146 research outputs found

    Profiling evolutionary landscapes underlying drug resistance

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    Preterm Birth Among Opioid-Using Women and High-Risk Controls: The Potential Moderating Role of Borderline Features

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    Opioid use is a growing problem within this country (Maeda, Bateman, Clancy, Creanga, & Leffert, 2014). One implication of this is an increased incidence of preterm birth, defined as birth before 37 weeks gestation (Kramer et al., 2000; Norwitz & Robinson, 2001). Previous research supports an association between opioid use and preterm birth (Nørgaard, Nielsson, & Heide-Jørgensen, 2015). No research has evaluated the role mental health diagnoses aside from anxiety and depression (Benningfield et al., 2010) play in conjunction with opioid use in exacerbating the risk of preterm birth. In the proposed study, the focus is on Borderline Personality Disorder (BPD). BPD is a severe and chronic disorder that can be assessed with a categorical diagnosis or along a continuum of self-reported features (affective instability, identity disturbance, presence of negative relationships, and self-harm/impulsivity; Morey, 1991). While research suggests that BPD features are associated with opioid use (Kurdziel-Adams et al., in press), no research has evaluated how borderline features may relate to the relationship between opioid use and preterm birth and may serve to exacerbate the biological risks presented by opioid use. Results suggest that BPD (operationalized as \u3e38 self-reported BPD features) predicts preterm birth; however, this relationship does not hold true when the variables are conceptualized continuously as borderline features and gestational age at birth. Furthermore, participants who used opioids during pregnancy were not more likely to give birth preterm than controls, who were women who had high-risk pregnancies for reasons aside from substance use. Additionally, BPD did not serve as a moderator between opioid use and preterm birth

    Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs

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    Understanding the evolutionary processes that lead to antibiotic resistance can help to achieve better treatment strategies. Yet, little is known about the dynamics of the resistance alleles during adaptation. Here, we use population sequencing to monitor genetic changes in putative resistance loci at several time-points during adaptive evolution experiments involving five different antibiotic conditions. We monitor the mutational spectra in lineages evolved to be resistant to single antibiotics [amikacin (AMK), chloramphenicol (CHL), and ciprofloxacin (CIP)], as well as antibiotic combinations (AMK + CHL and CHL + CIP). We find that lineages evolved to antibiotic combinations exhibit different resistance allele dynamics compared with those of single-drug evolved lineages, especially for a drug pair with reciprocal collateral sensitivity. During adaptation, we observed interfering, superimposing and fixation allele dynamics. To further understand the selective forces driving specific allele dynamics, a subset of mutations were introduced into the ancestral wild type enabling differentiation between clonal interference and negative epistasis

    Evaluating the cost-effectiveness of existing needle and syringe programmes in preventing hepatitis C transmission in people who inject drugs

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    AIM: To evaluate the cost-effectiveness of needle and syringe programmes (NSPs) compared with no NSPs on hepatitis C virus (HCV) transmission in the United Kingdom. DESIGN: Cost-effectiveness analysis from a National Health Service (NHS)/health-provider perspective, utilizing a dynamic transmission model of HCV infection and disease progression, calibrated using city-specific surveillance and survey data, and primary data collection on NSP costs. The effectiveness of NSPs preventing HCV acquisition was based on empirical evidence. SETTING AND PARTICIPANTS: UK settings with different chronic HCV prevalence among people who inject drugs (PWID): Dundee (26%), Walsall (18%) and Bristol (45%) INTERVENTIONS: Current NSP provision is compared with a counterfactual scenario where NSPs are removed for 10 years and then returned to existing levels with effects collected for 40 years. MEASUREMENTS: HCV infections and cost per quality-adjusted life year (QALY) gained through NSPs over 50 years. FINDINGS: Compared with a willingness-to-pay threshold of £20 000 per QALY gained, NSPs were highly cost-effective over a time-horizon of 50 years and decreased the number of HCV incident infections. The mean incremental cost-effectiveness ratio was cost-saving in Dundee and Bristol, and £596 per QALY gained in Walsall, with 78, 46 and 40% of simulations being cost-saving in each city, respectively, with differences driven by coverage of NSP and HCV prevalence (lowest in Walsall). More than 90% of simulations were cost-effective at the willingness-to-pay threshold. Results were robust to sensitivity analyses, including varying the time-horizon, HCV treatment cost and numbers of HCV treatments per year. CONCLUSIONS: Needle and syringe programmes are a highly effective low-cost intervention to reduce hepatitis C virus transmission, and in some settings they are cost-saving. Needle and syringe programmes are likely to remain cost-effective irrespective of changes in hepatitis C virus treatment cost and scale-up

