"Even if you're HIV-positive there's life after if you take your medication": experiences of people on long-term ART in South Africa: a short report.

South Africa's national antiretroviral treatment (ART) programme, initiated in 2004, is the largest HIV treatment programme in the world with an estimated 4.2 million people on ART. Today, an HIV diagnosis is no longer associated with certain death, but is rather a manageable chronic disease, with all HIV-positive patients now eligible to receive treatment. In this study, we explore patient experiences at the onset of the ART programme, including facilitators and barriers around decision-making along the HIV care cascade (HIV testing, ART initiation, retention, and adherence). We conducted twenty-four in-depth interviews among adults (≥18 years old) who initiated ART between April 2004 and March 2005 and were alive, on treatment at enrolment (October 2015-March 2016) at a large public-sector clinic in Johannesburg, South Africa. Data were analysed using a thematic analysis approach. Patients cited physical wellbeing, responsibility for raising children, supportive clinic staff and noticeable improvements in health on ART as key facilitators to continued care. In contrast, changing clinic conditions, fear of side-effects and stigma were mentioned as barriers. This study provides a unique lens through which to evaluate factors associated with long-term retention and adherence to ART at a crucial time in ART programming when more people will be initiating life-long treatment. We must continue to focus on supportive and empathetic clinic environments, more convenient ways to access medication for patients, and developing tools or interventions that continue to address the issues of stigma and discrimination and build the support networks for all those on treatment.

On implementing maximum economic yield in commercial fisheries.

Economists have long argued that a fishery that maximizes its economic potential usually will also satisfy its conservation objectives. Recently, maximum economic yield (MEY) has been identified as a primary management objective for Australian fisheries and is under consideration elsewhere. However, first attempts at estimating MEY as an actual management target for a real fishery (rather than a conceptual or theoretical exercise) have highlighted some substantial complexities generally unconsidered by fisheries economists. Here, we highlight some of the main issues encountered in our experience and their implications for estimating and transitioning to MEY. Using a bioeconomic model of an Australian fishery for which MEY is the management target, we note that unconstrained optimization may result in effort trajectories that would not be acceptable to industry or managers. Different assumptions regarding appropriate constraints result in different outcomes, each of which may be considered a valid MEY. Similarly, alternative treatments of prices and costs may result in differing estimates of MEY and their associated effort trajectories. To develop an implementable management strategy in an adaptive management framework, a set of assumptions must be agreed among scientists, economists, and industry and managers, indicating that operationalizing MEY is not simply a matter of estimating the numbers but requires strong industry commitment and involvement.

Leveraging routine data in impact evaluation: Understanding data systems in primary healthcare prior to a matched cluster-randomised evaluation of adherence guidelines in South Africa.

BACKGROUND: An essential part of providing high-quality patient care and a means of efficiently conducting research studies relies upon high-quality routinely collected medical information. OBJECTIVES: To describe the registers, paper records and databases used in a sample of primary healthcare clinics in South Africa (SA) with the view to conduct an impact evaluation using routine data. METHODS: Between October 2015 and December 2015, we collected information on the presence, quality and completeness of registers, clinical stationery and databases at 24 public health facilities in SA. We describe each register and type of clinical stationery we encountered, their primary uses, and the quality of completion. We also mapped the ideal flow of data through a site to better understand how its data collection works. RESULTS: We identified 13 registers (9 standard, 4 non-standard), 5 types of stationery and 4 databases as sources of medical information within a site. Not all clinics used all the standardised registers, and in those that did, registers were kept in various degrees of completeness: a common problem was inconsistent recording of folder numbers. The quality of patient stationery was generally high, with only the chronic patient record being considered of varied quality. The TIER.Net database had high-quality information on key variables, but national identification (ID) number was incompletely captured (42% complete). Very few evaluation sites used electronic data collection systems for conditions other than HIV/AIDS. CONCLUSION: Registers, databases and clinical stationery were not implemented or completed consistently across the 24 evaluation sites. For those considering using routinely collected data for research and evaluation purposes, we would recommend a thorough review of clinic data collection systems for both quality and completeness before considering them to be a reliable data source.

Safety, tolerability and pharmacokinetics of single escalating doses of indacaterol, a once-daily beta2-agonist bronchodilator, in subjects with COPD.

OBJECTIVES: To assess the safety and tolerability of 4 doses of indacaterol, a once-daily beta2-agonist, in subjects with chronic obstructive pulmonary disease (COPD). The 24-h bronchodilator effect and pharmacokinetics of indacaterol were also investigated. METHODS: 16 subjects aged 43 - 72 years with mild/moderate COPD were each given single doses of indacaterol of 400, 1,000, 2,000 and 3,000 µg, via a single-dose dry powder inhaler. RESULTS: Changes from predose (400, 1,000, 2,000, 3,000 µg doses, respectively) were as follows. Maximum mean decreases in fasting (up to 2 h post-dose) serum potassium were 0.12, 0.30, 0.38, 0.26 mmol/l; maximum mean increases (up to 2 h post-dose) in fasting serum glucose were 0.12, 0.40, 0.87, 1.01 mmol/l. The maximum increase in heart rate (by 3, 6, 12, 13 beats/min, respectively) was within 1 h post-dose. No clinically significant electrocardiogram abnormalities were reported. Most adverse events were mild or moderate, with none considered serious or leading to withdrawal. Indacaterol was rapidly absorbed and displayed multiphasic disposition kinetics. The terminal elimination phase with a half-life of 50 - 63 h could only be seen for doses of 1,000 µg or higher. Mean systemic exposure to indacaterol (AUC0-24) increased by ~ 9-fold from 400 to 3,000 µg. CONCLUSION: Even at doses far in excess of the therapeutic range, indacaterol had minimal systemic effects; such changes would be considered within safe limits for a single dose.

Do behavioural differences help to explain variations in HIV prevalence in adolescents in sub-Saharan Africa?

OBJECTIVE: To compare adolescent risk factors for HIV infection in two countries with high adolescent HIV prevalence and two lower prevalence countries with the aim of identifying risk factors that may help explain differences in adolescent HIV prevalence. METHODS: Data were available from two nationally representative surveys (South Africa, Zimbabwe), two behavioural intervention trials (Tanzania, Zimbabwe) and one population-based cohort (Uganda). Data on variables known or postulated to be risk factors for HIV infection were compared. RESULTS: Few risk behaviours were markedly more common in the high HIV prevalence populations. Risk factors more common in high HIV prevalence settings were genital ulcers and discharge, and women were more likely to report older male partners. DISCUSSION: Age mixing may be an important determinate of HIV prevalence in adolescents. Potential reasons for the general lack of association between other adolescent risk factors and adolescent HIV prevalence include adult HIV prevalence, misreported behaviour, different survey methods and other unmeasured adolescent behaviours. If adult factors dominate adolescent HIV risk, it would help explain the failure of behavioural interventions targeted at adolescents and suggests future interventions should include adults.

Increased risk of HIV-infection among school-attending orphans in rural Zimbabwe.

In Zimbabwe around 1.1 million children have been orphaned due to AIDS. We conducted a survey among school-attending youth in rural south-eastern Zimbabwe in 2003, and examined the association between orphaning and risk of HIV. We enrolled 30 communities in three provinces. All students attending Year 2 of secondary school were eligible. Each completed a questionnaire and provided a finger-prick blood specimen for testing for HIV-1 and HSV-2 antibodies. Female participants were tested for pregnancy. Six thousand seven hundred and ninety-one participants were recruited (87% of eligible); 35% had lost one or both parents (20% of participants had lost their father; 6% their mother; and 9% both parents). Orphans were not poorer than non-orphans based on reported access to income, household structure and ownership of assets. There was strong evidence that orphans, and particularly those who had lost both parents, were at increased sexual risk, being more likely to have experienced early sexual debut; to have been forced to have sex; and less likely to have used condoms. Fifty-one students were HIV positive (0.75%). Orphans were three times more likely to be HIV infected than non-orphans (adjusted odds ratio = 3.4; 95% confidence interval: 1.8-6.6). Over 60% of those HIV positive were orphaned. Among school-going youth, the rates of orphaning were very high; there was a strong association between orphaning and increased risk of HIV, and evidence of greater sexual risk taking among orphans. It is essential that we understand the mechanisms by which orphaned children are at increased risk of HIV in order to target prevention and support appropriately.

Bronchodilator effects of indacaterol and formoterol in patients with COPD.

BACKGROUND: Resting inspiratory capacity (IC) reflects static hyperinflation in chronic obstructive pulmonary disease (COPD). This study compared the effects of formoterol and indacaterol, a novel once-daily ultra-long-acting beta(2)-agonist (or ultra-LABA), on resting IC and forced expiratory volume in 1 s (FEV(1)). METHODS: Thirty patients with COPD (mean FEV(1)/FVC 0.49, mean FEV(1) 56% predicted) each inhaled three treatments (two in randomized sequence followed by open-label formoterol) on separate study days: a single dose of indacaterol 300 microg, matching placebo, and two doses of formoterol 12 microg 12 h apart. RESULTS: Indacaterol and formoterol increased FEV(1) and IC at all time points relative to placebo (p<0.001). Peak effects on FEV(1) were similar, while indacaterol had a greater effect on peak IC (31% vs 23% from pre-dose; p=0.034). Indacaterol had a greater effect than formoterol on FEV(1) at 8 h (1.47 vs 1.39 L; p=0.014) and 24 h (1.44 vs 1.35 L; p=0.003), and on IC from 4 to 24 h (differences of 0.13-0.19 L; p<0.05). At 24 h, indacaterol and formoterol increased FEV(1) by 17.7% and 7.5%, respectively, from pre-dose. CONCLUSIONS: This study discriminated between the effects on IC and FEV(1) of once daily indacaterol and twice daily formoterol. The greater effect of indacaterol on IC may translate into improved long-term clinical outcomes.

A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers.

OBJECTIVES: To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers. METHODS: 214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women. RESULTS: All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced. CONCLUSION: Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.

Risk factors associated with the salmonella status of dairy farms in England and Wales.

Between October 1999 and February 2001 the salmonella status of 449 dairy farms in England and Wales was determined by environmental sampling on up to four occasions. Data were collected through interview-based questionnaires, and multivariable analyses were used to identify risk factors associated with the farms either being Salmonella positive (prevalence data) or becoming Salmonella positive (incidence data). Region, herd size, month of visit and the lack of a clean visitor parking area were significantly associated with the prevalence of Salmonella species, and there was a significant trend towards an increased risk in late summer and autumn. The introduction of six- to 24-month-old cattle into a herd was associated with a reduced prevalence, but the introduction of adult cattle only, or calves with other cattle, was associated with an increased (but not significant) risk of farms being Salmonella positive. Month of visit, the lack of a clean visitor parking area, the use of part-time workers and not feeding calves whole milk, but not region or herd size, were associated with an increased incidence of salmonella.

Expression of the homebox gene Hex during early stages of chick embryo development.

Whole mount in situ hybridization studies were performed to investigate the expression pattern of the homeobox gene Hex (also known as Prh) during early stages of chick embryogenesis. At the time of laying, cHex transcripts are detected in Koller's sickle and the forming hypoblast. During gastrulation (HH stage 4), cHex is expressed in anteriorly-displaced hypoblast cells. At stage 6, cHex transcripts are observed within endoderm in an anterior are that overlaps the cardiogenic region. Later cHex expression is observed within pharyngeal endoderm immediately adjacent to the forming myocardium, in the endocardium and in the liver and thyroid gland primordia. cHex transcripts are also detected within blood islands beginning at stage 4, and in extraembryonic and intraembryonic vascular endothelial cells as vessels form.

Persistence of Salmonella Typhimurium DT120 in abattoir paddocks holding sheep.

In the summer of 1999 there was an outbreak of Salmonella Typhimurium DT120 in people in the north of England which was unusual in being sensitive to antimicrobial drugs. The outbreak was linked to mutton and lamb from a local abattoir, and attention focused on four holding paddocks used to retain sheep before slaughter. In November 1999, samples of soil and faeces were taken from these paddocks and samples of faeces were taken from the concrete race leading from them. Salmonella Typhimurium was isolated from 59 of the 100 samples. Between January 2000 and October 2000 seven visits were made to the abattoir at each of which 100 samples were taken from the paddocks and concrete race and examined for the presence of Salmonella. The paddocks remained heavily contaminated with S Typhimurium DT120 until April when there was a marked reduction in the recovery of the organism. By June the contamination was minimal and by August it had disappeared, and the organism was not recovered in September or October.

Prevalence, incidence and geographical distribution of serovars of Salmonella on dairy farms in England and Wales.

