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Biomedical subjects

S Barton

Publications and source records attributed to S Barton.

At least 37 records · Page 2Linked to original sources

Virological failure among patients on HAART from across Europe: results from the EuroSIDA study.

OBJECTIVES: To monitor the response to highly active antiretroviral therapy (HAART) over time and the proportions of patients with poor virological control in order to help provide some insight into drug resistance. DESIGN: Analysis of data from the EuroSIDA study; an observational study initiated in 1994 of almost 8500 patients with HIV from across Europe. METHODS: Patients who initiated HAART, and had both a CD4 lymphocyte count and viral load measured in the 3 months prior to starting HAART, were included in analyses. The proportion of patients with a poor virological response (defined as a viral load of > 10,000 copies/ml, using either a single measure or two consecutive measures) at 16 and 48 weeks was determined. Multivariate logistical regression was used to determine the factors associated with a poor virological response at both time points. RESULTS: Median CD4 cell count at starting HAART was 218 cells/mm3 [interquartile range (IQR), 113-327 cells/mm3] and median viral load was 4.36 log10 copies/ml (IQR, 3.57-5.04 log10 copies/ml). At 16 weeks, 16% had a viral load of > 10,000 copies/ml based on a single viral load measure and 10% if the more stringent definition of two consecutive viral loads above this level was used. At 48 weeks these proportions were 19% and 13%, respectively. Compared with patients from Southern Europe, patients from both Central and Northern Europe had approximately half the chance of a poor virological response at 16 weeks (odds ratios 0.53 and 0.47, P = 0.0015 and P < 0.0001, respectively), while at 48 weeks both regions still had approximately a 25% reduced chance of a poor virological response, but this was no longer statistically significant (odds ratio 0.77 and 0.75, P = 0.17 and P = 0.13, respectively). CONCLUSIONS: There were marked difference in virological response to HAART across regions of Europe, which may be partly explained by regional differences in access to HAART and utilisation. If drug resistance is closely related to virological failure, these results may help to provide an early insight into the potential problem of drug resistance across Europe. Continued follow-up is essential to monitor patients with poor virological control.

Anti-HIV Agents↗

Evaluation of sperm washing as a potential method of reducing HIV transmission in HIV-discordant couples wishing to have children.

OBJECTIVE: A number of discordant couples, in whom the man is HIV positive and the woman is HIV negative, wish to have children. To conceive they must abandon protected sex, posing a risk of HIV transmission to the woman and so to the child. In such circumstances purification of spermatozoa ('sperm-washing') to inseminate the woman artificially has been proposed as a method of reducing the risk of transmission. Here we evaluate whether this does represent a true risk reduction. METHODS: Semen samples from HIV-positive patients were separated into spermatozoa, non-sperm cells (NSCs) and plasma fractions. The amount of viral RNA present in each fraction was measured and compared with the level in the peripheral blood. Each fraction was also assessed for the presence of proviral DNA. The ability of spermatozoa to be infected was assessed by evaluating for the presence of HIV receptors, i.e. CD4, CCR5 and CXCR4 on the surface of the sperm, by flow cytometry. RESULTS: A poor correlation was found between the levels of HIV in blood and semen. Within the semen the virus was restricted to the plasma and/or NSCs. All spermatozoa were negative for viral RNA or proviral DNA. Spermatozoa did not express significant levels of CD4, CCR5 or CXCR4, suggesting that they are unlikely to be major targets for HIV infection. CONCLUSIONS: These data suggest that spermatozoa are not major targets of HIV infection. Purifying spermatozoa reduced the level of HIV RNA and proviral DNA to below the detection limit of the assays irrespective of the amount of virus present in the unfractionated semen. On the basis of these data we would recommend 'sperm-washing' followed by insemination as a safer alternative to natural conception for HIV-discordant couples wishing to have children.

DNA, Viral↗

The association of some practice characteristics with antibiotic prescribing.

BACKGROUND: Antibiotic prescribing in general practice is often considered inappropriate, and its volume excessive. Considerable variation in antibiotic prescribing volume and costs exists among practices. OBJECTIVE: To investigate some factors behind the variation in antibiotic prescribing among general practices, by examining the contribution to this variation of the level of deprivation in the practice population, training status, partnership status, and fundholding status. METHOD: Analysis of prescribing data (PACT) from 351 practices in the Mersey region for the year ending March 1991 and the year ending March 1994; prescribing data standardized for variation in practice population demography. Use of multiple linear regressions to investigate the variation among practices in standardized prescribing volume and standardized prescribing costs, in both years. RESULTS: Level of deprivation, training status and partnership status contributed to the models explaining variation in prescribing volume. The same variables contributed to the model explaining variation in prescribing costs in the year ending March 1991. For the year ending March 1994, level of deprivation, training status, and fundholding status contributed to all models. CONCLUSION: Higher levels of antibiotic prescribing occur in practices serving more deprived communities, in single-handed practices, and in non-training practices. These higher levels of prescribing may be due to higher levels of morbidity, but may also reflect the organization and attitudes of these practices.

