Biomedical subjects

Caroline Fenton

Publications and source records attributed to Caroline Fenton.

13 recordsLinked to original sources

PubMed2005

Candesartan cilexetil: a review of its use in the management of chronic heart failure.

Candesartan cilexetil is the orally administered pro-drug of candesartan, a highly selective antagonist of the angiotensin II subtype 1 receptor that mediates the pressor activities of angiotensin II. Candesartan cilexetil is widely used for the treatment of hypertension and has recently been approved in Europe for the treatment of chronic heart failure (CHF) in patients with impaired left ventricular (LV) systolic function. Results of the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme suggest that oral candesartan cilexetil reduces morbidity and mortality in patients with CHF and LV ejection fraction (LVEF) < or =40%. There are cardiovascular benefits when candesartan cilexetil is administered as an alternative to an ACE inhibitor, or as an add-on to current treatment regimens that include an ACE inhibitor, in symptomatic CHF. While tolerability is generally good, renal monitoring is required. The recent approval of candesartan cilexetil as both add-on and alternative therapy to ACE inhibitors in patients with CHF and impaired LV systolic function recognises the cardiovascular benefits of candesartan cilexetil in both types of treatment regimens.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Gemtuzumab ozogamicin: a review of its use in acute myeloid leukaemia.

Gemtuzumab ozogamicin (Mylotarg) is a conjugate of a monoclonal antibody and calicheamicin, which targets the membrane antigen CD33 in CD33-positive acute myeloid leukaemia (AML) and, after cell internalisation, releases a derivative of the cytotoxic calicheamicin component. In the US, it is approved as monotherapy in patients aged > or =60 years with a first relapse of AML who are ineligible for other cytotoxic therapy. Monotherapy with gemtuzumab ozogamicin results in complete remission (CR) or CR with incomplete platelet recovery (CRp) in approximately =25% of adults (including those aged > or =60 years) with CD33-positive AML in first relapse. Preliminary data indicate a potential role for gemtuzumab ozogamicin as a component of induction or consolidation regimens in adults and, based on an early study, in the treatment of children with AML, although randomised, controlled studies are needed. Serious adverse events, notably hepatotoxicity, characterise its tolerability profile, but gemtuzumab ozogamicin is comparatively well tolerated by most patients. Gemtuzumab ozogamicin is a valuable new treatment option for patients aged > or =60 years with CD33-positive AML in first relapse for whom other cytotoxic chemotherapy is not considered appropriate; patients with a first CR (CR1) of >12 months are likely to have the best outcome.

Acute Disease↗

PubMed2005

Docetaxel: a review of its use in metastatic breast cancer.

Docetaxel (Taxotere), a cytotoxic taxane, is an antimicrotubule agent effective in the treatment of patients with breast cancer. The clinical profile of docetaxel as an effective cytotoxic agent in the treatment of metastatic breast cancer is well established. As yet, no single standard regimen has been identified as optimal for the treatment of patients with metastatic breast cancer after failure of prior chemotherapy. However, the efficacy of docetaxel monotherapy administered every 3 weeks as a 1-hour infusion is similar to or better than that of doxorubicin, paclitaxel and fluorouracil plus vinorelbine, and better than that of methotrexate plus fluorouracil or mitomycin plus vinblastine. Although docetaxel is associated with neutropenia and other adverse events, its overall tolerability profile is generally acceptable in the majority of patients. Docetaxel, therefore, is an effective option in the treatment of patients with metastatic breast cancer after failure of prior chemotherapy.

Animals↗

PubMed2005

Risperidone: a review of its use in the treatment of bipolar mania.

