Injecting drug use among gay and bisexual men in Sydney: prevalence and associations with sexual risk practices and HIV and hepatitis C infection

Injecting drug use is commonly reported among gay and bisexual men in Australia. We examined the prevalence and covariates of injecting drug use among men participating in the Sydney Gay Community Periodic Survey between 2004–06 and 2011. In 2004–06, data was collected about which drugs were injected, while in 2011, data was collected about hepatitis C (HCV) and esoteric sexual practices. In 2004–06, 5.6 % of men reported injecting drugs in the previous 6 months; 3.4 % reported methamphetamine injection and 0.4 % heroin injection. In 2011, men who injected drugs were less likely to be employed full-time, and more likely to be HCV-positive, HIV-positive, to have used party drugs for sex, and to have engaged in esoteric sexual practices. The strong associations between injecting drug use, sexual risk practices and blood-borne virus infection suggests the need for combined sexual health and harm reduction services for gay and bisexual men who inject drugs.     

Diagnostic value of symptoms of oesophagogastric cancers in primary care: a systematic review and meta-analysis

Background

Selection of primary care patients for investigation of potential oesophagogastric cancer is difficult, as the symptoms may represent benign conditions, which are also more common.

Aim

To review systematically the presenting features of oesophagogastric cancers in primary care, including open-access endoscopy clinics.

Design and setting

Systematic review and meta-analysis.

Method

MEDLINE^®, Embase, the Cochrane Library, and CINAHL were searched for studies of adults who were symptomatic and presented in primary care or open-access endoscopy clinics. Exclusions were being asymptomatic, screening, or recurrent cancers. Data were extracted to estimate the diagnostic performance of features of oesophagogastric cancers and summarised in a meta-analysis.

Results

Fourteen studies were identified. The strongest summary sensitivity and specificity estimates were for: dyspepsia 0.42 (95% confidence interval [CI] 0.29 to 0.56) and 0.48 (95% CI = 0.31 to 0.65); pain 0.41 (95% CI = 0.24 to 0.62) and 0.75 (95% CI = 0.51 to 0.89); and dysphagia 0.32 (95% CI = 0.17 to 0.52) and 0.92 (95% CI = 0.81 to 0.97). Summary positive likelihood ratios (LR+) and diagnostic odds ratios were: dyspepsia 0.79 (95% CI = 0.55 to 1.15) and 0.65 (95% CI = 0.32 to 1.33); pain 1.64 (95% CI = 1.20 to 2.24) and 2.09 (95% CI = 1.57 to 2.77); and dysphagia 4.32 (95% CI = 2.46 to 7.58) and 5.91 (95% CI = 3.56 to 9.82). Corresponding LR+ were: anaemia 4.32 (95% CI = 2.64 to 7.08); nausea/vomiting/bloating 1.07 (95% CI = 0.52 to 2.19); reflux 0.78 (95% CI = 0.47 to 1.78) and; weight loss 5.46 (95% CI = 3.47 to 8.60).

Conclusion

Dysphagia, weight loss, and anaemia show the strongest association but with relatively low sensitivity and high specificity. The findings support the value of investigation of these symptoms, but also suggest that, in a population of patients who are low risk but not no-risk, investigation is not currently recommended.     

‘Outside the Original Remit’: Co‐production in UK mental health research,lessons from the field

The aim of this discursive paper was to explore the development of co‐production and service user involvement in UK university‐based mental health research and to offer practical recommendations for practitioners co‐producing research with service users and survivors, informed by an overview of the key literature on co‐production in mental health and from a critical reflection on applied research through the medium of a case study. The paper is co‐written by a mental health nurse academic and a service user/survivor researcher academic. The authors argue that the implications of co‐production for mental health research remain underexplored, but that both the practitioner and service user/survivor researcher experience and perspective of co‐production in research can provide practical reflections to inform developing research practice. The theories and values of emancipatory research can provide a framework from which both practitioners and service users can work together on a research project, in a way that requires reflection on process and power dynamics. The authors conclude that whilst co‐produced investigations can offer unique opportunities for advancing emancipatory and applied research in mental health, practitioner researchers need to be more radical in their consideration of power in the research process.     

Toxicity profiles and solvent–toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure

To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound‐induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent–toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short‐ (1 day) and long‐term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l^?1) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long‐term exposure set‐up, a concentration of 500 µl l^?1 DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l^?1 DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l^?1 DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l^?1 in this organism. In the second part of our study, we propose a statistical approach to account for solvent–toxicant interactions and discuss full‐scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea. Copyright © 2014 John Wiley & Sons, Ltd.     

Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas

Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.     

Islets of Langerhans from prohormone convertase‐2 knockout mice show α‐cell hyperplasia and tumorigenesis with elevated α‐cell neogenesis

Antagonism of the effects of glucagon as an adjunct therapy with other glucose‐lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α‐cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase‐2 knockout mice (PC2‐ko), in which α‐cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2‐ko and wild‐type (WT) mice were maintained drug‐free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2‐ko animals displayed marked changes in islet morphology from α‐cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6–8 months. Islet hyperplasias and tumours primarily consisted of α‐cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α‐cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2‐ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis.