Seroprevalence of HCV, HBV and HIV in two inner-city London emergency departments.

SUMMARY: In this paper we build on work investigating the feasibility of human immunodeficiency virus (HIV) testing in emergency departments (EDs), estimating the prevalence of hepatitis B, C and HIV infections among persons attending two inner-London EDs, identifying factors associated with testing positive in an ED. We also undertook molecular characterisation to look at the diversity of the viruses circulating in these individuals, and the presence of clinically significant mutations which impact on treatment and control.Blood-borne virus (BBV) testing in non-traditional settings is feasible, with emergency departments (ED) potentially effective at reaching vulnerable and underserved populations. We investigated the feasibility of BBV testing within two inner-London EDs. Residual samples from biochemistry for adults (⩾18 years) attending The Royal Free London Hospital (RFLH) or the University College London Hospital (UCLH) ED between January and June 2015 were tested for human immunodeficiency virus (HIV)Ag/Ab, anti-hepatitis C (HCV) and HBsAg. PCR and sequence analysis were conducted on reactive samples. Sero-prevalence among persons attending RFH and UCLH with residual samples (1287 and 1546), respectively, were 1.1% and 1.0% for HBsAg, 1.6% and 2.3% for anti-HCV, 0.9% and 1.6% for HCV RNA, and 1.3% and 2.2% for HIV. For RFH, HBsAg positivity was more likely among persons of black vs. white ethnicity (odds ratio 9.08; 95% confidence interval 2.72-30), with anti-HCV positivity less likely among females (0.15, 95% CI 0.04-0.50). For UCLH, HBsAg positivity was more likely among non-white ethnicity (13.34, 95% CI 2.20-80.86 (Asian); 8.03, 95% CI 1.12-57.61 (black); and 8.11, 95% CI 1.13-58.18 (other/mixed)). Anti-HCV positivity was more likely among 36-55 year olds vs. ⩾56 years (7.69, 95% CI 2.24-26.41), and less likely among females (0.24, 95% CI 0.09-0.65). Persons positive for HIV-markers were more likely to be of black vs. white ethnicity (4.51, 95% CI 1.63-12.45), and less likely to have one ED attendance (0.39, 95% CI 0.17-0.88), or female (0.12, 95% CI 0.04-0.42). These results indicate that BBV-testing in EDs is feasible, providing a basis for further studies to explore provider and patient acceptability, referral into care and cost-effectiveness.

Prevalence of diagnosed HIV infection among persons with hepatitis C virus infection: England, 2008-2014.

OBJECTIVES: In persons with hepatitis C virus (HCV) infection, HIV coinfection leads to faster progression to advanced liver disease. The aim of our study was to estimate diagnosed HIV prevalence among people with evidence of current HCV infection (polymerase chain reaction positive) and examine predictors of coinfection. METHODS: Adults (≥ 15 years old) with a current HCV infection reported to the Public Health England (PHE) sentinel surveillance of blood-borne viruses were linked to the PHE national HIV database using a deterministic methodology. Descriptive and multivariate analyses were conducted. RESULTS: Between 2008 and 2014, 5.0% (999/20 088) of adults with a current HCV infection were diagnosed with HIV coinfection. The majority acquired HIV through sex between men (441; 64.9%), followed by injecting drug use (153; 22.5%) and heterosexual contact (84; 12.4%). Of persons who were coinfected, 65.5% had been diagnosed with HIV infection > 6 months before their HCV diagnosis, 41.4% of whom had a negative anti-HCV test between their HIV and HCV diagnoses. In a multivariable model among persons with current HCV infection, an HIV diagnosis was more likely among men [adjusted odds ratio (aOR) 3.29; 95% confidence interval (CI) 2.60-4.16] and persons of black ethnicity (aOR 3.19; 95% CI 1.36-7.46), and less likely among older adults (aOR 0.85 per 10-year increase; 95% CI 0.79-0.92) and persons of Asian ethnicity (aOR 0.59; 95% CI 0.41-0.86). CONCLUSIONS: Our results indicate that the majority of diagnosed HIV and current HCV coinfections are among men who have sex with men. Safer sex campaigns should include awareness of transmission of HCV among MSM living with HIV.

Goal Attainment Scaling for haemophilia (GAS-Hem): testing the feasibility of a new patient-centric outcome measure in people with haemophilia.

INTRODUCTION: To address the need for a patient-reported outcome that can measure clinically and personally meaningful change in people with haemophilia (PwH) on prophylaxis, an approach based on Goal Attainment Scaling (GAS) was developed: the GAS-Hem. AIM: To establish real-world feasibility of GAS-Hem in PwH. METHODS: Patients aged 5-65 years were enroled from four North American centres for a 12-week study. The primary outcome was the proportion of participants who completed GAS-Hem interviews at baseline, 6 and 12 weeks. GAS-Hem scores were obtained by subject- and clinician-rated goal attainment at Weeks 6 and 12, and compared with quality of life (QoL) measures and annualized bleed rate (ABR) for construct validity. Goals were evaluated qualitatively for content validity. Responsiveness was calculated using standardized response means (SRM). RESULTS: Forty-two participants set 63 goals. Participants preferred to define (37/63) their own goals or further individualize (23/63) from the GAS-Hem menu. Thirty of the 37 self-defined goals were matched to goals on the GAS-Hem menu. The most common goal areas were: weight, exercise and nutrition (n = 17); leisure activities (n = 8); and joint problems (n = 7). Both participant- and clinician-rated GAS-Hem scores at 6 weeks (n = 40) and 12 weeks (n = 41) demonstrated satisfactory goal attainment (SRM [subject-rated] at 12 weeks for adult and paediatric groups was 1.25 and 1.16, respectively). Correlations of GAS-Hem scores with QoL measures and ABR were uniformly small. CONCLUSION: GAS-Hem was feasible and tapped constructs not captured by ABR or QoL measures.

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals.

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case finding, referral, treatment uptake and retention in care. Using data from the sentinel surveillance of blood-borne virus (SSBBV) testing between 2005 and 2014, we investigate the continuum of care of those tested for HCV in England. Persons ≥1 year old with an anti-HCV test and subsequent RNA tests between 2005 and 2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment and patient outcomes. Between 2005 and 2014, 2 390 507 samples were tested for anti-HCV, corresponding to 1 766 515 persons. A total of 53 038 persons (35 190 men and 17 165 women) with anti-HCV positive were newly reported to SSBBV. An RNA test was conducted on 77.0% persons who were anti-HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models, confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat.

Evaluation of hepatitis C testing in men who have sex with men, and associated risk behaviours, in Manchester, UK.

OBJECTIVE: To determine the prevalence of newly diagnosed hepatitis C virus (HCV) and associated risk behaviours among men who have sex with men (MSM) in Manchester. METHOD: A survey among MSM attending four genitourinary medicine clinics in Manchester was carried out over 9 months in 2013. Participants were asked about recent sexual behaviour, recreational drug use and HIV status. All men were offered an HCV test. RESULTS: Overall, 2030 MSM completed a questionnaire and accepted an HCV test. Of whom, 0.9% (18) were newly diagnosed with HCV, including 1.8% (13/735) of HIV-positive MSM, 0.7% (3/440) of MSM of unknown HIV status and 0.2% (2/855) of HIV-negative MSM. HCV positivity was significantly associated with HIV status (p<0.001). When compared with HIV-negative MSM, HIV-positive MSM had higher rates of sharing snorting drug equipment, injecting drugs/'slamming' and using recreational drugs (all p<0.05) but lower rates of five or more sexual partners and insertive unprotected anal intercourse (p<0.05). MSM newly diagnosed with HCV had significantly higher prevalence of unprotected sex, sex with someone HCV positive, fisting, group sex, ever injecting drugs/'slamming' and recreational drug use (p<0.002). CONCLUSIONS: In this survey, HIV-positive MSM had significantly different drug use behaviour which may explain the higher HCV burden. However, HCV was also associated with HIV-negative MSM engaging in high-risk sexual practices. All MSM attending sexual health clinics must have a risk assessment and HCV screening should be offered based on the risk. Further studies are warranted to explore the interplay between HCV and HIV risk associated with drug use versus sexual practices.

Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign.

OBJECTIVES: Routine HIV screening is recommended in those UK hospitals and primary care settings where the HIV prevalence is > 0.2%. For hepatitis B virus (HBV) and hepatitis C virus (HCV), however, testing is targeted at at-risk groups. We investigated the prevalence of these blood-borne viruses (BBVs) during a routine testing pilot in UK Emergency Departments (EDs). METHODS: During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in areas of high HIV prevalence offered routine tests for HIV, HBV and HCV to adults having blood taken as part of routine care. Patients who tested positive were linked to care. RESULTS: A total of 7807 patients had blood taken during their ED visit; of these, 2118 (27%) were tested for BBVs (range 9-65%). Seventy-one BBV tests were positive (3.4%) with 32 (45.1%) new diagnoses. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged 25-54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Assuming the cost per diagnosis is £7, the cost per new case detected would be £988 for HCV, £1351 for HBV and £2478 for HIV. CONCLUSIONS: In the first study in the UK to report prospectively on BBV prevalence in the ED, we identified a high number of new viral hepatitis diagnoses, especially hepatitis C, in addition to the HIV diagnoses. Testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.

Assessment of neonatal platelet adhesion, activation, and aggregation.

