring novel risk factors for HCV transmission (non-injecting drug use, sexual practices with increased likelihood of trauma, and presence of genital ulcers). Sequencing was performed to determine the local molecular epidemiology of HCV co-infection. Demographics of newly co-infected MSM, traditional versus novel risk factors for HCV acquisition, prior knowledge of potential for sexual transmission of HCV, and association between viral sequences. Thirty-one patients with HIV were identified from 3365 notifications of hepatitis C. The median age was 42 years, and median time from HIV to HCV diagnosis was 22 months. Most patients were asymptomatic, with abnormal liver function tests prompting HCV testing. Interviews with 14 patients identified a high prevalence of novel risk factors and limited knowledge of HCV risk. Two clusters of matching viral sequences were identified. Novel HCV transmission routes have emerged in Victoria. These data reinforce the need for targeted testing and prevention strategies among HIV-infected MSM.
Publisher: Wiley
Date: 30-04-2010
DOI: 10.1002/CLC.20734
Publisher: Wiley
Date: 2018
DOI: 10.1002/JIA2.25059
Publisher: AMPCo
Date: 07-2012
DOI: 10.5694/MJA12.10678
Publisher: American Chemical Society (ACS)
Date: 07-07-2006
DOI: 10.1021/JM051207B
Abstract: To locate the binding sites of general anesthetics on ligand-gated ion channels, two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been replaced by photoactivable groups based on either aryl diazirine or benzophenone chemistry, have been synthesized and characterized pharmacologically. TDBzl-etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate are both potent general anesthetics with half-effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents resembled etomidate in enhancing currents elicited by low concentrations of GABA on heterologously expressed GABAA receptors and in shifting the GABA concentration-response curve to lower concentrations. They also allosterically enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both agents were also effective and selective photolabels, photoincorporating into some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a degree that was allosterically regulated by an agonist or a noncompetitive inhibitor. Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia.
Publisher: Wiley
Date: 05-2021
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JHEP.2019.01.012
Abstract: Treatment programs for people who inject drugs (PWID), including prisoners, are important for achieving hepatitis C elimination targets. There are multiple barriers to treatment of hepatitis C in prisons, including access to specialist physicians, testing and antiviral therapy, short prison sentences, and frequent inter-prison transfer. We aimed to assess the effectiveness of a nurse-led model of care for the treatment of prisoners with hepatitis C. A statewide program for assessment and management of hepatitis C was developed in Victoria, Australia to improve access to care for prisoners. This nurse-led model of care is supported by telemedicine to provide decentralized care within all prisons in the state. We prospectively evaluated the feasibility and efficacy of this nurse-led model of care for hepatitis C within the 14 adult prisons over a 13-month period. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) using per protocol analysis. There were 416 prisoners included in the analysis. The median age was 41 years, 90% were male, 50% had genotype 3 and 44% genotype 1 hepatitis C and 21% had cirrhosis. Injecting drug use was reported by 68% in the month prior to prison entry, 54% were receiving opioid substitution therapy, and 86% reported never previously engaging with specialist HCV care. Treatment duration was 8 weeks in 24%, 12 weeks in 59%, and 24 weeks in 17% of treatment courses. The SVR12 rate was 96% (301/313) per protocol. Inter-prison transfer occurred during 26% of treatment courses but was not associated with lower SVR12 rates. No treatment-related serious adverse events occurred. Hepatitis C treatment using a decentralized, nurse-led model of care is highly effective and can reach large numbers of prisoners. Large scale prison treatment programs should be considered to support hepatitis C elimination efforts. There is a high burden of hepatitis C infection among prisoners worldwide. Prisoners who continue to inject drugs are also at risk of developing new infections. For this reason, the prison setting provides an opportunity to treat those people at greatest risk of infection and to stop transmission to others. We developed a new method of providing hepatitis C treatment to prisoners, in which nurses rather than doctors assessed prisoners locally at each prison site. Treatment was safe and most prisoners were cured. Such programs will contribute greatly to achieving the World Health Organization's hepatitis C elimination goals.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CLD.2019.04.009
Abstract: Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/934854
Abstract: Objectives . To design a series of e-learning tools within the framework of a defined educational pedagogy to complement the conventional pharmacology curriculum at Griffith University and evaluate the impact of this strategy on student level of understanding through taxonomic classification of student final exam answers. Methods . A series of 148 e-learning tools was designed for 3rd year undergraduate pharmacy students and incorporated into their curriculum during 2012. The educational benefits of the e-learning tools were evaluated by analyses of student level of understanding (by SOLO taxonomy) at the final exams between the control group (standard curricula) in 2011 and the intervention group (standard curricula + e-learning tools) in 2012. Results . Backward linear regression analysis demonstrated GPA to be the most significant predictor of level of understanding, while the intervention group was a highly significant predictor for greater level of understanding in semester two. Conclusion . E-learning tools appeared to significantly improve student level of understanding as scored by the SOLO taxonomy when students engaged highly with the tools.
