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Biomedical subjects

A H Thomson

Publications and source records attributed to A H Thomson.

At least 19 recordsLinked to original sources
PubMed2006

'Losing my touch': decline in self-reported confidence in performing practical procedures in consultant oncologists.

This study aimed to compare the confidence of oncology consultants and specialist registrars (SpRs) in the performance of practical procedures, to contrast this with confidence in other areas of practice and to determine at what grade they felt most confident. Questionnaires were sent to all 57 oncology consultants and SpRs in the South-West region. Respondents scored confidence on a five-point Likert scale. The response rate was 70%. SpRs were significantly more confident in cardiopulmonary resuscitation (p = 0.003) and central line insertion (p = 0.006). Consultants were significantly more confident in developing management plans (p = 0.001) and performing committee work (p = 0.002). Only 6% of consultants felt most confident performing practical procedures as a consultant, and were less confident about these than other tasks (p = 0.001). Some 86% of SpRs considered they were more confident performing practical procedures as senior house officers (SHOs). In conclusion, self-reported confidence in performing practical procedures declines during career progression in oncology. This raises questions about the teaching and supervision of these procedures. If there is a greater emphasis on a consultant-provided service, their educational needs will need to be recognized and retraining or outsourcing of these procedures to other specialties may be necessary.

Clinical Competence↗
PubMed2005

Medical management of parapneumonic pleural disease.

Considerable heterogeneity exists in the management of parapneumonic pleural disease. A randomized controlled trial (RCT) demonstrated the effectiveness of small-catheter drainage with fibrinolysis, but surgical devotees suggest this may only be applicable to "early" cases. We examined evidence-based medical management in "all-comers." We performed a retrospective database analysis of the management of all children with complex pleural effusion admitted to the John Radcliffe Hospital over the 7-year period 1996-2003. One hundred and ten children were admitted. Ten were excluded as they were part of a multicenter RCT and had received intrapleural saline instead of urokinase. Of the remaining 100, 51 were female and 49 male. Median age on admission was 5.8 years (range, 0.3-16.5). Symptoms preadmission averaged 11 days, with December the most common month for presentation. Ninety-six underwent chest ultrasound, confirming an effusion in all, described as loculated/septated (68) or echogenic (11). In 17 cases, no specific comment was made regarding the nature of the fluid seen on ultrasound. Ninety-five had subsequent chest tube drainage and then received intrapleural fibrinolysis with urokinase. An etiological organism was identified in 21 cases (21%) (Streptococcus pneumoniae in 10, group A Streptococcus in 5, Staphylococcus aureus in 4, Haemophilus influenzae in 1, and coliform in 1). In a further 9 cases (9%), Gram-positive organisms were seen on pleural fluid microscopy, but did not grow on culture. Two (2%) required surgery due to the persistence of symptoms and an inadequate response to medical management. Median duration of admission was 7 days (range, 2-21 days); median duration of stay from intervention was 5 days (range, 2-19 days). At median follow-up of 8 weeks (range, 3-20 weeks), all children were symptom-free, with minimal pleural thickening on chest X-ray. In conclusion, antibiotic therapy with chest drain insertion and intrapleural urokinase is effective in treating complex parapneumonic effusion and is associated with a good long-term outcome.

Adolescent↗
PubMed2005

Cost-effectiveness of therapeutic drug monitoring: a systematic review.

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked interpatient pharmacokinetic variability. Individualized therapy with such drugs requires therapeutic drug monitoring (TDM) to obtain the desired clinical effects safely. Cost-effectiveness analysis in health care is still at an early stage of development, especially for TDM. A systematic review was carried out to document studies that have addressed the cost-effectiveness of TDM. The Cochrane database and Medline were searched. References identified by this approach were then searched manually for relevant articles. Very few studies have been performed that document the cost-effectiveness of TDM, and TDM has been demonstrated to be cost-effective only for aminoglycosides. For the other classes of drugs that are monitored, the rationale for TDM has been supported, but appropriate cost-effectiveness analyses have not been performed. Because the use of many of these drugs without TDM would increase the risk of under- or overdosing, emphasis should not be placed solely on cost-effectiveness but rather on how such interventions can be applied in the most cost-effective and clinically useful manner.

Cost-Benefit Analysis↗
PubMed2004

Reduced gains in fat and fat-free mass, and elevated leptin levels in children and adolescents with cystic fibrosis.