BACKGROUND: Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates, owing to difficulties in obtaining an adequate blood volume, a lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. OBJECTIVE: To develop small-volume, whole blood platelet function assays in order to quantify and compare neonatal and adult platelet function. METHODS AND RESULTS: Peripheral blood was obtained from healthy, full-term neonates at 24 h of life. Platelet activation, secretion and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared with adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein IIbIIIa activation were significantly reduced in response to the G-protein-coupled receptor (GPCR) agonists thrombin receptor activator peptide-6 (TRAP-6), ADP, and U46619, and the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP and rhodocytin as compared with adult platelets. The extents of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor were similar. CONCLUSIONS: As compared with adult platelets, we found that neonatal platelet activation and secretion were blunted in response to GPCR or ITAM agonists, whereas the extent of neonatal platelet adhesion and aggregate formation was similar to that of adult platelets.

Recent infection testing algorithm (RITA) applied to new HIV diagnoses in England, Wales and Northern Ireland, 2009 to 2011.

In 2009, Public Health England (PHE) introduced the routine application of a recent infection testing algorithm (RITA) to new HIV diagnoses, where a positive RITA result indicates likely acquisition of infection in the previous six months. Laboratories submit serum specimens to PHE for testing using the HIV 1/2gO AxSYM assay modified for the determination of HIV antibody avidity. Results are classified according to avidity index and data on CD4 count, antiretroviral treatment and the presence of an AIDS-defining illness. Between 2009 and 2011, 38.4% (6,966/18,134) of new HIV diagnoses in England, Wales and Northern Ireland were tested. Demographic characteristics of those tested were similar to all persons with diagnosed HIV. Overall, recent infection was 14.7% (1,022/6,966) and higher among men who have sex with men (MSM) (22.3%, 720/3,223) compared with heterosexual men and women (7.8%, 247/3,164). Higher proportions were among persons aged 15-24 years compared with those ≥50 years (MSM 31.2% (139/445) vs 13.6% (42/308); heterosexual men and women 17.3% (43/249) vs 6.2% (31/501)). Among heterosexual men and women, black Africans were least likely to have recent infection compared with whites (4.8%, 90/1,892 vs 13.3%, 97/728; adjusted odds ratio: 0.6; 95% CI: 0.4-0.9). Our results indicate evidence of ongoing HIV transmission during the study period, particularly among MSM.

The Recent Infection Testing Algorithm (RITA) in clinical practice: a survey of HIV clinicians in England and Northern Ireland.

OBJECTIVES: In order to estimate HIV incidence among high-risk groups, in January 2009 the Health Protection Agency introduced the Recent Infection Testing Algorithm (RITA) in England and Northern Ireland (E&NI), currently the only regions to inform patients of RITA results. This survey of HIV specialists aimed to investigate the role of RITA in patient management and explore clinicians' views on its role in clinical practice and during partner notification. METHODS: An online questionnaire was distributed to HIV specialists via the British HIV Association membership email list in February 2011. RESULTS: Forty-two HIV specialists from 32 HIV centres responded to the survey among 90 centres enrolled in the programme (response rate 36%). Testing for recent infection was considered standard of care by 83% of respondents, 80% felt confident in interpreting results and 92% discussed results with patients, particularly in the context of a possible HIV seroconversion illness (96%) or when deciding when to start antiretroviral therapy (70%). A third (36%) of specialists were initially concerned that RITA results may cause additional anxiety among patients; however, no adverse events were reported. The majority (90%) felt that results could assist with contact tracing by prioritizing patients with likely recent infection. However, only a few centres have currently incorporated RITA into their HIV partner notification protocols. CONCLUSIONS: RITA has been introduced into clinical practice with no reported patient adverse events. Access to results at centre level should be improved. National guidance regarding use of RITA as a tool for contact tracing is required.

Situation of HIV infections and STIs in the United Kingdom in 2007.

In the United Kingdom (UK) in 2007, an estimated 77,400 persons were living with human immunodeficiency virus (HIV) of whom 28% are unaware of their infection. A total of 7,734 persons were newly diagnosed with HIV infection in 2007, of which 31% were diagnosed late. This highlights the need for wider HIV testing, especially in those areas with a high diagnosed prevalence, as recommended in recent national guidelines. Among newly diagnosed cases of HIV in 2007, 41% acquired their infection through sex between men (four in five of whom acquired their infection in the UK) and 55% through heterosexual contact (four in five of whom acquired their infection abroad, mainly in sub-Saharan Africa). Young persons aged 16 to 24 years are disproportionally affected by sexually transmitted diseases (STIs) accounting for 65% of genital chlamydia infections, 50% of cases of genital warts and 50% of cases of gonorrhoea that were diagnosed in 2007.

Setting up an enhanced surveillance of newly acquired hepatitis C infection in men who have sex with men: a pilot in London and South East region of England.

Preliminary findings suggest ongoing HCV transmission among MSM infected with human immunodeficiency virus (HIV) and that enhanced surveillance for newly acquired HCV in MSM is feasible.

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets.

The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up- and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially promising candidates for new diagnostic and treatment strategies. The analysis of liver metastases revealed a previously unknown high level of similarity with the primary lesions.