The natural history, treatment strategies and clinical outcomes of HIV/HCV coinfection

While the rate of AIDS-related death has declined, as a consequence of the effectiveness of antiviral treatment for HIV, HIV/HCV coinfection and in particular liver-related death (LRD) has assumed increasing importance. This thesis aims to analyse important epidemiological areas of HIV/HCV coinfection to improve the knowledge base of the subject and provide guidance to clinicians in a fast moving area of research. Data for this thesis are from the EuroSIDA study, which is a large multi-centre pan-European prospective observational cohort study with over 18,000 HIV-positive individuals including approaching 5,000 HIV/HCV coinfected individuals. The study was initiated in 1994 and continues to expand and diversify to meet current research needs. Results from the studies included in this thesis have shown that treatment for HIV in coinfected individuals can also have a beneficial effect on the natural course of HCV, with HCV viral load remaining stable over time in those treated for HIV compared with increasing HCV viral load in those not yet treated. The incidence of treatment for HCV has steadily increased in Europe to 4.7 per 100 PYFU in 2010, but remains low with just 25% of eligible patients receiving treatment. LRD accounts for more than a fifth of deaths in this population, with significant liver fibrosis and those triple infected with HBV at increased risk. The 5-year probability of LRD is low for those with F0/F1 fibrosis (2.2%), but increases substantially for those with F2/F3 (10.3%) and F4 (14.0%) fibrosis. With potent new treatments for HCV coming to market, it is clear that while they remain prohibitively expensive they should be targeted at those at the greatest risk of LRD. The prognostic LRD score derived here will help clinicians to make difficult decisions on who should be prioritised for HCV treatment

A ‘healthy baby’: The double imperative of preimplantation genetic diagnosis

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 The Authors.This article reports from a study exploring the social processes, meanings and institutions that frame and produce ‘ethical problems’ and clinical dilemmas for practitioners, scientists and others working in the specialty of preimplantation genetic diagnosis (PGD). A major topic in the data was that, in contrast to IVF, the aim of PGD is to transfer to the woman’s womb only those embryos likely to be unaffected by serious genetic disorders; that is, to produce ‘healthy babies’. Staff described the complex processes through which embryos in each treatment cycle must meet a double imperative: they must be judged viable by embryologists and ‘unaffected’ by geneticists. In this article, we focus on some of the ethical, social and occupational issues for staff ensuing from PGD’s double imperative.The Wellcome Trus

Hepatitis B and C co-Infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults

Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR 800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60–5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD

Early empirical TB treatment in HIV-positive patients admitted to hospital in South Africa: an observational cohort study

Background: Empirical TB treatment in HIV-positive inpatients is common and may undermine the impact of new diagnostics. We sought to describe empirical TB treatment and compare characteristics and outcomes with patients treated for TB after screening. Methods: Retrospective observational cohort study of HIV-positive inpatients treated empirically for TB prior to TB screening. Data on clinical characteristics, investigations and outcomes were collected from medical records. Comparison cohorts with microbiologically-confirmed or empirical TB treatment after TB screening with Xpert MTB/RIF and urine lipoarabinomannan assays were taken from South African STAMP trial site. In-hospital mortality was compared using a competing-risks analysis adjusted for age, sex and CD4 count. Results: Between January 2016 and September 2017, 100 patients excluded from STAMP were treated for TB empirically prior to TB screening. After enrolment in STAMP and TB screening, 240/1177 (20.4%) patients received TB treatment, of whom 123 had positive TB tests and 117 were treated empirically. Characteristics were similar among early empirically treated patients and those treated after TB screening. 50% of early empirical TB treatment was based on radiological investigations, 22% on cerebrospinal or pleural fluid testing, and 28% on clinical features alone. Only 11/100 empirically treated patients had subsequent microbiological confirmation. In-hospital mortality was lower in patients with microbiologically-confirmed TB compared to those treated empirically (adjusted sub-distribution HR 0.5, 95% CI 0.3-0.9). Conclusions: Empirical TB treatment remains common in severely ill HIV-positive inpatients. These patients may benefit from TB screening using existing rapid diagnostics, both to improve confirmation of TB disease and reduce over-treatment for TB

Risk of acute respiratory infection and acute cardiovascular events following acute respiratory infection among adults with increased cardiovascular risk in England between 2008 and 2018: a retrospective, population-based cohort study