Risperidone (Risperdal) is an atypical antipsychotic with high affinity for 5-hydroxytryptamine (5-HT)2A, dopamine D2 and alpha1- and alpha2-adrenergic receptors. Risperidone is now approved in the UK and the US for use in bipolar mania. Risperidone < or =6 mg/day, as monotherapy or adjunctive therapy with first-line mood stabilisers, significantly improves moderate and severe bipolar mania and improves global functioning over 3 weeks. Improvements in Young Mania Rating Scale (YMRS) scores in double-blind trials were greater with risperidone than with placebo over 3 weeks, and similar to those with haloperidol over 3 and 12 weeks. Risperidone was reasonably well tolerated. Limited data are available on the combination of risperidone and carbamazepine. Risperidone, as monotherapy or combined therapy with lithium or valproate semisodium, is an effective treatment option in bipolar mania.

Animals↗

PubMed2004

Vulnerability to malaria, tuberculosis, and HIV/AIDS infection and disease. Part 1: determinants operating at individual and household level.

A high burden of malaria, tuberculosis, and HIV infection contributes to national and individual poverty. We have reviewed a broad range of evidence detailing factors at individual, household, and community levels that influence vulnerability to malaria, tuberculosis, and HIV infection and used this evidence to identify strategies that could improve resilience to these diseases. This first part of the review explores the concept of vulnerability to infectious diseases and examines how age, sex, and genetics can influence the biological response to malaria, tuberculosis, and HIV infection. We highlight factors that influence processes such as poverty, livelihoods, gender discrepancies, and knowledge acquisition and provide examples of how approaches to altering these processes may have a simultaneous effect on all three diseases.

Communicable Disease Control↗

PubMed2004

Vulnerability to malaria, tuberculosis, and HIV/AIDS infection and disease. Part II: Determinants operating at environmental and institutional level.

This review summarises a wide range of evidence about environmental and institutional factors that influence vulnerability to malaria, tuberculosis, and HIV infection. By combining this information with that obtained on factors operating at individual, household, and community level, we have identified potential common strategies for improving resilience to all three diseases simultaneously. These strategies depend on collaborations with non-health sectors and include progress in rapid access to funds, provision of education about disease transmission and management, reduction of the burden on carers (predominantly women), and improvement in the quality of health services.

Communicable Disease Control↗

PubMed2004

Daptomycin.

Daptomycin is a lipopeptide antibacterial with rapid in vitro activity against Gram-positive cocci. It is approved for use in patients with complicated skin and skin structure infections (cSSSIs) caused by specified Gram-positive cocci. In vitro, daptomycin was active against Staphylococcus aureus (including meticillin-resistant strains), Streptococcus pyogenes, S. agalactiae, group C and G beta-haemolytic streptococci and vancomycin-susceptible Enterococcus faecalis. Bactericidal activity in vitro was rapid and concentration dependent. In two randomised, investigator-blinded, multicentre trials in patients with cSSSIs, intravenous daptomycin 4 mg/kg once daily was as effective as standard therapy (intravenous semi-synthetic penicillin 4-12 g/day or vancomycin 1 g 12-hourly). Clinical success rates assessed 6-20 days after treatment end were 82.1% in daptomycin recipients and 82.9% in recipients of standard therapy (pooled data). In patients with cSSSIs, the adverse event profiles of daptomycin and vancomycin were similar. Creatine phosphokinase (CPK) levels increased in 2.8% of daptomycin recipients and 1.8% of patients who received standard therapy; only one daptomycin recipient (0.2%) experienced increased CPK levels and muscle symptoms that were not associated with any comorbid factors.

Animals↗

PubMed2004

Letrozole: a review of its use in postmenopausal women with breast cancer.

Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate. Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring. In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.

Antineoplastic Agents↗

PubMed2004

Inhaled salmeterol/fluticasone propionate: a review of its use in chronic obstructive pulmonary disease.

