Attitudes to and Understanding of Risk of Acquisition of HIV Over Time: Design and Methods for an Internet-based Prospective Cohort Study Among UK Men Who Have Sex With Men (the AURAH2 Study)

Background: The annual number of new HIV infections among men who have sex with men (MSM) has risen in the UK and, of those HIV positive, the proportion undiagnosed is high. The prospective AURAH2 study aims to assess factors associated with HIV acquisition among MSM in the UK, and to investigate changes over time within individuals in sexual behaviour and HIV-testing practices. / Methods/Design: AURAH2 is a prospective study among MSM without diagnosed HIV, aiming to recruit up to 1000 sexually active MSM attending sexual health clinics in London and Brighton. Participants complete an initial paper-based questionnaire, followed by four monthly online follow-up questionnaires collecting socio-demographic, health and behavioural data, including sexual behaviour, recreational and other drug use, HIV testing practices and Pre-Exposure Prophylaxis use, over a planned three year period. / Discussion: The results from AURAH2 study will provide an important insight into established and emerging risk behaviours that may be associated with acquisition of HIV in MSM, in the UK, changes over time within individuals in sexual behaviour, and inform on HIV testing practices. This data will be crucial to inform future HIV prevention strategies

Effect of Peptide Size on Antioxidant Properties of African Yam Bean Seed (Sphenostylis stenocarpa) Protein Hydrolysate Fractions

Enzymatic hydrolysate of African yam bean seed protein isolate was prepared by treatment with alcalase. The hydrolysate was further fractionated into peptide sizes of <1, 1–3, 3–5 and 5–10 kDa using membrane ultrafiltration. The protein hydrolysate (APH) and its membrane ultrafiltration fractions were assayed for in vitro antioxidant activities. The <1 kDa peptides exhibited significantly better (p < 0.05) ferric reducing power, diphenyl-1-picryhydradzyl (DPPH) and hydroxyl radical scavenging activities when compared to peptide fractions of higher molecular weights. The high activity of <1 kDa peptides in these antioxidant assay systems may be related to the high levels of total hydrophobic and aromatic amino acids. In comparison to glutathione (GSH), the APH and its membrane fractions had significantly higher (p < 0.05) ability to chelate metal ions. In contrast, GSH had significantly greater (p < 0.05) ferric reducing power and free radical scavenging activities than APH and its membrane fractions. The APH and its membrane fractions effectively inhibited lipid peroxidation, results that were concentration dependent. The activity of APH and its membrane fractions against linoleic acid oxidation was higher when compared to that of GSH but lower than that of butylated hydroxyl toluene (BHT). The results show potential use of APH and its membrane fractions as antioxidants in the management of oxidative stress-related metabolic disorders and in the prevention of lipid oxidation in food products

Protocol, rationale and design of SELPHI: A randomised controlled trial assessing whether offering free HIV self-testing kits via the internet increases the rate of HIV diagnosis 11 Medical and Health Sciences 1117 Public Health and Health Services 11 Medical and Health Sciences 1103 Clinical Sciences

BACKGROUND: Among men who have sex with men (MSM) in the UK, an estimated 28% have never tested for HIV and only 27% of those at higher risk test at least every 6 months. HIV self-testing (HIVST), where the person takes their own blood/saliva sample and processes it themselves, offers the opportunity to remove many structural and social barriers to testing. Although several randomised controlled trials are assessing the impact of providing HIVST on rates of HIV testing, none are addressing whether this results in increased rates of HIV diagnoses that link to clinical care. Linking to care is the critical outcome because it is the only way to access antiretroviral treatment (ART). We describe here the design of a large, internet-based randomised controlled trial of HIVST, called SELPHI, which aims to inform this key question. METHODS/DESIGN: The SELPHI study, which is ongoing is promoted via social networking website and app advertising, and aims to enroll HIV negative men, trans men and trans women, aged over 16 years, who are living in England and Wales. Apart from the physical delivery of the test kits, all trial processes, including recruitment, take place online. In a two-stage randomisation, participants are first randomised (3:2) to receive a free baseline HIVST or no free baseline HIVST. At 3 months, participants allocated to receive a baseline HIVST (and meeting further eligibility criteria) are subsequently randomised (1:1) to receive the offer of regular (every 3 months) free HIVST, with testing reminders, versus no such offer. The primary outcome from both randomisations is a laboratory-confirmed HIV diagnosis, ascertained via linkage to a national HIV surveillance database. DISCUSSION: SELPHI will provide the first reliable evidence on whether offering free HIVST via the internet increases rates of confirmed HIV diagnoses and linkage to clinical care. The two randomisations reflect the dual objectives of detecting prevalent infections (possibly long-standing) and the more rapid diagnosis of incident HIV infections. It is anticipated that the results of SELPHI will inform future access to HIV self-testing provision in the UK. TRIAL REGISTRATION: DOI 10.1186/ISRCTN20312003 registered 24/10/2016

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC):a multicentre, double-blind, randomised controlled trial

