Does sexuality matter? A cross-sectional study of drug use, social injecting, and access to injection-specific care among men who inject drugs in Melbourne, Australia.

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are overrepresented in cohorts of people who inject drugs. GBMSM's substance use is usually explored in the context of its contribution to sexual risk. We examined drug use practices, connectedness to other people who inject drugs, peer-to-peer injecting, and access to care among men who inject drugs in Melbourne, Australia. We aim to describe similarities and differences in these parameters for GBMSM and other men. METHODS: Data were drawn from a prospective cohort study of people who inject drugs conducted in Melbourne, Australia, since 2009. This cross-sectional study used data collected between 2016 and 2021. Descriptive statistics were used to assess differences between GBMSM and other men. RESULTS: Of 525 men who injected drugs over the study period, 48 (9%) identified as gay or bisexual, or reported sex with other men in the past 12 months. GBMSM and other men reported similar socio-demographics, drug practices (age of injecting initiation, most injected drug, peer-to-peer injecting, receptive syringe sharing) and access to injecting-specific care (drug treatment, source of needle-syringes). A significantly greater percentage of GBMSM reported past 12-month hepatitis C testing (69% vs. 52%, p = 0.028) and preferring methamphetamine (31% vs. 16%, p = 0.022). A higher percentage of GBMSM reported knowing > 50 other people who inject drugs (46% vs. 37%), but this difference was not statistically significant. Both groups primarily obtained injecting equipment from needle-syringe programs; a minority had accessed injecting-specific primary care. CONCLUSION: Men who injected drugs in this cohort and those who identified as GBMSM reported similar drug and health-seeking practices. The higher prevalence of methamphetamine injecting among GBMSM may warrant different harm reduction support for this group. Health promotion should utilise opportunities to connect men who inject drugs in Melbourne to injecting-specific primary health care.

Constructing a 'target population': A critical analysis of public health discourse on substance use among gay and bisexual men, 2000-2020.

BACKGROUND: Gay and bisexual men (GBM) have higher substance use prevalences than general population samples - often attributed to stigmatisation of sexual minority identities. We examined how influential public health research on substance use among GBM interprets this behaviour and what GBM-specific identities emerge through the discourses employed. METHODS: We searched Web of Science for publications on substance use among GBM, selecting 60 of the most cited papers published during 2000-2020. We studied the language used to describe and interpret drug-using behaviour using critical discourse analysis, focusing on interpretive repertoires and subject positions. RESULTS: Three distinct discursive tendencies were identified. First, in constructing a target population, GBM who use illicit drugs are positioned as deficient, socially irresponsible, and maladapted to dealing with stigmatisation and HIV risks. Second, in shifting the focus beyond the individual, the gay community is conceptualised as offering a safe space for socialisation. Nonetheless, gay community spaces are problematised as promoting substance use among vulnerable GBM through aggravating loneliness and normalising drug use as a form of maladaptive (avoidance) coping. Third, counterdiscursive movements add nuance, context, and comparisons that relativise rather than generalise substance use and focus on pleasure and self-determination. Such discourses centre the need for interventions that disrupt homophobic socio-structures instead of individualising approaches to limit non-conformity. CONCLUSION: 'Expert' assessments of substance use among GBM perpetuate pathologising understandings of this behaviour and promote abject subject positions, contributing to perpetuations of intergroup stigma and social exclusion based on drug and sexual practices. Our findings highlight the need for deliberate and critical engagement with prior research and a conscious effort to disrupt dominant discourses on GBM's substance use.

