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Biomedical subjects

J P Reckless

Publications and source records attributed to J P Reckless.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy and tolerability of fluvastatin extended-release delivery system: a pooled analysis.

BACKGROUND: At high doses, the pharmacokinetics of fluvastatin immediate-release (IR) are nonlinear, possibly due to saturation of hepatic uptake. Fluvastatin delivery to the liver in a slower but sustained fashion would be expected to avoid hepatic saturation without elevating systemic drug levels. OBJECTIVE: This pooled analysis compared the efficacy and tolerability of extended-release (XL) 80-mg and IR 40-mg formulations of fluvastatin in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and raising high-density lipoprotein cholesterol (HDL-C) levels in patients with hypercholesterolemia. METHODS: Data were pooled from 3 double-blind, randomized, active-controlled, multicenter, parallel-group studies that compared changes in lipid and apolipoprotein levels with fluvastatin XL 80 mg at bedtime (HS) with changes in fluvastatin IR 40 mg HS or BID in patients aged > or =18 years with primary hypercholesterolemia (consistently elevated LDL-C level [> or =160 mg/dL] and plasma TG levels < or =400 mg/dL). The primary efficacy variable was percent change in LDL-C from baseline. RESULTS: The pooled analysis provided an intent-to-treat efficacy study population of 1674 patients. At 4 weeks, fluvastatin XL 80 mg HS reduced LDL-C levels by a mean of 36.3% (median 38%), significantly greater than a mean reduction of 25.9% (median 27%) seen with fluvastatin IR 40 mg HS, and an incremental additional mean reduction in LDL-C of 10.4% (P < 0.001). At 4 and 24 weeks, fluvastatin XL 80 mg HS provided an LDL-C reduction equivalent to fluvastatin IR 40 mg BID (P < 0.001 for noninferiority). Significant, dose-related changes in HDL-C, LDL-C:HDL-C ratio, total cholesterol, TG, and apolipoprotein A-I and apolipoprotein B levels also occurred. Mean HDL-C level increased by 8.7% and median TG level decreased by 19% with fluvastatin XL 80 mg HS (P < 0.001 and P < 0.05 vs fluvastatin IR 40 mg HS, respectively). Maximum mean increases in HDL-C level (21%) and median decreases in TG level (31%) with fluvastatin XL 80 mg HS occurred in patients with type IIb dyslipidemia and the highest baseline TG. Adverse events were mild, with similar frequency in all treatment groups. CONCLUSIONS: Once-daily administration of fluvastatin XL 80 mg provides enhanced efficacy with an additional 10.4% reduction in LDL-C levels compared with fluvastatin IR 40 mg HS, and superior increases in HDL-C levels, particularly in patients with elevated TG levels (P < 0.05 vs fluvastatin IR 40 mg HS). Fluvastatin XL 80 mg HS has a good tolerability profile and is effective as starting and maintenance lipid-lowering treatment in patients with type II hypercholesterolemia.

Adult↗
PubMed2001

Difficult insulinoma.

Explore the source record for details and available documents.

Drug Therapy, Combination↗
PubMed2001

Actos (pioglitazone): a new treatment for type 2 diabetes.

Type 2 diabetes is increasingly common and can be difficult to control. By directly targeting insulin resistance, the thiazolidinediones offer a new mode of treatment. Here, the pharmacology, clinical trial evidence, side-effects and current clinical uses of pioglitazone are reviewed.

Adult↗
PubMed2000

Cost-effectiveness of statins.

The efficacy of lipid-lowering with statins has become clear. Indirect estimations, and direct measurements from long-term randomized trials have also demonstrated cost-effectiveness, both in secondary and primary prevention of coronary heart disease. Targeting care efficiently to high-risk groups by calculating absolute risk is essential. However, it is clear that what would normally be very cost-effective interventions will put substantial strain on health care resources because of the common nature of coronary disease and risk factors.

Clinical Trials as Topic↗
PubMed2000

Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease.

