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Biomedical subjects

David Price

Publications and source records attributed to David Price.

At least 73 records · Page 4Linked to original sources
PubMed2003

Pharmacoeconomics of asthma treatment.

The burden of asthma is increasing in terms of prevalence, severity of symptoms and other markers of asthma control. Poor control of symptoms is a major issue that can result in adverse clinical and economic outcomes. Prescribing costs are the most obvious and visible expense in asthma care but these are but the tip of the iceberg. We need to take all factors into account when considering the overall costs of asthma treatments and recognise that treatment that results in better asthma control may result in lessening of both direct and indirect costs. To assess this accurately, health economic evaluations need to be undertaken in relevant settings, on representative populations. They need to use appropriate measures of asthma outcome. Drug-related costs need to take into account savings made by decreased costs of other prescribed medication and patient factors must be taken into account. We need information that is applicable to the types of patients we see in the real world to make proper cost analyses. Such information can come from 'pragmatic' randomised trials, from retrospective claims analysis from observational studies or using primary care clinical and prescribing databases.

Anti-Asthmatic Agents↗
PubMed2003

Database studies in asthma pharmacoeconomics: uses, limitations and quality markers.

Asthma is a common chronic disease resulting in significant morbidity and health resource utilisation, and multiple therapeutic options exist. Clinicians and healthcare providers need accurate information on the clinical and cost- effectiveness of asthma treatments to make informed decisions on management strategies. Randomised, controlled trials demonstrate cause and effect relationships between treatments and outcomes, but their tight entry criteria and strict study protocols mean that their results cannot automatically be generalised or used for economic modelling. There is a need for observational data to examine the effectiveness of alternative interventions in routine practice. Clinical and administrative databases are a possible information source for observational studies, and are increasingly used in asthma clinical, epidemiological and economic research. This paper examines the types of database used, the advantages and limitations of such studies and considers quality markers. High quality database studies can provide important epidemiological and economic information that can be of value in understanding the causes and effective management of asthma.

Anti-Asthmatic Agents↗
PubMed2002

Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection.

BACKGROUND: National and international guidelines call for the treatment of primary HIV infection (PHI) with combination antiretroviral therapy, although the ideal timing and duration of this intervention is unknown. Recent immunological studies of antiretroviral therapy on small numbers of patients with PHI have reported preservation of HIV-specific CD4 T-helper responses, ordinarily lost in the absence of intervention. We sought to investigate whether a short course of antiretroviral therapy (SCART) at PHI was sufficient to preserve HIV-specific cellular immunity. METHODS: Forty-five subjects with confirmed PHI were offered SCART at diagnosis. HIV specific cellular immune responses and virological parameters were assessed at monthly intervals. RESULTS: Thirty-seven of the subjects chose SCART at PHI, and achieved a plasma viral load < 50 RNA copies/ml by a median of 10 weeks (range, 4-32 weeks). Two of the 45 individuals had evidence of genotypic HIV drug resistance at baseline, and none developed new mutations following therapy. All patients who received SCART at PHI showed preservation of HIV-specific CD4 T-helper responses up to 64 weeks off SCART. CONCLUSION: SCART at PHI was safe, did not induce the development of drug resistance, and appeared sufficient to preserve HIV-specific CD4 T-helper responses. However, PHI is highly heterogeneous, and a large-scale randomized trial of SCART at PHI is now needed.

Adult↗
PubMed2002

Comparative study of human steroid 5alpha-reductase isoforms in prostate and female breast skin tissues: sensitivity to inhibition by finasteride and epristeride.

Steroid 5alpha-reductase (5-AR) catalyses the reduction of testosterone (T) to dihydrotestosterone (DHT). The 5alpha-reductase found in human benign prostatic hyperplasia (BPH) has been compared with that found in human breast skin tissue in respect of sensitivity to inhibition by Finasteride and Epristeride. Kinetic studies showed the presence of two isoforms of 5alpha-reductase in benign prostatic hyperplasia indicated by low and high Km isoforms for testosterone, while female breast skin tissue contained only one isoform. The isoforms differ in their affinity for the inhibitors Finasteride and Epristeride, both compounds being more effective for the low Km 5alpha-reductase isoform than the high Km 5alpha-reductase of prostatic tissue, with Finasteride displaying competitive inhibition and Epristeride uncompetitive. Finasteride and Epristeride are also inhibitors of skin 5alpha-reductase, which possesses a comparable Ki for Finasteride to that of the low Km prostatic enzyme, but Epristeride was a less potent inhibitor of the skin enzyme relative to the prostate isoform. These results suggest that the inhibitors have therapeutic potential, other than for treatment of benign prostatic hyperplasia, for treating skin disorders influenced by the action of dihydrotestosterone and warrant further investigation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

Developmental expression of monoamine oxidases A and B in the central and peripheral nervous systems of the mouse.