Publisher: Elsevier BV
Date: 2015
Publisher: Public Library of Science (PLoS)
Date: 29-06-2016
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.5688/AJPE776125
Publisher: Sri Lanka Journals Online (JOL)
Date: 26-11-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: Elsevier BV
Date: 11-2014
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.TOXICON.2016.09.013
Abstract: Spinoxin (SPX α-KTx6.13), isolated from venom of the scorpion Heterometrus spinifer, is a K
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.DRUGPO.2019.06.021
Abstract: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised in iduals living with HCV infection.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CLD.2019.04.011
Abstract: Patients with malignancies require chemotherapy and other immunosuppressive therapies for treatment. Because of this immunosuppression, in patients who have ever been exposed to hepatitis B it is possible for reactivation to occur. This reactivation can be fatal. Reactivation is particularly likely in patients who receive B cell-active agents such as rituximab. The occurrence of reactivation flares may also delay further chemotherapy, which can negatively affect the outcome of the underlying malignancy. Accordingly, it is important to screen patients for markers of hepatitis B and institute antiviral prophylaxis to prevent reactivation.
Publisher: Elsevier BV
Date: 03-2010
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CLD.2019.04.010
Abstract: Organ transplantation is a lifesaving procedure for many patients. To prevent rejection or graft-versus-host disease, recipients require long-term immunosuppression. In patients who have ever been exposed to hepatitis B, it is possible for reactivation to occur this includes patients who are anti-hepatitis B core antibody-positive only or both anti-hepatitis B core antibody-positive and hepatitis B surface antibody-positive. The susceptibility to this varies with the nature of the transplant. Hepatitis B can be transmitted from donor to recipient. It is important to assess the hepatitis B status and formulate a strategy to prevent transmission and prevent reactivation.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CLD.2019.04.012
Abstract: Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.
Publisher: Sri Lanka Journals Online (JOL)
Date: 29-12-2019
Publisher: Elsevier BV
Date: 05-2002
Publisher: American Chemical Society (ACS)
Date: 24-09-2005
DOI: 10.1021/BI051209Y
Abstract: The interactions of a photoreactive analogue of benzoylcholine, 4-azido-2,3,5,6-tetrafluorobenzoylcholine (APFBzcholine), with nicotinic acetylcholine receptors (nAChRs) were studied using electrophysiology and photolabeling. APFBzcholine acted as a low-efficacy partial agonist, eliciting maximal responses that were 0.3 and 0.1% of that of acetylcholine for embryonic mouse and Torpedo nAChRs expressed in Xenopus oocytes, respectively. Equilibrium binding studies of [3H]APFBzcholine with nAChR-rich membranes from Torpedo electric organ revealed equal affinities (K(eq) = 12 microM) for the two agonist binding sites. Upon UV irradiation at 254 nm, [3H]APFBzcholine was photoincorporated into the nAChR alpha, gamma, and delta subunits in an agonist-inhibitable manner. Photolabeled amino acids in the agonist binding sites were identified by Edman degradation of isolated, labeled subunit fragments. [3H]APFBzcholine photolabeled gammaLeu-109/deltaLeu-111, gammaTyr-111, and gammaTyr-117 in binding site segment E as well as alphaTyr-198 in alpha subunit binding site segment C. The observed pattern of photolabeling is examined in relation to the predicted orientation of the azide when APFBzcholine is docked in the agonist binding site of a homology model of the nAChR extracellular domain based upon the structure of the snail acetylcholine binding protein.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Wiley
Date: 13-08-2019
DOI: 10.1111/LIV.14201
Abstract: Despite highly effective direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection, some patients experience virological relapse. Salvage regimens should include multiple agents to suppress emergence of resistance-associated substitutions (RAS) and minimise treatment failure. The combination of sofosbuvir (SOF) and elbasvir/grazoprevir (ELB/GZR) ±ribavirin (RBV) is an effective retreatment strategy for HCV genotype (GT)1 and 4 infection. We hypothesised that SOF and ELB/GZR (±RBV) would also be an effective salvage regimen for DAA-experienced GT3 patients. We evaluated the efficacy and safety of SOF/ELB/GZR ± RBV in DAA-experienced participants with chronic HCV infection who had prior relapse. Participants were treated at four hospitals between December 2016 and March 2018 for either 12- or 16-weeks. The primary endpoint was sustained virological response at week 12 post-treatment (SVR12) using intention-to-treat analysis. There were 40 participants included in the analysis. The mean age was 53 years, 53% had GT3, 33% had GT1 infection and 63% had cirrhosis. Fifty-eight percent were treated for 12 weeks, 42% were treated for 16 weeks and 90% received RBV. The SVR12 rate was 98% overall, 100% in non-GT3 participants and 95% in GT3 participants. One GT3 cirrhotic participant relapsed. ELB/GZR was stopped at week 6 in one GT3 cirrhotic participant who switched to SOF/velpatasvir/RBV for a further 12 weeks and achieved SVR12. RBV dose reduction was required in two participants. Treatment was otherwise well tolerated. The combination of SOF/ELB/GZR ± RBV is effective and safe for difficult-to-cure patients who relapse after first-line DAA, including those with cirrhosis and GT3 infection.
