Biomedical subjects

Neil A Reynolds

Publications and source records attributed to Neil A Reynolds.

10 recordsLinked to original sources

PubMed2005

Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection.

Tenofovir disoproxil fumarate (tenofovir DF; Viread), an ester prodrug of the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir, is indicated in combination with other antiretroviral agents in the treatment of HIV infection. As a component of an antiretroviral regimen, oral tenofovir DF 300 mg once daily effectively reduces viral load in patients with HIV infection who are treatment-experienced with baseline NRTI resistance mutations or treatment-naive. Tenofovir DF provides a simple and convenient once-daily dosage regimen, and is generally well tolerated and able to produce sustained suppression of viral replication.

Adenine↗

PubMed2005

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma.

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Acetates↗

PubMed2005

Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension.

Trandolapril/verapamil sustained release (SR) [Tarka] is an oral, fixed-dose combination of the ACE inhibitor trandolapril and the SR formulation of the phenylalkylamine calcium channel antagonist verapamil. It is indicated for the treatment of hypertension in patients who require more than one agent to achieve blood pressure (BP) targets. In the large, randomised, multicentre INVEST (INternational VErapamil SR/trandolapril STudy), a verapamil SR-based treatment strategy that included trandolapril in most patients was as effective as an atenolol-based treatment strategy in reducing the risk of the primary outcome (first occurrence of death [all-cause], nonfatal myocardial infarction [MI] or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD) and was as well tolerated. Trandolapril/verapamil SR is generally more effective at controlling hypertension than either component as monotherapy, and is as effective as a number of other fixed-dose combination therapies. The combination is as well tolerated as trandolapril monotherapy and is at least as well tolerated as verapamil SR monotherapy. In hypertensive patients with type 2 diabetes mellitus in the BENEDICT (BErgamo NEphrologic DIabetes Complications Trial), trandolapril/verapamil SR prolonged the time to the onset of persistent microalbuminuria compared with placebo, as did trandolapril monotherapy. Thus, trandolapril/verapamil SR is an effective option for the treatment of essential hypertension in patients requiring more than one agent to achieve BP targets, including those with compelling indications, such as CAD or type 2 diabetes.

Adult↗

PubMed2005

Rotigotine: in Parkinson's disease.

Rotigotine is a nonergolinic dopamine D3/D2/D1 receptor agonist delivered via a transdermal system and has been evaluated for the treatment of idiopathic Parkinson's disease. Patients with early Parkinson's disease receiving rotigotine monotherapy experienced significantly greater improvements in parkinsonian symptoms (as measured by Unified Parkinson's Disease Rating Scale scores) compared to placebo in two large, well designed clinical trials. Significant beneficial effects versus placebo were observed with the 30 and 40 cm2 rotigotine patches in both trials.black triangle Patients with advanced Parkinson's disease receiving rotigotine as adjunctive therapy with levodopa experienced clinically significant reductions from baseline in 'off' time in two well designed clinical trials. In one trial, a large placebo effect was observed, therefore, there was no significant difference between placebo and active treatment (20, 40 and 60 cm2) for this primary efficacy variable, However, a recent study found a significant (p < or = 0.003) reduction in 'off' time in rotigotine 40 and 60 cm2 recipients versus that in the placebo group. Rotigotine was generally well tolerated in clinical trials as both monotherapy and when administered with levodopa; adverse events were generally mild or moderate in severity.

Dopamine Agonists↗

PubMed2005

Alendronate/colecalciferol.

Alendronate/colecalciferol 70 mg/2800 IU, a once-weekly tablet containing the bisphosphonate alendronate and colecalciferol (the precursor of the biologically active form of vitamin D), has been approved for the treatment of osteoporosis in women and for increasing bone mass in men with osteoporosis. The mean oral bioavailability of alendronate or colecalciferol is similar when administered alone or as one once-weekly tablet containing alendronate/colecalciferol 70 mg/2800 IU. In a 15-week, randomized, double-blind, multicenter study in patients with osteoporosis, the proportion of patients with serum 25-hydroxyvitamin D3 levels <15 ng/mL was significantly lower with alendronate/colecalciferol than with alendronate alone. Markers of bone turnover were not significantly different in recipients of alendronate/colecalciferol or alendronate alone. Alendronate is generally well tolerated in men and women with osteoporosis, with adverse events being mainly transient and associated with the upper gastrointestinal tract. The treatment-related adverse event profile of once-weekly alendronate/colecalciferol 70 mg/2800 IU was similar to that of once-weekly alendronate in the 15-week, double-blind study in patients with osteoporosis.