Monoamine oxidases A (MAOA) and B (MAOB) are key players in the inactivation pathway of biogenic amines. Their cellular localization has been well established in the mature brain, but nothing is known concerning the localization of both enzymes during development. We have combined in situ hybridization and histochemistry to localize MAOA and MAOB in the developing nervous system of mice. Our observations can be summarized as five key features. (1) MAOA is tightly linked to catecholaminergic traits. MAOA is expressed in all noradrenergic and adrenergic neurons early on, and in several dopaminergic cell groups such as the substantia nigra. MAOA is also expressed in all the neurons that display a transient tyrosine hydroxylase expression in the brainstem and the amygdala and in neurons with transient dopamine-beta-hydroxylase expression in the cranial sensory ganglia. (2) MAOA and MAOB are coexpressed in the serotoninergic neurons of the raphe from E12 to P7. During postnatal life, MAOA expression declines, whereas MAOB expression remains stable. (3) MAOA is transiently expressed in the cholinergic motor nuclei of the hindbrain, and MAOB is expressed in the forebrain cholinergic neurons. (4) MAOA- and MAOB-expressing neurons are also detected in structures that do not contain aminergic neurons, such as the thalamus, hippocampus, and claustrum. (5) Starting at birth, MAOB expression is found in a variety of nonneuronal cells, the choroid plexus, the ependyma, and astrocytes. These localizations are of importance for understanding the effects of monoaminergic transmission during development.

Acetylcholine↗
PubMed2002

Functional coupling of capping and transcription of mRNA.

In humans, 5' m(7)G cap addition is accomplished cotranscriptionally by the sequential action of the capping enzyme (Hce1) and the cap methyltransferase (Hcm1). We found that guanylylation and methylation occur efficiently during transcription with t(1/2)'s of less than 15 and 70 s, respectively. A two to four order of magnitude increase was found in the rate of guanylylation of RNA in transcription complexes compared to free RNA. This stimulation required only the RNA polymerase II elongation complex and Hce1. Capping activity was weakly associated with elongation but not preinitiation complexes. The CTD was not required for functional coupling but stimulated the rate of capping 4-fold. Inhibition of Cdk7 but not Cdk9 similarly slowed the rate of capping.

Antibodies↗
PubMed2002

Evaluation of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer.

OBJECTIVE: To prospectively evaluate the use of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in the initial staging of squamous cell head and neck carcinoma. SUMMARY BACKGROUND DATA: The status of cervical lymph nodes is an important prognostic factor and determinant of management approach in squamous cell head and neck cancer. METHODS: FDG-PET findings were compared with those of computed tomography (CT) before removal of the primary tumor and/or neck dissection. Histopathologic analysis was used as the gold standard for assessment of the sensitivity and specificity of these modalities. RESULTS: FDG-PET correctly identified the primary tumor in 35 of 40 patients in whom the site of the primary was known clinically and still present (sensitivity 88%). None of four unknown primaries were detected. Tumors not detected by FDG-PET were generally superficial, with depths of less than 4 mm. CT correctly identified 18 of the 35 primary tumors (sensitivity 51%). Eleven of 17 CT false-negative tumors were detected by FDG-PET. The sensitivity and specificity for the presence of metastatic neck disease on FDG-PET were 82% and 100%, respectively; those for CT were 81% and 81%, respectively. FDG-PET was true positive for metastatic neck disease in two of the three CT false-negative patients. CONCLUSIONS: FDG-PET shows promise in the initial staging of head and neck cancer and provides additional accuracy to a conventional staging process using CT.

Adult↗
PubMed2002

The cost effectiveness of chlorofluorocarbon-free beclomethasone dipropionate in the treatment of chronic asthma: a cost model based on a 1-year pragmatic, randomised clinical study.