BACKGROUND: Although acute respiratory infections can lead to cardiovascular complications, the effect of underlying cardiovascular risk on the incidence of acute respiratory infections and cardiovascular complications following acute respiratory infection in individuals without established cardiovascular disease is unknown. We aimed to investigate whether cardiovascular risk is associated with increased risk of acute respiratory infection and acute cardiovascular events after acute respiratory infection using 10 years of linked electronic health record (EHR) data in England. METHODS: In this retrospective, population-based cohort study we used EHRs from primary care providers registered on the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases in England. Eligible individuals were aged 40-64 years, did not have established cardiovascular disease or a chronic health condition that would make them eligible for influenza vaccination, were registered at a general practice contributing to the CPRD, and had linked Hospital Episode Statistics Admitted Patient Care data in England from Sept 1, 2008, to Aug 31, 2018. We classified cardiovascular risk on the basis of diagnosed hypertension and overall predicted cardiovascular risk, estimated by use of the QRISK2 risk-prediction tool (comparing a score of ≥10% [increased risk] with a score of <10% [low risk]). Using multivariable Poisson regression models, we calculated incidence rate ratios (IRRs) for systemic acute respiratory infection. Among individuals who had an acute respiratory infection, we used multivariable Cox regression to calculate hazard ratios (HRs) for the risk of acute cardiovascular events within 1 year of infection. FINDINGS: We identified 6 075 321 individuals aged 40-64 years with data in the CPRD and linked data in the Hospital Episode Statistics Admitted Patient Care database between Sept 1, 2008, and Aug 31, 2018. Of these individuals, 4 212 930 (including 526 480 [12·5%] with hypertension and 607 087 [14·4%] with a QRISK2 score of ≥10%) were included in the assessment of the incidence of acute respiratory infection. After adjusting for confounders (age, sex, ethnicity, socioeconomic status, body-mass index, alcohol consumption, smoking status, and consultation frequency in the hypertension analysis; and alcohol consumption and consultation frequency in the QRISK2 analysis), the incidence of acute respiratory infection was higher in individuals with hypertension than those without (IRR 1·04 [95% CI 1·03-1·05]) and higher in those with a QRISK2 score of 10% or higher than in those with a QRISK2 score of less than 10% (1·39 [1·37-1·40]). Of the 442 408 individuals who had an acute respiratory infection, 4196 (0·9%) had an acute cardiovascular event within 1 year of infection. After adjustment (for age, sex, ethnicity, socioeconomic status, body-mass index, alcohol consumption, and smoking status in the hypertension analysis; and for alcohol consumption in the QRISK2 analysis), hypertension (HR 1·98 [95% CI 1·83-2·15]) and a QRISK2 score of 10% or higher (3·65 [3·42-3·89]) were associated with a substantially increased risk of acute cardiovascular events after acute respiratory infection. INTERPRETATION: People with increased cardiovascular risk but without diagnosed cardiovascular disease, measured by diagnosed hypertension or overall predicted cardiovascular risk, could benefit from influenza and pneumococcal vaccine prioritisation to reduce their risk of both acute respiratory infection and cardiovascular complications following an acute respiratory infection. FUNDING: British Heart Foundation and the Wellcome Trust

Identity and belonging in social learning groups : the importance of distinguishing social, operational and knowledge-related identity congruence

Collaborative learning has much to offer but not all learners participate fully and peer groups can be exclusive. The paper examines how belonging or 'congruence' in learning groups is related to identities of gender, age, ethnicity and socio-economic status. A study of student experiences of collaborative learning on three different blended learning courses illustrated how learners negotiate identity congruence with peer groups to belong and engage. An analytical framework that distinguishes social, operational and knowledge-related identity congruence has emerged. Contrary to received wisdom, the social aspect appears least important for learner engagement while knowledge-related identity congruence is fundamental. Some of the consequences of identity incongruence, particularly concerning gender and maturity, are discussed and the paper points towards the pedagogies which might enable identities of group members to shift so that collaborative learning can flourish

Incidence of acute complications of herpes zoster among immunocompetent adults in England:a matched cohort study using routine health data

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN

Accuracy of diabetes screening methods used for people with tuberculosis, Indonesia, Peru, Romania, South Africa

Objective To evaluate the performance of diagnostic tools for diabetes mellitus, including laboratory methods and clinical risk scores, in newly-diagnosed pulmonary tuberculosis patients from four middle-income countries. Methods In a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen initial random plasma glucose was ≥ 6.1 mmol/L. Findings The overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6–14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75–0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81–0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru. Conclusion Random plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemia, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation

Bodies, technologies and action possibilities: when is an affordance?

Borrowed from ecological psychology, the concept of affordances is often said to offer the social study of technology a means of re-framing the question of what is, and what is not, ‘social’ about technological artefacts. The concept, many argue, enables us to chart a safe course between the perils of technological determinism and social constructivism. This article questions the sociological adequacy of the concept as conventionally deployed. Drawing on ethnographic work on the ways technological artefacts engage, and are engaged by, disabled bodies, we propose that the ‘affordances’ of technological objects are not reducible to their material constitution but are inextricably bound up with specific, historically situated modes of engagement and ways of life