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Biomedical subjects

Greg L Plosker

Publications and source records attributed to Greg L Plosker.

At least 19 recordsLinked to original sources
PubMed2007

Limaprost.

Limaprost, an alprostadil (prostaglandin E1) analogue, is a vasodilator that increases blood flow and inhibits platelet aggregation. The efficacy of oral limaprost was evaluated in adult Japanese patients in three randomised, double-blind, 6-week trials. One study included patients with thromboangiitis obliterans and two trials included patients with lumbar spinal canal stenosis. Limaprost was generally well tolerated and serious adverse events were uncommon. THROMBOANGIITIS OBLITERANS: In a randomised, double-blind trial in Japanese patients primarily with thromboangiitis obliterans (n=136), there was no significant difference between patients receiving limaprost 30 microg/day and those receiving oral ticlopidine 500 microg/day in the improvement of ischaemic symptoms. LUMBAR SPINAL CANAL STENOSIS: Limaprost 15 microg/day was superior to limaprost 3 microg/day for overall drug usefulness and overall improvement from baseline to study end in a phase III trial in 146 patients with lumbar spinal canal stenosis. Assessment of overall improvement considered various objective symptoms (e.g. muscle strength, walking ability) and subjective symptoms (e.g. pain or numbness in extremities), while overall usefulness also considered safety issues. The efficacy of limaprost 15 microg/day was not significantly different from that of 30 microg/day, but tended to be better than that of 6 microg/day in a phase II trial in patients with lumbar spinal canal stenosis and normal straight leg raise test results. The optimal dosage of limaprost for this indication was therefore deemed to be 15 microg/day.

Alprostadil↗
PubMed2006

Pioglitazone: a review of its use in type 2 diabetes mellitus.

Pioglitazone is an antihyperglycaemic 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 oedema 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 sulphonylurea, induced both long- and short-term improvements in glycaemic 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

Trastuzumab: a review of its use in the management of HER2-positive metastatic and early-stage breast cancer.

Trastuzumab (Herceptin) is a humanised monoclonal antibody used in the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), which is associated with clinically aggressive disease and a poor prognosis. The addition of intravenous trastuzumab to first-line chemotherapy improved the time to disease progression, objective response rate, duration of response, and overall survival in randomised, multicentre trials in women with HER2-positive metastatic breast cancer. As such, trastuzumab has become the standard of care in this setting, despite its high acquisition cost and potential for cardiac events, and is licensed for use in combination with paclitaxel (Europe and the US) or docetaxel (Europe). In addition, trastuzumab monotherapy is approved for use in patients with HER2-positive metastatic breast cancer who have previously received chemotherapy for their metastatic disease. Recent data from large phase III trials with trastuzumab in the adjuvant setting revealed significant improvements in disease-free and overall survival. Thus, trastuzumab is also rapidly becoming a standard component of adjuvant therapy for patients with HER2-positive early-stage breast cancer.

Antibodies, Monoclonal↗
PubMed2006

Hexyl aminolevulinate: in the detection of bladder cancer.

Hexyl aminolevulinate, the hexyl ester of 5-aminolevulinic acid, is a photosensitising agent designed to enhance the detection of bladder cancer tumours, in particular highly malignant carcinoma in situ (CIS). After cellular uptake, hexyl aminolevulinate and/or hydrolysed 5-aminolevulinic acid enter the haem biosynthetic pathway and induce accumulation of the photoactive compound protoporphyrin IX (PpIX) in malignant as opposed to nonmalignant cells. PpIX emits red fluorescence when illuminated under blue light. Blue-light fluorescence cystoscopy with hexyl aminolevulinate (hexyl aminolevulinate cystoscopy) was more effective than standard (white-light) cystoscopy for detecting non-muscle-invasive ('superficial') disease in two European, multicentre, phase III trials, which evaluated hexyl aminolevulinate cystoscopy as an adjunct to standard cystoscopy in patients with known or suspected bladder cancer. In one trial, hexyl aminolevulinate cystoscopy detected 96% of the patients with CIS; it identified 28% more patients with CIS than standard cystoscopy. In the other trial, 17% of patients were selected to receive more complete treatment following hexyl aminolevulinate cystoscopy than standard cystoscopy, because of the improved tumour detection rate. Hexyl aminolevulinate cystoscopy is well tolerated as an adjunct to standard cystoscopy; adverse events were those typically associated with standard cystoscopy/biopsy (e.g. postoperative pain).

