Biomedical subjects

Gillian M Keating

Publications and source records attributed to Gillian M Keating.

At least 55 records · Page 3Linked to original sources

PubMed2005

Enfuvirtide: a review of its use in the management of HIV infection.

Enfuvirtide (Fuzeon), a fusion inhibitor, is indicated in combination with other antiretroviral agents in the treatment of HIV infection in treatment-experienced adults and children aged >6 years. The addition of subcutaneous enfuvirtide to an optimised antiretroviral background regimen improved the virological and immunological response in treatment-experienced HIV-infected patients in the two large, well designed TORO (T-20 vs Optimised Regimen Only) trials. Although injection-site reactions occurred almost universally in enfuvirtide recipients, they were rarely treatment-limiting. Enfuvirtide was otherwise generally well tolerated. The challenge for clinicians is in determining the appropriate timing for enfuvirtide initiation, which requires consideration of the likelihood of a better virological response with the construction of an active background regimen versus the potential for a low rate of adherence to therapy in patients in the early stages of treatment and/or disease development. Enfuvirtide is a novel antiretroviral that is effective in HIV-infected patients whose treatment options are limited by multi-class antiretroviral resistance.

Enfuvirtide↗

PubMed2005

Infliximab: in ankylosing spondylitis.

Infliximab is a monoclonal antibody that binds to tumour necrosis factor-alpha and blocks its biological activity. It is approved for use in patients with rheumatoid arthritis, Crohn's disease and ankylosing spondylitis.black triangle In well designed, placebo-controlled trials of 12 or 24 weeks' duration in patients with active ankylosing spondylitis, more infliximab 5 mg/kg recipients achieved a response than placebo recipients according to Ankylosing Spondylitis Assessment Study 20% (61.2% vs 19.2%) or Bath Ankylosing Spondylitis Disease Activity Index 50% (53% vs 9%) criteria (primary endpoints). black triangle Infliximab was also superior to placebo in terms of various secondary clinical endpoints and in reducing spinal inflammation (as assessed by magnetic resonance imaging).black triangle Prolonged efficacy has been demonstrated in patients with ankylosing spondylitis who received infliximab for up to 3 years.black triangle Infliximab is generally well tolerated in patients with ankylosing spondylitis, with most adverse events being of mild-to-moderate severity.

Antibodies, Monoclonal↗

PubMed2005

Posaconazole.

Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit (primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase II study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for >or=1 year.

Animals↗

PubMed2005

Pegaptanib: in exudative age-related macular degeneration.

Pegaptanib, an aptamer, is an antagonist of vascular endothelial growth factor that has shown efficacy in the treatment of patients with exudative age-related macular degeneration (AMD). In two randomised, double-masked trials in patients with exudative AMD (n=1208), the proportion of responders (those losing <15 letters of visual acuity) at 54 weeks was significantly higher in intravitreous pegaptanib 0.3 mg recipients than in those receiving sham injections (70% vs 55%; p<0.001). These trials were conducted concurrently and analysed as a single study; the treatments were given every 6 weeks for 48 weeks. The improvement in visual acuity with pegaptanib was maintained in a 1-year extension of these trials. Similar favourable results with pegaptanib 0.3 mg were seen in terms of the secondary efficacy endpoints (e.g. proportion of patients experiencing severe loss of visual acuity or legal blindness in the study eye). These vision-improving effects of pegaptanib were associated with beneficial angiographic effects. Intravitreous pegaptanib 0.3-3 mg was well tolerated with most ocular adverse events being mild-to-moderate and transient. Serious injection-related adverse events occurred in <or=1.3% of patients treated with pegaptanib. There were no systemic adverse events that could be definitely attributed to pegaptanib.

Animals↗

PubMed2005

Exenatide.

Exenatide is an incretin mimetic. It improves glycaemic control via various glucoregulatory mechanisms, including glucose-dependent insulinotropism, suppression of inappropriately high glucagon levels, delayed gastric emptying and reduction of food intake. In three large, well designed, phase III trials in adults with type 2 diabetes mellitus and suboptimal glycaemic control despite treatment with metformin and/or a sulfonylurea, mean changes from baseline in glycosylated haemoglobin (HbA(1c)) significantly favoured subcutaneous exenatide 5 or 10microg twice daily over placebo after 30 weeks' treatment (primary endpoint). Relative to placebo, reductions from baseline in bodyweight were significantly greater with twice-daily exenatide 5microg (in two studies) or 10microg (in all three studies). Post hoc completer analyses revealed that the beneficial effects of exenatide on HbA(1c) and bodyweight were maintained for up to 82 weeks. Adjunctive therapy with subcutaneous exenatide 10microg twice daily improved glycaemic control to a similar extent as insulin glargine in patients with type 2 diabetes suboptimally controlled with metformin plus a sulfonylurea in a large, well designed, 26-week, phase III trial. Subcutaneous exenatide was generally well tolerated in patients with type 2 diabetes. The incidence of hypoglycaemia in patients receiving exenatide plus metformin was similar to that seen in placebo plus metformin recipients; however, in patients receiving a sulfonylurea (with or without metformin), the incidence of hypoglycaemia was numerically higher with exenatide than with placebo.