OBJECTIVES: (a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality. METHODS: Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls. RESULTS: High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL(3) cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL(3), was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL(3) cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant. CONCLUSION: Raised levels of LDL(3) and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.

Adult↗
PubMed2000

Pioglitazone.

Pioglitazone is a thiazolidinedione. As a PPAR-gamma agonist it alters the expression of a number of genes, resulting in a reduction in insulin resistance. Clinical trial data involving over 4500 patients with type 2 diabetes suggest it is effective both as monotherapy and in combination with sulphonylureas, metformin and insulin, producing both significant falls in HbA1c and favourable improvements in lipid parameters. It is well tolerated, with a low incidence of side-effects. Unlike troglitazone, its use has not been associated with hepatotoxicity. It has recently been licensed in the US for use as monotherapy and in combination with insulin, metformin and sulphonylureas. Its European license is more restrictive, allowing use in combination with metformin, and in combination with sulphonylureas in those intolerant of metformin. It provides a useful new option in the treatment of type 2 diabetes mellitus.

Clinical Trials as Topic↗
PubMed1998

Elderly patients with hypercholesterolaemia: a double-blind study of the efficacy, safety and tolerability of fluvastatin.

BACKGROUND: Coronary heart disease is a major cause of morbidity and mortality in the elderly, a rapidly growing section of the population. Elderly patients have been excluded from most preventative risk factor trials. METHODS: We evaluated fluvastatin, a fully synthetic hydroxymethyl glutaryl coenzyme A reductase inhibitor, in white patients older than 60 years, in seven hospital centres. After an 8-week cholesterol-decreasing diet phase, patients were allocated to groups to receive fluvastatin 40 mg daily (n = 33) or placebo (n = 36) given for 12 weeks. All patients had low-density lipoprotein cholesterol concentrations > or = 4.1 mmol/l 1 week before they were allocated to a treatment at random. After receiving randomised treatment for 12 weeks, 50 patients then received fluvastatin 40 mg daily on an open basis for a further 12 weeks. RESULTS: Mean +/- SD age was 70.7 +/- 5.2 years for fluvastatin patients and 68.3 +/- 5.6 years for placebo. Mean +/- SD percentage changes in lipid concentrations from randomisation to the end of 12 weeks were calculated (n = 63) by intent-to-treat analysis. Total cholesterol decreased by 21.64 +/- 8.7% in the fluvastatin group and by 2.91 +/- 7.25% in the placebo group (P < 0.01); high-density lipoprotein cholesterol increased by 4.98 +/- 10.84% in the fluvastatin group and decreased by 0.05 +/- 8.68% in the placebo group (P = 0.05); low-density lipoprotein cholesterol decreased by 27.14 +/- 8.45% in the fluvastatin group and by 2.16 +/- 9.68% in the placebo group (P < 0.01); very-low-density lipoprotein cholesterol decreased by 30.70 +/- 30.65% in the fluvastatin group and by 9.80 +/- 28.6% in the placebo group (P < 0.01); triglyceride decreased by 18.13 +/- 17.35% in the fluvastatin group and by 2.97 +/- 21.85% in the placebo group (P < 0.01). There were no statistically significant differences between treatment groups for any other biochemical or haematological parameters. Adverse events were mainly mild, diminishing with continued treatment, and no event was serious by standard criteria. Patient-assessed tolerability after randomised treatment was 'very good' for 18 fluvastatin patients and for 26 placebo patients (P = 0.79). Seven patients withdrew from the 12-week follow-up (four from the fluvastatin group and three from the placebo group). CONCLUSIONS: We conclude that fluvastatin decreases lipid concentrations effectively and safely in elderly patients, producing clinically significant decreases in total cholesterol, low-density lipoprotein cholesterol, triglyceride and, especially, very-low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol moderately.

Aged↗
PubMed1996

Economic issues in coronary heart disease prevention.

The effectiveness of cholesterol lowering is well established, but cost-effectiveness is an increasing issue because of financial pressures on healthcare services. New statin studies have prospectively demonstrated that secondary prevention of coronary heart disease is almost always cost-effective, as is primary prevention in individuals at higher risk who have one or more other additional risk factors.