Journal Article↗

Therapeutic substitution and therapeutic conservatism as cost-containment strategies in primary care: a study of fundholders and non-fundholders.

BACKGROUND: General practice (GP) fundholders contained prescribing costs by restricting the rise in volume of prescribing and by increasing generic prescribing. It is uncertain whether they used more sophisticated approaches to medicine choice in attempts to contain costs. AIM: To examine whether fundholding practices have adopted medicine-specific strategies to contain prescribing costs--i.e. switching to less expensive but equally effective medicines or resisting the uptake of newer more expensive medicines--by examination of the prescribing of ulcer-healing and antidepressant medicines in the period before and after practices became fundholders. METHOD: Comparison of prescribing data of 52 fundholding practices before fundholding and after fundholding with that of matched non-fundholding practices. Measures examined were prescribing costs (net ingredient cost in each therapeutic area per ASTRO-pu); prescribing volume (defined daily doses per ASTRO-pu); the proportion of all ulcer-healing medicines prescribed as cimetidine, ranitidine, nizatidine, and as proton pump inhibitors; and the proportion of all antidepressant medicines prescribed as selective serotonin re-uptake inhibitors. RESULTS: In comparison with non-fundholding practices, fundholders increasingly prescribed less expensive medicines (cimetidine and nizatidine) within the class of histamine2 receptor antagonists. However, fundholders adopted proton pump inhibitors or selective serotonin re-uptake inhibitors at the same rate as non-fundholders. CONCLUSION: Fundholders have used therapeutic substitution with medicines of equal effectiveness to contain prescribing costs. There is no evidence that fundholders have been slower than non-fundholders to use newer, more expensive medicines.

Aged↗

Addressing barriers to change: an RCT of practice-based education to improve the management of hypertension in the elderly.

BACKGROUND: In the future, primary care groups (PCGs) will have to consider how best to apply audit and education to fulfil their commitment to clinical governance and to facilitate the implementation of research findings. AIM: To establish whether an exploration of 'barriers to change' can enhance the effectiveness of an educational intervention designed to improve the management of hypertension in the elderly. METHOD: A parallel-arm, randomized, single-blind, controlled trial of practice-based educational visits in 18 practices. These practices had previously taken part in a multipractice audit of the management of hypertension in the elderly. Both groups received outreach visits in their own practice, during which they received the results of the previous audit. The nine 'intervention' practices were encouraged to explore barriers that would prevent them from implementing pertinent research findings. The control group was not encouraged to do this. The main outcome measure of the trial was determined in advance as 'the stated management of systolic hypertension in patients aged 70 to 79'. A secondary endpoint was the stated management of a specific patient scenario. The endpoints were tested by questionnaire before and after the educational intervention. RESULTS: For the primary endpoint, there was a statistically significant difference in the stated threshold for treating systolic hypertension between intervention and control groups after the visits (161.8 mmHg versus 167.2 mmHg; P = 0.007). For the secondary endpoint, there was also a statistically significant difference between the two groups, after the visits, in their willingness to treat a 70-year-old male with mild hypertension (89% of doctors would treat in the intervention group versus 57% in the control group; P = 0.047). CONCLUSION: The effectiveness of an educational intervention is significantly improved by addressing the barriers preventing practitioners from implementing the findings of research.

Aged↗

A study of imidazole-based nuclear magnetic resonance probes of cellular pH.

A number of imidazole-based compounds were tested for their utility as (1)H NMR molecular probes of intracellular pH. Imidazole, previously found useful as a probe of erythrocyte pH, reported a pH in perfused canine glioma cells that was more than 1 pH unit lower than that reported by inorganic phosphate, consistent with the known lysosomal compartmentation of the molecule. Imidazole acetate, also proposed as an NMR probe of cellular pH, was found not to enter the cells of this study. Histidine was found to be readily taken up by cells and reported a pH consistent with that reported by inorganic phosphate. Using the chemical shift of the histidine H2 proton in cells incubated with 10 mM histidine, cellular pH measurements could be obtained in less than 1 s. This compares quite favorably with the measurement time, typically several minutes, needed to assess in vivo pH by (31)P NMR. The use of histidine as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH.

Animals↗

Survival in 2367 zidovudine-treated patients according to use of other nucleoside analogue drugs. The EuroSIDA Study Group.

To evaluate survival according to use of different nucleoside drugs in a routine clinical setting, we studied a large group of zidovudine-treated patients seen in clinics across Europe. A total of 3128 subjects was recruited to the observational, prospective EuroSIDA study in May 1994. These were consecutive patients (up to a predefined limit) seen at outpatient clinics in 37 centers from 16 European countries and followed at 6-month intervals by use of standardized forms completed by clinicians at the respective centers. This report concerns 2367 subjects who began antiretroviral therapy with a regime that included zidovudine either before study entry or during the course of follow-up. Cox proportional hazards models were fitted, with use of other antiretroviral drugs, CD4 count, and date of development of AIDS fitted as time-dependent covariates. Survival times from start of therapy were left truncated at study entry to avoid survival bias. In addition to zidovudine, antiretroviral drugs used included didanosine (ddI) (n = 1119; median 1.6 years after starting zidovudine), dideoxycytidine (ddC) (n = 592; median 1.9 years after starting zidovudine), stavudine (d4T) (n = 241; median 2.9 years after starting zidovudine) and lamivudine (3TC) (n = 33 ; median 2.7 years after starting zidovudine). Of the 2367 patients, 613 died during follow-up. Overall, risk of death was reduced in those zidovudine-treated patients who began at least one other nucleoside analogue drug with or after taking zidovudine (relative hazard [RH], 0.61; 95% confidence interval [CI], 0.51-0.72, adjusting for CD4 count, development of AIDS, and age). Fitting each drug separately, there was a larger association with reduced mortality for starting 3TC (RH, 0.41; 95% CI, 0.28-0.62) than for starting ddl (RH, 0.79; 95% CI, 0.67-0.93), ddC (RH, 0.74; 95% CI, 0.59-0.92) or d4T (RH, 0.67; 95% CI, 0.49-0.91). These results suggest that the beneficial effect of nucleoside combination therapy identified in controlled trials can be seen in routine clinical practice.

Adult↗

The influence of practice characteristics on the prescribing of benzodiazepines and appetite suppressant drugs.

BACKGROUND: The prescribing volume of benzodiazepines and of appetite suppressant drugs have been suggested as possible indicators of prescribing quality. OBJECTIVE: To investigate the variation among general practices in the prescribing of benzodiazepines and appetite suppressants by examining the contribution to this variation of training status, partnership status, fundholding status and the level of deprivation in the practice population. METHODS: Prescribing data (PACT) were analysed for 350 practices in the former Mersey Regional Health Authority, for the year ending March 1991 and the year ending March 1994. Data were first standardized for variation in practice population demography. Multiple linear regressions were used to investigate the variation among practices in standardized prescribing volume in both years. RESULTS: For benzodiazepines, training status and partnership status contributed to all models and level of deprivation contributed to some (percentage of variation explained for year ending March 1991: 10% to 21%, year ending March 1994: 8% to 20%). For appetite suppressant drugs fundholding status and an interaction between training status and level of deprivation contributed to all models in both years (percentage of variation explained for year ending March 1991: 19% to 20%, year ending March 1994: 20% to 21%). CONCLUSION: The prescribing of benzodiazepines is lower in training practices, in multi-partner practices and in practices serving a less deprived population, while the prescribing of appetite suppressant drugs is lower in training practices and in fundholding practices. Variation in prescribing knowledge, organizational and management capabilities and patient demand may be explanatory factors.

Journal Article↗

Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study.

BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.

Acetylcysteine↗

Health promotion in different medical settings: women's health, community health and private practice.

This paper describes the health promotion role of doctors in two medical practice settings: women's and community health centres, and fee-for-service practice. It proposes the establishment of divisions of primary health care in Australia which would be multi-disciplinary and focus on community-wide health issues. The paper is based on data from an interview survey of medical practitioners who had worked in metropolitan Adelaide women's and community health centres and from a questionnaire survey of GPs in private practice. The types of health promotion activity by the doctors in the different settings are discussed. It is concluded that private practice GPs are involved primarily in providing health education advice to individual patients. Doctors within women's and community health centres are more likely to report involvement in group health promotion activity and broader community development initiatives. The study concludes that health promotion which focuses on the health of the local community is best conducted within multidisciplinary health centres. GPs in private practice are limited by the structure of their setting (particularly the fee-for-service basis and reliance on a single discipline) to health promotion which focuses on the needs of individual patients.

Attitude of Health Personnel↗

Findings of mild traumatic brain injury in combat veterans with PTSD and a history of blast concussion.

Veterans with chronic posttraumatic stress disorder were evaluated for a history of blast concussion, controlling for confounding conditions. Electroencephalograms were analyzed by discriminant function for traumatic brain injury. A difference was found in discriminant scores between veterans with and without blast concussion. More members of the blast group had attentional symptoms and attentional dysfunction. Combat veterans with a remote history of blast injury have persistent electroencephalographic features of traumatic brain injury as well as attentional problems. The authors hypothesize that these constitute a type of chronic postconcussive syndrome that has cognitive and mood symptoms overlapping those of posttraumatic stress disorder.

Adult↗

Development of an economic model for the management of upper gastrointestinal disease in primary care. Preliminary findings.

Health economic models for identifying therapeutic options that maximise health benefits from limited healthcare resources are being developed in a number of therapeutic areas. The development of such a model for upper gastrointestinal (UGI) symptoms to support decision-making by primary care clinicians is of particular importance, given the prevalence of this symptomatology. This economic model was based upon the clinical guidelines aimed at improving the management of UGI disorders at the primary care level that were developed by the International Gastro Primary Care Group. This paper discusses the derivation, methodology and results of the economic model developed to assess the resource implications arising from these clinical guidelines. In order to construct the economic model, it was necessary to identify the following: every therapeutic pathway followed by patients resource use along each pathway the probabilities of following alternative pathways. One crucial factor underlying the interpretation of results obtained from any economic model is the time period covered by the model. The model presented here analysed the initial 12-month treatment period of 'new' patients presenting with UGI symptoms. In order to test the implications of a longer term perspective, the model is currently being developed to analyse resource use over a 24-month period. The model demonstrates that utilising the predominant symptom approach to the diagnosis and treatment of patients with UGI disorders appears to provide significant benefits in terms of patient management and effective resource use. This factor, together with the more intensive use of Helicobacter pylori eradication therapy, provides the potential to reduce the cost of drugs for the treatment of UGI disorders by approximately 15% in the UK. A major strength of the model is its adaptability to a wide range of clinical and cost scenarios. Such adaptability enables the model to effectively reflect the potential resource implications in countries exhibiting significantly different levels of cost and patient management. In this manner, the model provides one valuable method by which clinicians can be supported in optimising the management of UGI disorders within current resource constraints.

Cost-Benefit Analysis↗

Self-administration of drugs for cystic fibrosis.

Self-administration of medication encourages individuals to participate in their own health care and provides structure for regular assessment and teaching about their drugs. Patient-friendly drug leaflets can provide consistent information to patients cared for by a number of staff. Self-administration studies found in the nursing literature must be interpreted cautiously because of the lack of true experimental trials.

Adult↗

The management of hypertension in the elderly by general practitioners in Merseyside: the rule of halves revisited.

BACKGROUND: Treatment of hypertension in the elderly significantly reduces cardiovascular events and confers greater absolute benefit compared with treating younger adults. However, this group has been undertreated in the past. AIM: To perform a reliable and valid multipractice audit of the current management of elderly hypertensive patients. METHOD: An observational study conducted as multiple standardized audits in general practices. The notes of 6139 patients aged 65 years or over from 76 general practices in Merseyside were examined to determine the percentage of elderly patients who had their blood pressure recorded. The percentages of hypertensive patients who were diagnosed, treated, and controlled was also recorded. RESULTS: Eighty-one per cent of the sample had their blood pressure recorded. Fifty-three per cent of patients over the age of 65 were identified as hypertensive; 64% of hypertensive patients are receiving antihypertensive medication and 54% of treated hypertensive patients can be considered controlled. However, very small changes in the criteria used to define blood pressure control have dramatic effects on the results. Digit preference and the number of available blood pressure recordings also significantly affect the results. CONCLUSION: The management of hypertension in the elderly by Merseyside general practitioners (GPs) gives better results than predicted by the 'rule of halves'. Elderly hypertensive patients are more likely to be detected and treated, but only half achieve control to 160/90. The results are particularly sensitive to the degree of digit preference, the number of available recordings, and to the precise definition used for control.

Aged↗

Auditing the management of hypertension in British general practice: a critical literature review.

Hypertension is a common condition almost exclusively managed by general practitioners (GPs), making it an ideal subject for practice-based audit. However, the conduct and interpretation of such audits is complex. Even minor variations in methodology can produce dramatic differences in results obtained. We used a focus group of seven GPs with a special interest in audit to establish a standardized method for the planning and reporting of audits for the management of hypertension. In order to enhance the reliability and comparability of hypertension audits, 13 key areas of audit methodology were produced by the focus group. Eleven audits were identified in a literature search using pre-determined selection criteria. These were then assessed to compare their methodology with the criteria produced by the focus group. None of the recently published audits in this subject covered all of the key areas (range: 27-65% of the areas covered). One key area, that of digit preference, was not mentioned by any. Other problematic key areas included the selection of patient records without bias, the determination of the prevalence of hypertension, the number of recordings used to determine the diagnosis of hypertension and its subsequent control, the time period examined by the audit, and the approach taken to notes containing an inadequate number of blood pressure recordings. Significant variability in the methods used by different authors in these key areas calls into question the reliability of their results and makes comparisons between them very difficult. We propose a standardized method for hypertension audits comprising 13 key areas, which will enhance the reliability of results and facilitate such comparisons.

Family Practice↗