OBJECTIVE: To compare the cost effectiveness of hydrofluoroalkane 134a-beclomethasone dipropionate (HFA-BDP; Qvar) [corrected] with chlorofluorocarbon-beclomethasone dipropionate (CFC-BDP) in patients with chronic stable asthma previously receiving CFC-BDP, from the perspective of a healthcare provider. DESIGN: Cost-effectiveness analysis based on a 12-month pragmatic, randomised, parallel group, open-label clinical trial assessing safety and efficacy of HFA-BDP at approximately half the dose of CFC-BDP in patients with stable asthma. SETTING: International, multicentre study at 57 study sites in the US, UK, The Netherlands, and Belgium. Healthcare costs were calculated for UK-based healthcare [in 1999 as pounds (pounds sterling)]. PATIENTS AND PARTICIPANTS: Patients (n = 473) > or =12 years of age with currently stable asthma that had been stable (i.e. no exacerbations requiring oral corticosteroid use in the last 4 weeks) for at least the preceding month. MAIN OUTCOME MEASURES: Average and incremental cost-effectiveness ratios based upon symptom-free days, improvement in health-related quality of life, and total and drug-only direct healthcare costs. RESULTS: Patients in the HFA-BDP group experienced a significantly higher percentage of symptom-free days than patients in the CFC-BDP group by the end of the study period (42.4 vs 20.0%; p = 0.006). A greater percentage of patients in the HFA-BDP group had a clinically significant improvement in health-related quality of life than in the CFC-BDP group [35.3 (n = 116/329) vs 16.1% (n = 18/112)]. Total per patient healthcare costs were similar between the two groups. The average cost per symptom-free day per patient was 1.36 pounds sterling for HFA-BDP and 1.81 pounds sterling for CFC-BDP based on total healthcare costs. The incremental cost per symptom-free day for using HFA-BDP instead of CFC-BDP was negative, indicating that HFA-BDP is a dominant strategy and may be a cost-saving intervention compared with CFC-BDP. A sensitivity analysis varying both cost and outcome parameters further supported this finding for most scenarios tested. The cost to achieve a clinically significant improvement in health-related quality of life over the study period was 13.24 pounds sterling per improved patient per week for HFA-BDP and 29.38 pounds sterling per patient per week for CFC-BDP. CONCLUSIONS: These findings indicate that HFA-BDP is a cost-effective intervention when compared with CFC-BDP in this group of patients with stable asthma. In the majority of scenarios HFA-BDP provides more effective asthma control at a similar cost to CFC-BDP.

Asthma↗
PubMed2002

General practitioners with a special clinical interest: a model for improving respiratory disease management.

Health care technology is continuously moving forward with great advances in all fields of medicine. The way in which health care is delivered has been stuck in a primary care/secondary care model, which is failing to meet patients' needs. Existing structures are inefficient because they do not maximise use of skills. A new way of delivering services is proposed using an intermediate level specialist--a general practitioner with a special clinical interest (GPSCI), to increase access at a location close to the patient while giving support to the wider primary health community. We explore how the role of GPSCI might work using the field of respiratory medicine as an exemplar. The concept is transferable to other therapeutic areas.

Family Practice↗
PubMedDate not supplied

Aprotinin decreases ischemic damage during coronary revascularization.

BACKGROUND AND AIM: This study sought to determine whether the favorable anti-inflammatory effects of aprotinin might limit ischemic damage during the revascularization of ischemic myocardium. METHODS: Twenty pigs underwent 90 minutes of coronary occlusion followed by 45 minutes of blood cardioplegic arrest and 180 minutes of reperfusion. Ten animals received a loading dose of aprotinin (40,000 kallikrein inhibiting units/kg) during the start of coronary occlusion followed by an infusion of 20,000 kallikrein inhibiting units/kg/hour. Ten other animals received no aprotinin. Summary statistics are expressed as the mean +/- standard error. RESULTS: The aprotinin-treated animals required less cardioversions for ventricular arrhythmias (1.0 +/- 0.7 vs. 3.6 +/- 0.6; p < 0.001), accumulated less lung water (1.0 +/- 0.2% change vs. 6.2 +/- 0.9% change; p = 0.038), had more complete coronary relaxation to bradykinin (34.1 +/- 5.9% change vs. 9.2 +/- 3.5% change; p = 0.01), and had reduced infarct size (area necrosis/area risk = 20 +/- 1.1% vs. 39 +/- 1.2%; p = 0.003). CONCLUSIONS: Aprotinin limits ischemic injury during acute coronary revascularization by decreasing ventricular arrhythmias and lung edema, preserving endothelial function, and minimizing myocardial necrosis.

Animals↗