Biomedical subjects

Gillian M Keating

Publications and source records attributed to Gillian M Keating.

At least 37 records · Page 2Linked to original sources

PubMed2006

Tacrolimus: in heart transplant recipients.

Tacrolimus is a calcineurin inhibitor recently approved in the US and throughout the EU for the prevention of allograft rejection in heart transplant recipients. It is commonly administered orally for long-term immunosuppression. The incidence of mild to severe acute rejection in the first 6 months following heart transplantation was significantly lower in tacrolimus recipients than in ciclosporin recipients (54% vs 66%) in a large, phase III trial conducted in Europe. A large, phase III trial conducted in the US did not show a significant difference between tacrolimus and ciclosporin in the incidence of severe rejection or haemodynamic compromise rejection requiring treatment within the first 6 months post-transplant (22% vs 32%), but did show a significant difference in the incidence at 1 year (23% vs 37%). In phase III trials, 1-year patient survival was similar between tacrolimus and ciclosporin recipients in the EU (93% vs 92%) and the US (95% vs 90%). Tacrolimus was shown to be effective in the prevention of rejection in paediatric and African American heart transplant recipients. The tolerability profile of tacrolimus in heart transplant recipients was broadly similar to that of ciclosporin, although tacrolimus was usually associated with lower incidences of post-transplant hypertension and dyslipidaemia.

Clinical Trials as Topic↗

PubMed2006

Sertindole : a review of its use in schizophrenia.

Oral sertindole (Serdolect) is an atypical antipsychotic approved in the EU for once-daily use in patients with schizophrenia who are intolerant to at least one other antipsychotic agent. Extensive data from post-marketing studies do not indicate an excess of overall mortality with sertindole. Sertindole is at least as effective as haloperidol and risperidone in the treatment of neuroleptic-responsive schizophrenia. Sertindole improves negative symptoms, and is also effective for the treatment of neuroleptic-resistant schizophrenia. Sertindole is generally well tolerated and is associated with a low rate of extrapyramidal symptoms (EPS). Thus, sertindole is a useful option in the treatment of patients with schizophrenia.

Antipsychotic Agents↗

PubMed2006

Spotlight on quetiapine 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↗

PubMed2006

Spotlight on remifentanil: its analgesic and sedative use in the intensive care unit.

Remifentanil (Ultivatrade), a 4-anilidopiperidine derivative of fentanyl, is an ultra-short-acting micro-opioid receptor agonist indicated to provide analgesia and sedation in mechanically ventilated intensive care unit (ICU) patients. Analgesia-based sedation with remifentanil is a useful option for mechanically ventilated patients in the ICU setting. Its unique properties (e.g. organ-independent metabolism, lack of accumulation, rapid offset of action) set it apart from other opioid agents. Remifentanil is at least as effective as comparator opioids such as fentanyl, morphine and sufentanil in providing pain relief and sedation in mechanically ventilated ICU patients. Moreover, it allows fast and predictable extubation, as well as being associated with a shorter duration of mechanical ventilation and quicker ICU discharge than comparators in some studies. In addition, remifentanil is generally well tolerated in this patient population. Thus, remifentanil is a welcome addition to the currently available pharmacological agents employed in the management of mechanically ventilated ICU patients.

Drug Tolerance↗

PubMed2006

Varenicline: a review of its use as an aid to smoking cessation therapy.

Varenicline is an orally administered alpha4beta2 nicotinic acetylcholine (ACh) receptor partial agonist. It has been approved by the US FDA (Chantix) and the European Commission (Champix) for use as an aid to smoking cessation therapy. Varenicline is an effective and generally well tolerated treatment for use in smokers who want to quit. In two well designed, phase III trials, 12 weeks' treatment with varenicline was associated with significantly higher continuous abstinence rates at weeks 9-12 than placebo or bupropion sustained-release (SR). In the longer term, continuous abstinence rates for weeks 9 through 52 demonstrated that the odds of remaining abstinent were 2.7 to 3.1 times higher with 12 weeks of varenicline treatment than with placebo; the significant difference between varenicline and bupropion SR was also maintained in the longer term in one trial. Moreover, varenicline appeared to attenuate the urge to smoke, negative affect withdrawal symptoms and the reinforcing effects of smoking. Among those achieving abstinence, an additional 12 weeks of varenicline therapy helped increase the likelihood of long-term abstinence. Thus, varenicline is a valuable new agent for use as an aid to smoking cessation treatment.

Benzazepines↗

PubMed2006

Spotlight on eletriptan in migraine.

Eletriptan (Relpax) is an orally administered, lipophilic, highly selective serotonin 5-HT(1B/1D) receptor agonist ('triptan') that is effective in the acute treatment of moderate to severe migraine attacks in adults. It has a rapid onset of action and demonstrates superiority over placebo as early as 30 minutes after the administration of a single 40 or 80 mg oral dose. The efficacy of eletriptan 20 mg was similar to that of sumatriptan 100 mg, while eletriptan 40 and 80 mg displayed greater efficacy than sumatriptan 50 or 100 mg for most endpoints. Eletriptan 40 mg was generally superior to naratriptan 2.5 mg and equivalent to almotriptan 12.5 mg, rizatriptan 10 mg and zolmitriptan 2.5 mg, while eletriptan 80 mg was superior to zolmitriptan 2.5 mg for most efficacy parameters. Eletriptan 40 and 80 mg were consistently superior to ergotamine/caffeine. Eletriptan is generally well tolerated, reduces time lost from normal activities, improves patients' health-related quality of life and appears to be at least as, if not more, cost effective than sumatriptan. Eletriptan is therefore a useful addition to the triptan family and a first-line treatment option in the acute management of migraine attacks.

Humans↗

PubMed2006

Spotlight on pioglitazone in type 2 diabetes mellitus.

Pioglitazone (Actos(trade mark)) is an antihyperglycemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and edema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin, or a sulfonylurea, induced both long- and short-term improvements in glycemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.

Blood Glucose↗

PubMed2006

Spotlight on eptifibatide in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention.

Eptifibatide (Integrilin) is a highly specific, reversible, intravenously administered glycoprotein 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 ischemic 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.

Angioplasty, Balloon, Coronary↗

PubMed2006

Spotlight on darbepoetin alfa in the treatment of anemia in patients with cancer receiving chemotherapy.

Darbepoetin alfa (Aranesp) is an analog of recombinant human erythropoietin (rHuEPO) produced using recombinant DNA technology. The high number of sialic acid moieties in darbepoetin alfa results in a prolonged half-life and enhanced in vivo biologic activity compared with rHuEPO (as demonstrated in animal studies), and permits a reduction in the frequency of administration. Subcutaneous darbepoetin alfa 2.25 microg/kg once weekly or 500microg once every 3 weeks (with a provision for dosage adjustments) is an effective and well tolerated erythropoietic agent in anemic patients with cancer receiving chemotherapy. In randomized, controlled clinical trials, the drug increased hemoglobin levels and reduced the need for blood transfusions in patients with various types of nonmyeloid malignancies, and also ameliorated anemia-related fatigue, thereby improving their health-related quality of life scores. The once-every-3-weeks dosage regimen provides further convenience by offering the possibility of synchronizing its administration with most chemotherapy regimens. Direct comparisons between approved dosages of darbepoetin alfa and other erythropoietic agents have not been conducted. Such comparisons would be very helpful in formulating definitive conclusions about their relative efficacy and cost effectiveness. Darbepoetin alfa provides an effective and well tolerated treatment option for the treatment of anemia in patients with cancer receiving chemotherapy.

Journal Article↗

PubMed2006

Reduced-antigen, combined diphtheria, tetanus, and acellular pertussis vaccine (Boostrix): a review of its use as a single-dose booster immunization.

Reduced-antigen, combined diphtheria, tetanus, and acellular pertactin-containing pertussis vaccine (dTpa; Boostrix) contains reduced quantities of the same toxoids/antigens found in a diphtheria, tetanus, and acellular pertussis vaccine (DTPa; Infanrix) used for the primary immunization series in children. A single dose of dTpa (Boostrix) is indicated for booster vaccination against diphtheria, tetanus, and pertussis in individuals aged >or=4 years in Europe and Canada, in individuals aged >or=10 years in Australia, and in adolescents aged 10-18 years in the US.A single booster dose of dTpa (Boostrix) was safe and highly immunogenic for all its component toxoids/antigens when administered to adults, adolescents (including those previously unvaccinated), and children aged >or=4 years in clinical trials conducted in various countries worldwide. It was also well tolerated, as was a second (repeat) dose administered to a small number of adolescents who had previously received the vaccine as a preschool booster. Vaccinees generally reported a low incidence of severe/grade 3, solicited, local and general adverse events during the 1-month postvaccination period.Current recommendations for dTpa usage vary from country to country; they include one dose only in adolescence or adulthood (e.g. Australia, Canada, France, Switzerland, and the US), one dose at preschool age and one in adolescence (Germany), and one dose in adolescence followed by regular (10-year) doses during adulthood (Austria). Available data support the use of dTpa (Boostrix) in place of the combined diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) or DTPa booster dose in preschool children and/or the reduced-antigen, combined diphtheria, tetanus vaccine (Td) booster dose in adolescents, as well as in place of a regular Td booster dose in adults who have not previously received the vaccine.