The salmeterol/fluticasone propionate dry powder inhaler (DPI) [Advair Diskus, Seretide Accuhaler] contains the long-acting beta2-adrenoceptor agonist salmeterol and the inhaled corticosteroid fluticasone propionate. In the US, twice-daily salmeterol/fluticasone propionate 50/250 microg is approved for use in adults with chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis, and in the EU, the twice-daily 50/500 microg dosage is approved for use in patients with severe COPD, repeat exacerbations and significant symptoms despite bronchodilator therapy. In patients with moderate-to-severe COPD, twice-daily inhaled salmeterol/fluticasone propionate 50/250 or 50/500 microg for 24-52 weeks improves predose forced expiratory volume in 1 second (FEV1) significantly more than salmeterol monotherapy, improves postdose or postbronchodilator FEV1 significantly more than fluticasone propionate monotherapy and results in clinically significant improvements in health-related quality of life. Salmeterol/fluticasone propionate 50/500 microg significantly reduced annual COPD exacerbations, especially in severe COPD. Some corticosteroid-related adverse events were increased in recipients of fluticasone propionate with or without salmeterol versus salmeterol monotherapy or placebo; withdrawal from fluticasone propionate, including combination therapy, needs careful management to minimise COPD exacerbations. The DPI combining a corticosteroid and long-acting beta2-agonist provides benefits over monotherapy and may encourage patient compliance in COPD.

Administration, Inhalation↗

PubMed2004

Calcipotriol/betamethasone dipropionate: a review of its use in the treatment of psoriasis vulgaris.

The two-compound product containing calcipotriol 50 microg/g plus betamethasone dipropionate 0.5 mg/g (Dovobet, Daivobet) [referred to here as calcipotriol/betamethasone dipropionate], is a topical treatment for psoriasis vulgaris, combining a vitamin D analog and a corticosteroid. For most adult patients with psoriasis vulgaris on the trunk and limbs, up to 4 weeks of therapy with calcipotriol/betamethasone dipropionate provides an effective and well tolerated treatment. In clinical trials, patients with a mean baseline psoriasis area and severity index (PASI) of 9.5-10.9 experienced a mean 65.0-74.4% PASI improvement within 4 weeks, significantly better than improvements with calcipotriol 50 microg/g monotherapy, betamethasone dipropionate 0.5 mg/g monotherapy, or placebo. In addition, in 6.4%-20.1% of patients, lesions cleared. In patients who were subsequently treated with calcipotriol maintenance therapy, benefits were retained for at least 4 weeks. The safety of calcipotriol/betamethasone dipropionate in patients treated for up to 1 year was generally good; fewer than 5% of patients experienced adverse events possibly associated with long-term corticosteroid use.

Betamethasone↗

PubMed2004

Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection.

Palivizumab (Synagi) is a humanized monoclonal antibody that provides immunoprophylaxis against serious lower respiratory tract infections (LRTIs) caused by respiratory syncytial virus (RSV). RSV is the leading cause of hospitalization for LRTIs in infants, causing winter- or wet-season epidemics. In two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg every 30 days for 5 months significantly reduced RSV-related hospitalizations by 55% in 1502 infants with prematurity and/or bronchopulmonary dysplasia/chronic lung disease (BPD/CLD) and by 45% in 1287 infants with hemodynamically significant congenital heart disease (HSCHD). Reductions were statistically significant versus placebo in infants with BPD/CLD, with all degrees of prematurity, and with acyanotic/other heart disease. Palivizumab was generally well tolerated, with < or =1.9% of recipients discontinuing treatment for tolerability reasons. In placebo-controlled trials, the most common potentially drug-related adverse events were fever, nervousness, injection-site reactions, and diarrhea. Drug-related events occurred in 7.2-11% of palivizumab recipients in controlled trials (vs 6.9-10% with placebo) and 0-7.9% in open-label trials. Very few serious potentially drug-related adverse events occurred in clinical trials; four occurred in 2 of 285 patients in one open-label trial. No significant anti-palivizumab antibodies developed during palivizumab use. Palivizumab trough serum concentrations were below the recommended 40 microg/mL in about 33% and up to 14% of children prior to their second and third palivizumab injections. In pharmacoeconomic studies, the cost of palivizumab per hospitalization averted was generally lowest in the highest-risk infants. Drug cost was generally the most influential factor in sensitivity analyses. In conclusion, prophylaxis with palivizumab significantly reduces the incidence of RSV-related hospitalization relative to placebo and is generally well tolerated in high-risk infants aged <2 years, including those with prematurity and BPD/CLD or HSCHD, which are risk factors for early or serious RSV infection. Palivizumab is approved for use in these patients. Other high-risk infants in whom palivizumab has not been formally assessed, such as those with immunodeficiency, cystic fibrosis, or location-specific risk factors (including extended hospital stays) might potentially benefit from palivizumab. The use of palivizumab in these other high-risk populations is likely to be determined as much by pharmacoeconomic considerations as by efficacy outcomes.

