Biomedical subjects

Monique P Curran

Publications and source records attributed to Monique P Curran.

8 recordsLinked to original sources

PubMed2003

DTPa-HBV-IPV/Hib vaccine (Infanrix hexa).

Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B recombinant (adsorbed)-inactivated poliomyelitis-adsorbed conjugated Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib; Infanrix hexa)-inactivated poliomyelitis-absorbed conjugated Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) refers to Infanrix hexa trade mark.) provided high levels of seroprotection against diphtheria toxoid, tetanus toxoid, poliovirus 1, 2 and 3, pertussis antigens (pertussis toxoid, filamentous haemagglutinin and pertactin), hepatitis B virus surface antigen and H. influenzae polyribosyl-ribitol-phosphate (PRP) antigen. Most infants (97%) had anti-PRP levels >/=0.15 micro g/mL after a booster dose at 18 months. Primary vaccination with the DTPa-HBV-IPV/Hib vaccine produced a similar immune response to that with two different pentavalent plus monovalent vaccine combinations. Coadministration of DTPa-HBV-IPV/Hib vaccine and a heptavalent pneumonococcal conjugate vaccine resulted in a high level of seroprotection and was well tolerated. Primary or booster vaccination with DTPa- HBV-IPV/Hib vaccine was well tolerated. Commonly reported local adverse reactions included redness, pain and swelling. Systemic symptoms were usually mild to moderate, and included fussiness, fever, restlessness and sleepiness.

Antibody Formation↗

PubMed2003

Lovastatin extended release: a review of its use in the management of hypercholesterolaemia.

UNLABELLED: Lovastatin extended release (ER) provides a new form of delivery for lovastatin, an HMG-CoA reductase inhibitor. Lovastatin ER delivers the drug in a more sustained fashion, as shown by a smoother plasma concentration-time profile, a lower maximum plasma concentration and a prolonged half-life compared with that of lovastatin immediate release (IR). At dosages of 10-60 mg/day, lovastatin ER significantly reduced levels of total cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides, and increased levels of high density lipoprotein-cholesterol, in patients with primary hypercholesterolaemia in a randomised, double-blind study of 12 weeks' duration. These effects were maintained in a 6-month extension study in which patients received lovastatin 40 or 60 mg/day. In a randomised 4-week study in 24 patients with primary hypercholesterolaemia, the reduction in plasma LDL-cholesterol levels was significantly greater with lovastatin ER 40 mg/day than with the IR formulation administered at the same dosage. Lovastatin ER was well tolerated in all studies and adverse events were usually mild to moderate and transient. The tolerability profile of lovastatin ER was similar to that of lovastatin IR. There were no reports of clinically relevant elevations in liver transaminases or creatine phosphokinase attributed to the drug in recipients of lovastatin ER. CONCLUSION: The ER formulation of lovastatin provides smooth and sustained delivery of this established and well-tolerated agent over the dosage interval, significantly reducing LDL-cholesterol in patients with primary hypercholesterolaemia. If, as expected, the beneficial changes in lipid levels are maintained during long-term treatment and further clinical experience confirms the greater efficacy of the lovastatin ER formulation than the IR formulation, then lovastatin ER is likely to supplant lovastatin IR and provide a useful option in the management of patients with dyslipidaemia and prevention of coronary heart disease.

Absorption↗

PubMed2003

Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in the management of chronic hepatitis C.