Aminolevulinic Acid↗
PubMed2006

Triflusal: a review of its use in cerebral infarction and myocardial infarction, and as thromboprophylaxis in atrial fibrillation.

Triflusal (Aflen, Disgren, Tecnosal, Triflux) is a novel platelet antiaggregant with structural similarities to salicylates, but which is not derived from aspirin. It has similar efficacy to aspirin in patients with cerebral or myocardial infarction, but has a reduced risk of haemorrhagic complications. In addition, triflusal plus moderate-intensity anticoagulation has demonstrated efficacy when used as thromboprophylaxis in atrial fibrillation. As such, triflusal has a role in the primary prevention of cerebrovascular events in atrial fibrillation, and for the secondary prevention of cerebral and myocardial infarction, primarily as an alternative to aspirin in patients for whom aspirin is unsuitable.

Atrial Fibrillation↗
PubMed2006

Ibandronic acid: a review of its use in the treatment of bone metastases of breast cancer.

Ibandronic acid (Bondronat) is a potent, new-generation, nitrogen-containing bisphosphonate, available in both intravenous and oral formulations, which effectively inhibits osteoclast-mediated bone resorption. In clinical trials, the two formulations were equally effective in preventing skeletal-related events and improving quality of life in patients with bone metastases of breast cancer. Both intravenous and oral ibandronic acid reduced metastatic bone pain scores below baseline levels for up to 2 years. Oral ibandronic acid is administered as a single 50 mg tablet taken once daily. It suppressed bone resorption in breast cancer patients with bone metastases to an extent similar to that observed with intravenous zoledronic acid. Both intravenous and oral ibandronic acid were well tolerated with no evidence of renal toxicity. Ibandronic acid is therefore a valuable addition to the bisphosphonates used in the treatment of bone metastases of breast cancer, offering high potency and the convenience of oral administration, combined with the absence of renal toxicity.

Bone Density Conservation Agents↗
PubMed2006

Lubiprostone.

Lubiprostone (Amitiza) is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the gastrointestinal epithelium, resulting in increased fluid secretion. In two pivotal, randomised, double-blind, multicentre phase III studies in patients with chronic idiopathic constipation, the frequency of spontaneous bowel movements (SBMs) was significantly greater in patients receiving lubiprostone 24microg twice daily than in those receiving placebo at each weekly timepoint throughout both 4-week studies (p < 0.05). At week 1 in one pivotal trial, the mean frequency of SBMs in the lubiprostone group was 5.9 per week compared with 4.0 per week in the placebo group (p < 0.0001) [baseline SBMs 1.3 and 1.5 per week]. Significantly greater improvements occurred with lubiprostone than placebo in the degree of straining, stool consistency and constipation severity (where reported) in both pivotal studies (p < 0.05 for all comparisons at all timepoints). Lubiprostone was generally well tolerated in clinical trials with no reports of treatment-related serious adverse events in pivotal trials. Nausea was the most common adverse event, occurring in up to 31% of patients receiving lubiprostone.

Adult↗
PubMed2006

Inhaled mometasone furoate: A review of its use in persistent asthma in adults and adolescents.

Inhaled mometasone furoate (Asmanex) is a synthetic corticosteroid indicated for the first-line maintenance prophylactic therapy of persistent asthma in adults and adolescents. It is formulated for delivery via a breath-actuated dry powder inhaler (DPI) [Twisthaler].Inhaled mometasone furoate delivered by DPI is effective in treating patients with persistent asthma. It improves pulmonary function and health-related quality of life, reduces symptoms and decreases oral corticosteroid requirements in severe disease. It is a potent anti-inflammatory agent and is at least as clinically effective as other inhaled corticosteroids. Inhaled mometasone furoate is equally effective in controlling asthma when administered in two divided doses or as a single daily dose. Once-daily administration of mometasone furoate 200 microg in the evening was more effective than administration of the same dosage in the morning. The drug is well tolerated, with low systemic bioavailability and minimal systemic activity. Therefore, it is an effective and convenient option for controller therapy of persistent asthma in adults and adolescents.

Administration, Inhalation↗
PubMed2006

Lopinavir/ritonavir: a review of its use in the management of HIV infection.