Publisher: AMPCo
Date: 19-05-2019
DOI: 10.5694/MJA2.50160
Abstract: In iduals with chronic hepatitis B virus (HBV) infection or past exposure to HBV infection have a substantial risk of reactivation during immunosuppressive cancer therapy. HBV reactivation can lead to liver failure, cancer treatment interruption or death. Clinical concordance with screening and treatment guidelines is inconsistent in practice, and existing international guidelines are not specific to the Australian context. We developed an Australian consensus statement with infectious diseases, hepatology, haematology and oncology specialists to inform hepatitis B screening and antiviral management for immunocompromised patients with haematological and solid organ malignancies in Australia. Recommendations address four key areas of HBV infection management for immunocompromised patients with haematological and solid organ malignancies: who to test for HBV infection, when to start antiviral agents, when to stop antiviral agents, and how to monitor patients during cancer therapy. We recommend testing all patients undergoing cancer treatment for hepatitis B (including HBV surface antigen [HBsAg], HBV core antibody [anti-HBc], and HBV surface antibody) before cancer treatment. In iduals with chronic HBV infection (HBsAg positive) or past exposure (HBsAg negative and anti-HBc positive) receiving higher risk chemotherapy require antiviral prophylaxis using entecavir or tenofovir. This consensus statement will simplify the approach to testing and prophylaxis for HBV infection during cancer therapy, and harmonise approaches to discontinuing and monitoring in iduals which have been highly variable in practice. We advocate for broader Medicare Benefits Schedule and Pharmaceutical Benefits Scheme access to HBV testing and treatment for patients undergoing cancer therapy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.BPG.2012.09.004
Abstract: Understanding of the natural history and treatment responsiveness of chronic hepatitis C virus (HCV) infection has evolved rapidly in recent years. Advances in HCV molecular virology and host genetics can now better predict spontaneous clearance and treatment outcomes. HCV genotype is the most important viral factor predicting interferon-α treatment responsiveness HCV-1 subtype is emerging as a key determinant of the efficacy of direct acting antiviral therapy. Genome-wide association studies have recently identified several clinically important host determinants of the outcomes of peginterferon-α and ribavirin treatment outcome: IL28B polymorphism is associated with spontaneous clearance and treatment responsiveness ITPA polymorphism protects against ribavirin-induced anaemia and dose reductions genetic determinants of liver fibrosis progression rate have been proposed. In this review, we evaluate the role of viral and host genetics in the natural history and treatment outcomes of chronic HCV infection, and consider how this knowledge might help in idualize clinical management in the era of DAA therapy.
Publisher: Elsevier BV
Date: 08-2012
Publisher: Oxford University Press (OUP)
Date: 04-08-2014
DOI: 10.1093/CID/CIU602
Abstract: Increased global access and use of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) has been postulated to undermine HIV prevention efforts by changing in idual risk-taking behavior. This review aims to determine whether ART use is associated with changes in sexual or injecting risk-taking behavior or diagnosis of sexually transmitted infections (STIs). A systematic review and meta-analysis was conducted of HIV-seropositive participants receiving ART compared with no ART use in experimental or observational studies. Primary outcomes included (1) any unprotected sexual intercourse, (2) STI diagnoses, and (3) any unsafe injecting behavior. Fifty-eight studies met the selection criteria. Fifty-six studies containing 32 857 participants reported unprotected sex 11 studies containing 16 138 participants reported STI diagnoses and 4 studies containing 1600 participants reported unsafe injecting behavior. All included studies were observational. Unprotected sex was lower in participants receiving ART than in those not receiving ART (odds ratio [OR], 0.73 95% confidence interval [CI], .64-.83 P < .001 heterogeneity I(2) = 79%) in both high-income (n = 38) and low-/middle-income country (n = 18) settings, without any evidence of publication bias. STI diagnoses were also lower among in iduals on ART (OR, 0.58 95% CI, .33-1.01 P = .053 I(2) = 92%) however, there was no difference in injecting risk-taking behavior with antiretroviral use (OR, 0.90 95% CI, .60-1.35 P = .6 I(2) = 0%). Despite concerns that use of ART might increase sexual or injecting risk-taking, available research suggests that unprotected sex is reduced among HIV-infected in iduals on treatment. The reasons for this are not yet clear, although self-selection and mutually reinforcing effects of HIV treatment and prevention messages among people on ART are likely.
Publisher: Wiley
Date: 18-01-2023
DOI: 10.1002/ASE.2250
Abstract: The objective structured practical examination (OSPE) is a reliable assessment of practical skills in anatomy teaching. It is often administered as low‐stake assessments to track progress at multiple time points in anatomy curricula. Standard‐setting OSPEs to derive a pass mark and to ensure assessment quality and rigor is a complex task. This study compared standard‐setting outcomes of clinical anatomy OSPEs determined by traditional criterion‐referenced (Ebel) and norm‐referenced (“mean minus standard deviation”) methods in comparison to hybrid methods which apply both criterion‐referenced and norm‐referenced approaches in setting examination standards. The hybrid approaches utilized included the “Cohen method” and an adaptation of the “Taylor's method,” which is an improvement on the Cohen method. These erse standard‐setting methods were applied retrospectively to 16 anatomy OSPEs conducted over 4 years for first‐ and second‐year medical students in a graduate Doctor of Medicine Program at Griffith Medical School, Australia and the pass marks, failure rates, and variances of failure rates were compared. The application of the adaptation of Taylor's method to standard set OSPEs produced pass marks and failure rates comparable to the Ebel method, whereas the variability of failure rates was higher with the Ebel method than with the Cohen and Taylor's methods. This underscores this study's adaptation of Taylor's method as a suitable alternative to the widely accepted but resource intensive, panel‐based criterion‐referenced standard‐setting methods such as the Ebel method, where panelists with relevant expertise are unavailable, particularly for the multiple low‐stakes OSPEs in an anatomy curriculum.
