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Biomedical subjects

S M Burns

Publications and source records attributed to S M Burns.

At least 37 records · Page 2Linked to original sources

Prevalence of hepatitis C in prisons: WASH-C surveillance linked to self-reported risk behaviours.

We used cross-sectional willing anonymous salivary hepatitis C (WASH-C) surveillance linked to self-completed risk-factor questionnaires to estimate the prevalence of salivary hepatitis C antibodies (HepCAbS) in five Scottish prisons from 1994 to 1996. Of 2121 available inmates, 1864 (88%) participated and 1532/1864 (82%) stored samples were suitable for testing. Overall 311/1532 (20.3%, prevalence 95% CI 18.3-22.3%) were HepCAbS-positive: 265/536 (49%, 95% CI 45-54%) injector-inmates but only 27/899 (3%, 95% CI 2-4%) non-injector-inmates. Among injectors, HepCAbS positivity was only slightly higher (p = 0.03) in those who had injected inside prison (53%, 162/305) than in those who had not (44%, 98/224). Those who began injecting in 1992-96 were much less likely to be HepCAbS-positive than those who started pre-1992 (31%, 35/114 vs. 55%, 230/422; p < 0.001). Even with injectors who began in 1992-96 but had never injected inside prison, the prevalence of hepatitis C carriage was 17/63 (95% CI 16-38%). The prevalence and potential transmissibility of hepatitis C in injector-inmates are both high. Promoting 'off injecting' before 'off drugs' (both inside and outside prison), methadone prescription during short incarcerations, alternatives to prison, and support of HepCAbS-positive inmates in becoming eligible for treatment, all warrant urgent consideration.

Adult↗

Loss of resistance to ingestion and phagocytic killing by O(-) and K(-) mutants of a uropathogenic Escherichia coli O75:K5 strain.

To determine the importance of the O75 O antigen and the K5 capsular antigen in resistance to phagocytosis and phagocytic killing, we used previously described O75(-) and K5(-) mutants from an O75(+) K5(+) wild-type uropathogenic Escherichia coli strain in phagocytosis assays with polymorphonuclear leukocytes (PMNs) and monocytes. At a 10-to-1 ratio of bacteria to phagocytes and in the presence of 10% serum, the parental strain GR-12 was resistant to both PMNs and monocytes over a 2-h incubation period. The O75(-) and K5(-) mutants were similar in sensitivity to killing by both PMNs and monocytes, decreasing in viability by 80% in the first hour. Yet, a significant difference in killing between the O75(-) and K5(-) mutants was observed in the first 15 min of incubation. The K5(-) mutant decreased in numbers by almost 60%, while the O75(-) mutant increased in numbers similarly to GR-12 in the first 15 min. The difference in killing was found not to be due to the rate of opsonization. To further determine the mechanism of resistance, a fluorescence assay was used to differentiate attached and internalized bacteria. The K5 capsule hindered the association of both the wild-type strain and the O75(-) mutant in the initial incubation time with PMNs. In conclusion, both the K5 capsule and O75 O antigen play crucial roles in resistance to phagocytosis over time.

Antigens, Bacterial↗

Making weaning easier. Pathways and protocols that work.

Clinical pathways and weaning protocols are useful tools for improving the care of patients requiring LTMV. The value of the pathways and protocols rests in large part on the systematic multidisciplinary nature of the tools. Nevertheless, for the pathways and protocols to truly affect outcomes, they must be carefully designed. It is critical that this occurs with the input of experts, and especially in the case of pathways, a seasoned knowledgeable clinician should guide the process. The success of such care delivery models rests with the quality of those who design, test, and revise them. If developed in a careful and thoughtful manner using the best science available, the pathways and protocols may truly be powerful tools for clinical practice.

Benchmarking↗

Pilot study to estimate survivors to 1995 of 1983-1984 prevalent hepatitis C infections in Lothian patients who tested positive or negative for hepatitis B surface antigen in 1983-1984.