Prevalence of baseline HCV NS5A resistance associated substitutions in genotype 1a, 1b and 3 infection in Australia.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) treatment, and most regimens include an NS5A inhibitor. Certain amino-acid substitutions confer resistance to NS5A inhibitors, termed resistance-associated substitutions (RAS). If present at baseline, they can reduce virological response rates. Population-based sequencing (PBS) is generally used for baseline sequencing, however next generation sequencing (NGS) reduces the threshold for detection of sequences encoding RAS from 20% to 5%. We determined the prevalence of NS5A RAS at baseline amongst Australian chronically infected with genotype (GT)1a, GT1b and GT3 HCV, using both PBS and NGS. METHODS: Samples from DAA-naïve individuals were received at the Victorian Infectious Disease Reference Laboratory between June 2016 and December 2018. All samples were analysed for NS5A RAS using PBS. A subset of GT1 HCV samples were processed using NGS technology (Vela Diagnostics, Singapore) to determine the improvement in sensitivity. RESULTS: In total, 672 samples were analysed using PBS. The baseline prevalence of NS5A RAS was 7.6% for GT1a (n = 25/329), 15.7% for GT1b (n = 8/51) and 15.1% for GT3 (n = 44/292). NGS only marginally increased sensitivity for NS5A RAS at baseline in GT1a (16% vs 17%) and GT1b (29% vs 36%). CONCLUSION: The prevalence of NS5A RAS in GT1a HCV in Australia was low compared with international data, and was similar to other reported international prevalence for GT1b and GT3 infection. NGS at baseline only marginally increased sensitivity for the detection of NS5A RAS in patients with GT1 HCV and cannot be recommended for routine use at baseline in clinical practice.

Community-based provision of direct-acting antiviral therapy for hepatitis C: study protocol and challenges of a randomized controlled trial.

BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment. METHODS: Consenting patients with HCV infection attending 13 PHCS in Australia or New Zealand are randomized to receive DAA treatment at the local tertiary institution (standard care arm), or their PHCS (intervention arm). The primary endpoint is the proportion commenced on DAAs and cured. Treatment providers at the PHCS include: hepatology nurses, primary care practitioners, or, in two sites, a specialist physician. All PHCS offer opioid substitution therapy. DISCUSSION: The Prime Study is the first real-world, randomized, model of care study exploring the impact of community provision of DAA therapy on HCV-treatment uptake and cure. Although the study has faced challenges unique to this period of time characterized by changing treatment and service delivery, the data gained will be of critical importance in shaping health service policy that enables the elimination of HCV. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT02555475 . Registered on 15 September 2015.

HIV and Sexual Risk Among Men Who Have Sex With Men and Women in Asia: A Systematic Review and Meta-Analysis.

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 samples 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.

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

The contemporary surgical management of spasticity in children.

Orthopedics and neurosurgery offer multiple surgical modalities for improving the function, care, and well-being of children with spasticity. One surgical approach is not the best for all children with spasticity not adequately controlled with more conservative measures. For that reason, a multidisciplinary evaluation is important to optimize outcome for these children.

Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice.

BACKGROUND & AIMS: Interleukin (IL)-10 gene-deficient mice, raised under germfree conditions, do not develop colitis, implying a role for bacteria. This study mapped the appearance of luminal colonic bacteria and, using antibiotic treatment, determined their association with colitis in IL-10 gene-deficient mice. METHODS: Mice were treated with ciprofloxacin or with neomycin and metronidazole. The intestine was harvested for histological scoring and bacterial assessment. RESULTS: At 2 weeks of age, before the development of colitis, IL-10 gene-deficient mice demonstrated an earlier appearance of Streptococcus and Clostridium sp., and had a greater proportion (P < 0.01) of bacteria adherent to the colonic mucosa. This pattern of increased adherent bacteria persisted for the 12 weeks of study. Treatment of mice before the onset of colonic inflammation, with either antibiotic regime, reduced mucosal adherent bacteria and prevented colitis (P < 0.01). In contrast, treatment of established colitis with neomycin and metronidazole did not reduce adherent bacterial levels, yet was more efficacious (P < 0.05) in treating established colitis than ciprofloxacin, which did reduce adherent colonic bacteria. CONCLUSIONS: In the IL-10 gene-deficient mouse model, the appearance and number of mucosal adherent colonic bacteria are altered before the onset of colitis. Antibiotics both prevent and treat the colitis through correction of this primary bacterial alteration.

Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora.