Publisher: Elsevier BV
Date: 03-2002
DOI: 10.1016/S1056-8719(02)00204-6
Abstract: The anococcygeus and retractor penis muscles are part of the erectile machinery in male rodents. The rat anococcygeus muscle is a widely used smooth muscle preparation for the study of the effects of test substances on adrenergic, nitrergic, and cholinergic transmission. There is, however, little information available on the process of autonomic transmission in the rat retractor penis muscle, although its autonomic innervation has generally been assumed to be similar to that of the anococcygeus muscle because of the contiguous nature of the two muscles. The present study investigated the involvement of nitrergic transmission in mediating relaxant responses of the rat retractor penis muscle to electrical field stimulation. The retractor penis muscle was isolated from Sprague-Dawley rats and mounted in Krebs solution. Phentolamine (5 microM) was added to the bath to block the adrenergic responses of the muscle, which was then precontracted with carbachol (10 microM). Electrical field stimulation (20-30 V, 1 ms pulse width, at 0.5-20 Hz for 10 s) of the carbachol precontracted muscle elicited frequency-dependent relaxant responses (0.9-68%). Tetrodotoxin (1 microM), N(G)-nitro-L-arginine (L-NOARG) (50 microM), N(G)-nitro-L-arginine methylester (L-NAME) (100 microM), and haemoglobin (100 microM) inhibited these relaxant responses by 99.3%, 93.9%, 86.9%, and 77.5%, respectively. L-Arginine (250 microM) (but not its D-isomer) reversed the blockade produced by L-NOARG (72.7%) and L-NAME (81.5%). Our results provide clear evidence that the inhibitory (relaxant) responses of the rat retractor penis muscle to electrical field stimulation are mediated by nitric oxide involving the L-arginine-nitric oxide synthase-nitric oxide pathway. The rat retractor penis muscle is a versatile preparation that can replace the cumbersome preparations from the pig, ox, and horse, hitherto used as pharmacological models for the study of the retractor penis muscle.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2018
Publisher: Wiley
Date: 06-2003
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.DRUGPO.2019.02.012
Abstract: The prevalence of hepatitis C virus (HCV) has been reported to be high among people experiencing homelessness. People who are homeless often have multiple needs that may take precedence over HCV testing and treatment. We quantitatively evaluated the outcomes of a service providing HCV treatment to people attending homeless services. Clients attending homeless services were referred to a nurse specialising in HCV-related care. The nurse provided HCV testing, education and case-management while prescriptions were provided by an affiliated doctor. Logistic regression was used to explore factors associated with treatment commencement. Fifty-two clients referred (78%) underwent testing, thirty-nine were HCV-RNA positive among whom 18 (46%) reported sleeping rough and 29 (74%) reported injecting drug use 66% had injected less than three months ago. Twenty-four (62%) clients commenced treatment, of whom thirteen (54%) had a sustained virological response test all were cured. Treatment commencement was lower among people who reported sleeping rough (aOR 0.15, 95%CI 0.029-0.73). There was no difference in treatment commencement based on injecting drugs (aOR 1.06, 95%CI 0.21-5.2). Most clients' commenced treatment and the majority were successfully cured using a dedicated nursing service. Clients who reported sleeping rough may still face personal and/or system level barriers to HCV treatment.
Publisher: Oxford University Press (OUP)
Date: 26-12-2017
Abstract: There is a paucity of patient-reported outcomes (PROs) data for people undergoing hepatitis C virus (HCV) treatment who are treated with opioid substitution therapy (OST) for addiction. Patients enrolled in phase 3 clinical trials of sofosbuvir completed 4 PRO instruments-SF-36v2, FACIT-F, CLDQ-HCV, and WPAI-HCV-before, during, and after treatment. A total of 8450 HCV-infected subjects were included 4.8% (407) were receiving OST. At baseline, OST recipients had significantly (P < .0001) lower PRO scores (by -3.5 to -15.6 on a 0-100 scale). By the end of treatment, subjects receiving pegylated interferon, ribavirin, and sofosbuvir (IFN+RBV+SOF) experienced significant decreases in PROs regardless of OST use. Subjects receiving IFN-free RBV-containing regimens had significant but smaller PRO decreases, again similar in the OST and non-OST groups. Finally, subjects treated with regimens free of both IFN and RBV (IFN/RBV-free) showed improvements in nearly all PROs during treatment, with improvements more pronounced in OST recipients. Achieving a sustained virological response for 12 consecutive weeks after treatment cessation (SVR-12) was associated with improvement of PROs in OST recipients treated with IFN/RBV-free regimens. In contrast, OST recipients who achieved SVR-12 with IFN+RBV+SOF did not have consistent PRO gains after the SVR-12. Receiving IFN-free regimens leads to PRO improvement during treatment and after the SVR-12, regardless of OST status. HCV-infected subjects receiving OST did not experience similar PRO improvements with IFN-containing therapy, suggesting that IFN-based therapy may be less suitable for this vulnerable population.
