David A. Barr

Towards an improved investment approach for an effective response to HIV/AIDS

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US

Outpatient parenteral antimicrobial therapy (OPAT) in a teaching hospital-based practice: a retrospective cohort study describing experience and evolution over 10 years.

22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at

The claim for patient choice and equity

1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

Assessment of Bone Mineral Density in Tenofovir-Treated Patients With Chronic Hepatitis B: Can the Fracture Risk Assessment Tool Identify Those at Greatest Risk?

Use of outpatient parenteral antimicrobial therapy (OPAT) is increasing in settings with advanced healthcare systems internationally. This study describes a large OPAT service cohort developed in the west of Scotland and includes trends over a 10-year period of this service. Data were retrieved from a prospectively maintained electronic case database. Patient and logistic variables were collated for all OPAT episodes (n=2638, resulting in 39035 days of patient care over 10 years). Skin and soft-tissue infections and bone and joint infections accounted for 77% of OPAT cases, but a wide range of other conditions have been treated in this cohort. Outcome variables were evaluated for all first OPAT attendances (n=2233), amongst which a successful outcome (cure or improvement) was found for 2063 (92.4%). Unplanned admission was observed in 9.1% of patients (6.3 events per 1000 OPAT patient days). Healthcare-associated infection rates were low: amongst first OPAT attendances, 14 intravenous line infections were observed (0.4 per 1000 OPAT patient days). Statistically significant trends over time included: a decrease in OPAT treatment time; increased referrals from non-local and secondary care sources; increased rate of co-morbidity of OPAT referrals; and increased self/carer administration of antimicrobials. Outcome proportions (success and adverse events) did not vary over time. This cohort study adds to the increasing observational data suggesting that OPAT is safe, effective and acceptable for treating a wide variety of infections. Observed trends over a 10-year period suggest that this model of infection management is adaptable and sustainable.

Risk factors for failure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis

Recently, commentators close to and within the UK government have claimed that patient choice can increase equity in the context of the National Health Service. This article critically examines the basis for this claim through analysis of recent speeches and publications authored by secretaries of state for health and their policy advisers. It is concluded that this claim has not developed prospectively from an analysis of the causes of healthcare inequity, or even with a consistent normative definition of equity. The limited justification that is “framed in causal explanations” of inequity has suffered from an apparent disregard of the available evidence.

Self-administration of outpatient parenteral antibiotic therapy and risk of catheter-related adverse events: a retrospective cohort study.

BACKGROUND Tenofovir disoproxil fumarate (TDF) is an established nucleotide analogue in the treatment of chronic hepatitis B. Bone mineral density loss has been described in TDF-treated patients with human immunodeficiency virus infection, but limited data exist for patients with chronic hepatitis B. Dual X-ray absorptiometry (DEXA) was used to determine bone mineral density changes in TDF-exposed patients. We evaluated the accuracy of the Fracture Risk Assessment Tool (FRAX) as an alternative to DEXA in clinical practice. METHODS A total of 170 patients were studied: 122 were exposed to TDF, and 48 were controls. All patients underwent DEXA, and demographic details were recorded. FRAX scores (before and after DEXA) were calculated. RESULTS TDF was associated with a lower hip T score (P = .02). On univariate and multivariate analysis, advancing age, smoking, lower body mass index, and TDF exposure were independent predictors of low bone mineral density. In addition, the pre-DEXA FRAX score was an accurate predictor of the post-DEXA FRAX treatment recommendation (100% sensitivity and 83% specificity), area under the curve 0.93 (95% CI, .87-.97, P < .001). CONCLUSIONS TDF-treated patients with chronic hepatitis B have reduced bone mineral density, but the reduction is limited to 1 anatomical site. Age and advanced liver disease are additional contributing factors, underlining the importance of multifactorial fracture risk assessment. FRAX can accurately identify those at greatest risk of osteoporotic fracture.

First confirmed case of Crimean-Congo haemorrhagic fever in the UK

Objectives To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). Patients and methods We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. ‘OPAT failure’ was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan–Meier survival analysis up to 36 months following OPAT. Results We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84–29.66), P = 0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01–37.47), P = 0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P = 0.016 log-rank test). Conclusions These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated.

Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays

Despite increasing use, limited data has been published comparing safety of different outpatient parenteral antimicrobial therapy (OPAT) models. Potential risks of self-administration at home include venous access device infection and other line complications. This study aims to investigate rates and predictors of intravenous access device complications in a large OPAT cohort. This is a retrospective cohort study of all uses of midlines, peripherally inserted central catheters (PICCs) and tunnelled central venous catheters (TCVCs) with univariate and multivariate (logistic regression) analysis of factors associated with line infections (LIs) and with other line events (OLEs). On univariate analysis, line infections were associated with length of line use, female sex and TCVC lines (compared to midlines). Patients self-administering OPAT in the home had a non-significantly lower rate of LIs. On multivariate analysis only duration of line use was a significant predictor of LIs—OR 1.012 (95%CI 1.001–1.023). For OLEs, multivariate analysis suggested that only line type and use of flucloxacillin were significant explanatory variables. In this cohort, there is no evidence that self-administration of OPAT is associated with higher rates of venous access device complications after controlling for confounding variables.

Clinicopathological correlates in HIV seropositive tuberculosis cases presenting with jaundice after initiating antiretroviral therapy with a structured review of the literature.

In October, 2012, a 38-year-old Afghan man presented to an emergency department in Glasgow, UK, 2 h after returning on a fl ight from Kabul via Dubai, after a 3 week stay in Afghanistan, where he had attended a wedding in Samangan Province. His symptoms had started 5 days before presentation and included fever, epigastric pain, bloody diarrhoea, and haematemesis. On examination he was languid but orientated, with physical observations within normal limits. Conjunctival suff usion was present and a haematoma rapidly developed at the site of venepuncture. Initial blood results showed transaminitis and thrombocytopenia (appendix). The patient was transferred to the Brownlee Centre for Infectious Diseases, Glasgow, and isolated in a negative-pressure room. Formal viral haemorrhagic fever risk assessment was implemented according to the 2012 guidelines published by the Advisory Committee on Dangerous Pathogens (ACDP); the patient reported no contact with ticks (the vector of Crimean-Congo haemorrhagic fever [CCHF]) or with animals and was therefore classifi ed as “possibility of viral haemorrhagic fever” (appendix). Infection control measures were applied in line with ACDP guidance. He was discussed with the Rare and Imported Pathogens Department (RIPD) of the Health Protection Agency, Greater Glasgow and Clyde Public Health Department, and the High Security Infectious Diseases Unit at the Royal Free Hospital, London. Samples of blood and urine were sent by courier to the RIPD laboratory at Porton Down, UK, for rapid CCHF virus testing by PCR: laboratory con fi rmation of the diagnosis of CCHF was made within 36 h of the patient’s presentation. After diagnosis, the patient’s wife discovered that during the Afghan wedding ceremony her husband had been close to a slaughtered calf, the probable source of infection. Despite intravenous ribavirin, the patient’s condition deteriorated, with fl uctuating Glasgow Coma Scale scores, and rising respiratory rate and pulse. 60 h after initial presentation, in keeping with national guidelines, he was transported to Glasgow International Airport by the Scottish Ambulance Service Special Operations Response Team and a dedicated RAF Air Transport Isolator team, and then transferred to the Royal Free Hospital High Security Infectious Diseases Unit in an RAF Hercules and dedicated ambulance where he was managed in a modi fi ed Trexler isolator (Putlock Chimney Systems Ltd, Whitchurch, UK) which provided a sealed environment and pro tection for the staff caring for him. During the fl ight further clinical deterioration was evident including anuria, vascular leak, and a decerebrate response to pain suggesting an intracerebral haemorrhage. Over the subsequent 24 h, he deteriorated further and developed pulmonary haemorrhage. The patient died 96 h after initial presentation. Viral haemorrhagic fever is a rare diagnosis in nonendemic areas and we report the fi rst confi rmed case of CCHF in the UK. Caused by a tick-borne virus, CCHF virus is endemic to more than 30 countries in Central and south western Asia, south eastern Europe, and Africa. Human beings can be infected from tick bites, contact with body fl uid, or, as suspected in the present case, contact with tissue from viraemic livestock. After a variable incubation period (average 2–7 days), fever and myalgia develop; haemorrhagic features start around the fourth day of illness, with mortality rate up to 30%. With increasing international travel to viral haemorrhagic fever endemic areas, clinicians in all countries must maintain a high index of suspicion for cases. In this instance, following infectious diseases consultant assessment, the possibility of viral haemor rhagic fever was recognised within 6 h of presentation, and the diagnosis of CCHF confi rmed rapidly. Consequently, the patient was promptly isolated. Surveillance has not identifi ed any onward transmission. This situation contrasts with multiple previously reported incidences of CCHF where late diagnosis and gaps in infection control procedure have been associated with nosocomial outbreaks. The case also highlights the value of a collateral history and asking about contact with blood from animal carcasses. Our patient is the fi rst confi rmed case of viral haemorrhagic fever in the UK since the 2012 guidelines for management of human infectious diseases of high consequence were published.

Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB

HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3–6.4; and 2.4, 95%CI = 1.3–4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials.