Biomedical subjects

Antona J Wagstaff

Publications and source records attributed to Antona J Wagstaff.

At least 19 recordsLinked to original sources

PubMed2006

T-SPOT.TB: an in vitro diagnostic assay measuring T-cell reaction to Mycobacterium tuberculosis-specific antigens.

The overall sensitivity of the RD1 ELISPOT assay (T-SPO.TB), which counts T cells sensitized to specific Mycobacterium tuberculosis peptide sequences, was 81-97% in populations with confirmed tuberculosis, in whom 39-78% had immunosuppressive conditions. In patients with confirmed tuberculosis, the respective RD1 ELISPOT versus tuberculin skin test (TST) sensitivities were 100% versus 89% in adults and 77% versus 35% in children (of whom 39% were HIV-positive). In contrast to that of the TST, the sensitivity of the RD1 ELISPOT assay was not significantly affected by age <36 months, or the immunological or nutritional status of the subjects. Specificity was 100% in two UK-based studies. Isolated false positives have been recorded in patients infected with non-tuberculous M. kansasii. A study investigating latent tuberculosis infection found no significant difference in results between HIV-positive and -negative participants for the RD1 ELISPOT assay, while the TST varied significantly with HIV status. Contact-tracing studies have demonstrated concordance between the RD1 ELISPOT assay and the TST of 65-89%. There is a significant correlation between a positive result and the degree of exposure to the index case for the RD1 ELISPOT assay, but not for the TST, in contact-tracing studies. Unlike the TST, the RD1 ELISPOT assay is not confounded by bacille Calmette-Guérin vaccination.

Antigens, Bacterial↗

PubMed2006

Anagrelide: a review of its use in the management of essential thrombocythaemia.

Anagrelide (Agrylin, Xagrid) is an oral imidazoquinazoline agent which is indicated in Europe for the reduction of elevated platelet counts in at-risk patients with essential thrombocythaemia who are intolerant of or refractory to their current therapy, and in the US for the reduction of elevated platelet counts and the amelioration of thrombohaemorrhagic events in patients with thrombocythaemia associated with myeloproliferative disorders. Anagrelide is well established as an effective platelet-lowering agent in most patients with essential thrombocythaemia, including both treatment-naive patients and those refractory to other cytoreductive therapy. Results of the only randomised trial to date (the Primary Thrombocythaemia 1 [PT1] study) indicated that the composite primary endpoint (arterial or venous thrombosis, serious haemorrhage or death from vascular causes) occurred more often in recipients of anagrelide plus aspirin than in those receiving hydroxycarbamide (hydroxyurea) plus aspirin. This trial also indicated that the incidence of the secondary endpoints transient ischaemic attack and gastrointestinal bleeding favoured hydroxycarbamide plus aspirin, while the incidence of venous thrombosis favoured anagrelide plus aspirin. There were no differences between the groups in the incidence of secondary endpoints myocardial infarction, stroke, unstable angina, pulmonary embolism, hepatic-vein thrombosis, other serious haemorrhage or related deaths. The design of the PT1 study has been queried with respect to the heterogeneous nature of the study population (possible inclusion of patients with early myelofibrotic disease) and the concomitant use of aspirin (interaction with anagrelide causing increased bleeding events). Further data are therefore required before the role of anagrelide in essential thrombocythaemia can be finalized. In the meantime, when considering treatment options for patients with this disorder, anagrelide's positive effects on platelet function, lack of mutagenicity and lack of association with leukaemia or angiogenesis must be balanced against its comparative expense and positive inotropic effects. Thus, the role of anagrelide in the management of high-risk patients with essential thrombocythaemia will ultimately depend on individual patient assessment and future clarification of the potential leukaemogenicity of hydroxycarbamide.

Blood Platelets↗

PubMed2006

Mammalian cell-derived somatropin : a review of its use in the management of HIV-associated wasting.

HIV-associated wasting, characterised by progressive loss of lean body mass and bodyweight, remains a significant problem in the era of highly active antiretroviral therapy (HAART). Loss of body cell mass, a component of lean body mass, is associated with decreased survival. Somatropin (recombinant human growth hormone) derived from mammalian cells (Serostim) is the only US FDA-approved treatment indicated to increase lean body mass, bodyweight and physical endurance in HIV-associated wasting. Somatropin 0.1 mg/kg/day administered subcutaneously for 12 weeks effectively increased work output, bodyweight and lean body mass and improved health-related quality of life (HR-QOL), compared with placebo, and had a generally manageable tolerability profile in a large randomised study in patients with HIV-associated wasting. Potential areas for further research include determination of longer-term efficacy and tolerability, the cost effectiveness of treatment, the optimal somatropin dosage, management of patients after 12 weeks' therapy and whether maintenance strategies might exist to maintain accrued lean body mass with lower doses of somatropin. Nevertheless, indications to date are that somatropin is likely to have an important role in the treatment of patients with HIV-associated wasting.