OBJECTIVE: To estimate Hepatitis C prevalence in 1983-1984, and survivorship to 1 January 1995, of patients who tested were for Hepatitis B surface antigen in 1983-1984; and to do so according to risk of blood-borne virus transmission, including injector status. SETTING: Regional Virus Laboratory in Edinburgh. SAMPLES: Sera from 1983-1984 which were originally received for hepatitis B surface antigen testing and were classified as being at high, medium, or low risk for blood-borne virus transmission. RESULTS: Available 1983-1984 sera were tested from: (i) all 246 patients aged 15-55 years who were Hepatitis B surface antigen positive in 1983-1984; and (ii) a 10% systematic sample of 355 patients aged 15-55 years who had tested Hepatitis B surface antigen negative in 1983-1984. Patients' survival status at 1 January 1995 was established via the records of the Registrar General for Scotland. A Hepatitis C prevalent case cohort of 500 survivors to 1 January 1995- who were already infected with Hepatitis C in 1983-1984--could be established from group (i) and high or medium risk group (ii) patients with, as controls, 1460 individuals of similar age and risk group whose 1983-1984 sample was negative when tested retrospectively for Hepatitis C antibodies. Two hundred out of these 500 cases are not known to be injecting drug users, and the total would rise to 300 out of 600 if the case cohort were expanded to include low risk group (ii) surviving patients who were Hepatitis C antibody positive in 1983-1984. Between 82% (40/49) and 97% of injectors (57/59 if also HIV-infected) who were Hepatitis B surface antigen positive in 1983-1984 were already Hepatitis C antibody positive; and 72% (95% confidence interval (CI) 51%-93%) of injectors who were Hepatitis B surface antigen negative in 1983-1984 were nonetheless infected with Hepatitis C. Known drug user/contacts (excluding the major group of 59 identified HIV-infecteds) had Hepatitis C prevalence in 1983-1984 of 79% (53/67, with 95% CI 69%-89%), substantially higher than our prior assumption, which was 50%. Hepatitis C prevalence in 1983-1984 for patients who were not known to be injectors, were Hepatitis B surface antigen negative and were rated as moderate risk for blood-borne virus transmission was 13% (95% CI 4%-23%) and 8% (95% CI 3%-14%) even for low risk patients. Deaths by end December 1994 in 1983-1984 prevalent Hepatitis C infections were low: 2/35 (6%) for patients who were Hepatitis B surface antigen negative in 1983-1984 and 2/40 (5%) for Hepatitis B surface antigen positive injectors who were not HIV-infected. The latter rate with upper 95% confidence limit of 12% is modest when compared to the 10% mortality that would be expected of injectors over 11 years. CONCLUSION: Retrospective Hepatitis C testing of 1700 stored sera from high or medium risk group (ii) patients who were not known to be injectors will identify an estimated 200 (11.7%) who were already Hepatitis C infected in 1983-1984 and still alive on 1 January 1995. Retrospective Hepatitis C testing of 1300 low risk samples is expected to yield 100 (7.6%) apparently non-injector patients who were already Hepatitis C infected in 1983-1984 and still alive on 1 January 1995.

Adolescent↗

Early mortality of undiagnosed but prevalent (in 1983-1984) HIV infection in Lothian injectors who tested hepatitis B surface antigen positive (group A) or negative but were high risk for blood-borne virus transmission (group B) in 1983-1984.

