Going into the groin: Injection into the femoral vein among people who inject drugs in three urban areas of England

Background: There have been increasing concerns about injection into the femoral vein – groin injecting – among people who inject drugs in a number of countries, though most studies have been small. The extent, reasons and harms associated with groin injecting are examined. Method: Participants were recruited using respondent driven sampling (2006–2009). Weighted data was examined using bivariate analyses and logistic regression. Results: The mean age was 32 years; 25% were women (N = 855). During the preceding 28 days, 94% had injected heroin and 13% shared needles/syringes. Overall, 53% reported ever groin injecting, with 9.8% first doing so at the same age as starting to inject. Common reasons given for groin injecting included: “Can’t get a vein elsewhere” (68%); “It is discreet” (18%); and “It is quicker” (14%). During the preceding 28 days, 41% had groin injected, for 77% this was the only body area used (for these “It is discreet” was more frequently given as a reason). In the multivariable analysis, groin injection was associated with: swabbing injection sites; saving filters for reuse; and receiving opiate substitution therapy. It was less common among those injecting into two body areas, and when other people (rather than services) were the main source of needles. Groin injection was more common among those with hepatitis C and reporting ever having deep vein thrombosis or septicaemia. Conclusions: Groin injection was common, often due to poor vascular access, but for some it was out of choice. Interventions are required to reduce injecting risk and this practice

Not in the vein: 'missed hits', subcutaneous and intramuscular injections and associated harms among people who inject psychoactive drugs in Bristol, United Kingdom

Background: The extent of intentional or accidental subcutaneous and intramuscular injections and the factors associated with these have rarely been studied among people who inject drugs, yet these may play an important role in the acquisition bacterial infections. This study describes the extent of these, and in particular the factors and harms associated with accidental subcutaneous and intramuscular injections (i.e. ‘missed hits’). Methods: People who inject drugs were recruited using respondent driven sampling. Weighted data was examined using bivariate analyses and logistic regression. Results: The participants mean age was 33 years (31% aged under 30-years), 28% were women, and the mean time since first injection was 12 years (N = 329). During the preceding three months, 97% had injected heroin, 71% crack-cocaine, and 16% amphetamines; 36% injected daily. Overall, 99% (325) reported that they aimed to inject intravenously; only three aimed to inject subcutaneously and one intramuscularly. Of those that aimed to inject intravenously, 56% (181) reported ever missing a vein (for 51 this occurred more than four times month on average). Factors associated with ‘missed hits’ suggested that these were the consequence of poor vascular access, injection technique and/or hygiene. ‘Missed hits’ were twice as common among those reporting sores/open wounds, abscesses, or redness, swelling and tenderness at injection sites. Conclusion: Intentional subcutaneous and intramuscular injections are rare in this sample. ‘Missed hits’ are common and appear to be associated with poor injection practice. Interventions are required to reduce risk through improving injecting practice and hygiene

HIV Epidemics in the European Region: Vulnerability and Response

This report provides a systematic review of the evidence on HIV vulnerability and response in all 53 countries of the WHO European Region, stretching from Iceland to the borders of China. It focuses on key populations most at risk of HIV infection: people who inject drugs, sex workers and men who have sex with men. It confirms that these populations are disproportionately affected by the growing HIV epidemic in Europe. Twenty-five percent of HIV diagnoses in Europe are associated with injecting drug use, with much higher proportions in Eastern Europe (33%) than in Western Europe (5%) and Central Europe (7%). Sex between men accounted for 10% of all HIV diagnoses, with higher rates reported in Western Europe (36%), followed by Central Europe (22%) and Eastern Europe (0.5%). HIV remains relatively low among female sex workers who do not inject drugs, (less than 1%), but higher among those who inject drugs (over 10%) as well as among male and transgender sex workers. The analysis highlights the pivotal role of social and structural factors in shaping HIV epidemics and HIV prevention responses. Poverty, marginalization and stigma contribute to the HIV epidemic in Europe and Central Asia. Economic volatility and recession risks are increasing vulnerability to HIV and infections. Barriers to successful HIV responses include the criminalization of sex work, of sex between men, and of drug use combined with social stigmatization, violence and rights violations. HIV prevention requires social and environmental change. The report calls for policymakers and HIV program implementers to target the right policies and programs to maximize the health and social impacts of Europe’s HIV responses and get higher returns on HIV-related investments. The report is a product of a collaboration between the World Bank, the London School of Hygiene and Tropical Medicine, the WHO Regional Office for Europe and UNAIDS