Antigens, Bacterial↗

PubMed2006

Rotavirus vaccine (RotaTeq).

RotaTeq is a live, oral, pentavalent human-bovine reassortant rotavirus vaccine approved for use in the prevention of G1-G4 rotavirus gastroenteritis in infants and children. Rotavirus vaccine demonstrated good immunogenicity in healthy infants. Three oral doses of rotavirus vaccine had a protective efficacy against G1-G4 rotavirus gastroenteritis of any severity of 74%, and a protective efficacy against severe G1-G4 rotavirus gastroenteritis of 98%, in the randomized, double-blind, placebo-controlled, multicenter REST (Rotavirus Efficacy and Safety Trial) study; the per-protocol efficacy analysis included >4500 infants. Healthcare resource use was reduced by rotavirus vaccine, with a 94.5% reduction in the incidence of hospitalization or emergency department care because of G1-G4 rotavirus gastroenteritis. This analysis of the REST trial included >57,000 infants. Rotavirus vaccine did not increase the risk of intussusception within 42 days of any dose, according to an analysis of the REST trial including almost 70,000 infants. Rotavirus vaccine and placebo were associated with serious adverse events in <3% of infants in either group.

Administration, Oral↗

PubMed2006

Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review of its use in the treatment of children and adolescents with attention-deficit hyperactivity disorder.

Controlled-delivery methylphenidate (methylphenidate CD) [EquasymXL, Metadate CD], an oral stimulant, is approved in the US and EU to treat children aged>or=6 years who have been diagnosed with attention-deficit hyperactivity disorder (ADHD). Once-daily methylphenidate CD is generally well tolerated and effective in the treatment of children and adolescents with ADHD. Methylphenidate CD resulted in superior control of ADHD symptoms compared with osmotic release oral system (OROS) methylphenidate over a time period corresponding to that of an average school day in a laboratory classroom. In 3-week clinical trials conducted in a community setting, methylphenidate CD was superior to placebo and noninferior to methylphenidate immediate-release (IR) in the treatment of children and adolescents with ADHD. Thus, methylphenidate CD should be considered an important primary treatment on its own or in addition to behavioral and psychosocial interventions, for when a reduction in ADHD symptoms is required during the school day in preference to the evening.

Adolescent↗

PubMed2006

Rotavirus vaccine RIX4414 (Rotarix).

RIX4414 is a human, live attenuated rotavirus vaccine containing a rotavirus strain of G1P[8] specificity; it is administered orally using a two-dose schedule. RIX4414 showed good immunogenicity in healthy infants in several well designed trials in terms of both seroconversion rates and vaccine take. Moreover, RIX4414 did not impair the immune response of infants to other vaccines. RIX4414 provided significant protection against severe rotavirus gastroenteritis. In a subgroup analysis (n = 20 169) of a large (n = 63 225), well designed, placebo-controlled, phase III trial (conducted in Latin America and Finland), the efficacy of RIX4414 against severe rotavirus gastroenteritis was 85% in healthy infants, with an efficacy against hospitalization for severe rotavirus gastroenteritis of 85%. RIX4414 provided cross-protection against non-G1 serotypes containing the P[8] antigen. Moreover, in this trial, RIX4414 had a protective efficacy against severe gastroenteritis of any cause of 40%, with an efficacy against hospitalization because of severe gastroenteritis of any cause of 42%. In another well designed, placebo-controlled, phase III trial (conducted in Europe; n = 3874), RIX4414 had an efficacy against rotavirus gastroenteritis of any severity of 87%, an efficacy against severe rotavirus gastroenteritis of 96%, and an efficacy against hospitalization because of rotavirus gastroenteritis of 100%. RIX4414 protected against rotavirus gastroenteritis from the first dose onwards. A meta-analysis revealed that RIX4414 had a protective efficacy against rotavirus gastroenteritis of any severity caused by the G2P[4] serotype of 81% and against severe rotavirus gastroenteritis caused by the G2P[4] serotype of 71%. RIX4414 was generally well tolerated in healthy infants. The vaccine did not appear to be associated with an increased risk of intussusception.

Clinical Trials as Topic↗

PubMed2005

Amoxicillin/clavulanic acid 2000mg/125mg extended release (XR): a review of its use in the treatment of respiratory tract infections in adults.

Amoxicillin/clavulanic acid 2000mg/125mg 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 above 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 empirical 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).

Adult↗

PubMed2005

Peginterferon alpha-2a (40KD) plus ribavirin: a review of its use in the management of patients with chronic hepatitis C and persistently 'normal' ALT levels.

Combination therapy with subcutaneous peginterferon alpha-2a (40KD) [Pegasys] plus oral ribavirin (Copegus) has been evaluated previously in patients with chronic hepatitis C and elevated ALT levels. A recent randomised, nonblind, multicentre trial examined the efficacy of this combination therapy in the treatment of patients with persistently 'normal' ALT levels. These trial results showed that combination therapy with peginterferon alpha-2a (40KD) plus ribavirin is effective in patients with chronic hepatitis C and persistently normal ALT levels. Overall, a sustained virological response occurred in over 50% of patients who received combination therapy for 48 weeks, albeit with a low daily dosage of ribavirin. The tolerability profile of combination therapy in patients with persistently normal ALT levels is similar to that seen in patients with elevated ALT levels. The decision as to whether or not treatment should be initiated in patients with chronic hepatitis C and persistently normal ALT levels should be made on an individual basis. If a decision is made to treat, combination therapy with peginterferon alpha-2a (40KD) plus ribavirin can be considered a first-line treatment option.

Alanine Transaminase↗

PubMed2005

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

Gatifloxacin (Tequin) is an 8-methoxy fluoroquinolone approved in the US for use in the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute sinusitis, uncomplicated and complicated urinary tract infections (UTIs), pyelonephritis, gonorrhoea and uncomplicated skin and skin structure infections. Gatifloxacin has a broad spectrum of antibacterial activity in vitro and good clinical and bacteriological efficacy in patients with indicated infections following once-daily administration by the intravenous or oral routes. It is generally well tolerated; the most common adverse events are associated with the gastrointestinal tract and CNS. Recent approvals for the use of gatifloxacin in the treatment of CAP due to multidrug-resistant Streptococcus pneumoniae (MDRSP) and in uncomplicated skin and skin structure infections extend the role of this drug in the treatment of bacterial infections in the US.

Bacterial Infections↗

PubMed2005

Mycophenolate sodium delayed release: prevention of renal transplant rejection.

Mycophenolate sodium delayed release is an enteric-coated formulation designed to release the active agent (mycophenolic acid) in the small intestine. Mycophenolate sodium delayed release was equivalent in efficacy to, and had a similar tolerability profile as, mycophenolate mofetil in de novo renal transplant patients treated with ciclosporin (cyclosporin) and corticosteroids in a well designed study of 12 month's duration. Maintenance renal transplant patients treated with ciclosporin and corticosteroids were converted from mycophenolate mofetil to mycophenolate sodium delayed release without any alteration in efficacy or tolerability in a well designed study of 12 month's duration. The incidence of gastrointestinal adverse events with mycophenolate sodium delayed release was similar to that with mycophenolate mofetil.

Delayed-Action Preparations↗

PubMed2005

Peginterferon-alpha-2a (40kD): a review of its use in the management of patients with chronic hepatitis B.

Subcutaneous peginterferon-alpha-2a (40kD) [Pegasys] is an effective and reasonably well tolerated treatment for the management of patients with hepatitis B e antigen (HBeAg)-negative or -positive chronic hepatitis B. It was significantly more effective than lamivudine monotherapy at inducing sustained virological response and ALT normalisation in both HBeAg-negative and -positive patients. Notably, the addition of lamivudine to peginterferon-alpha-2a (40kD) conferred no additional benefit versus peginterferon-alpha-2a (40kD) monotherapy. Moreover, in HBeAg-positive patients significantly more peginterferon-alpha-2a (40kD) recipients experienced HBeAg seroconversion than lamivudine recipients. The position of peginterferon-alpha-2a (40kD) relative to other treatment options remains to be fully determined. In the meantime, this agent appears to be a valuable new option for the management of patients with HBeAg-negative or -positive chronic hepatitis B.

Disease Management↗