The normal intestinal epithelium provides a barrier relatively impermeable to luminal constituents. However, patients with inflammatory bowel disease experience enhanced intestinal permeability that correlates with the degree of injury. IL-10 gene-deficient mice were studied to determine whether increased intestinal permeability occurs as a primary defect before the onset of mucosal inflammation or is secondary to mucosal injury. At 2 weeks of age, IL-10 gene-deficient mice show an increase in ileal and colonic permeability in the absence of any histological injury. This primary permeability defect is associated with increased mucosal secretion of interferon-gamma and tumor necrosis factor-alpha, and does not involve an increase in nitric oxide synthase activity. Colonic permeability remains elevated as inflammation progresses, while ileal permeability normalizes by 6 weeks of age. IL-10 gene-deficient mice raised under germ-free conditions have no inflammation, and demonstrate normal permeability and cytokine levels. This data suggests that the intestinal permeability defect in IL-10 gene-deficient mice occurs due to a dysregulated immune response to normal enteric microflora and, furthermore, this permeability defect exists prior to the development of mucosal inflammation.

Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice.

BACKGROUND & AIMS: Intestinal luminal microflora, or their products, are likely an important initiating factor in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine the role of colonic aerobic luminal bacteria and Lactobacillus species in the development of colitis in interleukin (IL)-10 gene-deficient mice. METHODS: Intestine from 2-16-week-old mice was scored histologically and cultured for bacteria. Lactobacillus sp. repopulation of the colonic lumen was achieved via daily rectal delivery of Lactobacillus reuteri or oral lactulose therapy. RESULTS: At 2 weeks of age, IL-10 gene-deficient mice showed no colonic injury but did display abnormal colonic bacterial colonization with increased colonic mucosal aerobic adherent and translocated bacteria in conjunction with reduced Lactobacillus sp. levels. In association with the abnormal colonic bacterial colonization, colitis developed by 4 weeks of age. Restoring Lactobacillus sp. to normal levels reduced levels of colonic mucosal adherent and translocated bacteria and attenuated the development of the colitis. CONCLUSIONS: In the neonatal period, IL-10 gene-deficient mice have decreased levels of colonic Lactobacillus sp. and an increase in colonic mucosal adherent and translocated bacteria. Normalizing Lactobacillus sp. levels reduced colonic mucosal adherent and translocated bacteria and prevented colitis.

"Golf ball liver": agent orange hepatitis.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective weedkiller which works by uncoupling oxidative phosphorylation and is in widespread use. It is known as "agent orange". A 65 year old man had acute hepatitis, thought to be caused by exposure to 2,4-D. The patient ingested 2,4-D as a result of habitual licking of his golf ball. Clinical and histological data together with a challenge test confirmed the diagnosis of "golf ball liver".

Polymorphonuclear leukocyte-mediated bone degradation and influence of blood mononuclear cells on the mouse calvarial model.

OBJECTIVE: To investigate the relationships between degradation of bone and activated blood polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (ML) as well as their soluble products in vitro. MATERIALS AND METHODS: A neonatal mouse calvarial bone model was used to assess the activity of degradation (by measuring the amount of 45Ca release) by normal human blood leukocytes, separated PMNL and ML following 24-hour incubation. The effects of conditioned culture medium obtained from Staphylococcus aureus-stimulated ML on PMNL-mediated calvarial bone loss were also studied. RESULTS: It was demonstrated that isolated human PMNL rapidly degraded bone in a dose and time dependent manner. The PMNL-mediated bone degradation was enhanced by conditioned medium obtained from Staphylococcus aureus-stimulated ML. CONCLUSION: These findings implicate PMNL as major contributors to early bone loss in infectious diseases such as acute haematogenous osteomyelitis.

Complications and long-term outcome of upper cervical spine arthrodesis in patients with Down syndrome.

STUDY DESIGN: A retrospective review of 15 patients with Down syndrome who had undergone arthrodesis of the upper cervical spine for instability. OBJECTIVES: To determine the complication rate and long-term outcome after posterior cervical arthrodesis for upper cervical instability in patients with Down syndrome. SUMMARY OF BACKGROUND DATA: Atlantoaxial instability is common in patients with Down syndrome, and fusion of the upper cervical spine has been recommended for patients who have instability, with or without myelopathy. Unfortunately, the results of posterior cervical arthrodesis are not well reported, and the natural history of this condition is unknown. METHODS: Fifteen patients with an average follow-up period of 74.6 months (range, 24-142 months) were reviewed after posterior arthrodesis of the upper cervical spine. Twelve patients were reexamined by the investigators specifically for the purpose of this study, and three patients had long-term follow-up results available from chart review. RESULTS: Eleven of 15 patients (73%) sustained 23 major complications including nonunion, loss of reduction, neurologic deterioration, late subaxial instability, infection, and wound dehiscence. Six patients (40%) required seven reoperations to address a complication. Ultimately, 12 patients (80%) obtained osseous union, but a definite clinical improvement was identifiable in only three patients, whereas two others had worsened neurologically at latest follow-up evaluation. CONCLUSIONS: A high complication rate should be anticipated after posterior arthrodesis of the upper cervical spine in patients with Down syndrome. A cautious approach to asymptomatic instability in this condition is advocated.