Animals↗

PubMed2003

Telmisartan/hydrochlorothiazide: in the treatment of essential hypertension.

Oral telmisartan/hydrochlorothiazide (HCTZ) combines two antihypertensive agents, a selective angiotensin II receptor antagonist with a long half-life and once-daily administration, and a thiazide diuretic. In two large, 8-week, double-blind trials, patients with hypertension unresponsive to monotherapy who received combined telmisartan/HCTZ 80/12.5 or 40/12.5 mg/day, achieved significantly larger reductions in diastolic and systolic blood pressure (BP), than recipients of continued telmisartan monotherapy (p < 0.05 for all). Compliance with telmisartan/HCTZ 80/12.5 mg/day was 98.9%. In patients with hypertension, telmisartan/HCTZ resulted in similar BP reductions to oral enalapril/HCTZ and atenolol/HCTZ in 26-week double-blind trials and greater reductions than oral losartan/HCTZ 50/12.5 mg/day in a 6-week randomised open-label trial (p < 0.001). Up to one-third of patients with hypertension initially responsive to telmisartan 40 or 80 mg/day in a 4-year study required the eventual addition of HCTZ 12.5 or 25 mg/day and/or another agent to maintain BP control. BP was controlled in about 75% of these by adding only HCTZ. In clinical trials of up to 4 years, including elderly patients, telmisartan/HCTZ had similar tolerability to placebo, with few reports of hypokalaemia. Most adverse events were mild to moderate.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Novolizer: a multidose dry powder inhaler.

Novolizer is a multidose breath-actuated dry powder inhaler (DPI) approved for use with salbutamol (albuterol) and budesonide. It has multiple patient feedback mechanisms and an inspiratory flow rate threshold designed to optimise dosage. In two studies, children aged 4-11 years with asthma correctly used Novolizer and generated mean peak inspiratory flow rates (PIFRs) through Novolizer of 76 and 92.7 L/min, well above the Novolizer threshold of 35-50 L/min. In healthy volunteers, median lung deposition of budesonide administered via Novolizer was 19.9-32.1% at mean PIFRs of 54-99 L/min. In a randomised, double-blind, single-dose study in patients with chronic obstructive pulmonary disease (COPD) and asthma, the 1-hour improvement from baseline in mean maximum forced expiratory volume in 1 second (FEV(1)) was 21.3% with inhalation of salbutamol through Novolizer, and 19.5% through Sultanol pressurised metered-dose inhaler (MDI). FEV(1) increased significantly in patients with asthma and COPD treated for 4 weeks in a randomised, open-label comparison of salbutamol through either Novolizer or Sultanol MDI. A randomised open-label study in adults with asthma treated with inhaled budesonide found equivalent improvements in FEV(1) and symptoms with Novolizer and Turbuhaler. Novolizer was well accepted overall. Most patients preferred it to previously used MDIs or DPIs. Only 4-5% found the taste feedback unacceptable. Physicians observed improved compliance over 4 weeks in 80% of patients with asthma using Novolizer.

Administration, Inhalation↗