Alendronate↗

PubMed2004

Cetuximab: in the treatment of metastatic colorectal cancer.

Cetuximab is a chimeric monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is over-expressed by 25-80% of colorectal cancer tumours and associated with advanced disease. Cetuximab induces a broad range of cellular responses in tumours expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. In a large, randomised, open-label, multicentre study in adult patients with irinotecan-refractory, metastatic colorectal cancer expressing EGFR, cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly plus irinotecan (various doses) produced a greater rate of partial response and disease control (partial response plus stable disease), and increased time to disease progression, compared with cetuximab monotherapy; survival was similar in both groups. The same dosage of cetuximab combined with irinotecan, fluorouracil and folinic acid (various regimens) produced partial responses in 43-58% of patients, a complete response in 5% of patients (one study only) and stable disease in 32-52% of patients with treatment-naive metastatic colorectal cancer expressing EGFR in three small, open-label trials. The most common grade 3/4 adverse events associated with cetuximab monotherapy were acne-like rash, asthenia, abdominal pain and nausea/vomiting. In patients receiving cetuximab plus irinotecan, these were diarrhoea, asthenia, leucopenia and neutropenia.

Antibodies, Monoclonal↗

PubMed2004

Budesonide/formoterol: in chronic obstructive pulmonary disease.

Budesonide/formoterol is a fixed-dose combination of the corticosteroid budesonide and the long-acting beta2-agonist formoterol, and is inhaled via the Turbuhaler device. In two large, randomised, double-blind, 12-month studies, patients with severe chronic obstructive pulmonary disease (COPD) receiving budesonide/formoterol 320/9 microg twice daily had a significantly higher forced expiratory volume in 1 second (FEV1) and significantly higher morning and evening peak expiratory flow at trial endpoint than recipients of budesonide or placebo; FEV1 was significantly higher than with formoterol in the larger study. In both studies, the rate of COPD exacerbations and exacerbations requiring oral corticosteroids was significantly reduced with budesonide/formoterol versus formoterol and placebo. Moreover, the time to first exacerbation was significantly prolonged with budesonide/formoterol versus all other treatment arms in the larger study. At 12 months, significant improvements in health-related quality-of-life scores were seen with budesonide/formoterol versus placebo in both studies. The reduction in total and individual symptom scores was significantly greater with budesonide/formoterol than with budesonide or placebo in the smaller study. Budesonide/formoterol was generally well tolerated by patients with severe COPD. The tolerability profile of the combination was similar to that of the individual components with no increase in the incidence of adverse events.

Administration, Inhalation↗

PubMed2004

Ciclesonide.

Ciclesonide is an inhaled corticosteroid (delivered via a hydrofluoroalkane metered-dose inhaler) that is converted to an active metabolite, desisobutyryl-ciclesonide, in the lung, thereby minimising effects on endogenous cortisol. In two 12-week, randomised studies in patients with asthma, ciclesonide 80 or 320 microg once daily was at least as effective as budesonide 400 microg/day at increasing forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline; ciclesonide 320 microg daily was significantly more effective than budesonide 400 microg once daily in one study. In a randomised, double-blind study in patients with asthma controlled with high-dosages of inhaled corticosteroids, FEV(1) and FVC decreased significantly from baseline at 12 weeks in patients receiving ciclesonide 320 microg daily or budesonide 400 microg daily; peak expiratory flow values decreased significantly only in patients receiving budesonide. Inhaled ciclesonide 80 or 320 microg daily improved asthma symptom scores and decreased the use of rescue medication by a similar, significant amount to budesonide 400 microg/day in two 12-week studies. Inhaled ciclesonide was generally well tolerated in patients with asthma. Ciclesonide did not suppress biochemical markers of adrenal function in 52-week studies. The long-term (>52 weeks) systemic effects of ciclesonide remain unknown.

Administration, Inhalation↗

PubMed2004

Fondaparinux sodium: a review of its use in the prevention of venous thromboembolism following major orthopaedic surgery.