Body Composition↗

PubMed2006

Ultra-short-course seasonal allergy vaccine (Pollinex Quattro).

This novel ultra-short-course seasonal allergy vaccine, containing glutaraldehyde-modified allergens and the adjuvants 3-deacylated monophosphoryl lipid A (MPL) and L-tyrosine, requires a preseasonal course of only four injections to be effective in the treatment of seasonal allergic rhinitis. In patients with seasonal allergic rhinitis and/or allergic asthma, a four-injection vaccination course with either the grass pollen or tree pollen allergy vaccine significantly reduced skin prick sensitivity reactions, significantly elevated allergen-specific IgG levels and significantly reduced the seasonally induced boost of IgE. Preseasonal vaccination of adult patients with either grass pollen or tree pollen allergy vaccine significantly reduced the median combined symptom/medication score compared with placebo. Similarly, preseasonal vaccination of children and adolescents with allergies to grass pollen or tree pollen significantly reduced the global symptom and medication use scores compared with the previous pollen season. Postmarketing surveillance indicated that after a course of vaccination, 82% of patients experienced reduced symptoms and 62% reduced their rescue medication use compared with the previous season. The allergy vaccine was generally well tolerated. Local reactions, mainly injection-site redness and swelling, were more common than systemic reactions. There were no serious adverse events.

Adjuvants, Immunologic↗

PubMed2006

Nebivolol: a review of its use in the management of hypertension and chronic heart failure.

Nebivolol is a third-generation beta-adrenoceptor antagonist. It differs from other beta-adrenoceptor antagonists as it combines highly selective beta(1)-adrenoceptor antagonist properties with nitric oxide-mediated vasodilatory actions and beneficial effects on endothelial function. Nebivolol is approved in Europe and several other countries for the treatment of essential hypertension and in Europe for the treatment of stable mild or moderate chronic heart failure (CHF) in addition to standard therapies in elderly patients aged >or=70 years. Nebivolol is an effective antihypertensive agent and is well tolerated in patients with hypertension. The drug also effectively decreased the composite endpoint of mortality and cardiovascular hospital admission in elderly patients with CHF and was generally well tolerated in this population. Nebivolol should be considered as an alternative first-line treatment option for patients with uncomplicated mild to moderate essential hypertension and in elderly patients with CHF.

Adrenergic beta-1 Receptor Antagonists↗

PubMed2006

Valsartan/hydrochlorothiazide: a review of its use in the management of hypertension.

Valsartan/hydrochlorothiazide is a fixed-dose (valsartan 80, 160 or 320mg plus hydrochlorothiazide 12.5 or 25mg) angiotensin II receptor blocker/diuretic drug combination indicated for the treatment of patients with essential hypertension not adequately controlled by monotherapy.There is ample evidence that valsartan/hydrochlorothiazide is an effective fixed-dose combination antihypertensive agent. However, efficacy and tolerability data pertaining to the 320mg dose of valsartan in the combination are currently relatively few. There is also some evidence of potential benefits associated with the relatively favourable tolerability profile of the combination, the low occurrence of new-onset diabetes mellitus versus amlodipine and the valsartan-associated improvements in cardiac and endothelial function.

Antihypertensive Agents↗

PubMed2006

Panitumumab: in the treatment of metastatic colorectal cancer.

Panitumumab is a fully human immunoglobulin G2 monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is overexpressed in 25-77% of colorectal cancers. This overexpression is frequently associated with a poor prognosis. In a large, randomised, nonblind, multicentre phase III study in pretreated adult patients with metastatic colorectal cancer and EGFR staining in >or=1% tumour cells, panitumumab 6 mg/kg every 2 weeks plus best supportive care (BSC) was significantly (p < 0.0001) more effective in improving progression-free survival than BSC alone; recipients of panitumumab plus BSC had a 46% lower disease progression rate than those receiving BSC alone after a median follow-up of 19 weeks. Panitumumab 6 mg/kg every 2 weeks or 2.5 mg/kg/week, administered as monotherapy, produced partial response rates of 8-13% and stable disease rates of 21-30% in pretreated patients with metastatic colorectal cancer in three noncomparative, multicentre phase II studies. Preliminary phase II results also suggest a potential role for panitumumab as first-line therapy in combination with fluorouracil, folinic acid and irinotecan in patients with metastatic colorectal cancer. Panitumumab was generally well tolerated. Grade 3/4 skin-related toxicities were reported in 14% of patients receiving panitumumab plus BSC in the phase III study (versus 0% of patients receiving BSC alone). An analysis of pooled data found that high-affinity binding antibodies to panitumumab were detected in <1% of patients.