Publisher: Oxford University Press (OUP)
Date: 26-12-2013
DOI: 10.1093/IJE/DYT243
Abstract: Needle and syringe programmes (NSP) aim to reduce the risk of HIV by providing people who inject drugs (PWID) with sterile injecting equipment. A recent review of reviews (ROR) concluded that there was only tentative evidence to support the effectiveness of NSP in reducing HIV. We carried out a systematic review and meta-analysis to assess the association between NSP and HIV transmission. Relevant primary articles presenting data on the risk of HIV transmission associated with NSP were identified in two stages: (i) from reviews identified in two published RORs (covering the period 1980-2008) and (ii) a literature search of CINAHL, Cochrane Library, EMBASE, MEDLINE and PsychINFO for primary articles published since the most recent high quality review (covering the period 2008-12). Study results were synthesized using random-effects meta-analysis. There were 12 studies comprising at least 12 000 person-years of follow-up. Exposure to NSP was associated with a reduction in HIV transmission: pooled effect size 0·66 [95% confidence interval (CI) 0·43, 1·01] across all studies, and 0·42 (95% CI 0·22, 0·81) across six higher quality studies (according to the Newcastle-Ottawa tool). There is evidence to support the effectiveness of NSP in reducing the transmission of HIV among PWID, although it is likely that other harm reduction interventions have also contributed to the observed reduction in HIV risk. NSP should be considered as just one component of a programme of interventions to reduce both injecting risk and other types of HIV risk behaviour.
Publisher: Wiley
Date: 10-08-2016
DOI: 10.1111/PIN.12448
Abstract: Human cadavers offer a great opportunity for histopathology students for the learning and teaching of tissue pathology. In this study, we aimed to implement an integrated learning approach by using cadavers to enhance students' knowledge and to develop their skills in gross tissue identification, handling and dissection techniques. A total of 35 students enrolled in the undergraduate medical science program participated in this study. A 3-hour laboratory session was conducted that included an active exploration of cadaveric specimens to identify normal and pathological tissues as well as tissue dissection. The majority of the students strongly agreed that the integration of normal and morbid anatomy improved their understanding of tissue pathology. All the students either agreed or strongly agreed that this laboratory session was useful to improve their tissue dissection and instrument handling skills. Furthermore, students from both cohorts rated the session as very relevant to their learning and recommended that this approach be added to the existing histopathology curriculum. To conclude, an integrated cadaver-based practical session can be used effectively to enhance the learning experience of histopathology science students, as well as improving their manual skills of tissue treatment, instrument handling and dissection.
Publisher: Japanese Pharmacological Society
Date: 2004
DOI: 10.1254/JPHS.94.1
Abstract: The discovery, about forty years ago, of alpha-bungarotoxin, a three-finger alpha-neurotoxin from Bungarus multicinctus venom, enabled the isolation of the nicotinic acetylcholine receptor (nAChR), making it one of the most thoroughly characterized receptors today. Since then, the sites of interaction between alpha-neurotoxins and nAChRs have largely been delineated, revealing the remarkable plasticity of the three-finger toxin fold that has optimally evolved to utilize different combinations of functional groups to generate a panoply of target specificities to discern subtle differences between nAChR subtypes. New facets in toxinology have now broadened the scope for the use of alpha-neurotoxins in scientific discovery. For instance, the development of short, combinatorial library-derived, synthetic peptides that bind with sub-nanomolar affinity to alpha-bungarotoxin and prevent its interaction with muscle nAChRs has led to the in vivo neutralization of experimental alpha-bungarotoxin envenomation, while the successful introduction of pharmatopes bearing "alpha-bungarotoxin-sensitive sites" into toxin-insensitive nAChRs has permitted the use of various alpha-neurotoxin tags to localize and characterize new receptor subtypes. More ambitious strategies can now be envisaged for engineering rationally designed novel activities on three-finger toxin scaffolds to generate lead peptides of therapeutic value that target the nicotinic pharmacopoeia. This review details the progress made towards achieving this goal.
