The views of general practitioners and practice nurses towards the barriers and facilitators of proactive, internet-based chlamydia screening for reaching young heterosexual men

Background: Chlamydia trachomatis is a common bacterial sexually transmitted infection (STI), which disproportionately affects young people under 25 years. Commonly, more women are offered screening than men. This study obtained the views of general practitioners and practice nurses towards Internet-based screening and assessed levels of support for the development of proactive screening targeting young heterosexual men via the Internet. Methods: Semi-structured telephone interviews with 10 general practitioners and 8 practice nurses, across Central Scotland. Topics covered: experience of screening heterosexual men for chlamydia, views on the use of the Internet as a way to reach young men for chlamydia screening, beliefs about the potential barriers and facilitators to Internet-based screening. Transcripts from audio recordings were analysed with Framework Analysis, using QSR NVivo10. Results: Experiences of chlamydia screening were almost exclusively with women, driven by the nature of consultations and ease of raising sexual health issues with female patients; few practice nurses reported seeing men during consultations. All participants spoke in favour of Internet-based screening for young men. Participants reported ease of access and convenience as potential facilitators of an Internet-based approach but anonymity and confidentiality could be potential barriers and facilitators to the success of an Internet approach to screening. Concerns over practical issues as well as those pertaining to gender and socio-cultural issues were raised. Conclusions: Awareness of key barriers and facilitators, such as confidentiality, practicality and socio-cultural influences, will inform the development of an Internet-based approach to screening. However, this approach may have its limits in terms of being able to tackle wider social and cultural barriers, along with shifts in young people's and health professionals' attitudes towards screening. Nevertheless, employing innovative efforts as part of a multi-faceted approach is required to ensure effective interventions reach the policy agenda

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

Severe Acute Respiratory Syndrome–associated Coronavirus in Lung Tissue

Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 109 viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths

Sexually transmitted infections: challenges ahead.

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health

Shear stress induces osteogenic differentiation of human mesenchymal stem cells

Aim: To determine whether fluid flow-induced shear stress affects the differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) into osteogenic cells. Materials & methods: hMSCs cultured with or without osteogenic differentiation medium were exposed to fluid flow-induced shear stress and analyzed for alkaline phosphatase activity and expression of osteogenic genes. Results: Immediately following shear stress, alkaline phosphatase activity in osteogenic medium was significantly increased. At days 4 and 8 of culture the mRNA expression of bone morphogenetic protein-2 and osteopontin was significantly higher in hMSCs subjected to shear stress than those cultured in static conditions. However, hMSCs cultured in osteogenic differentiation medium were less responsive in gene expression of alkaline phosphatase and bone morphogenetic protein-2. Conclusion: These data demonstrate that shear stress stimulates hMSCs towards an osteoblastic phenotype in the absence of chemical induction, suggesting that certain mechanical stresses may serve as an alternative to chemical stimulation of stem cell differentiation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London