OBJECTIVE: To estimate the early death-rate in HIV infected injectors whose HIV infection was during the injection-related HIV outbreak in Lothian region in Scotland in 1983-1984, which was coincident with Hepatitis B transmissions. SETTING: Regional Virus Laboratory in Edinburgh. SAMPLES: Sera from 1983-1984, originally received for Hepatitis B surface antigen testing, from individuals aged 15-55 years who were positive for Hepatitis B surface antigen in 1983-1984 (group A: census) or tested negative but were at high risk for blood-borne virus transmission according to their reason for testing (group B: 50% sample). METHODS: Survival status of individuals in groups A and B who had not been diagnosed with HIV disease by the end of December 1995 was checked against the deaths' records of the Registrar General for Scotland. Stored sera from 1983-1984 for patients who had died early (that is: in 1983-1984) were tested anonymously for HIV and Hepatitis C antibodies; and prior to testing, causes of death were scored by RPB according to the likelihood of their being HIV or drugs related. RESULTS: Three early deaths were found in group A patients who were not known to be HIV infected. None of the deaths was likely to be HIV-related; the sera were not tested in order not to risk deductive disclosure. Twenty-four early deaths were found in group B patients who were not known to be HIV-infected, five of whom were both HIV and Hepatitis C antibody positive, and one other was HIV antibody negative but Hepatitis C positive. Reclassification after unlinked anonymous testing and multiplying up of the group B results (to account for 50% sample) gave the early death rate (that is: in 1983-1986) as 15/155 (10%) for HIV-infected drug users (95% CI: 6%-13%). CONCLUSION: Injection-related outbreaks of HIV infection in Lothian in 1983-1984 and at Glenochil Prison in 1993 were each associated with substantial--estimated 10%--early death-rate in HIV-infected injectors. Both HIV outbreaks were coincident with Hepatitis B transmissions, which may be relevant. Further investigations of the death-rate within 2 years of HIV infection are warranted in other exposure categories than injection-related and for injectors who have been immunized against Hepatitis B.

Adolescent↗

The impact of chronic hepatitis C virus infection on HIV disease and progression in intravenous drug users.

OBJECTIVE: It is unclear whether co-infection with hepatitis C virus (HCV) can influence HIV related morbidity or mortality, either by accelerating HIV-related disease progression, or by contributing to end stage liver disease. The aim of this study was to examine the effect of HCV infection on the severity and progression of HIV disease in a cohort of Edinburgh intravenous drug users (IDUs). METHODS: In 240 (47%) out of 508 patients in the Edinburgh IDU cohort both HIV seroconversion dates and anti-HCV serology were available. Demographic variables and HIV-related progression between anti-HCV positive and anti-HCV negative groups were compared. Parameters assessed included clinical endpoints (time of development of significant symptoms attributable to HIV (CDC stage IV), time of development of AIDS, and time of death) and immunological endpoints (time of CD4+ counts dropping below 200/mm3, 100/mm3 and 50/mm3). RESULTS: Two hundred and two out of 240 patients (84%) had positive anti-HCV serology. There was no significant difference in the frequency of clinical and immunological endpoints between the anti-HCV positive and negative groups. Progression analysis from HIV seroconversion to HIV related clinical endpoints indicated that anti-HCV serology was not a significant factor influencing the rate of HIV progression (relative risks (RR) for anti-HCV positive group: seroconversion to CDC IV, 1.01; seroconversion to AIDS, 1.05; seroconversion to death, 0.90). Likewise, HCV serostatus did not significantly affect progression to immunological endpoints (RR for anti-HCV positive group: seroconversion to CD4+ < 200/mm3, 1.04; seroconversion to CD4+ < 100/mm3, 1.13; seroconversion to CD4+ < 50/mm3, 0.97. Overall mortality from end stage liver failure was 4% in HCV-seropositive patients without AIDS. This suggests that HCV has had a clinically (though not statistically) significant impact on overall survival in this cohort. CONCLUSIONS: This study demonstrates that HCV co-infection does not influence the rate of progression to either clinical or immunological endpoints in our population of HIV-infected drug users. Further data are required to assess the effect of HIV on thge progression of HCV-related liver disease.

Adult↗

Comparison of loss of serum resistance by defined lipopolysaccharide mutants and an acapsular mutant of uropathogenic Escherichia coli O75:K5.

In order to determine the importance of the O75 O antigen versus the K5 capsular antigen and the bimodal distribution of lipopolysaccharides (LPSs) in protection from complement-mediated lysis, mutants were made by insertion of a cat or an aphA gene in or in place of genes necessary for the synthesis of LPS and/or the K antigen of an O75(+) K5(+) uropathogenic Escherichia coli strain, GR-12. Mutations were made in the following genes: the rfbD gene (required for the synthesis of TDP-rhamnose), the rfbKM genes (necessary for the synthesis of GDP-mannose), the rol gene (regulating O-antigen length), the kfiC gene (encoding a putative glycosyltransferase), and the kfiC-rfbD genes. The resulting phenotypes were rough (O75(-)), core plus one partial O-antigen subunit, random distribution of O-antigen chain lengths, acapsular (K5(-)), and O75(-) K5(-), respectively. All five mutants and GR-12 were analyzed for survival in 80% serum. The GR-12 parent was resistant, exhibiting a 500% increase in numbers. The rol, rfbKM, rfbD, and kfiC-rfbD mutants were sensitive, experiencing 99%, 99.9%, 99.9%, and at least 99.999% killing, respectively, in the first hour. The kfiC mutant, however, increased in numbers in the first hour but experienced delayed sensitivity, decreasing in viability by 80% in the third hour. Single mutants were complemented with the wild-type gene in trans, showing restoration of the wild-type phenotype and serum resistance. Therefore, the O75 antigen is more important for survival in serum than the K5 antigen, and regulation of the O75 O-antigen chain length is crucial for protection of the bacteria from complement-mediated lysis.

Bacterial Capsules↗

Design, testing, and results of an outcomes-managed approach to patients requiring prolonged mechanical ventilation.

BACKGROUND: Outcomes management that uses critical pathways may decrease costs while improving outcomes for patients who require prolonged mechanical ventilation. OBJECTIVE: To study the efficacy of an outcomes-managed approach to weaning patients from prolonged (more than 3 days) mechanical ventilation. METHODS: A method of multidisciplinary care delivery was designed that included an outcomes manager, a care pathway for patients receiving mechanical ventilation, and weaning protocols. Data collection consisted of three parts: a retrospective review of 124 patients who required prolonged ventilation during a 1-year period before implementation of the care model, a 6-month prospective study in which 91 patients were alternately assigned by month to an outcomes-managed approach or a non-outcomes-managed approach, and a 6-month prospective study of 90 patients in which an outcomes-managed approach without alternate-month assignment was used. RESULTS: Outcomes management had no significant effect on total duration of mechanical ventilation or length of stay in the hospital, days of mechanical ventilation without tracheostomy, days of mechanical ventilation with tracheostomy, or outcome (weaned, withdrawal from mechanical ventilation, death, or transfer without weaning). However, duration of mechanical ventilation was 1.3 days shorter, length of stay in the hospital was 2.1 days shorter, and the cost per case was $ 3341 less for patients in the outcomes-managed group than for patients in the non-outcomes-managed group. CONCLUSION: Outcomes-managed care did not have a significant effect on duration of ventilation, length of stay in the hospital, or outcome in patients receiving long-term mechanical ventilation.

Adult↗

The long-term mechanically ventilated patient. An outcomes management approach.

As noted previously, prior to permanently instituting an outcomes approach, we compared the effects of such a model to a nonoutcomes-managed approach. The positive trend noted during the study interval has been sustained 2 years later, and the variables of cost, LOS, and ventilator duration (median = 9 days for DRG 475, 483 combined) for these patients continue to be favorably affected (see Figure 2). In addition, the outcomes-management model has been well accepted by all members of the health care team. The outcomes manager is a respected and valued member of the team and is central to the ongoing success of the approach. Although the clinical pathway is an essential tool for focusing and delineating multidisciplinary best-practice, the pathway (and processes of care contained within) must be continually evaluated and changed as needed. The pathway cannot be static if care is to be progressive. Essential to the process is a method of collecting and processing data in a timely way. Further, it is important that data collection, while important, not be the focus of the role of outcomes manager. Instead, the focus is the delivery of timely and effective care. Our current outcomes model applies to management of patients beyond the boundaries of the MICU or pulmonary suite. In other words, once weaned and transferred to a regular floor the outcomes manager no longer manages the patients (although she does track selected outcomes). Management of patients throughout hospitalization is a future goal, but we are convinced that this cannot be accomplished by a single outcomes manager. Although we are aware that other outcomes models do follow patients throughout the continuum of hospitalization and beyond, our highly clinically interactive model precludes that possibility. We are currently considering other similar unit-based positions to provide the desired continuity following discharge from the MICU or pulmonary suite. Despite our enthusiasm for the outcomes-management model, we recognize that other models may also result in comparable, favorable outcomes. It is important that those who adopt similar models of care delivery for managing patients requiring prolonged ventilation be scientific in their approach. Long-term studies of the efficacy of these models are essential if we are to truly provide quality care for our patients in the future. Unfortunately, as noted earlier, bias will be hard to overcome. Hospitals vested in rapidly establishing a stable financial bottom-line are likely to embrace quick applications. Projects with a true experimental design to evaluate efficacy, such as this one, will be rare in these organizations. Finally, it is critical that variables of interest be inclusive of specific quality indicators such as ventilator duration and complications rather than global institutional markers such as LOS. Standardization of variables of interest is imperative if outcomes are to be compared. For example, patients requiring long-term mechanical ventilation are identified by the AACN's Third National Study Group on weaning as those who require mechanical ventilation for more than 3 days. If we are to compare other variables of interest such as total ventilator duration, such as definition is essential or we will be comparing apples and oranges in the future. Provision of quality, cost-effective care for patients requiring prolonged ventilation is a true clinical challenge. Outcomes management is a multidisciplinary method of care delivery that is systematic and comprehensive in approach. Although little science exists related to the application of the model for patients requiring prolonged ventilation, preliminary reports are promising and warrant future applications and evaluation of the same.

Benchmarking↗

In vitro measurement of cytotoxic T cell activity does not predict clinical progression in paediatric HIV disease--two case studies.

Cytotoxic T cells are believed to be an important immune response in HIV infection, both in the initial response to viraemia, and in controlling HIV replication and maintaining clinical stability. We report here the detailed findings in two vertically infected children, from the Edinburgh perinatal cohort. Both were clinically stable for the first 7 years of life. One had vigorous HIV-specific cytotoxic T lymphocyte (CTL) responses, and non-lytic suppression, measured in vitro, while the second had no CTL activity against HIV. Despite her HIV-specific immunity, the first child had a declining CD4 count, and a high and fluctuating viral load, whereas the second child maintained a stable CD4 count, a low viral load and had a virus which could not be cultured in peripheral blood mononuclear cells (PBMC) in vitro. The first child subsequently progressed to AIDS and has now died, while the second remains clinically well. More detailed investigations showed the clinically stable child to be heterozygous for the CCR5 receptor, and to be HLA-B49--both of which markers have been associated with slow HIV disease progression. These findings question the role of CTL in maintaining stable HIV disease, and stress the need for immunological investigations to be considered in the light of the genetic make-up of the patient. They may also reflect a different immunopathogenesis of HIV disease in children compared with adults.

Adult↗

A volunteers in participatory sampling survey of weaning practices. The Third National Study Group on Weaning from Mechanical Ventilation.

The survey results of the VIPs membership described in this article add qualitative information to the growing body of scientific knowledge on weaning patients off ventilators. Clearly, quantitative studies exploring the efficacy of different weaning practices across the continuum must be done if we are to accurately compare practices and prescribe the "when" and "how" of weaning. To this end, the Third National Study Group is revising the proposed weaning model and model in order to further elucidate the state of the art and science of weaning.

Adult↗

The epidemiology of HIV infection in Edinburgh related to the injecting of drugs: an historical perspective and new insight regarding the past incidence of HIV infection derived from retrospective HIV antibody testing of stored samples of serum.

The pattern of sudden explosive outbreaks of HIV infection among drug users has been seen in several countries but is as yet incompletely understood. The epidemic of injecting drugs in Edinburgh was associated with at least four overlapping epidemics of blood-borne viruses (hepatitis B, C, D and HIV). Only hepatitis B was initially recognized, being followed by HIV and latterly hepatitis C. Retrospective HIV testing of stored samples of serum from clinically diagnosed patients with HIV has allowed the HIV epidemic to be delineated and more accurate seroconversion dates identified for most of the patients. There is evidence to suggest that the explosive drug-related Edinburgh HIV epidemic may have been self-terminating and that the epidemic in male drug users preceded that in female drug users by around 3 months. We suggest that the self-terminating nature of this epidemic may have been related to changes in drug injecting behaviour or to varying infectivity of the virus. This latter possibility should be explored in future studies of HIV transmission.

Adult↗