    Acceptability of, and barriers and facilitators to, a pilot physical health service for people who inject drugs:A qualitative study with service users and providers

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    BACKGROUND: People who inject drugs may experience difficulty accessing or maintaining involvement with traditional healthcare services. This is associated with increased health inequalities and bio-psychosocial difficulties. Embedding physical healthcare services within community-based drug services may provide a practical and feasible approach to increase access and delivery of healthcare. This study explored the acceptability of, and barriers and facilitators to, embedding a pilot physical healthcare service within a community-based drug service in the United Kingdom (Bristol, England). METHODS: Semi-structured interviews were conducted with service users (people who inject drugs) (n = 13), and a focus group was conducted with service providers (n = 11: nine harm reduction workers, two nurses, one service manager). Topic guides included questions to explore barriers and facilitators to using and delivering the service (based on the COM-B Model), and acceptability of the service (using the Theoretical Framework of Acceptability). Transcripts were analysed using a combined deductive framework and inductive thematic analysis approach. RESULTS: The service was viewed as highly acceptable. Service users and providers were confident they could access and provide the service respectively, and perceived it to be effective. Barriers included competing priorities of service users (e.g. drug use) and the wider service (e.g. equipment), and the potential impact of the service being removed in future was viewed as a barrier to overall healthcare access. Both service users and providers viewed embedding the physical health service within an existing community-based drug service as facilitating accessible and holistic care which reduced stigma and discrimination. CONCLUSIONS: The current study demonstrated embedding a physical health service within an existing community-drug based and alcohol service was acceptable and beneficial. Future studies are required to demonstrate cost-effectiveness and ensure long-term sustainability, and to determine transferability of findings to other settings, organisations and countries

    Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 during the Early Pandemic

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    Background: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. Methods: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. Results: We identified 14 variant sites >= 5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 x 10(-3)substitutions per year. Conclusions: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches

    Dissemination of Resistant Escherichia coli Among Wild Birds, Rodents, Flies, and Calves on Dairy Farms

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    Antimicrobial resistance (AMR) in bacteria in the livestock is a growing problem, partly due to inappropriate use of antimicrobial drugs. Antimicrobial use (AMU) occurs in Swedish dairy farming but is restricted to the treatment of sick animals based on prescription by a veterinary practitioner. Despite these strict rules, calves shedding antimicrobial resistant Enterobacteriaceae have been recorded both in dairy farms and in slaughterhouses. Yet, not much is known how these bacteria disseminate into the local environment around dairy farms. In this study, we collected samples from four animal sources (fecal samples from calves, birds and rodents, and whole flies) and two environmental sources (cow manure drains and manure pits). From the samples, Escherichia coli was isolated and antimicrobial susceptibility testing performed. A subset of isolates was whole genome sequenced to evaluate relatedness between sources and genomic determinants such as antimicrobial resistance genes (ARGs) and the presence of plasmids were assessed. We detected both ARGs, mobile genetic elements and low rates of AMR. In particular, we observed four potential instances of bacterial clonal sharing in two different animal sources. This demonstrates resistant E. coli dissemination potential within the dairy farm, between calves and scavenger animals (rodents and flies). AMR dissemination and the zoonotic AMR risk is generally low in countries with low and restricted AMU. However, we show that interspecies dissemination does occur, and in countries that have little to no AMU restrictions this risk could be under-estimated

    Exploring the Antibiotic Resistance Burden in Livestock, Livestock Handlers and Their Non-Livestock Handling Contacts: A One Health Perspective

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    Antibiotics are freqeuently used in the livestock sector in low- and middle-income countries for treatment, prophylaxis, and growth promotion. However, there is limited information into the zoonotic prevalence and dissemination patterns of antimicrobial resistance (AMR) within these environments. In this study we used pig farming in Thailand as a model to explore AMR; 156 pig farms were included, comprising of small-sized (= 100 sows) farms, where bacterial isolates were selectively cultured from animal rectal and human fecal samples. Bacterial isolates were subjected to antimicrobial susceptibility testing (AST), and whole-genome sequencing. Our results indicate extensive zoonotic sharing of antibiotic resistance genes (ARGs) by horizontal gene transfer. Resistance to multiple antibiotics was observed with higher prevalence in medium-scale farms. Zoonotic transmission of colistin resistance in small-scale farms had a dissemination gradient from pigs to handlers to non-livestock contacts. We highly recommend reducing the antimicrobial use in animals' feeds and medications, especially the last resort drug colistin
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