Aseptic loosening in uncemented total hip arthroplasty in a canine model.

An in vivo canine model was developed to investigate the histologic and biochemical parameters associated with aseptic loosening. Thirty-eight canines had cementless total hip arthroplasty. Experimental groups were designed specifically to investigate the relative contributions of implant motion and particulate debris (cobalt chrome alloy, titanium aluminum vanadium, and polyethylene) on the resultant periprosthetic tissues. Tissues from a stable, well-ingrown prosthesis provided a control. Importantly, the histologic and biochemical characteristics of the experimentally induced membranes consistently correlated with previous in vitro reports of tissues retrieved at revision surgery for aseptic loosening. Implant motion and all 3 particulate debris groups resulted in increased numbers of macrophages in the periprosthetic membranes. The histologic findings paralleled the increase in levels of biochemical mediators of bone resorption as measured by collagenase, gelatinase, prostaglandin E2, and interleukin-1 activity. The most striking results were seen in the histology and biochemistry of the particle groups with highly cellular membranes showing increased biochemical activity when compared with controls. The clinical relevance of this work lies in the description of an in vivo model of aseptic loosening that can be used to investigate the effects of numerous variables implicated in aseptic loosening. Ultimately, the model may serve as a basis for developing therapeutic interventions.

Angiodysplasia and ileal carcinoid.

A case of angiodysplasia, symptomatic for 18 years, is presented. This case highlights the difficulty of establishing a diagnosis. Associated findings included aortic stenosis and a carcinoid tumour of the ileum. Despite transfusion of a total of 1200 units of blood the liver was normal at necropsy.

Granulomatous gastritis: part of a vasculitic syndrome.

The previously unreported association of granulomatous gastritis and mononeuritis multiplex occurring in the setting of a vasculitic syndrome is described. The two conditions are considered to be associated and to be immune mediated. The previously accepted concept of isolated granulomatous gastritis is disputed.

Audit of cranial computerised tomography in a general medical unit.

Over a two year period 108 patients had cranial computerised tomographic (CCT) scans while under the care of a general medical team. Sixty eight scans showed 70 abnormalities. Completed stroke, transient ischaemic attacks (TIA), epilepsy and headache were the most common indications for CTT while infarct, atrophy, haemorrhage and tumour were the most common abnormalities. Eight tumours were identified comprising 12% of epileptics and 9% of stroke patients.

Vasoactive intestinal peptide: behavioral effects in the rat and hamster.

The behavioral effects of intracerebroventricular (ICV) injection of the brain-gut peptide vasoactive intestinal peptide (VIP) were quantified with a behavioral sampling technique in home-caged, nondeprived, male and female albino rats and golden hamsters. ICV VIP sex-dependently decreased observed resting behavior during 1 hr after injections in both rats and hamsters at 0.1-10.0 micrograms. Grooming behavior was increased in hamsters, and rearing and standing behaviors were increased in rats, sex-dependently at VIP doses that decreased resting. Drinking behavior was suppressed in rats by VIP at 10.0 micrograms. Intraperitoneal (IP) VIP (100.0 micrograms/kg) increased 5% ethanol intake and decreased eating behavior in fluid-deprived male rats. The increase in ethanol intake produced by IP VIP was prevented by IP cholecystokinin octapeptide (CCK, 4.0 micrograms/kg). VIP potently controls resting and ingestive behaviors, suggesting a role for this neuropeptide, along with CCK, in the feedback regulation of rodent behavior.