Animals↗

PubMed2006

Intravenous droperidol: a review of its use in the management of postoperative nausea and vomiting.

Droperidol (Dehydrobenzperidol, Dehidrobenzoperidol, Dridol, Droleptan, Inapsine) is a dopamine D(2) receptor antagonist that has been widely used in adults and children for the prevention and treatment of postoperative nausea and vomiting (PONV) over several decades and, more recently, for the prevention of opioid-induced PONV during patient-controlled analgesia (PCA) in adults. In well controlled clinical trials of patients undergoing surgery, the efficacy of single-dose intravenous (IV) droperidol in preventing PONV was similar to that of ondansetron and dexamethasone. Droperidol significantly reduced opioid-induced PONV in adults during PCA and had a morphine-sparing effect. Droperidol is generally well tolerated and the incidence of adverse effects is similar to that observed with placebo and the serotonin 5-HT(3) receptor antagonists (setrons). Guidelines recommend that, in adults, droperidol monotherapy be considered for those at moderate risk of PONV, and droperidol in combination with a setron and/or dexamethasone be considered for patients at moderate or high risk of PONV. In children with moderate or high risk of PONV, droperidol is recommended for first-line use in some countries, and second-line use in others.

Adolescent↗

PubMed2006

Fentanyl buccal tablet: in breakthrough pain in opioid-tolerant patients with cancer.

The fentanyl buccal tablet (FBT) is a new formulation of fentanyl that uses an effervescent drug delivery system to enhance penetration across the buccal mucosa for the treatment of breakthrough pain in opioid-tolerant patients with cancer. Fentanyl is rapidly absorbed from FBT across the buccal mucosa and into the bloodstream. Fentanyl is more rapidly absorbed and bioavailability is higher from FBT than from the oral transmucosal fentanyl citrate formulation. In a well designed phase III trial in opioid-tolerant patients with cancer, a single dose of FBT 100-800 microg provided clinically significant improvements in pain intensity from 15 to 60 minutes after the dose. Single FBT doses of 100-800 microg were generally well tolerated; the majority of adverse events were mild to moderate in nature and typical of those associated with opioids.

Administration, Buccal↗

PubMed2006

Rivastigmine: in Parkinson's disease dementia.

Rivastigmine is a carbamate-type dual inhibitor of brain acetyl- and butyrylcholinesterases that has been evaluated in the symptomatic treatment of patients with mild to moderate dementia associated with idiopathic Parkinson's disease. Oral rivastigmine 3-12 mg/day for 24 weeks was significantly more effective than placebo in ameliorating cognitive and functional decline, including attentional deficits, in patients with Parkinson's disease dementia in a randomised, double-blind trial. The beneficial effects of rivastigmine observed in the double-blind trial were generally maintained in a 24-week extension of this study in which all patients received active treatment; placebo recipients who switched to rivastigmine also experienced improvements in their cognitive and functional symptoms at week 48. Rivastigmine appeared to be generally well tolerated, with the most common adverse events being mild to moderate in intensity and cholinergic in nature. Parkinsonian symptoms (mainly tremor) were more common in rivastigmine than placebo recipients.

Animals↗

PubMed2006

Spotlight on mammalian cell-derived somatropin in HIV-associated wasting.

HIV-associated wasting, characterized by progressive loss of lean body mass and bodyweight, remains a significant problem in the era of highly active antiretroviral therapy. Loss of body cell mass, a component of lean body mass, is associated with decreased survival. Somatropin (recombinant human growth hormone) derived from mammalian cells (Serostim) is the only US FDA-approved treatment indicated to increase lean body mass, bodyweight, and physical endurance in HIV-associated wasting. Somatropin 0.1 mg/kg/day administered subcutaneously for 12 weeks effectively increased work output, bodyweight, and lean body mass, and improved health-related quality of life, compared with placebo, and had a generally manageable tolerability profile in a large randomized study in patients with HIV-associated wasting. Potential areas for further research include determination of longer-term efficacy and tolerability, the cost effectiveness of treatment, the optimal somatropin dosage, management of patients after 12 weeks' therapy, and whether maintenance strategies might exist to maintain accrued lean body mass with lower doses of somatropin. Nevertheless, indications to date are that somatropin is likely to have an important role in the treatment of patients with HIV-associated wasting.