Fondaparinux sodium (Arixtra; fondaparinux) is the first of a new class of synthetic pentasaccharide anticoagulants that bind to antithrombin and inhibit the action of factor Xa. In three large, well designed trials, subcutaneous fondaparinux 2.5mg once daily was more effective than subcutaneous enoxaparin sodium (enoxaparin) 30 mg twice daily or 40 mg once daily at preventing venous thromboembolism (VTE) at day 11 in patients undergoing hip replacement, elective major knee or hip fracture surgery; a fourth trial demonstrated similar efficacy to enoxaparin 30 mg twice daily in hip replacement. Fondaparinux recipients had a lower incidence of proximal deep vein thrombosis (DVT) in two studies. In a meta-analysis of the four trials, patients receiving fondaparinux had a >50% reduction in the relative risk of VTE at day 11. Fondaparinux compared favourably with enoxaparin in several pharmacoeconomic analyses. In a large, controlled trial in hip fracture patients, extended prophylaxis with fondaparinux (duration 25-31 days) substantially reduced the incidence of VTE at day 25-32 compared with prophylaxis for 6-8 days, and was a cost-effective treatment strategy. Moreover, extended prophylaxis significantly decreased the rate of proximal, total and distal DVT and symptomatic VTE. Fondaparinux was generally well tolerated in clinical trials in patients undergoing major orthopaedic surgery. However, following major knee surgery and in a meta-analysis of pooled data from four trials, fondaparinux recipients had a significantly higher incidence of overt bleeding with a bleeding index > or =2, but no increase in fatal bleeding, bleeding into a critical organ or bleeding leading to reoperation. The bleeding risk is related to the timing of the first dose and when fondaparinux was initiated between 6 and 8 hours after surgery, the bleeding risk was similar to enoxaparin. Extended prophylaxis with fondaparinux was not associated with a significantly increased risk of bleeding events. In conclusion, fondaparinux is more effective than enoxaparin at preventing postoperative VTE in patients undergoing elective hip replacement, major knee or hip fracture surgery. Extended therapy with fondaparinux considerably increases its efficacy without a significant increase in the incidence of bleeding episodes. Fondaparinux was generally well tolerated in clinical trials. Fondaparinux is an effective and useful alternative to low molecular weight heparins for the prevention of VTE following major orthopaedic surgery.

Clinical Trials as Topic↗

PubMed2004

Insulin aspart: a review of its use in the management of type 1 or 2 diabetes mellitus.

Insulin aspart (NovoRapid, NovoLog) is a short-acting insulin analogue, which has a faster onset and shorter duration of action than regular human insulin. Insulin aspart administered immediately before meals provided significantly greater improvements in glycosylated haemoglobin and better postprandial glycaemic control than regular human insulin administered 30 minutes before meals, when used in a basal-bolus regimen with neutral protamine Hagedorn (NPH) insulin, in randomised, nonblind studies in patients with type 1 diabetes mellitus. In patients with type 2 diabetes, insulin aspart provided similar glycaemic control to regular human insulin, administered in a basal-bolus regimen with NPH insulin. Small studies suggest that the use of insulin aspart in combination with oral hypoglycaemic agents may be beneficial. Insulin aspart, administered by continuous subcutaneous insulin infusion (CSII) provided better glycaemic control than insulin aspart multiple daily injection regimens in patients with type 1 (but not type 2) diabetes, and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Limited studies show insulin aspart to be effective in children, adolescents and young adults with type 1 diabetes. Insulin aspart had a tolerability profile similar to that of regular human insulin in clinical trials. The incidence of major or nocturnal hypoglycaemic events reported in patients receiving insulin aspart was lower than that of regular human insulin in several studies. In conclusion, insulin aspart, administered immediately before meals in a basal-bolus regimen with NPH insulin, provided better long-term glycaemic control than regular human insulin administered 30 minutes before meals in patients with type 1 diabetes, and was as effective as regular human insulin in patients with type 2 diabetes. A significantly lower risk of hypoglycaemia was seen in several trials. Insulin aspart CSII provided better glycaemic control than insulin aspart multiple daily subcutaneous injection (MDI) in patients with type 1 (but not type 2) diabetes and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Insulin aspart is an effective and well tolerated alternative to regular human insulin and insulin lispro for the maintenance of glycaemic control in patients with type 1 or 2 diabetes.

Adolescent↗