Publisher: Elsevier BV
Date: 07-2017
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/PY19074
Publisher: Springer Science and Business Media LLC
Date: 23-08-2012
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.DRUGPO.2015.05.006
Abstract: The hepatitis C virus (HCV) epidemic is a major health issue in most developed countries it is driven by people who inject drugs (PWID). Injecting networks powerfully influence HCV transmission. In this paper we provide an overview of 10 years of research into injecting networks and HCV, culminating in a network-based approach to provision of direct-acting antiviral therapy. Between 2005 and 2010 we followed a cohort of 413 PWID, measuring HCV incidence, prevalence and injecting risk, including network-related factors. We developed an in idual-based HCV transmission model, using it to simulate the spread of HCV through the empirical social network of PWID. In addition, we created an empirically grounded network model of injecting relationships using exponential random graph models (ERGMs), allowing simulation of realistic networks for investigating HCV treatment and intervention strategies. Our empirical work and modelling underpins the TAP Study, which is examining the feasibility of community-based treatment of PWID with DAAs. We observed incidence rates of HCV primary infection and reinfection of 12.8 per 100 person-years (PY) (95%CI: 7.7-20.0) and 28.8 per 100 PY (95%CI: 15.0-55.4), respectively, and determined that HCV transmission clusters correlated with reported injecting relationships. Transmission modelling showed that the empirical network provided some protective effect, slowing HCV transmission compared to a fully connected, homogenous PWID population. Our ERGMs revealed that treating PWID and all their contacts was the most effective strategy and targeting treatment to infected PWID with the most contacts the least effective. Networks-based approaches greatly increase understanding of HCV transmission and will inform the implementation of treatment as prevention using DAAs.
Publisher: Wiley
Date: 25-03-2013
DOI: 10.1111/JGH.12041
Abstract: To assess the cost-effectiveness of hepatitis C virus treatment with pegylated interferon alfa-2a and ribavirin in current and former people who inject drugs (PWID). A decision analytic model simulated the lifetime costs and outcomes of four treatment options: early treatment with mild fibrosis, standard treatment with moderate fibrosis, late treatment with compensated cirrhosis, and no treatment. Treatment modalities were simulated across current, former, and never-injector cohorts of 1000 hypothetical patients with chronic hepatitis C virus. The main outcome measures were incremental costs ($AUD) per quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were calculated for each cohort. Treatment of current PWID during mild fibrosis resulted in a discounted average gain of 1.60 QALYs (95% confidence interval 0.93-2.26) for an added cost of $12,723 ($11,153-$14,396) compared with no treatment, yielding an ICER of $7941 per QALY gained ($6347-$12,017). Former PWID gained 1.80 QALYs (1.29-2.33) for $10,441 ($8843-$12,074) for early treatment compared with no treatment, resulting in an ICER of $5808 per QALY gained ($5189-$6849). Never-injectors gained 2.33 QALYs (1.87-2.80) for $9290 ($7642-$10,912) compared with no treatment-an ICER of $3985 per QALY gained ($3896-$4080). Early treatment was more cost-effective than late treatment in all cohorts. Despite comorbidities, increased mortality, and reduced adherence, treatment of both current and former PWID is cost-effective. Our estimates fall below the unofficial Australian cost-effectiveness threshold of $AUD 50,000 per QALY for public subsidies. Scaling up treatment for PWID can be justified on purely economic grounds.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2020
DOI: 10.1038/S41598-020-58215-Z
Abstract: Organ transplant guidelines in many settings recommend that people with potential hepatitis C virus (HCV) exposure or infection are deemed ineligible to donate. The recent availability of highly-effective treatments for HCV means that this may no longer be necessary. We used a mathematical model to estimate the expected difference in healthcare costs, difference in disability-adjusted life years (DALYs) and cost-effectiveness of removing HCV restrictions for lung and kidney donations in Australia. Our model suggests that allowing organ donations from people who inject drugs, people with a history of incarceration and people who are HCV antibody-positive could lead to an estimated 10% increase in organ supply, population-level improvements in health (reduction in DALYs), and on average save AU$2,399 (95%CI AU$1,155-3,352) and AU$2,611 (95%CI AU$1,835-3,869) per person requiring a lung and kidney transplant respectively. These findings are likely to hold for international settings, since this policy change remained cost saving with positive health gains regardless of HCV prevalence, HCV treatment cost and waiting list survival probabilities. This study suggests that guidelines on organ donation should be revisited in light of recent changes to clinical outcomes for people with HCV.
Publisher: Public Library of Science (PLoS)
Date: 12-11-2015
Publisher: AMPCo
Date: 08-2012
DOI: 10.5694/MJA12.10221
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 22-06-2015
DOI: 10.1111/JVH.12429
Publisher: Wiley
Date: 11-04-2022
DOI: 10.1111/DAR.13471
Abstract: Injection‐related infections (IRI) cause morbidity and mortality in people who inject drugs. Hospital administrative datasets can be used to describe hospitalisation trends, but there are no validated algorithms to identify injecting drug use and IRIs. We aimed to validate International Classification of Diseases (ICD) codes to identify admissions with IRIs and use these codes to describe IRIs within our hospital. We developed a candidate set of ICD codes to identify current injecting drug use and IRI and extracted admissions satisfying both criteria. We then used manual chart review data from 1 January 2017 to 30 April 2019 to evaluate the performance of these codes and refine our algorithm by selecting codes with a high‐positive predictive value (PPV). We used the refined algorithm to describe trends and outcomes of people who inject drugs with an IRI at Alfred Hospital, Melbourne from 2008 to 2020. Current injecting drug use was best predicted by opioid‐related disorders (F11), 80% (95% confidence interval [CI] 74–85%), and other stimulant‐related disorders (F15), 82% (95% CI 70–90%). All PPVs were ≥67% to identify specific IRIs, and ≥84% for identifying any IRI. Using these codes over 12 years, IRIs increased from 138 to 249 per 100 000 admissions, and skin and soft tissues infections (SSTI) were the most common (797/1751, 46%). Validated ICD‐based algorithms can inform passive surveillance systems. Strategies to reduce hospitalisation with IRIs should be supported by early intervention and prevention, particularly for SSTIs which may represent delayed access to care.