AIM: Bodyweight is an important prognostic indicator in children with cystic fibrosis (CF), but the relationships between body composition and clinical outcomes are less clear. We have investigated the role of leptin (a potential satiety factor) and changes in body composition, height and weight with respect to age and clinical outcome. METHODS: 143 children (77 boys) with CF and a median age (range) of 5.99 (2.27-17.98) y were followed with annual measurements of height, weight, skinfolds, forced expiratory volume (FEV1), Shwachman score assessment and fasting blood sample. Our control group comprised 40 children (20 boys, 20 girls) aged 8.6-10.2 y at recruitment who were participating in a longitudinal study of growth and puberty. RESULTS: SD scores for height, weight and BMI decreased with age; fat and fat-free mass was lower in both sexes compared to controls. Shwachman score decreased with age in both sexes and was related to fat-free mass in girls, and to both fat-free and fat mass in boys. FEV1 decreased with age only in boys and was related to fat-free mass. Leptin levels by age and by fat mass were higher in CF children compared to controls. CONCLUSION: Despite improvements in management, contemporary children with CF still gain less body fat and fat-free mass and are shorter than controls. The higher leptin levels we observed may be due to stimulatory effects of inflammatory cytokines and we postulate that they may contribute to the anorexia, poor weight gain and growth of these children.

Adolescent↗
PubMed2002

Vancomycin therapeutic drug monitoring: is there a consensus view? The results of a UK National External Quality Assessment Scheme (UK NEQAS) for Antibiotic Assays questionnaire.

This study investigated vancomycin therapeutic drug monitoring (TDM) and issues related to patient management. Questionnaires were distributed to 310 participants in the UK National External Quality Assessment Scheme (NEQAS) for Antibiotic Assays. The response rate was 57.4%. The majority (76%) had an 'in-house' assay service based, almost exclusively, in the microbiology department, and a fluorescence polarization immunoassay (FPIA) was used by 97%. Almost half (48.7%) had an assay service available for 24 h/day, 7 days/week and 92.7% expected same-day results. The majority (80%) had issued guidelines for vancomycin use. A 12 hourly initial dosing regimen was used by 89%. Trough assay samples were taken <10 min before the dose by 91.5%. For post-dose assay samples, 44% took a sample at 1 h, 28% at 2 h and the remainder at 'other' times. For trough target ranges, 93% quoted <10 mg/L or 5-10 mg/L. There was no consensus with regard to post-dose assay sample times and 23 ranges were quoted. The majority (74.4%) regarded a trough level of >or=10 mg/L as 'toxic' but 13 concentrations were quoted as toxic post-dose measurements. In conclusion, there was a wide variability and poor consensus with regard to post-dose vancomycin assay sampling times, target ranges and what constituted a toxic level.

Drug Monitoring↗
PubMed2002

Randomised trial of intrapleural urokinase in the treatment of childhood empyema.

BACKGROUND: The role of intrapleural fibrinolytic agents in the treatment of childhood empyema has not been established. A randomised double blind placebo controlled trial of intrapleural urokinase was performed in children with parapneumonic empyema. METHODS: Sixty children (median age 3.3 years) were recruited from 10 centres and randomised to receive either intrapleural urokinase 40 000 units in 40 ml or saline 12 hourly for 3 days. The primary outcome measure was length of hospital stay after entry to the trial. RESULTS: Treatment with urokinase resulted in a significantly shorter hospital stay (7.4 v 9.5 days; ratio of geometric means 1.28, CI 1.16 to 1.41 p=0.027). A post hoc analysis showed that the use of small percutaneous drains was also associated with shorter hospital stay. Children treated with a combination of urokinase and a small drain had the shortest stay (6.0 days, CI 4.6 to 7.8). CONCLUSION: Intrapleural urokinase is effective in treating empyema in children and significantly shortens hospital stay.

Adolescent↗
PubMed2001

External quality assessment of laboratory performance in analysis of toxicological cases.

A mean of 44 members of the United Kingdom national external quality assessment scheme (UKNEQAS) for toxicology reported analytical findings on 10 toxicological cases circulated between December 1995 and February 2000. Material distributed usually consisted of a 5ml blood and a 20ml urine sample simulated by quantitative addition of drugs and their metabolites to material donated by volunteers and patients. The samples were accompanied by a brief outline of the circumstances surrounding the case. Laboratories were requested to report their analytical findings, list methods of analysis, and provide interpretation of their findings. The mean overall success rate for identification of drugs or their pharmacological group was 76%, failure being largely by laboratories providing an immunoassay-based screening service for a fixed range of drug groups. The latter laboratories indicated that cases would be referred to regional toxicology centres for further investigation or confirmation. The coefficient of variation of measurements was <7% for routine analytes, such as ethanol and paracetamol, but 26-44% for tricyclics and opiates. There were 3% false positive reports. The quantity and content of interpretative comment provided by the laboratories was very variable. A number provide nothing in addition to the analytical result.

Adolescent↗
PubMed2001

A survey of extraction techniques for drugs of abuse in urine.