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) - a resistant subpopulation within a susceptible strain - is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans. METHODS: A cohort of 20 patients with HIV-associated CM in Tanzania was prospectively observed during therapy with either FLC monotherapy or in combination with flucytosine (5FC). Total and resistant subpopulations of Cryptococcus spp. were quantified directly from patient cerebrospinal fluid (CSF). Stored isolates underwent whole genome sequencing and phenotypic characterization. RESULTS: Heteroresistance was detectable in Cryptococcus spp. in the CSF of all patients at baseline (i.e., prior to initiation of therapy). During FLC monotherapy, the proportion of resistant colonies in the CSF increased during the first 2 weeks of treatment. In contrast, no resistant subpopulation was detectable in CSF by day 14 in those receiving a combination of FLC and 5FC. Genomic analysis revealed high rates of aneuploidy in heteroresistant colonies as well as in relapse isolates, with chromosome 1 (Chr1) disomy predominating. This is apparently due to the presence on Chr1 of ERG11, which is the FLC drug target, and AFR1, which encodes a drug efflux pump. In vitro efflux levels positively correlated with the level of heteroresistance. CONCLUSION: Our findings demonstrate for what we believe is the first time the presence and emergence of aneuploidy-driven FLC heteroresistance in human CM, association of efflux levels with heteroresistance, and the successful suppression of heteroresistance with 5FC/FLC combination therapy. FUNDING: This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z and the Daniel Turnberg Travel Fellowship

Fentanyl self-testing outside supervised injection settings to prevent opioid overdose: Do we know enough to promote it?

Since 2013, North America has experienced a sharp increase in unintentional fatal overdoses: fentanyl, and its analogues, are believed to be primarily responsible. Currently, the most practical means for people who use drugs (PWUD) to avoid or mitigate risk of fentanyl-related overdose is to use drugs in the presence of someone who is in possession of, and experienced using, naloxone. Self-test strips which detect fentanyl, and some of its analogues, have been developed for off-label use allowing PWUD to test their drugs prior to consumption. We review the evidence on the off-label sensitivity and specificity of fentanyl test strips, and query whether the accuracy of fentanyl test strips might be mediated according to situated practices of use. We draw attention to the weak research evidence informing the use of fentanyl self-testing strips

Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation

Objective: Colorectal cancer (CRC) is a major contributor to cancer mortality and morbidity. LIM kinase 2 (LIMK2) promotes tumour cell invasion and metastasis. The objectives of this study were to determine how LIMK2 expression is associated with CRC progression and patient outcome, and to use genetically modified Drosophila and mice to determine how LIMK2 deletion affects gastrointestinal stem cell regulation and tumour development.<p></p> Design: LIMK2 expression and activity were measured by immunostaining tumours from CRC-prone mice, human CRC cell lines and 650 human tumours. LIMK knockdown in Drosophila or Limk2 deletion in mice allowed for assessment of their contributions to gastrointestinal stem cell homeostasis and tumour development.<p></p> Results: LIMK2 expression was reduced in intestinal tumours of cancer-prone mice, as well as in human CRC cell lines and tumours. Reduced LIMK2 expression and substrate phosphorylation were associated with shorter patient survival. Genetic analysis in Drosophila midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. Limk2 deletion increased colon tumour size in a colitis-associated colorectal mouse cancer model.<p></p> Conclusions: This study revealed that LIMK2 expression and activity progressively decrease with advancing stage, and supports the hypothesis that there is selective pressure for reduced LIMK2 expression in CRC to relieve negative constraints imposed upon gastrointestinal stem cells.<p></p&gt

The decline and rise of neighbourhoods: the importance of neighbourhood governance

There is a substantial literature on the explanation of neighbourhood change. Most of this literature concentrates on identifying factors and developments behind processes of decline. This paper reviews the literature, focusing on the identification of patterns of neighbourhood change, and argues that the concept of neighbourhood governance is a missing link in attempts to explain these patterns. Including neighbourhood governance in the explanations of neighbourhood change and decline will produce better explanatory models and, finally, a better view about what is actually steering neighbourhood change

Prevalence and temporal trends of crack injection among injection drug users in eastern central Canada

Background: Little is known about crack injection and its temporal trends in North America. This article describes the extent of crack injection and examines temporal trends among injection drug users (IDUs) recruited from 2003 to 2010 in the SurvUDI network. Methods: IDUs who injected recently (past 6 months) were recruited in harm reduction and health programs in eastern central Canada. Trend analyses were performed using generalized estimating equations. Some IDUs participated multiple times; first interview was retained for the descriptive analyses, while first interview per year was retained for the trend analyses. Results: Of the 4088 IDUs recruited, 15.2% (621) reported crack injection; large variations across sites were noted (range: 0.3%-39.5%). Trend analyses were limited to Ottawa (449 crack injectors) and Montréal (121). For Ottawa, a significant decline was observed, from 48.3% to 36.9%, with a prevalence ratio (PR) of 0.97 per year (95%CI: 0.94-0.99). For Montréal, a significant rise was observed, from 6.0% to 18.4%, with a PR of 1.29 per year (95%CI: 1.19-1.40). Conclusions: Strong variations in crack injection exist throughout the SurvUDI network, and reversed temporal trends have been observed in Ottawa and Montréal. These data will be useful to local harm reduction programs to evaluate the need to distribute items required by crack injectors and to develop prevention messages