Publisher: Korean Association of Anatomists
Date: 2015
Publisher: Portland Press Ltd.
Date: 10-2000
DOI: 10.1042/BST028A437A
Publisher: Informa UK Limited
Date: 09-2006
Publisher: Wiley
Date: 02-08-2002
DOI: 10.1046/J.1440-1681.2002.03726.X
Abstract: 1. The autonomic effects of venoms and toxins from several species of scorpions, including the Indian red scorpion Mesobuthus tamulus, the Chinese scorpion Buthus martensi Karsch and the Israeli scorpion Leiurus quinquestriatus quinquestriatus, all belonging to Buthidae, and the Asian black scorpions Heterometrus longimanus and Heterometrus spinifer, belonging to Scorpionidae, are reviewed. 2. The effects of the venoms of M. tamulus and L. q. quinquestriatus on noradrenergic and nitrergic transmission in the rat isolated anococcygeus muscle revealed that both venoms mediated their pharmacological effects via a prejunctional mechanism involving the activation of voltage-sensitive sodium channels with consequent release of neurotransmitters that mediate target organ responses, similar to the effects mediated by other alpha-scorpion toxins. 3. Two new toxins, Makatoxin I and Bukatoxin, were purified to homogeneity from the venom of B. martensi Karsch. Determination of their complete amino acid sequences confirmed that both toxins belonged to the class of alpha-scorpion toxins. The effects of both toxins on noradrenergic and nitrergic transmission in the rat anococcygeus muscle provided firm evidence that their pharmacological actions also closely resembled those mediated by other alpha-scorpion toxins on neuronal voltage-sensitive sodium channels. 4. The venoms of H. longimanus and H. spinifer were found to have high concentrations of noradrenaline (1.8 +/- 0.3 mmol/L) and relatively high concentrations of acetylcholine (79.8 +/- 1.7 micromol/L) together with noradrenaline (146.7 +/- 19.8 micromol/L), respectively, which can account for their potent direct cholinergic and noradrenergic agonist actions in the rat anococcygeus muscle. 5. Our studies confirmed that the rat anococcygeus muscle is an excellent nerve-smooth muscle preparation for investigating the effects of bioactive agents on noradrenergic and nitrergic transmission, as well as the direct agonist actions of these agents on post-synaptic alpha-adrenoceptors and M3 muscarinic cholinoceptors. Although many studies, including our own, have documented that scorpion venoms and toxins mediate their primary effects via a prejunctional mechanism that leads to the marked release of various autonomic neurotransmitters, our studies have shown that there are exceptions to this generally accepted phenomenon. In particular, we have provided firm evidence to show that the venoms from H. longimanus and H. spinifer do not have such a prejunctional site of action but, instead, the venoms mediate their autonomic effects through direct agonist actions on post-junctional muscarinic M3 cholinoceptors and alpha-adrenoceptors.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.DRUGPO.2019.05.012
Abstract: Achieving hepatitis C elimination requires novel approaches to engage people at highest risk of infection into care pathways. Point-of-care-tests may help to overcome some of the barriers preventing people who inject drugs (PWID) accessing testing and progressing to treatment for hepatitis C virus (HCV). We assessed the feasibility and acceptability of HCV point-of-care testing at needle and syringe exchange programs (NSPs) co-located in three community health clinics in Melbourne, Australia. NSP clients were offered an oral fluid point-of-care test for HCV antibody by NSP staff. Positive HCV antibody tests were followed by a point-of-care test for HCV RNA alongside standard-of-care laboratory testing for hepatitis C treatment work-up. Participants were offered same-day point-of-care results on site, via phone or text message, or upon return to the service. Participants were scheduled for follow-up review with the study nurse for assessment and linkage to treatment. A total of 174 participants completed HCV antibody point-of-care test 150 (86%) had a reactive result. Of these, 140 (93%) underwent a HCV RNA point-of-care test and 76 (54%) tested positive few participants (5%) waited on site for results delivery, but the majority of RNA positive (63%) attended a follow-up visit for treatment work-up (median time to follow-up visit = 11 days IQR = 7-20 days). The majority of participants reported a preference for point-of-care tests (66%) and supported NSP staff involvement in testing (90%). Provision of HCV point-of-care tests, follow-up and linkage to treatment services through NSPs was feasible and acceptable to PWID. Despite few participants waiting to receive same-day results, there was effective linkage to care, suggesting value in further evaluation of this approach.