Sixty nine participants in the United Kingdom national external quality assessment scheme for drugs of abuse in urine reported details of their sample extraction technique by questionnaire. Laboratories were categorised by differences in technique and their analytical test results compared for samples containing D-amfetamine 0.4 (4) and 0.8 (3) mg/l, morphine 0.4 (4) and 0.8 (4)mg/l, and benzoylecgonine 0.15/0.2 (2) and 0.45/0.5 (4) mg/l. Values in parentheses are numbers of samples. For amfetamine, there was no significant difference in the frequency of true positive results between liquid-liquid or solid phase extraction and the Toxi-Lab A system at 0.8 mg/l. Toxi-Lab A gave significantly fewer positives when operating below its specified threshold at 0.4 mg/l. Paradoxically, laboratories using >5 ml urine volume performed less well. Acidification of the extract before volume reduction gave significantly more true positives. For extraction of morphine, solid phase systems significantly outperformed both liquid-liquid and the Toxi-Lab A system at both 0.8 and 0.4 mg/l. No significant differences between extraction techniques were demonstrated for analysis of benzoylecgonine.

Amphetamines↗
PubMed2000

Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno-venous hemofiltration or hemodiafiltration.

OBJECTIVE: To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy. DESIGN: A prospective, clinical study. SETTING: General intensive care unit of a university hospital. PATIENTS: Ten critically ill adult patients being treated with meropenem and receiving continuous veno-venous hemofiltration (hemofiltration rates, 1-2 L/hr) (n = 5) or continuous venovenous hemodiafiltration (hemofiltration rates, 1-1.5 L/hr; dialysis rates, 1-1.5 L/hr) (n = 5) via a polyacrylonitrile hollow fiber 0.9-m2 filter. INTERVENTIONS: Patients received a meropenem dose of 1 g iv every 12 hrs as a 5-min bolus. MEASUREMENTS AND MAIN RESULTS: Meropenem concentrations were measured by high-performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration-time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficients and filter clearances. The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations (MICs) for pathogens that may be encountered in intensive care patients. Serum concentrations exceeded 4 mg/L (MIC90 for Pseudomonas aeruginosa) during 67% of the dosage period in all patients. Sub-MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follows: elimination half-life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving coefficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important. CONCLUSIONS: A meropenem dose of 1g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno-venous hemofiltration or continuous venovenous hemofiltration with a 0.9-m2 polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr. A lower dose would not be sufficient for the empirical treatment of potentially life-threatening infections in all patients.

Acute Kidney Injury↗
PubMed2000

Expiratory airflow patterns in children and adults with cystic fibrosis.

STUDY OBJECTIVE: To determine whether tidal expiratory airflow patterns change with increasing airways obstruction in patients with cystic fibrosis. DESIGN: An observational study. SETTING: Lung function laboratory. PATIENTS: Sixty-four children and young adults with cystic fibrosis. MEASUREMENTS: After measuring FEV(1) and airways resistance using body plethysmography, each subject was seated and asked to mouth breathe through a pneumotachograph for 2 min. The collected data were analyzed, and three expiratory airflow pattern-sensitive indexes were computed. The first index was derived from the ratio of the time to reach peak expiratory flow to the total expiratory time (tPTEF/tE). The second index, Trs, was an estimate of the time constant of the passive portion of expiration. The third index, f1.gif" BORDER="0">, describes the slope of the whole post-peak expiratory flow pattern after scaling. RESULTS: Compared with FEV(1), the index tPTEF/tE was a poor indicator of airways obstruction (r(2) = 0.15, p = 0.002). Trs showed a strong relationship with the severity of airways obstruction (r(2) = 0.46, p < 0.001). Using f1.gif" BORDER="0">, the postexpiratory profile could be categorized into three shapes, and provided a good indicator of airways obstruction when linear and concave-shaped profiles occurred (r(2) = 0.42, p < 0.001). Convex-shaped flow profiles had to be treated separately and were indicative of normal lung function. CONCLUSIONS: In a cross-sectional study of patients with cystic fibrosis, increase in airways resistance above normal is reflected by quantifiable changes in the expiratory airflow pattern.

Adolescent↗
PubMed1999

Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumours.

Doxorubicin pharmacokinetics were determined in 33 patients with solid tumours who received intravenous doses of 20-320 mg m(-2) HPMA copolymer bound doxorubicin (PK1) in a phase I study. Since assay constraints limited the data at lower doses, conventional analysis was not feasible and a 'population approach' was used. Bound concentrations were best described by a biexponential model and further analyses revealed a small influence of dose or weight on V1 but no identifiable effects of age, body surface area, renal or hepatic function. The final model was: clearance (Q) 0.194 I h(-1); central compartment volume (V1) 4.48 x (1+0.00074 x dose (mg)) I; peripheral compartment volume (V2) 7.94 I; intercompartmental clearance 0.685 I h(-1). Distribution and elimination half-lives had median estimates of 2.7 h and 49 h respectively. Free doxorubicin was present at most sampling times with concentrations around 1000 times lower than bound doxorubicin values. Data were best described using a biexponential model and the following parameters were estimated: apparent clearance 180 I h-(-1); apparent V1 (I) 1450 x (1+0.0013 x dose (mg)), apparent V2 (I) 21 300 x (1-0.0013 x dose (mg)) x (1+2.95 x height (m)) and apparent Q 6950 I h(-1). Distribution and elimination half-lives were 0.13 h and 85 h respectively.

Adult↗