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Biomedical subjects

P Griffiths

Publications and source records attributed to P Griffiths.

At least 19 recordsLinked to original sources

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience.

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.

Adult↗

Illicit drugs and driving: prevalence, beliefs and accident involvement among a cohort of current out-of-treatment drug users.

Drug-driving behaviour among out-of-treatment dependent drug users has not been investigated while a theoretical perspective on the propensity of certain drug users to drive while impaired has not been suggested. This paper examines illicit drugs and driving behaviour and accident involvement among out-of-treatment current drug users. Psychological evidence of belief-based mechanisms to account for the decision to drive while impaired by drugs are provided. A total of 210 out-of-treatment current drug users were interviewed in a non-clinical setting by privileged access interviewers. Questionnaire measures were: current illicit drug use, severity of dependence, illicit drugs and driving behaviour, impaired and unimpaired accident involvement and beliefs and perceptions about the impairing effects of a number of illicit drugs. Analyses are restricted to participants who reported driving during the previous 12 months (n = 71). Fifty-eight participants (81.7%) reported driving immediately after consuming illicit drugs, primarily heroin and cannabis. Of these 41.4% (n = 24) had at least one road accident as a driver, 15 of whom (62.4%) reported accident involvement following recent drug consumption. Belief-based results showed that participants who reported never driving after using illicit drugs perceived heroin, methadone and alcohol to be greater significance for accident risk and driving skills impairment than other drugs. Those drivers who reported drugs and driving behaviour believed only alcohol to be significantly more impairing than other drugs. Findings indicated that illicit drugs and driving behaviour is common among out-of-treatment drug users. Accident involvement among this cohort is characterised by the previous consumption of illicit substances. Differential beliefs about the effects of drugs on driving performance and accident risk were shown to be dependent upon frequency of drugs and driving behaviour. Results are discussed in terms of experiential factors and consistency theories of attitude formation and change.

Accidents, Traffic↗

The effectiveness of intermediate care in a nursing-led in-patient unit.

In order to assess the potential for a nursing-led in-patient unit (NLIU) to substitute for a period of care in the acute hospital environment and promote recovery before discharge, a randomised controlled trial was conducted. The setting was an acute inner London hospital trust, part of the UK's national health service. Of patients referred to a NLIU from acute wards, 80 were randomly assigned to usual care (remain in normal hospital system) and 97 to the NLIU (nursing-led care with no routine medical involvement). Patients were identified as medically stable but in need of additional nursing intervention by referring medical staff prior to full nursing assessment of suitability. Outcomes compared included functional dependence (Barthel Index), discharge destination and length of hospital stay. Inputs from nursing, paramedical and medical staff were measured. There was no significant difference in functional independence at discharge (p0.05). Patients undergoing usual care stayed in hospital for less time (mean difference 18 days, p<0.01) but the same number of patients were in hospital 90 days after recruitment (23% NLIU, 24% usual care p0.05) due to re-admissions. The model of care implemented differed considerably from that described in the literature with the NLIU having significantly fewer qualified nurses (RNs). Although the anticipated benefits of the NLIU were not demonstrated, the study does not conclude that the model should be rejected. Factors driving length of stay need to be further investigated, as does the possibility of post-discharge benefits. The NLIU does offer some potential to substitute for acute care but also appears to substitute for a period of primary care.

Activities of Daily Living↗

Influences on length of stay in intermediate care: lessons from the nursing-led inpatient unit studies.

A recent study found that intermediate care in a nursing-led in-patient unit (NLIU) led to dramatically increased hospital stay when compared to usual care in a hospital. This is despite a large body of work across a variety of settings, including the pilot for that same study, which suggests that the NLIU is effective. This paper presents a series of exploratory analyses that aim to explore the findings further. A number of changes were identified in the functioning of the NLIU between the main and pilot study including patient population, leadership and staffing levels. Two ANCOVA analyses reveal that while performance of the NLIU declined between the two studies, that of usual care improved dramatically. Extended lengths of stay appear to be associated with the NLIU's location on a satellite site rather than the model of care per se. Reduction in the staffing levels on the NLIU and a change in patient population may well explain the findings.

Humans↗

Stable periodic vortex shedding studied using computational fluid dynamics, laser sheet flow visualization, and MR imaging.

Recirculating and detached flow patterns close to the carotid bifurcation are thought to play an important role in the development of carotid stenoses by promoting atherosclerosis. The aim of this study was to investigate a flow regime with strong transient characteristics, including vortex shedding and transport to develop methodologies appropriate to the analysis of carotid stenoses. The existence of a regular periodic vortex street behind a cylindrical flow obstruction was predicted and analysed in detail by Theodore van Karman in the early 20th century. This model was chosen in our study for both ease of phantom construction and of theoretical modelling using finite element computational fluid dynamics (CFD). The results of the theoretical calculations have been compared with two methods of flow visualization-laser sheet imaging and real-time echo planar magnitude MR imaging. Flow was investigated over a range of Reynold's number from 40 through 400 through which vortex shedding is predicted. Good overall agreement was obtained between the theoretical (16 mm-CFD) and experimental (16+/-2 mm-Laser, 17+/-2 mm-MRI) estimates of the Karman Vortex street wavelength for a Reynolds number of 200.

Carotid Arteries↗

Diversion of prescribed drugs by drug users in treatment: analysis of the UK market and new data from London.

AIMS: To review the available knowledge about the diversion to the illicit market of drugs prescribed to drug users in treatment in the United Kingdom, and to identify aspects of the London market in more detail. METHOD: An analysis of the literature and new data in terms of the extent and nature of the market, the practicalities of trade, motives for selling, reasons for demand and the influence of variations in prescribing practice on diversion. Prices of diverted prescription drugs and details of their availability in London are presented. FINDINGS: The size of the market is substantial and appears to involve a large number of individuals, each diverting small amounts of their own prescribed drugs. Major motives for selling prescribed drugs are to raise funds to buy other, preferred, drugs and/or to pay for a private prescription. Buyers in treatment appear to be motivated by a desire to supplement their own prescriptions because they are dissatisfied with the particular drug prescribed, dosage and formulation. Drug users in treatment can exploit the variations in prescribing practice--such as how much 'take-home' medication they are allowed and whether tests are conducted to ascertain if they are using it themselves--and divert their prescribed drugs. Prices of prescription drugs on the illicit market can fluctuate on a daily basis according to supply and demand. CONCLUSIONS: The results suggest that, to be effective, diversion control must simultaneously involve deterrents from prescribers, drug treatment services, law enforcement agencies and dispensing pharmacists. Finally, some suggestions for further research on this under-studied issue are suggested.

Benzodiazepines↗

Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis.

CONTEXT: Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. OBJECTIVE: To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. DESIGN: Prospective nonrandomized interventional trial performed from July 1997 to August 1999. SETTING: Clinical Center of the National Institutes of Health, Bethesda, Md. PATIENTS: Fourteen patients with stable CMV retinitis and HIV infection and CD4+ cell counts higher than 0.1 5 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. INTERVENTIONS: Discontinuation of specific anti-CMV therapy. MAIN OUTCOME MEASURES: Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. RESULTS: Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. CONCLUSIONS: Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4+ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.

AIDS-Related Opportunistic Infections↗

Preventing opiate overdose fatalities with take-home naloxone: pre-launch study of possible impact and acceptability.

AIMS: Before proceeding with the introduction of an overdose fatality prevention programme including teaching in cardio-pulmonary resuscitation and distribution of naloxone, a pre-launch study of treatment and community samples of injecting drug misusers has been undertaken to establish (i) the extent of witnessing overdoses, (ii) the acceptability of naloxone distribution and training; and (iii) the likely impact of such measures. DESIGN AND SETTING: Structured interview of two samples: (a) a community sample of injecting drug misusers recruited by selected privileged access interviewers (PAI) and interviewed by them in community settings and (b) a treatment sample of opiate addicts recruited from our methadone maintenance clinic (interviewed by in-house research staff). PARTICIPANTS: (a) Three hundred and twelve injecting drug misusers with a history of having injected and currently still using injectable drugs; and (b) 142 opiate addicts in treatment at our local catchment area methadone maintenance clinic in South London. FINDINGS: History of personal overdose was found with 38% of the community sample and 55% of the treatment sample--mainly involving opiates and in the company of friends. Most (54% and 92%, respectively) had witnessed at least one overdose (again mostly involving opiates), of whom a third had witnessed a fatal overdose. Only a few (35%) already knew of the existence and effects of naloxone. After explanation to the treatment sample, 70% considered naloxone distribution to be a good proposal. Of the 13% opposed to the proposal, half thought it may lead them to use more drugs. Eighty-nine per cent of those who had witnessed an overdose fatality would have administered naloxone if it had been available. We estimate that at least two-thirds of witnessed overdose fatalities could be prevented by administration of home-based supplies of naloxone. CONCLUSIONS: Substantial proportions of both community and treatment samples of drug misusers have witnessed an overdose death which could have been prevented through prior training in resuscitation techniques and administration of home-based supplies of naloxone. Such a new approach would be supported by most drug misusers. On the basis of these findings, we conclude that it is appropriate to proceed to a carefully constructed trial of naloxone distribution.

Adult↗

Self-reported overdose among injecting drug users in London: extent and nature of the problem.

AIMS: To estimate the extent and nature of overdose and factors associated with overdose among injecting drug users in London. DESIGN: Three hundred and twelve current injecting drug users were recruited and interviewed in community settings by a team of "privileged access interviewers". MEASUREMENTS: A structured questionnaire was used that covered the following areas: demographic characteristics, drug use, injecting behaviour, sharing practices, severity of drug dependence, experience of overdose, injecting-related health problems and treatment history. FINDINGS: The results showed that experience of overdose was common (38%). A majority (54%) had witnessed someone else overdose. Overdosing was not a solitary experience; over 80% of subjects who had overdosed had done so in the presence of someone else, but only 27% reported ambulances having been called. Factors found to be associated with overdose were: age at which injecting began; gender (women being more likely to experience overdose); use of alcohol; and polydrug injection. The overall rate of overdosing was one per 6 years of injecting; however, once an individual had an overdose the chance of having another increased. The risk of experiencing a first overdose fell with years of injecting. CONCLUSIONS: Harm-reduction interventions with drug injectors should educate users on the risk factors associated with overdose and actions that should be taken when someone has overdosed. Interventions designed to reduce the risk of overdose may be more effective if they are differentially targeted on drug injectors who have already experienced an overdose.

Adolescent↗

Substance use among young people: the relationship between perceived functions and intentions.

AIMS: To explore the relationship between young people's use of psychoactive substances, perceived functions for using, the experience of negative effects, and the influences of these variables on their intention to use substances again. DESIGN: Cross-sectional survey in which respondents were purposively recruited using snowballing techniques. SETTING: Interviews were conducted in informal community settings. PARTICIPANTS: One hundred young drug and alcohol users (45 females) aged between 16 and 21 years. MEASUREMENTS: Life-time prevalence, current frequency and intensity of substance use and intentions to use again were assessed for four target substances (alcohol, cannabis, amphetamines and ecstasy) together with measures of the perceived functions for their use and peer substance involvement. FINDINGS: The life-time experience of negative effects from using the assessed substances was not found to correlate with current consumption patterns. Statistically significant associations were observed between the reported frequency of taking substances and the perceived social/contextual and/or mood altering functions cited for their consumption. The substance use function measures together with the reported extent of peer use were significant predictors of intentions to use again. CONCLUSIONS: If these findings are confirmed in larger studies, educational and preventative efforts may need to acknowledge the positive personal and social functions which different substances serve for young people. The results also call into question the extent to which the experience of negative effects influences future patterns of use.

Adolescent↗

Heroin chasers and heroin injectors: differences observed in a community sample in London, UK.

"Chasing the dragon" has spread rapidly as a method of use of heroin in many countries over the last quarter of a century, and is now the most widely used method of heroin use worldwide. However, little examination has been made of the differences in characteristics and drug-taking patterns between heroin chasers and injectors. In this study, a comparison is made of the personal, social and drug-taking characteristics of heroin users in a community sample (i.e., not drawn from treatment services, contacted through a range of non-treatment access routes), according to whether the heroin user was currently a heroin chaser or injector, and according to whether or not they had ever injected. Data were examined on 400 heroin users contacted and interviewed in South London by privileged access interviewers using a structured interview schedule. Severity of dependence was measured using the Severity of Dependence Scale (SDS). Heroin chasing and injecting were almost equally prevalent among this community sample. Of the 400 heroin users, 178 (44.5%) identified "chasing the dragon" as their current route of heroin use, and 222 (55.5%) injecting. Heroin chasers were younger, though they had first used at an older age, had a larger proportion of non-using friends, and contained larger proportions of women and people of Afro-Caribbean origin. Injectors were using higher daily doses and were significantly more likely to be using on a daily basis. Those who had never injected were more likely to be women and to have friends who did not use drugs. Severity of Dependence (SDS) scores were greater amongst injectors, with scores for injectors almost all being above the informal clinical threshold of greater than 5; while one third of the chasers had SDS scores below this level. Heroin chasing had been a longstanding pattern of behavior for a large proportion of the study sample. Chasers were generally less deeply involved in a heroin-using culture and were less likely to be using heroin daily. Almost all low scores for severity of dependence were seen among the chasers, though a significant number of chasers had dependence scores at the most extreme. Heroin chasers display distinctly different personal and drug-taking characteristics and will need to be the subject of separate research studies and clinical programs.

Adolescent↗

Synthesis of qualitative research on drug use in the European Union: report on an EMCDDA project. European Monitoring Centre for Drugs and Drug Addiction.

This paper is a synthesis of the information in the report Inventory, Bibliography and Synthesis of Qualitative Research in the European Union which was co-ordinated for the European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal, by the National Addiction Centre, London, UK. It is based on the work of a network of qualitative researchers from the European Union. The report includes detailed information from each member state on current qualitative projects, relevant publications from the last 10 years and a directory of those researchers active in this area. The paper introduces the project, outlines its future direction and discusses what can be defined as 'qualitative research'. Historical developments and the role of qualitative methodology in relation to research into drug use are examined. A summary of the project's findings is presented, and the relevance of qualitative research for policy-making is discussed. Finally, the methodology used to collect data for the project is described.

Crime↗

Physician-assisted suicide and voluntary euthanasia: is it time the UK law caught up?

People who wish to end their lives when they consider that they cannot endure further pain and suffering cannot legally obtain help to produce a peaceful death. The reality of practice seems to be that, covertly, physician-assisted suicide and voluntary euthanasia do take place. The value of personal autonomy in issues of consent has been clarified in the courts in that a competent adult person has the right to refuse or choose alternative treatments even if death will be the outcome. This issue needs open discussion and regulation in order to protect those vulnerable people in our society.

Adult↗

Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide.

Glutathione peroxidases have been thought to function in cellular antioxidant defense. However, some recent studies on Gpx1 knockout (-/-) mice have failed to show a role for Gpx1 under conditions of oxidative stress such as hyperbaric oxygen and the exposure of eye lenses to high levels of H2O2. These findings have, unexpectedly, raised the issue of the role of Gpx1, especially under conditions of oxidative stress. Here we demonstrate a role for Gpx1 in protection against oxidative stress by showing that Gpx1 (-/-) mice are highly sensitive to the oxidant paraquat. Lethality was already detected within 24 h in mice exposed to paraquat at 10 mg.kg-1 (approximately (1)/(7) the LD50 of wild-type controls). The effects of paraquat were dose-related. In the 30 mg.kg-1-treated group, 100% of mice died within 5 h, whereas the controls showed no evidence of toxicity. We further demonstrate that paraquat transcriptionally up-regulates Gpx1 in normal cells, reinforcing a role for Gpx1 in protection against paraquat toxicity. Finally, we show that cortical neurons from Gpx1 (-/-) mice are more susceptible to H2O2; 30% of neurons from Gpx1 (-/-) mice were killed when exposed to 65 microM H2O2, whereas the wild-type controls were unaffected. These data establish a function for Gpx1 in protection against some oxidative stressors and in protection of neurons against H2O2. Further, they emphasize the need to elucidate the role of Gpx1 in protection against different oxidative stressors and in different disease states and suggest that Gpx1 (-/-) mice may be valuable for studying the role of H2O2 in neurodegenerative disorders.

Animals↗