Publisher: Wiley
Date: 04-2019
DOI: 10.1111/JVH.13087
Abstract: A barrier to hepatitis C treatment for people who inject drugs (PWID) is needing to attend multiple appointments for diagnosis. Point-of-care hepatitis C tests provide results within 20 to 105 minutes and can be offered opportunistically in nonclinical settings such as needle syringe programmes. In this nested qualitative study, we explored the acceptability of point-of-care testing for PWID. PWID attending participating needle syringe programmes were screened using the OraQuick HCV antibody mouth swab (result in 20 minutes) those with a reactive result then underwent venepuncture for a point-of-care RNA test: the Xpert HCV Viral Load (result in 105 minutes). Convenience s ling was used to select participants for a semi-structured interview. A hybrid thematic analysis was performed, guided by Sekhon's "Theoretical Framework of Acceptability." Nineteen participants were interviewed. Three core themes emerged: "people and place," "method of specimen collection," and "rapidity of result return." It was highly acceptable to be offered testing at the needle syringeprogrammes by nurses and community health workers, who were described as competent and nonjudgemental. Most participants reported that even if a finger-stick point-of-care RNA test were an option in the future, they would prefer venepuncture, as the s le could be used for pre-treatment workup and bundled testing. Waiting 20 minutes to receive the antibody test result was acceptable, whereas the 105 minutes required for the RNA result was unacceptable. Offering point-of-care hepatitis C testing at needle syringe programmes is acceptable to PWID, however tests that avoid venepuncture are not necessarily the most attractive to PWID.
Publisher: BMJ
Date: 24-06-2016
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 02-2011
Abstract: Amoebic encephalitis is an uncommon and usually fatal condition. This case describes successful treatment of a Balamuthia mandrillaris brain abscess using prolonged antimicrobial agents with complete excision. It illustrates the risk of dissemination from cutaneous to cerebral amoebic lesions, potential progression with corticosteroid therapy, and the prospect for curative excision.
Publisher: Worldwide Protein Data Bank
Date: 03-2005
DOI: 10.2210/PDB1V56/PDB
Publisher: AMPCo
Date: 03-2013
DOI: 10.5694/MJA12.11683
Abstract: Antimicrobial stewardship programs are recommended to reduce antimicrobial resistance by reducing inappropriate use of antimicrobials. We implemented an antimicrobial stewardship program and aimed to evaluate its effect on broad-spectrum antimicrobial use. Observational study with historical control using interrupted time series analysis conducted in a tertiary referral hospital. Hospital inpatients prescribed restricted antimicrobials for non-standard indications, where approval had expired or without approval. Baseline period of 30 months immediately followed by an 18-03 intervention period commencing January 2011. Number and type of interventions made by antimicrobial stewardship team monthly rate of use of broad-spectrum antimicrobial agents (in defined daily doses/1000 occupied bed-18s). The antimicrobial stewardship team made 1104 recommendations in 779 patients during the 18-03 intervention period. In 64% of cases, the recommendation was made to cease or de-escalate the antimicrobial therapy, or to change from intravenous to oral therapy. The introduction of the intervention resulted in an immediate 17% (95% CI, 13%-20%) reduction in broad-spectrum antimicrobial use in the intensive care unit and a 10% (95% CI, 4%-16%) reduction in broad-spectrum antimicrobial use outside the intensive care unit. Reductions were particularly seen in cephalosporin and glycopeptide use, although these were partially offset by increases in the use of β-lactam-β-lactamase inhibitors. The introduction of an antimicrobial stewardship program, including postprescription review, resulted in an immediate reduction in broad-spectrum antimicrobial use in a tertiary referral centre. However, the effect of this intervention reduced over time.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-12-2013
DOI: 10.1002/HEP.26623
Publisher: American Chemical Society (ACS)
Date: 09-08-2007
DOI: 10.1021/BI7008163
Abstract: Interactions of benzophenone (BP) with the Torpedo nicotinic acetylcholine receptor (nAChR) were characterized by electrophysiological analyses, radioligand binding assays, and photolabeling of nAChR-rich membranes with [3H]BP to identify the amino acids contributing to its binding sites. BP acted as a low potency noncompetitive antagonist, reversibly inhibiting the ACh responses of nAChRs expressed in Xenopus oocytes (IC50 = 600 microM) and the binding of the noncompetitive antagonist [3H]tetracaine to nAChR-rich membranes (IC50 = 150 microM). UV irradiation at 365 nm resulted in covalent incorporation of [3H]BP into the nAChR subunits (delta > alpha approximately beta > gamma), with photoincorporation limited to the nAChR transmembrane domain. Comparison of nAChR photolabeling in the closed state (absence of agonist) and desensitized state (equilibrated with agonist) revealed selective desensitized state labeling in the delta subunit of deltaPhe-232 in deltaM1 and deltaPro-286/deltaIle-288 near the beginning of deltaM3 that are within a pocket at the interface between the transmembrane and extracellular domains. There was labeling in the closed state within the ion channel at position M2-13 (alphaVal-255, betaVal-261, and deltaVal-269) that was reduced by 90% upon desensitization and labeling in the transmembrane M3 helices of the beta and gamma subunits (betaMet-285, betaMet-288, and gammaMet-291) that was reduced by 50-80% in the desensitized state. Labeling at the lipid interface (alphaMet-415 in alphaM4) was unaffected by agonist. These results provide a further definition of the regions in the nAChR transmembrane domain that differ in structure between the closed and desensitized states.
Location: Singapore
Location: Singapore
Start Date: 06-2021
End Date: 05-2025
Amount: $506,000.00
Funder: Australian Research Council
View Funded Activity