A study of randomly selected dairy farms in England and Wales was made between October 1999 and February 2001 to estimate the prevalence and incidence of Salmonella serovars. The farms were enrolled through five milk-buying companies, which represented 63 per cent of the dairy farms in England and Wales, and they were sampled on up to four occasions (449 farms at visit 1, 272 farms at visit 2, 251 farms at visit 3 and 243 farms at visit 4). In total, 19,296 samples of pooled faecal pats and slurry were collected. The farm-specific prevalence of all serovars of Salmonella ranged from 12.1 per cent (95 per cent confidence interval [CI] 8.2 to 16.0 per cent) to 24.7 per cent (95 per cent CI 19.4 to 30.1 per cent) at each visit. The most common serovars identified were Salmonella Dublin (3.7 to 6.6 per cent farm-specific prevalence at each visit), Salmonella Agama (1.8 to 7.6 per cent) and Salmonella Typhimurium (2.6 to 4.1 per cent) The prevalence varied by region and month of sampling and increased in late summer. The incidence rate of all serovars of Salmonella was 0.43 (95 per cent CI 0.34 to 0.54) cases per farm-year at risk. There was no significant difference between the incidence rates of the common serovars S Typhimurium (0.07), S Dublin (0.06) and S Agama (0.13). A total of 29 Salmonella serovars were isolated. Few of the isolates were resistant to the 16 antimicrobial agents tested, except the isolates of S Typhimurium dt104, of which 67.9 per cent were resistant to at least five of them.

Isolation of differentially expressed sequence tags from steroid-responsive cells using mRNA differential display.

Transcriptional control of steroid-regulated gene networks by nuclear receptor proteins results in the coordinate expression of a limited number of target genes. Although much is known about the structure and function of steroid receptors, relatively few cell-specific steroid-regulated genes have been isolated and characterized. In this paper we describe results using mRNA differential display reverse transcriptase PCR (DDPCR) to identify and isolate short cDNA sequence tags from thymocyte and prostate cells under various hormone conditions. Using this technique we have isolated several differentially expressed sequence tags (DESTs) from the mouse thymocyte cell line WEHI 7.2. Two of these DESTs, GIG10 and GIG18, are rapidly induced by dexamethasone within 2 h of treatment. GIG10 is a novel sequence and GIG18 is the mouse homologue of a human expressed sequence tag isolated from activated B lymphocytes. We also used DDPCR to isolate DESTs from androgen-modulated rat ventral prostate tissue, one of which we characterized and found to correspond to the 3' end of prostatic spermine binding protein mRNA, a known androgen-regulated gene. Modifications of the original DDPCR protocol, which we found can potentially decrease the frequency of isolating false-positive DESTs, are described and the merits of DDPCR, relative to other differential cDNA cloning strategies, are discussed.

The use of a simple haematoxylin and eosin staining procedure to demonstrate micronuclei within rodent bone marrow.

In the pharmaceutical industry, the majority of drug-safety evaluation studies are carried out preferentially in the rat. Consequently, drug absorption, distribution, metabolism and excretion profiles are available for this species. Such data usually have to be generated independently in the mouse, to allow validation of any micronucleus tests carried out in this species. Unfortunately, at the present time, the rat is not ideal for use in the micronucleus test due to the presence of large numbers of contaminating mast cell granules. Such granules are stained blue by the most commonly accepted staining procedure (May-Grunwald-Giemsa), and can be erroneously scored as micronuclei when they overlay erythrocytes. A simple haematoxylin and eosin staining procedure was evaluated in the micronucleus test using rats and mice. With this procedure, micronuclei stained blue-black and were readily distinguishable from cell inclusions resembling micronuclei such as mast cell granules, which remained unstained. Essentially similar quantitative data for micronucleus incidence and erythrocyte distribution were obtained in mice using this staining technique when compared to the use of the more established May-Grunwald-Giemsa staining procedure. However, unlike the use of the May-Grunwald-Giemsa procedure, the use of the haematoxylin and eosin stains allowed the accurate estimation of micronucleus incidence within the marrows of treated rats in the presence of contaminating mast-cell granules. Furthermore, unlike alternative procedures using fluorescent stains, the haematoxylin and eosin stained preparations are stable, constitute a permanent record of the experiment, and can be analysed at the convenience of the investigator. Therefore, this staining procedure may offer a useful alternative, for example, when evaluating rat bone-marrow smears within which considerable mast cell contamination can occur.

A trial of biosecurity as a means to control Campylobacter infection of broiler chickens.