Coformulated lopinavir/ritonavir (Kaletra) is a boosted protease inhibitor (PI) containing lopinavir and low-dose ritonavir. It is approved for use in combination with other antiretroviral drugs for the treatment of HIV infection in adults, adolescents and children aged >or=6 months (in the US) or >or=2 years (in the EU).Lopinavir/ritonavir-based antiretroviral therapy (ART) is generally well tolerated and has shown durable virological efficacy in clinical trials in ART-naive and -experienced patients with virological failure. Lopinavir/ritonavir is one of the preferred PIs for first-line treatment of HIV infection in adults, adolescents and children, according to US and British guidelines, reflecting its comparatively better virological efficacy than nelfinavir and low incidence of de novo resistance during long-term treatment. Lopinavir/ritonavir-based treatment may produce a more effective virological response than other PI-based regimens in single PI-experienced, non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive patients. In PI- and NNRTI-experienced patients, atazanavir/saquinavir was inferior to lopinavir/ritonavir; further well designed trials are required to determine the comparative efficacy of lopinavir/ritonavir versus other PIs such as ritonavir-boosted atazanavir, or fosamprenavir or tipranavir in these patients. Lopinavir/ritonavir is more likely than atazanavir (alone or boosted) or nelfinavir to cause hypertriglyceridaemia and is associated with a higher incidence of hypercholesterolaemia than atazanavir (alone or boosted). The new lopinavir/ritonavir tablet coformulation offers a reduced pill count and lack of food interaction, and ART-naive patients in the US and Canada, who are not receiving efavirenz, nelfinavir, nevirapine or amprenavir, may benefit from convenient once-daily administration of lopinavir/ritonavir. Thus, lopinavir/ritonavir is a convenient, effective option for use in the treatment of HIV infection in ART-naive and -experienced adults, adolescents and children.

HIV Infections↗
PubMed2006

VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases.

VSL#3 (VSL#3) is a high-concentration probiotic preparation of eight live freeze-dried bacterial species that are normal components of the human gastrointestinal microflora, including four strains of lactobacilli (Lactobacillus casei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), three strains of bifidobacteria (Bifidobacterium longum, B. breve and B. infantis) and Streptococcus salivarius subsp. thermophilus. Data from noncomparative trials suggest that VSL#3 has clinical potential in the treatment of active mild to moderate ulcerative colitis and as maintenance therapy for patients with ulcerative colitis in remission. In addition, a randomised, open-label, multicentre trial showed that VSL#3 in combination with low-dose balsalazide (a prodrug of mesalazine [mesalamine; 5-aminosalicylic acid]) was more effective than standard doses of basalazide or mesalazine monotherapy in the treatment of acute mild to moderate ulcerative colitis. Randomised, double-blind, placebo-controlled studies have shown VSL#3 is effective in preventing the onset of acute pouchitis in patients with newly formed surgical pouches, and in maintaining remission following antibacterial treatment of acute pouchitis in patients with a history of refractory or recurrent pouchitis. Treatment guidelines from the US and the UK include VSL#3 as a therapeutic option for the prevention of pouchitis relapse in patients with chronic pouchitis. In general, VSL#3 was well tolerated in clinical trials. Large, well designed, controlled confirmatory clinical trials will further determine the place of VSL#3 in the treatment of ulcerative colitis.

Colitis, Ulcerative↗
PubMed2006

Entecavir: a review of its use in chronic hepatitis B.

Entecavir (Baraclude) is a novel nucleoside analogue of 2'-deoxyguanosine whose intracellular triphosphate form inhibits replication of the hepatitis B virus (HBV). In large, randomised, double-blind, phase III clinical trials in patients with chronic HBV infection, oral entecavir 0.5 or 1.0mg once daily for up to 96 weeks was superior to lamivudine 100 mg/day in improving hepatic histology, normalising aminotransferase levels and suppressing viraemia to levels undetectable by polymerase chain reaction (PCR) assay in nucleoside-naive hepatitis B e antigen (HBeAg)-negative (precore or core promoter mutants) and/or HBeAg-positive patients, and in lamivudine-refractory (persistent viraemia during lamivudine therapy) HBeAg-positive patients. In addition, the tolerability profile of entecavir was generally similar to that of lamivudine. Thus, entecavir is a primary option in the treatment of chronic HBV infection in both nucleoside-naive and lamivudine-refractory patients.