Anticholesteremic Agents↗
PubMed1995

The effects of insulin on the level and activity of the GLUT4 present in human adipose cells.

Human adipose cells are much less responsive to insulin stimulation of glucose transport activity than are rat adipocytes. To assess and characterize this difference, we have determined the rates of 3-O-methyl-D-glucose transport in human adipose cells and have compared these with the levels of glucose transporter 4 (GLUT4) assessed by using the bis-mannose photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2-propyl-amine, ATB-BMPA. The rates of 3-O-methyl-D-glucose transport and the cell-surface level of GLUT4 are very similar in the human and rat adipocyte in the basal state. The Vmax for 3-O-methyl-D-glucose transport in fully insulin-stimulated human adipose cells is 15-fold lower than in rat adipose cells. Photolabelling of GLUT4 suggests that this low transport activity is associated with a low GLUT4 abundance (39 x 10(4) sites/cell; 19.9 x 10(4) sites at the cell surface). The turnover number for human adipose cell GLUT4 (5.8 x 10(4) min-1) is similar to that observed for GLUT4 in rat adipose cells and the mouse cell line, 3T3L1. Since 50% of the GLUT4 is at the cell surface of both human and rat adipose cells in the fully insulin-stimulated state, an inefficient GLUT4 exocytosis process cannot account for the low transport activity. The intracellular retention process appears to have adapted to release, in the basal state, a greater proportion of the total-cellular pool of GLUT4 to the cell surface of the larger human adipocytes. These cell-surface transporters are presumably necessary to provide the basal metabolic needs of the adipocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1994

Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia.

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.

Adult↗
PubMed1994

Severe deterioration in cognitive function and personality in five patients with long-standing diabetes: a complication of diabetes or a consequence of treatment?

Changes in mood, personality, and social function were examined in a group of five Type 1 diabetic patients, aged 50 to 66 years, with duration of diabetes from 24 to 47 years. Information on medical history was obtained from their carers and hospital records. All patients had experienced multiple episodes of severe hypoglycaemia and had impaired awareness of hypoglycaemia. Cerebral dysfunction predated the development of minimal diabetic complications and had been apparent for between 1 and 17 years. The carers assessed the pre-morbid and present behaviour and personality of the patients using standard questionnaires. Significant deteriorations were demonstrated in cognitive (p = 0.04) and social functions (p = 0.04), compared with assessment of pre-morbid function. Patients had tended to become more neurotic (p = 0.08) and less extravert (p = 0.07). All of the patients and three of the carers recorded scores suggestive of psychiatric morbidity on the General Health Questionnaire. The patients had experienced loss of employment and the carers described a reduction in the patients' social interactions. Although the aetiology of their cerebral dysfunction can not be definitely ascertained this case series emphasizes the need for long-term prospective studies in patients with diabetes of long duration to assess the impact of the disorder on cognitive and social abilities particularly where there is evidence of cerebral dysfunction. The need for professional support for the carers of such patients should be recognized.

Affect↗
PubMed1994

Using cost-effectiveness analysis for formulary decision making: from theory into practice.

The growth of expenditures on healthcare and pharmaceutical products is a concern to third-party payers because of the absence of market discipline (price signals that consumers face). Cost-effectiveness analysis is a method that allows third-party payers to systematically make judgements about the 'value for money' of these products. It moves beyond simple unit price comparisons of alternate interventions/products to consider the full stream of relevant cost and benefits. As formulary committees begin to adopt the systematic use of cost-effectiveness analyses to inform the debate, the exercise will move from an academic to a more practical application. This transition will require several important changes including defining the purpose of cost-effectiveness analysis, measurement of outcomes and data, format of reports, and contractual arrangements between the pharmaceutical industry and analysts. As more 'real world' experience is gained in the practical application of cost-effectiveness analysis, the quality of data will improve as will its value as an aid to decision making.

Cost-Benefit Analysis↗