Amino Acid Sequence↗

PubMed2005

Bivalirudin: a review of its use in patients undergoing percutaneous coronary intervention.

Bivalirudin (Angiox, Angiomax) is a synthetic 20-amino acid peptide analogue of hirudin. It is a direct thrombin inhibitor that binds specifically and reversibly to both fibrin-bound and unbound thrombin. Intravenous bivalirudin is approved in Europe for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI). In the US, bivalirudin is approved in patients with unstable angina pectoris undergoing percutaneous transluminal coronary angioplasty (PTCA) and has recently been approved for use with provisional glycoprotein (GP) IIb/IIIa inhibition in patients undergoing PCI. Bivalirudin plus provisional GP IIb/IIIa inhibition is effective in patients undergoing PCI. The large, well controlled REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) study showed that bivalirudin plus provisional GP IIb/IIIa inhibition was noninferior to heparin plus planned GP IIb/IIIa inhibition and that bivalirudin was associated with a reduced risk of bleeding complications. In patients with heparin-induced thrombocytopenia (HIT), bivalirudin was effective against ischaemic events and there was a low incidence of bleeding complications. Bivalirudin should be considered as an alternative to heparin plus planned GP IIb/IIIa inhibition in any patient undergoing urgent or elective PCI, especially in any patient with a high risk of bleeding complications.

Angioplasty, Balloon, Coronary↗

PubMed2005

Eptifibatide: a review of its use in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention.

Eptifibatide (Integrilin) is a highly specific, reversible, intravenously administered glycoprotein (GP) IIb/IIIa receptor antagonist that acts at the final common step of the platelet aggregation pathway. Data from large clinical trials indicate that intravenous eptifibatide as adjunctive therapy to standard care is effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and/or undergoing percutaneous coronary intervention (PCI). In the ESPRIT (Enhanced Suppression of the Platelet glycoprotein IIb/IIIa Receptor with Integrilin Therapy) trial in patients undergoing PCI with stenting, eptifibatide, compared with placebo, achieved significant reductions in death and ischaemic complications and was better than a strategy of reserving treatment for the bailout situation. In the large PURSUIT (Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial in patients with NSTE ACS, eptifibatide was associated with a significant reduction in the incidence of death or myocardial infarction (MI) compared with placebo. Eptifibatide is well tolerated in these trials. Ongoing trials are currently investigating the efficacy and tolerability of regimens that include this agent in other indications, including ST-segment elevation MI (STEMI).

Angioplasty, Balloon, Coronary↗

PubMed2005

Ertapenem: a review of its use in the treatment of bacterial infections.

The Group 1, 1 beta-methyl carbapenem ertapenem (Invanz) is approved for parenteral use in patients with complicated intra-abdominal infection (cIAI), community-acquired pneumonia (CAP) and acute pelvic infection caused by susceptible strains of certain designated organisms in both the US and the EU. Additional approved indications in the US include complicated skin and skin structure infection (cSSSI) and complicated urinary tract infection (cUTI). Ertapenem is approved for use in adults in both the US and the EU and in paediatric patients aged >or=3 months in the US. Ertapenem has a broad spectrum of in vitro activity against Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, Gram-positive pathogens and anaerobic pathogens. It has similar efficacy to comparator antibacterials such as piperacillin/tazobactam in cSSSI (including diabetic foot infection), cIAI and acute pelvic infection and ceftriaxone with or without metronidazole in cIAI, cUTI and CAP. The drug has also shown efficacy in the treatment of paediatric patients with complicated community-acquired bacterial infections. Ertapenem has a convenient once-daily administration schedule and is generally well tolerated. Thus, ertapenem is an important option for the empirical treatment of complicated community-acquired bacterial infections in hospitalised patients.

Adolescent↗

PubMed2005

Quetiapine: a review of its use in acute mania and depression associated with bipolar disorder.

Quetiapine (Seroquel), an atypical antipsychotic with established efficacy in the treatment of schizophrenia, shows efficacy in the treatment of acute mania and depression associated with bipolar disorder.Quetiapine, either as monotherapy or in combination with lithium or divalproex sodium (valproate semisodium), is generally well tolerated and effective in reducing manic symptoms in adult and adolescent patients with acute bipolar mania, and is approved for use in adults for this indication. As monotherapy, the drug is also effective in reducing depressive symptoms in patients with bipolar depression. It is associated with a low incidence of extrapyramidal symptom (EPS)-related adverse events and low EPS ratings in bipolar disorder. Quetiapine thus shows potential in the treatment of bipolar depression, and represents a useful agent for the treatment of acute bipolar mania.

Antipsychotic Agents↗

PubMed2005

Ropivacaine: a review of its use in regional anaesthesia and acute pain management.

Ropivacaine (Naropin) is the pure S(-)-enantiomer of propivacaine, and is a long-acting amide local anaesthetic agent, eliciting nerve block via reversible inhibition of sodium ion influx in nerve fibres. Ropivacaine is a well tolerated regional anaesthetic effective for surgical anaesthesia as well as the relief of postoperative and labour pain. The efficacy of ropivacaine is similar to that of bupivacaine and levobupivacaine for peripheral nerve blocks and, although it may be slightly less potent than bupivacaine when administered epidurally or intrathecally, equi-effective doses have been established. Clinically adequate doses of ropivacaine appear to be associated with a lower incidence or grade of motor block than bupivacaine. Thus ropivacaine, with its efficacy, lower propensity for motor block and reduced potential for CNS toxicity and cardiotoxicity, appears to be an important option for regional anaesthesia and for the management of postoperative and labour pain.

Acute Disease↗

PubMed2005

Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia.

Prolonged-release (PR) nicotinic acid (niacin) [Niaspan] is an oral, once-daily formulation of the lipid-modifying drug designed to produce less vasodilatory flushing than crystalline immediate-release (IR) nicotinic acid and less hepatotoxicity than previous sustained-release formulations of nicotinic acid.PR nicotinic acid appears to retain the same level of efficacy as crystalline IR nicotinic acid and be better tolerated than older nicotinic acid formulations. Nicotinic acid has beneficial effects on all traditional blood lipid and lipoprotein fractions and is the most effective agent for increasing high-density lipoprotein (HDL)-cholesterol (HDL-C) and reducing lipoprotein(a). The effects of PR nicotinic acid are often additive when used in combination with HMG-CoA reductase inhibitors (statins), making it a useful addition when lipid goals are not achieved with the usual statin monotherapy or when additional correction of a specific lipid abnormality is required. PR nicotinic acid also slows atherosclerotic progression and even appears to produce regression of atherosclerosis in patients on stable statin therapy. PR nicotinic acid is a logical drug choice for treating atherogenic dyslipidaemia commonly associated with type 2 diabetes mellitus and the metabolic syndrome, and has been shown to be effective in patients with diabetes without adversely affecting glycaemic control in the majority of patients. The incidence of vasodilatory flushing with PR nicotinic acid is lower than with IR nicotinic acid and it decreases substantially over time as tolerance develops. To date, there has been no clinically significant hepatotoxicity observed with PR nicotinic acid. Therefore, once-daily PR nicotinic acid appears to maximise the potential benefits of nicotinic acid, while minimising any historical tolerability or safety concerns.

Delayed-Action Preparations↗

PubMed2005

Zolpidem: a review of its use in the management of insomnia.

Zolpidem (Ambien, Stilnox, Myslee, an imidazopyridine, is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia. Zolpidem improves sleep in patients with insomnia. Its overall tolerability is favourable when administered according to the manufacturer's prescribing information, with a low propensity to cause clinical residual effects, withdrawal, dependence or tolerance. In addition, most evidence suggests that the drug is associated with minimal rebound insomnia. In the only clinical trials that investigated the use of a hypnosedative drug in an 'as-needed' regimen, zolpidem produced a global improvement in sleep. Thus, zolpidem continues to be a useful therapeutic option in the pharmacological treatment of patients with insomnia.

Age Factors↗

PubMed2005

Tolcapone: a review of its use in the management of Parkinson's disease.

Tolcapone (Tasmar) is a selective, reversible inhibitor of peripheral and central catechol-O-methyltransferase (COMT). Results of well designed studies indicate that oral tolcapone is an effective adjunct to levodopa plus a peripheral dopa-decarboxylase inhibitor (DDCI) in patients with fluctuating Parkinson's disease. Tolcapone significantly improves levodopa-induced motor fluctuations and significantly reduces levodopa requirements. The drug is generally well tolerated, with the most commonly occurring adverse events being dopaminergic related. Thus, tolcapone is a useful option in patients with fluctuating Parkinson's disease who are receiving levodopa/DDCI and are not responding to, or are not candidates for, other adjunctive treatments.

Antiparkinson Agents↗

PubMed2005

Extended-release carbamazepine capsules : in bipolar I disorder.

An extended-release capsule formulation of carbamazepine is approved for use in adult patients experiencing an acute manic or mixed episode associated with bipolar I disorder. A capsule of extended-release carbamazepine contains three types of bead: immediate release, extended release and enteric release, constituting 25%, 40% and 35% of the dose, respectively.black triangle Extended-release carbamazepine capsules 200--1600 mg/day demonstrated superior antimanic efficacy to placebo in two 3-week, well designed trials in adult patients with bipolar I disorder and acute manic or mixed episodes. At study end, reductions from baseline in Young Mania Rating Scale scores were significantly greater with carbamazepine than with placebo (primary endpoint). The active treatment was effective from the end of the first week of treatment (post hoc analysis).black triangle In the 3-week trials and a 6-month extension study, most treatment-emergent adverse events observed with extended-release carbamazepine were of mild or moderate severity. In the 3-week trials, although significantly greater reductions in white blood cell count occurred with extended-release carbamazepine than with placebo, only one case of leukopenia was deemed serious. There were no reports of agranulocytosis or aplastic anaemia with up to 6 months' treatment.

Anticonvulsants↗

PubMed2005

Modafinil : a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder.

Modafinil (Provigil is a wake-promoting agent that is pharmacologically distinct from CNS stimulants, such as amfetamine, dexamfetamine and methylphenidate. Modafinil is approved for use in the US and certain European countries for use in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome (OSA/HS) or shift work sleep disorder (SWSD). Oral modafinil promotes wakefulness in patients with OSA/HS and SWSD. It is an effective adjunctive therapy in patients with residual excessive sleepiness associated with OSA/HS who are receiving nasal continuous positive airway pressure (nCPAP) therapy. In SWSD, the drug improves night-time wakefulness without disrupting daytime sleep. Modafinil is generally well tolerated in patients with OSA/HS or SWSD and has a low abuse potential. Thus, modafinil is a valuable new treatment option for use in patients with excessive sleepiness associated with OSA/HS (as an adjunct to nCPAP) or SWSD.

Animals↗

PubMed2005

Spotlight on pegfilgrastim in chemotherapy-induced neutropenia.

Pegfilgrastim (Neulasta), the sustained-duration form of filgrastim (recombinant human granulocyte colony-stimulating factor [G-CSF]), is created by the addition of a polyethylene glycol (PEG) moiety to filgrastim. Its approved indication in the US is to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy.A single subcutaneous injection of pegfilgrastim once per chemotherapy cycle was more effective than placebo as an adjunct to moderately myelosuppressive chemotherapy for breast cancer, no less effective than daily injections of filgrastim as an adjunct to highly myelosuppressive chemotherapy for breast cancer, and as effective as daily filgrastim as an adjunct to chemotherapy for lymphoma (predominantly non-Hodgkin lymphoma [NHL]) and acute myeloid leukemia. Pegfilgrastim has also successfully supported delivery of dose-dense chemotherapy, stem cell mobilization, and stem cell transplantation after high-dose chemotherapy in patients with non-myeloid or myeloid malignancies. By offering a convenient alternative to daily filgrastim, once-per-cycle administration of pegfilgrastim has the potential to simplify the management of chemotherapy-induced neutropenia, further improve patient health-related quality of life, and reduce total treatment costs in breast cancer and NHL, and possibly other cancer settings. Pegfilgrastim should, likewise, permit simplification of G-CSF-based stem cell mobilization and transplantation procedures.

Antineoplastic Agents↗

PubMed2005

Imiquimod: in superficial basal cell carcinoma.

Imiquimod, available as a 5% cream, is a new topical treatment for adults with superficial basal cell carcinoma (BCC). The exact mechanism of action of imiquimod in superficial BCC is unknown. Imiquimod may act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. Topical imiquimod 5% cream effectively increased clinical and histologic clearance of single superficial BCC lesions compared with vehicle in patients enrolled in two large, well designed trials. Patients applied imiquimod five or seven times per week or vehicle for 6 weeks, and the composite clearance rates at 12 weeks post-treatment for the corresponding treatment groups were 75%, 73%, and 2%, respectively. In a trial investigating the long-term efficacy of imiquimod 5% cream following application five times per week for 6 weeks, a clinical clearance rate of 90% was reported at the initial 12-week post-treatment examination. The estimated rate of clinical clearance at the 1-year follow-up visit was 84%. Application site and local skin reactions were the most common adverse events reported by imiquimod recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.

Aminoquinolines↗

PubMed2005

Spotlight on amoxicillin/clavulanic acid 2000 mg/125 mg extended release (XR) in respiratory tract infections in adults.

Amoxicillin/clavulanic acid 2000 mg/125 mg extended release (Augmentin XR), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin.Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentrations >4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S. pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of < or = 2 microg/mL. Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin, and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis, or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations. While the incidence of amoxicillin- or multidrug-resistant S. pneumoniae is not currently sufficient in most regions to warrant the routine empiric use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e. those with S. pneumoniae isolates having amoxicillin MICs > or = 2 microg/mL but < or = 4 microg/mL).

Adolescent↗