Adolescent↗
PubMed2006

Extended-release intramuscular naltrexone.

An extended-release intramuscular formulation of naltrexone that provides sustained release of the drug over a 28-day period has been developed with the aim of improving treatment adherence in patients treated with naltrexone for alcohol dependence. Biodegradable polylactide-co-glycolide polymer microspheres containing 34% w/w naltrexone are reconstituted in an aqueous suspension just prior to intramuscular administration. Extended-release intramuscular naltrexone 380 mg administered once every 4 weeks, in combination with psychosocial therapy, demonstrated superior efficacy to placebo plus psychosocial therapy in reducing the heavy drinking event rate (primary endpoint) in adult patients with alcohol dependence in a 6-month well controlled trial. Among the subset of patients who abstained completely from drinking during the 7 days prior to the first dose of medication (n = 53; 8% of the total study population), those treated with extended-release intramuscular naltrexone 380 mg had greater reductions in the number of drinking days and the number of heavy drinking days compared with placebo recipients. Treatment with extended-release intramuscular naltrexone 380 mg once every 4 weeks for up to 18 months was generally well tolerated, with infrequent treatment-related serious adverse events. The most common treatment-emergent adverse events leading to treatment discontinuation were nausea, injection site reaction and headache. The proportion of patients with clinically significant plasma transaminase elevations was not different between patients receiving extended-release intramuscular naltrexone and those receiving placebo.

Adult↗
PubMed2006

Bimatoprost: a pharmacoeconomic review of its use in open-angle glaucoma and ocular hypertension.

Bimatoprost (Lumigan) is a prostamide analogue used for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. In comparative clinical trials of up to 1 year in duration, administration of 0.03% bimatoprost ophthalmic solution once daily was more effective than 0.5% timolol twice daily and at least as effective as the prostaglandin analogues 0.005% latanoprost and 0.004% travoprost once daily in terms of reducing IOP and/or achieving target IOP levels. Bimatoprost was also more effective than twice-daily administration of 0.5%/2% timolol/dorzolamide in patients refractory to topical timolol therapy. Although generally well tolerated, bimatoprost is associated with a higher incidence of conjunctival hyperaemia than latanoprost, timolol or the combination of timolol and dorzolamide. Three fully published modelled cost-effectiveness analyses of bimatoprost evaluating cost per treatment success in patients with glaucoma or ocular hypertension have been conducted in the US. The analyses incorporated results of randomised, multicentre clinical trials and used a 1-year time horizon. In the treatment algorithm used in the models, patients not achieving target IOP levels with bimatoprost or comparator required additional medical visits and adjunctive therapy. Bimatoprost was associated with lower costs per treatment success than latanoprost, timolol or timolol/dorzolamide across a range of clinically relevant target IOPs. Results were sensitive to changes in treatment success rates and/or drug acquisition costs. Along with the inherent limitations of economic models, other possible criticisms of the analyses are the use of selected IOP data, and the lack of inclusion of costs associated with conjunctival hyperaemia or other adverse effects of therapy. Various other cost-effectiveness analyses of bimatoprost are available, primarily as abstracts and/or posters. In general, most of these studies have also been favourable for bimatoprost, despite having been conducted in different countries and/or from different perspectives. In conclusion, in patients with open-angle glaucoma or ocular hypertension, bimatoprost is an effective and generally well tolerated therapeutic option, albeit with a relatively high incidence of conjunctival hyperaemia. Although results of modelled cost-effectiveness analyses should be interpreted with due consideration of the limitations of the studies, available pharmacoeconomic data generally support the use of bimatoprost as a cost-effective treatment in this patient population.

Amides↗
PubMed2006

Clopidogrel: a pharmacoeconomic review of its use in patients with non-ST elevation acute coronary syndromes.