We ran a controlled intervention trial to assess whether the risk of a broiler flock becoming infected with Campylobacter could be reduced by biosecurity measures. These were a standard method of cleansing and disinfecting the poultry house prior to stocking, and a standard hygiene protocol followed by all personnel who entered the study house during the flock's life. Thirty-nine flocks were allocated to intervention or control groups in a ratio of 1:2. Intervention flocks were asked to follow the specified biosecurity measures; all flocks were monitored weekly for Campylobacter infection. Analysis of infection at 42 days of age and over the life of the flock showed that the risk of thermophilic Campylobacter infection of broilers was reduced by over 50% in intervention flocks. Parts of the intervention identified as significant in the univariable analysis included twice weekly replenishment of boot dip disinfectant; potential independent risk factors identified included the location of ventilation fans and daily sanitisation of the water supply. The non-random allocation of 10 flocks to the control group may have introduced some study bias (the effect of which is discussed in the paper).

Faecal carriage of verocytotoxin-producing Escherichia coli O157 in cattle and sheep at slaughter in Great Britain.

A 12-month abattoir survey was conducted between January 1999 and January 2000, to determine the prevalence of faecal carriage of verocytotoxin-producing Escherichia coli O157 (VTEC O157) in cattle and sheep slaughtered for human consumption in Great Britain. Samples of rectum containing faeces were collected from 3939 cattle and 4171 sheep at 118 abattoirs, in numbers proportional to the throughput of the premises. The annual prevalence of faecal carriage of VTEC O157 was 4.7 per cent (95 per cent confidence interval 4.1 to 5.4) for cattle and 1.7 per cent (1.3 to 2.1) for sheep, values which were statistically significantly different from each other (P < 0.001). The organisms were recovered from both cattle and sheep slaughtered throughout the year and at abattoirs in all regions of the country, but the highest prevalence was in the summer. The most frequency recovered VTEC O157 isolates were phage types 2, 8 and 21/28 in cattle and 4 and 32 in sheep, the five most frequently isolated phage types associated with illness in people in Great Britain during the same period.

Prevalence of faecal excretion of verocytotoxigenic Escherichia coli O157 in cattle in England and Wales.

During the decade to 1999, the incidence of human infections with the zoonotic pathogen verocytotoxin-producing Escherichia coli O157 (VTEC O157) increased in England and Wales. This paper describes the results of a survey of 75 farms to determine the prevalence of faecal excretion of VTEC O157 by cattle, its primary reservoir host, in England and Wales. Faecal samples were collected from 4663 cattle between June and December 1999. The prevalence of excretion by individual cattle was 4.2 per cent (95 per cent confidence interval [CI] 2.0 to 6.4) and 10.3 per cent (95 per cent CI 5.8 to 14.8) among animals in infected herds. The within-herd prevalence on positive farms ranged from 1.1 to 51.4 per cent. At least one positive animal was identified on 29 (38.7 per cent; 95 per cent CI 28.1 to 50.4) of the farms, including dairy, suckler and fattening herds. The prevalence of excretion was least in the calves under two months of age, peaked in the calves aged between two and six months and declined thereafter. The phage types identified most widely were 4, 34 and 2, which were each found on six of the 29 positive farms.

Hospital admissions. Cold remedies.

The closure of a casualty department provoked a crisis in Hillingdon in the winter of 1996-97. Worried by the publicity, elderly people contacted the health authority to ask what would happen to them if they became ill. An all-day workshop, attended by elderly people, chief executives, nurses, social workers and representatives from the community health council and ambulance services, led to several initiatives, including a rapid response home service, which helped prevent a crisis last winter.

Low rate of active treatment of patients with hilar cholangiocarcinoma.

INTRODUCTION: The results of surgical resection and palliative chemotherapy use in hilar cholangiocarcinoma (HC) have been well publicised but the proportion of patients able to undergo these treatments and the comparative outcomes in a population of patients with HC are less well known. METHODS: Patients with HC were identified by review of all patients undergoing percutaneous cholangiography over a nine-year period (2002-2010) in a tertiary facility. The treatment undertaken and outcomes were recorded. RESULTS: Overall, 68 patients were identified (37 female) with a median age of 70 years. Forty-five (66%) were treated solely by insertion of a metal stent (median survival 4.73 months) and nine (13%) also received palliative chemotherapy (median survival 13.7 months). Persisting jaundice after stent insertion was noted in 18 of 35 patients (51%) tested within one month of death. Fourteen patients (21%) underwent surgical resection (median survival 20.2 months). CONCLUSIONS: Patients undergoing surgical resection had significantly longer survival than those receiving only a palliative stent but not compared with those also receiving palliative chemotherapy, with short-term follow-up. Only a third of patients, however, receive active treatment (surgery or chemotherapy) and improvements in long-term biliary palliation are needed.