Pegylation of interferon-alpha-2a is associated with improved sustained virological response rates in patients with chronic hepatitis C. Subsequently, combination therapy with peginterferon-alpha-2a (40kD) [Pegasys] and ribavirin (Copegus trade mark, Rebetol) was investigated to establish if the efficacy of peginterferon-alpha-2a (40kD) monotherapy could be further enhanced. Subcutaneous peginterferon-alpha-2a (40kD) was administered at a dosage of 180 micro g once weekly and oral ribavirin was usually administered at a dosage of 1000 or 1200 mg/day. In treatment-naive patients with chronic hepatitis C, the sustained virological response rate (assessed 24 weeks after the end of a 48-week treatment period) was significantly higher in peginterferon-alpha-2a (40kD) plus ribavirin recipients than in peginterferon-alpha-2a (40kD) plus placebo recipients or interferon-alpha-2b plus ribavirin recipients (56% vs 29% and 44%). Retrospective analysis revealed that peginterferon-alpha-2a (40kD) plus ribavirin recipients who did not achieve an early virological response were unlikely to achieve a sustained response. Treatment with peginterferon-alpha-2a (40kD) plus another antiviral agent (ribavirin, mycophenolate mofetil, amantadine, or ribavirin and amantadine) was beneficial in patients with chronic hepatitis C who had relapsed during or after, or had not responded to, treatment with interferon-alpha-2b plus ribavirin. In the relapse study, sustained virological response rates in recipients of peginterferon-alpha-2a (40kD) plus ribavirin were 45% with and 38% without amantadine. Peginterferon-alpha-2a (40kD) plus ribavirin appears beneficial in patients with chronic hepatitis C considered difficult to treat (e.g. patients infected with hepatitis C virus genotype 4, African-American patients, patients with advanced fibrosis or cirrhosis and patients co-infected with HIV). Flu-like symptoms and depression occurred significantly less frequently with peginterferon-alpha-2a (40kD) plus ribavirin than with interferon-alpha-2b plus ribavirin. Similar proportions of patients receiving peginterferon-alpha-2a (40kD) plus ribavirin, peginterferon-alpha-2a (40kD) plus placebo and interferon-alpha-2b plus ribavirin withdrew from treatment because of laboratory abnormalities or other adverse events. In conclusion, combination therapy comprising subcutaneous peginterferon-alpha-2a (40kD) and oral ribavirin is an important new treatment option for chronic hepatitis C. Peginterferon-alpha-2a (40kD) plus oral ribavirin is significantly more effective than peginterferon-alpha-2a (40kD) monotherapy or interferon-alpha-2b plus ribavirin at inducing a sustained virological response in treatment-naive patients with chronic hepatitis C. Preliminary data suggest that peginterferon-alpha-2a (40kD) plus ribavirin is also beneficial in treatment-experienced patients and in patients who have traditionally been considered difficult to treat. Combination therapy with peginterferon-alpha-2a (40kD) and oral ribavirin is poised to become a valuable first-line treatment option in chronic hepatitis C.

Adsorption↗

PubMed2002

Vinorelbine: a review of its use in elderly patients with advanced non-small cell lung cancer.

Vinorelbine is a semisynthetic vinca alkaloid that is effective as monotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC). In the large comparative Elderly Lung Cancer Vinorelbine Italian Study (ELVIS), patients receiving vinorelbine monotherapy achieved an objective response rate of 19.7%. The median survival time and the 1-year survival rate were significantly higher in recipients of vinorelbine plus best supportive care than in recipients of best supportive care alone. Vinorelbine recipients generally scored better than recipients of best supportive care on quality-of-life (QOL) functioning scales and experienced significantly fewer lung cancer-related symptoms; however, QOL scores were worse with vinorelbine for parameters relating to drug tolerability. Comparative phase III trials investigating the efficacy of combination therapy with vinorelbine and other agents specifically in elderly patients with advanced NSCLC have been conducted only for the combination of vinorelbine and gemcitabine [the Southern Italy Cooperative Oncology Group (SICOG) trial and the Multicenter Italian Lung Cancer in the Elderly Study (MILES)]. Objective response rates for vinorelbine/gemcitabine combination therapy in these phase III trials were 22 and 20%, respectively. The SICOG trial was closed early when an interim analysis demonstrated a significant survival advantage for combination therapy with vinorelbine plus gemcitabine over vinorelbine monotherapy. However, a survival advantage for combination therapy versus vinorelbine monotherapy was not demonstrated in the larger MILES trial. The main adverse effect of vinorelbine monotherapy in the elderly is myelosuppression. Adverse events associated with most antineoplastic agents, such as mild alopecia, nausea, vomiting and mucositis, were reported in clinical trials; however, these events were rarely severe. Mild-to-moderate neurotoxicity, including constipation (presumably from autonomic neuropathy), was also reported. The addition of gemcitabine to vinorelbine increased the incidence of both haematological and nonhaematological adverse events. However, there was no significant increase in the incidence of life-threatening toxicity. Vinorelbine as a single agent is effective in elderly patients with NSCLC and is associated with improved survival and at least a trend towards improved QOL parameters compared with best supportive care alone. Vinorelbine was associated with a generally manageable tolerability profile. The benefit of adding gemcitabine to vinorelbine for the treatment of NSCLC in the elderly is equivocal; improved survival was reported in one comparative trial, but not in another larger one. Vinorelbine is an effective and well tolerated palliative treatment option for elderly patients with advanced NSCLC.

Age Factors↗

PubMed2002

Pegfilgrastim.

Pegfilgrastim is a covalent conjugant of filgrastim (a recombinant human granulocyte colony-stimulating factor) and monomethoxypolyethylene glycol. It is administered as a single dose per myelosuppressive chemotherapy cycle to decrease the incidence of infection, as manifest by febrile neutropenia, in patients with nonmyeloid cancer. Pegfilgrastim increases the terminal elimination half-life and decreases the apparent serum clearance of the drug in patients with nonmyeloid cancer. Serum concentrations of pegfilgrastim remain elevated during neutropenia but decline when the neutrophil count increases. In phase III trials in patients with breast cancer and in a phase II trial in patients with non-Hodgkin's lymphoma or Hodgkin's disease, the mean duration of grade 4 neutropenia and the time to absolute neutrophil recovery during cycle 1 of chemotherapy was similar in recipients of single-dose pegfilgrastim or daily filgrastim. In the larger of two phase III trials in patients with breast cancer, the incidence of febrile neutropenia over four cycles of chemotherapy was significantly lower in recipients of single-dose pegfilgrastim than that in recipients of daily injections of filgrastim. Moreover, the mean duration of grade 4 neutropenia in cycles 2 to 4 of chemotherapy was significantly lower in recipients of pegfilgrastim than that in recipients of daily filgrastim. In comparative trials, there were no differences in the incidence and severity of adverse events, including skeletal pain, between single-dose pegfilgrastim and daily filgrastim in patients with nonmyeloid cancer receiving myelosuppressive chemotherapy.

Antineoplastic Agents↗

PubMed2002

Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension.

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Spotlight on amisulpride in schizophrenia.

UNLABELLED: Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D(2)/D(3) autoreceptors. At higher doses, amisulpride antagonises postsynaptic D(2) and D(3) receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or = 300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. CONCLUSION: In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

Amisulpride↗

PubMed2002

Bilayered bioengineered skin substitute (Apligraf): a review of its use in the treatment of venous leg ulcers and diabetic foot ulcers.

UNLABELLED: The bilayered bioengineered skin substitute (BBSS) [Apligraf] is used for the treatment of venous leg ulcers and diabetic foot ulcers. It has an epidermal layer formed from human keratinocytes and a dermal layer composed of human fibroblasts in a bovine type I collagen matrix. BBSS does not contain any antigen-presenting cells such as Langerhans cells, dermal dendritic cells, endothelial cells or leucocytes. In clinical trials, there was no evidence of clinical rejection and immunological tests indicated no humoral or cellular response to the keratinocytes or fibroblasts of BBSS. Further clinical trials are required to identify the exact mechanism of action of BBSS in chronic wounds. BBSS plus compression therapy was well tolerated and was superior in efficacy to compression therapy alone in a multicentre, randomised trial in patients with venous leg ulcers. At 6 months' follow-up, complete wound healing occurred in 63 versus 49% of patients and the median time to wound closure was 61 versus 181 days. In a subgroup of patients with hard-to-heal ulcers (>1 year's duration), wound healing was achieved in significantly more patients (47 vs 19%) and the median time to wound healing was significantly shorter (181 days vs not attained). In a multicentre, randomised trial, BBSS was well tolerated and effective in patients with full-thickness neuropathic diabetic foot ulcers. Ulcer healing occurred in significantly more patients (56 vs 38%) and the median time to wound healing was shorter (65 vs 90 days) with BBSS than with saline-moistened gauze at 12 weeks' follow-up. Patients in both groups also received standard diabetic foot care. The cost effectiveness of BBSS in patients with chronic ulcers has yet to be examined in well designed, prospective clinical trials. However, according to a modelled analysis incorporating data from a multicentre randomised trial, BBSS was cost effective in patients with hard-to-heal venous leg ulcers. The average annual medical cost of managing patients with ulcers of >1 year's duration was estimated to be 20,041 US dollars per patient treated with BBSS plus compression therapy and 27,493 US dollars per patient treated with compression therapy alone (1996 costs). CONCLUSIONS: Clinical trials have shown that BBSS in conjunction with standard compression therapy was effective and well tolerated in patients with venous leg ulcers, especially patients with ulcers of >6 months' duration or that extended to the subcutaneous tissue. In addition, BBSS in conjunction with standard diabetic foot care was effective and well tolerated in patients with full-thickness neuropathic diabetic foot ulcers. BBSS represents a useful adjuvant to standard ulcer therapy in patients with venous leg ulcers or full-thickness neuropathic diabetic foot ulcers that do not respond to conventional ulcer therapy.

Clinical Trials as Topic↗