Clopidogrel (Plavix) is a selective inhibitor of adenosine diphosphate-induced platelet aggregation. In patients with acute coronary syndromes (ACS) [unstable angina or non-ST-segment elevation myocardial infarction], clopidogrel plus aspirin (acetylsalicylic acid) for up to 1 year significantly reduced the risk of cardiovascular events relative to placebo plus aspirin in the well designed clinical trial CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) and its substudy in patients undergoing percutaneous coronary intervention (PCI) [PCI-CURE]. In pharmacoeconomic evaluations based on data from these trials conducted in a number of countries that used a variety of models, methods and/or type of costs, clopidogrel plus aspirin was consistently predicted to be cost effective relative to aspirin alone in the management of patients with ACS, including those undergoing PCI. Clopidogrel plus aspirin in patients with ACS reduced the incremental cost per cardiovascular event prevented and/or life-year gained (LYG) relative to aspirin alone in analyses using within-trial data (including longer-term analyses incorporating life-expectancy estimates) from the CURE or PCI-CURE studies. In Markov models of cost effectiveness with a lifetime horizon from a healthcare payer perspective based on the CURE trial, relative to aspirin alone, clopidogrel plus aspirin for 1 year was predicted to have incremental costs per LYG of 8132Euro in Spain (2003 values) and 1365Euro in Sweden (2000 values). In similar Swedish analyses from a healthcare payer perspective, clopidogrel plus aspirin for 1 year was predicted to have incremental costs per LYG of 10,993Euro (2004 values) relative to aspirin alone based on data from the PCI-CURE substudy. Broadly similar results have also been reported in modelled analyses from other countries. Cost-utility analyses based on the CURE trial suggest that, relative to lifelong aspirin alone, clopidogrel plus aspirin for 1 year followed by aspirin alone is associated with incremental costs per QALY gained that are below the traditional threshold of cost utility in Spain, the UK and the US. In patients with ACS, including those undergoing PCI, the addition of clopidogrel to standard therapy with aspirin is clinically effective in preventing cardiovascular events. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of clopidogrel plus aspirin for up to 1 year as a cost-effective treatment relative to aspirin alone in this patient population.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Candesartan cilexetil: a pharmacoeconomic review of its use in chronic heart failure and hypertension.

The addition of candesartan cilexetil (Atacand, Amias, Blopress, Kenzen, Ratacand) to standard therapy for chronic heart failure (CHF) provided important clinical benefits at little or no additional cost in France, Germany and the UK, according to a detailed economic analysis focusing on major cardiovascular events and prospectively collected resource-use data from the CHARM-Added and CHARM-Alternative trials in patients with CHF and left ventricular (LV) systolic dysfunction. Results of a corresponding cost-effectiveness analysis showed that candesartan cilexetil was either dominant over placebo or was associated with small incremental costs per life-year gained, depending on the country and whether individual trial or pooled data were used. Preliminary data from a US cost-effectiveness analysis based on CHARM data also showed favourable results for candesartan cilexetil. Two cost-effectiveness analyses of candesartan cilexetil in hypertension have been published, both conducted in Sweden. Data from the SCOPE trial in elderly patients with hypertension, which showed a significant reduction in nonfatal stroke with candesartan cilexetil-based therapy versus non-candesartan cilexetil-based treatment, were incorporated into a Markov model and an incremental cost-effectiveness ratio of euro12 824 per QALY gained was calculated (2001 value). Another modelled cost-effectiveness analysis of candesartan cilexetil was based on the ALPINE trial, in which the incidence of new-onset diabetes was significantly lower in patients with newly diagnosed hypertension who were randomised to candesartan cilexetil (with or without felodipine) than among those who received hydrochlorothiazide (with or without atenolol). Although candesartan cilexetil was dominant over hydrochlorothiazide, the ALPINE cost-effectiveness analysis relied on a small number of clinical events and did not evaluate the incremental cost of candesartan cilexetil per life-year or QALY gained. In conclusion, despite some inherent limitations, economic analyses incorporating CHARM data and conducted primarily in Europe have shown that candesartan cilexetil appears to be cost effective when added to standard CHF treatment in patients with CHF and compromised LV systolic function. The use of candesartan cilexetil as part of antihypertensive therapy in elderly patients with elevated blood pressure was also deemed to be cost effective in a Swedish analysis, primarily resulting from a reduced risk of nonfatal stroke (as shown in the SCOPE study); however, the generalisability of results to other contexts has not been established. Cost-effectiveness analyses comparing candesartan cilexetil with ACE inhibitors or other angiotensin receptor blockers in CHF or hypertension are lacking, and results reported for candesartan cilexetil in a Swedish economic analysis of ALPINE data focusing on outcomes for diabetes require confirmation and extension.

Angiotensin II Type 1 Receptor Blockers↗