SummaryBackgroundUp to 60% of patients with Crohn's disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease.MethodsWe did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohn's disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's disease (Crohn's Disease Activity Index >150 plus 100-point increase in score) and the need for anti-inflammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15).FindingsBetween June 6, 2008, and April 23, 2012, 240 patients with Crohn's disease were randomly assigned: 128 to mercaptopurine and 112 to placebo. All patients received at least one dose of study drug, and no randomly assigned patients were excluded from the analysis. 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohn's disease and needed anti-inflammatory rescue treatment or primary surgical intervention (adjusted hazard ratio [HR] 0·54, 95% CI 0·27–1·06; p=0·07; unadjusted HR 0·53, 95% CI 0·28–0·99; p=0·046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine group and 12 (46%) of 26 in the placebo group had a clinical recurrence that needed treatment (HR 0·13, 95% CI 0·04–0·46), compared with 13 (13%) of 99 non-smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group (0·90, 0·42–1·94; pinteraction=0·018). The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses (previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis). The incidence and types of adverse events were similar in the mercaptopurine and placebo groups. One patient on placebo died of ischaemic heart disease. Adverse events caused discontinuation of treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%) of 112 in the placebo group.InterpretationMercaptopurine is effective in preventing postoperative clinical recurrence of Crohn's disease, but only in patients who are smokers. Thus, in smokers, thiopurine treatment seems to be justified in the postoperative period, although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence.FundingMedical Research Council

Determinants of insecticide-treated net ownership and utilization among pregnant women in Nigeria

<p>Abstract</p> <p>Background</p> <p>Malaria during pregnancy is a major public health problem in Nigeria leading to increase in the risk of maternal mortality, low birth weight and infant mortality. This paper is aimed at highlighting key predictors of the ownership of insecticide treated nets (ITNs) and its use among pregnant women in Nigeria.</p> <p>Methods</p> <p>A total of 2348 pregnant women were selected by a multi-stage probability sampling technique. Structured interview schedule was used to elicit information on socio-demographic characteristics, ITN ownership, use, knowledge, behaviour and practices. Logistic regression was used to detect predictors of two indicators: ITN ownership, and ITN use in pregnancy among those who owned ITNs.</p> <p>Results</p> <p>ITN ownership was low; only 28.8% owned ITNs. Key predictors of ITN ownership included women who knew that ITNs prevent malaria (OR = 3.85; <it>p </it>< 0001); and registration at antenatal clinics (OR = 1.34; <it>p </it>= 0.003). The use of ITNs was equally low with only 7.5% of all pregnant women, and 25.7% of all pregnant women who owned ITNs sleeping under a net. The predictors of ITN use in pregnancy among women who owned ITNs (N = 677) identified by logistic regression were: urban residence (OR = 1.87; <it>p </it>= 0.001); knowledge that ITNs prevent malaria (OR = 2.93; <it>p </it>< 0001) and not holding misconceptions about malaria prevention (OR = 1.56; <it>p </it>= 0.036). Educational level was not significantly related to any of the two outcome variables. Although registration at ANC is significantly associated with ownership of a bednet (perhaps through free ITN distribution) this does not translate to significant use of ITNs.</p> <p>Conclusions</p> <p>ITN use lagged well behind ITN ownership. This seems to suggest that the current mass distribution of ITNs at antenatal facilities and community levels may not necessarily lead to use unless it is accompanied by behaviour change interventions that address the community level perceptions, misconceptions and positively position ITN as an effective prevention device to prevent malaria</p

Using Macro-Arrays to Study Routes of Infection of Helicobacter pylori in Three Families

allowed tracing the spread of infection through populations on different continents but transmission pathways between individual humans have not been clearly described.To investigate person-to-person transmission, we studied three families each including one child with persistence of symptoms after antibiotic treatment. Ten isolates from the antrum and corpus of stomach of each family member were analyzed both by sequencing of two housekeeping genes and macroarray tests. from outside the family appeared to be probable in the transmission pathways. infection may be acquired by more diverse routes than previously expected

The equilibria that allow bacterial persistence in human hosts

We propose that microbes that have developed persistent relationships with human hosts have evolved cross-signalling mechanisms that permit homeostasis that conforms to Nash equilibria and, more specifically, to evolutionarily stable strategies. This implies that a group of highly diverse organisms has evolved within the changing contexts of variation in effective human population size and lifespan, shaping the equilibria achieved, and creating relationships resembling climax communities. We propose that such ecosystems contain nested communities in which equilibrium at one level contributes to homeostasis at another. The model can aid prediction of equilibrium states in the context of further change: widespread immunodeficiency, changing population densities, or extinctions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62883/1/nature06198.pd

Endomyocardial Fibrosis: Still a Mystery after 60 Years

The pathologist Jack N. P. Davies identified endomyocardial fibrosis in Uganda in 1947. Since that time, reports of this restrictive cardiomyopathy have come from other parts of tropical Africa, South Asia, and South America. In Kampala, the disease accounts for 20% of heart disease patients referred for echocardiography. We conducted a systematic review of research on the epidemiology and etiology of endomyocardial fibrosis. We relied primarily on articles in the MEDLINE database with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title. The volume of publications on endomyocardial fibrosis has declined since the 1980s. Despite several hypotheses regarding cause, no account of the etiology of this disease has yet fully explained its unique geographical distribution

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study

Background The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. Methods The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. Findings Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). Interpretation Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV