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Biomedical subjects

G Murray

Publications and source records attributed to G Murray.

At least 19 recordsLinked to original sources
PubMed2000

Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group.

BACKGROUND: We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. METHODS: Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. FINDINGS: Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p<O.001). For all five trials the ACE inhibitor group had lower rates of death than the placebo group (1,467/6,391 [23.0%] vs 1,710/6,372 [26.8%]; 0.80 [0.74-0.87]) and lower rates of reinfarction (571 [8.9%] vs 703 [11.0%]; 0.79 [0.70-0.89]), readmission for heart failure (876 [13.7%] vs 1202 [18.9%]; 0.67 [0.61-0.74]), and the composite of these events (2161 [33.8%] vs 2610 [41.0%]; 0.72 [0.67-0.78]; all p<0.0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.

Aged↗
PubMed2000

Medical complications after stroke: a multicenter study.

BACKGROUND AND PURPOSE: This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. METHODS: We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. RESULTS: Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts, " pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. CONCLUSIONS: Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.

Accidental Falls↗
PubMed1999

The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials.

Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud (as well as unintentional errors), detecting it, and quantifying its impact on the outcome of clinical trials. We use the term 'fraud' specifically to refer to data fabrication (making up data values) and falsification (changing data values). Reported cases of such fraud involve cheating on inclusion criteria so that ineligible patients can enter the trial, and fabricating data so that no requested data are missing. Such types of fraud are partially preventable through a simplification of the eligibility criteria and through a reduction in the amount of data requested. These two measures are feasible and desirable in a surprisingly large number of clinical trials, and neither of them in any way jeopardizes the validity of the trial results. With regards to detection of fraud, a brute force approach has traditionally been used, whereby the participating centres undergo extensive monitoring involving up to 100 per cent verification of their case records. The cost-effectiveness of this approach seems highly debatable, since one could implement quality control through random sampling schemes, as is done in fields other than clinical medicine. Moreover, there are statistical techniques available (but insufficiently used) to detect 'strange' patterns in the data including, but no limited to, techniques for studying outliers, inliers, overdispersion, underdispersion and correlations or lack thereof. These techniques all rest upon the premise that it is quite difficult to invent plausible data, particularly highly dimensional multivariate data. The multicentric nature of clinical trials also offers an opportunity to check the plausibility of the data submitted by one centre by comparing them with the data from all other centres. Finally, with fraud detected, it is essential to quantify its likely impact upon the outcome of the clinical trial. Many instances of fraud in clinical trials, although morally reprehensible, have a negligible impact on the trial's scientific conclusions.

Biometry↗
PubMed1999

The impact of obesity and disease on busulfan oral clearance in adults.

The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P <.05) determinants of CL/F by linear regression were: actual body weight (BW; r2 = 0.300), body surface area (BSA; r2 = 0.277), adjusted ideal body weight (AIBW; r2 = 0.265), and ideal body weight (IBW; r2 = 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m2) was 16.2% lower (P <.001) than for obese patients (BMI, 27 to 35 kg/m2). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 +/- 24 v 110 +/- 24 mL/min/m2, P = 1.0) or AIBW (3.04 +/- 0.65 v 3.19 +/- 0.67 mL/min/kg, P =.597) were similar in normal and obese patients. Non-Hodgkin's lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative to BW, BSA, or AIBW compared with patients with chronic myelogenous leukemia (n = 73). Routine dosing on the basis of BSA or AIBW in adults and adolescents does not require a specific accommodation for the obese. However, dosing based on BSA may be improved by considering CL/F differences in certain diseases. Adjusting dose for body size or disease does not diminish interpatient variability sufficiently to obviate plasma level monitoring in many indications.

Administration, Oral↗
PubMed1999

An inexpensive sensor for measuring surface geometry.

A technique to measure surface geometry using a conductive ink sensor is described. In the human system distorted cylinders are common, and geometry can be reconstructed from local measures of curvature. An algorithm is presented to reconstruct the shape of a surface from a series of curvature measurements. The Abrams Gentile Entertainment patented bend sensor was evaluated as a curvature transducer. The sensor was tested at the extremes of the likely measurement range, from curvatures below 0.01 mm(-1) up to a curvature of 0.1 mm(-1). The upper curvature limit proved beyond the design specification of the sensor. The technique was applied at the lower curvature range to reconstruct one quadrant of the chest of a volunteer and record breathing movement. The bend sensor is inexpensive and can be applied to obtain an approximate reconstruction of surface geometry in the human system.

Adult↗
PubMed1999

Treatment of community-acquired pneumonia in the elderly: the role of cefepime, a fourth-generation cephalosporin.

In a prospective, multicentre double-blind trial, 151 patients over the age of 65 years were randomly assigned to receive either cefepime 2 g every 12 h for a minimum of 3 days and up to 14 days or ceftriaxone 1 g every 12 h for a minimum of 3 days and up to 14 days. Antibiotics were maintained until 48 h after fever had resolved; no other antibiotics were permitted. The average age in each group exceeded 77 years and significant co-morbidity was found in the majority of patients. The mean total duration of therapy was 5.8+/-2.4 days for the cefepime group and 6.7+/-2.7 days for the ceftriaxone group (P = 0.06). The clinical success rate at the end of therapy was 79.1% with cefepime and 75.4% with ceftriaxone (P = 0.62). At the end of follow-up, 91.7% of the cefepime-treated patients and 86.5% of the ceftriaxone patients had a satisfactory clinical response (P = 0.38). In 35 bacteriological evaluable patients, potential pathogens were eradicated in all but one patient receiving cefepime. Seven patients in each group died during the study period but in each case the death was unrelated to study drug. The commonest side-effect was diarrhoea (cefepime, five patients; ceftriaxone, two patients). The clinical and microbiological efficacy of cefepime is similar to that of ceftriaxone in elderly patients with community-acquired pneumonia requiring hospitalization. Cefepime is an appropriate choice for the treatment of community-acquired respiratory tract infections in the elderly.

Aged↗
PubMed1999

Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Gabapentin Paediatric Study Group.

PURPOSE: To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add-on therapy for refractory partial seizures in paediatric patients aged 3-12 years. METHODS: After a 6-week baseline period, 247 patients (54 centres) entered a 12-week double-blind phase and were randomized to receive either GBP (t.i.d., titrated to 23-35 mg/kg/ day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well-being. RESULTS: RRatio for all partial seizures was significantly lower (better) for GBP-treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (-17.0%) was better than that for the placebo group (-6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (-35%) and secondarily generalized seizures (-28%) when compared with placebo (-12%, +13%, respectively). A greater percentage of GBP-treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure-frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double-blind treatment period. GBP was well tolerated. CONCLUSIONS: GBP was effective and well tolerated as an add-on therapy for partial seizures in paediatric patients with previously drug-resistant seizures.

Acetates↗
PubMed1999

Human herpesvirus 8 DNA load in leukocytes of human immunodeficiency virus-infected subjects: correlation with the presence of Kaposi's sarcoma and response to anticytomegalovirus therapy.

Specific human herpesvirus 8 (HHV-8) DNA sequences were found in leukocytes of 12 of 29 (41.4%) AIDS subjects with Kaposi's sarcoma (KS), whereas they were found in 4 of 43 (9.3%) AIDS subjects without KS (P = 0.003), although the peak HHV-8 DNA load in PCR-positive subjects with KS (mean, 425 copies per 0.2 microgram of DNA) did not significantly differ from the one found in PCR-positive patients without KS (mean, 218 copies). The use of intravenous ganciclovir or foscarnet therapy to treat cytomegalovirus disease did not affect the HHV-8 DNA load in seven patients for whom serial samples were analyzed.

AIDS-Related Opportunistic Infections↗
PubMed1999

Model framework and principles of emergency management.

If not handled quickly and effectively, animal health emergencies can create significant problems for governments and industry. Placing strong emphasis on preventing a disease incursion in the first instance through the judicious use of quarantine and inspection measures will continue to be the major preventive strategy. However, the discovery of new and emerging diseases, some of which may already be present in a country or region, necessitates a rigorous emergency outbreak response mechanism premised on thorough preparation for an emergency. A generic approach to emergency management is the contemporary answer to preparing for, and dealing with, unpredictable events. In essence, generic emergency management plans encompass a set of core principles and key issues which are relevant to a particular industry or commodity. These principles and issues are then reflected in a model emergency management plan which guides participants through the various stages of preparing for, and responding to, an emergency situation and which forms the basis of more detailed farm/enterprise manuals and individual job cards. The authors illustrate the integrated nature of the model emergency management plan and the interrelationship with the core principles and key issues of emergency management planning.

Animal Diseases↗
PubMed1999

Approaches to managing aquatic animal health in Australia.

Despite a rapid and continuous expansion in aquaculture industries, Australia has not experienced significant disease emergencies in farmed aquatic animal populations. However, recent events in relation to wild, farmed, native and introduced aquatic animals have provided warning signals. The development of a national response mechanism for fisheries and aquaculture emergencies became a high priority following the pilchard mortality outbreak in 1995. In terms of more general policy, a special Task Force has provided a framework for managing exotic pests, weeds and diseases and identifying key principles and issues. This Task Force also recommended closer consultation between relevant industry organisations and government agencies. The authors describe the framework of the comprehensive five-year national strategic plan for aquatic animal health ('AQUAPLAN') developed by Australia, and the aquatic animal disease veterinary emergency plan developed within this framework ('AQUAVETPLAN').

Animals↗
PubMed1999

Dealing with unexpected or unknown emergencies: examples of Australian approaches.

Emergencies may derive from unknown agents or an unusual incident from a known exotic or endemic disease agent. Veterinary administrations must be able to deal rapidly with these occurrences, to allay public fears, media interpretations, and environmental or political concerns. The emergency approach to deal with such incidents should be based on well-established disease control principles. In dealing with the unknown, veterinary authorities must take a comprehensive approach to managing the problem. Events such as the bovine spongiform encephalopathy in the United Kingdom and Europe have shown that management becomes much more complex when animal health events also involve human disease. The absence of scientific knowledge creates an environment of speculation, fear and mistrust, which may seriously erode the ability of animal health authorities to respond as they would wish. An established structure which identifies the roles and responsibilities of key players and clearly states where accountability for handling the situation ultimately rests is essential. In addition, emergency plans which have been tested by training exercises, for example, are critical. Other operators who could be involved in the management of emergencies must also be fully aware of their roles in the event of a problem. Over recent years, Australia has experienced a number of new diseases which have had to be handled in an environment of uncertainty and in conditions where knowledge was lacking. The authors briefly outline a number of these incidents as case studies and list the key factors involved in dealing with each emergency.

Animal Diseases↗
PubMed1998

A comprehensive register for diabetic outpatients: experience with desktop computing from 1987-1996.

Diabetes mellitus affects all parts of the body, and all aspects of life for the patient. To manage patients effectively, we need a record of who has diabetes, where they are treated, by whom, and with what results. In 1985 we devised a standardised data collection form in our clinic and in 1987 we established a comprehensive register of patients treated in our clinics. Our Diabetes Care Centre serves a population of 287,460 based in an industrial area with high levels of social and economic deprivation. The database includes demographic details, risk factors including smoking and alcohol intake, duration of diabetes, type of treatment, biochemical results including blood glucose, glycosylated haemoglobin, details of blood lipids and renal function. We also record details of diabetic eye disease, foot disease, nerve pathway disease, cardiovascular disease, and skin complications. We record the type of treatment including diet, tablets, and insulin and we audit the incidence of diabetic complications including ketoacidosis, amputation, and blindness due to diabetes. From 1994 onwards we complied a district register of patients including those not seen by us. Our computerised database enables us to monitor our clinics, audit our results, pursue research, set targets, and facilitates contracting for diabetes care with our purchasers.

Diabetes Mellitus↗
PubMed1998

Measurement of how well a paediatric training programme prepares graduates for their chosen career paths.

To provide a sound basis for modification of our paediatric residency education programme, we surveyed graduates from the past 16 years. The questionnaire was designed to determine the adequacy of training rotations in preparing graduates for their career paths. Questionnaires were mailed to 81 graduates; 73 (90%) replied. A modified version was completed by 27 of 29 current residents (93%). For most rotations, responses were normally distributed. However, 10 or more respondents identified exposure in one area as 'excessive' and in 6 as 'inadequate'. Current residents scored many rotations as 'inadequate', likely indicative of their limited exposure to actual practice. Recommendations were consistent for subjects needing more instruction. All major issues raised by graduates had been identified by faculty, but the substantiation enabled changes to be made with widespread support. We recommend periodic survey of graduates to evaluate how well education is preparing residents for their ultimate career paths.

Career Choice↗
PubMed1998

Comparative evaluation of the cytomegalovirus DNA load in polymorphonuclear leukocytes and plasma of human immunodeficiency virus-infected subjects.

The cytomegalovirus (CMV) DNA load was determined in polymorphonuclear leukocytes (PMNL) and plasma samples from 106 human immunodeficiency virus-infected subjects at risk of developing CMV disease (group 1) and from 27 AIDS patients with documented CMV disease (group 2). For both groups, the number of CMV copies in PMNL was significantly higher than in plasma when results were derived from an equivalent blood volume (P < .001, PMNL vs. plasma). Additionally, group 2 (symptomatic) patients had a greater viral DNA load than group 1 (asymptomatic) subjects (P < .001 for both PMNL and plasma). The sensitivity, specificity, and positive and negative predictive values of qualitative polymerase chain reaction using PMNL (PCR-PMNL) for the presence of CMV disease were 100%, 58%, 38%, and 100%, respectively, compared with 70%, 93%, 74%, and 92% for qualitative PCR-plasma and 93%, 92%, 76%, and 98% for quantitative PCR-PMNL using a cutoff of 16,000 copies/mL. Thus, the best strategy for diagnosing CMV disease in these individuals relies on quantitative assessment of the viral DNA load in PMNL.

AIDS-Related Opportunistic Infections↗
PubMed1998

Analyzing outcome of treatment of severe head injury: a review and update on advancing the use of the Glasgow Outcome Scale.

The Glasgow Outcome Scale (GOS), two decades after its description, remains the most widely used method of analyzing outcome in series of severely head-injured patients. This review considers limitations recognized in the use of the GOS and discusses a new approach to assessment, using a structured questionnaire-based interview. Assignments can be made to an extended eight-point scale (GOSE) as well as the original five-point approach-in each case, with a high degree of interobserver consistency. The assignments are coherent with the principles of the World Health Organization classification of impairments, disabilities, and handicaps, and their validity is supported by strong associations with the results of neuropsychological testing and assessment of general health status. The need to allow for disability existing before injury, issues concerning the time of assessment after injury, and subdivisions of the scale into "favorable" and "unfavorable" categories are discussed. It is concluded that, in its improved structured format, the Glasgow Outcome Scale should remain the primary method of assessing outcome in trials of the management of severe head injury.

Craniocerebral Trauma↗