Clinical Trials as Topic↗

PubMed2005

Solifenacin in overactive bladder syndrome.

Solifenacin is a bladder-selective, muscarinic (M(1) and M(3)) receptor antagonist. In animal studies, the selectivity of solifenacin for the bladder over the salivary glands was greater than that of tolterodine, oxybutynin, darifenacin or atropine. In large, 12-week, randomised, double-blind, multicentre clinical trials, solifenacin 5 and 10mg once daily improved symptoms of overactive bladder syndrome (OAB) [urinary urgency, frequency, incontinence and nocturia] and increased functional bladder capacity to a significantly greater extent than placebo. Solifenacin 5 or 10mg once daily was noninferior to tolterodine extended release (ER) 4mg daily for improving urinary frequency and had significantly greater efficacy than tolterodine ER for improving other symptoms of OAB (episodes of urgency, incontinence and urge incontinence) and increasing functional bladder capacity. At least half of all patients receiving solifenacin who were incontinent at baseline were continent by study end in the three comparative studies reporting this parameter. Health-related quality of life was significantly improved with once-daily solifenacin 5 or 10mg versus placebo, as assessed in two 12-week double-blind studies; the improvement was maintained during a 40-week extension study. Solifenacin was generally well tolerated; the most frequently reported adverse events were dry mouth, constipation and blurred vision.

Humans↗

PubMed2005

Enoxaparin: a review of its use as thromboprophylaxis in acutely ill, nonsurgical patients.

Enoxaparin (Clexane), Lovenox) is a low molecular weight heparin (LMWH) that has been widely used in the prevention of venous thromboembolism (VTE) in surgical patients. More recently, with the recognition of the high incidence of VTE in acutely ill medical (nonsurgical) patients, enoxaparin has been evaluated for thromboprophylaxis in this patient population. Subcutaneous enoxaparin 40 mg once daily has shown efficacy in the short-term thromboprophylaxis of VTE in nonsurgical patients with severely restricted mobility due to acute illness in well controlled clinical trials. The drug is at least similar in efficacy to unfractionated heparin (UFH) and its pharmacological profile allows once-daily administration, in contrast to the twice- or three-times-daily administration required with UFH. The tolerability profile of enoxaparin is also similar to that of UFH, except that the incidences of local haematomas and increased liver enzymes are lower with enoxaparin. The optimal duration of prophylaxis in nonsurgical patients is currently being evaluated and the results of extended prophylaxis with enoxaparin evaluated in the EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill Medical patients) trial are awaited with interest. Currently, short-term enoxaparin appears to provide a cost-effective treatment alternative to UFH for VTE prophylaxis in nonsurgical patients.

Acute Disease↗

PubMed2005

Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension.

Trandolapril/verapamil sustained release (SR) [Tarka] is an oral, fixed-dose combination of the ACE inhibitor trandolapril and the SR formulation of the phenylalkylamine calcium channel antagonist verapamil. It is indicated for the treatment of hypertension in patients who require more than one agent to achieve blood pressure (BP) targets. In the large, randomised, multicentre INVEST (INternational VErapamil SR/trandolapril STudy), a verapamil SR-based treatment strategy that included trandolapril in most patients was as effective as an atenolol-based treatment strategy in reducing the risk of the primary outcome (first occurrence of death [all-cause], nonfatal myocardial infarction [MI] or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD) and was as well tolerated. Trandolapril/verapamil SR is generally more effective at controlling hypertension than either component as monotherapy, and is as effective as a number of other fixed-dose combination therapies. The combination is as well tolerated as trandolapril monotherapy and is at least as well tolerated as verapamil SR monotherapy. In hypertensive patients with type 2 diabetes mellitus in the BENEDICT (BErgamo NEphrologic DIabetes Complications Trial), trandolapril/verapamil SR prolonged the time to the onset of persistent microalbuminuria compared with placebo, as did trandolapril monotherapy. Thus, trandolapril/verapamil SR is an effective option for the treatment of essential hypertension in patients requiring more than one agent to achieve BP targets, including those with compelling indications, such as CAD or type 2 diabetes.

Adult↗

PubMed2005

Goserelin: a review of its use in the treatment of early breast cancer in premenopausal and perimenopausal women.

Goserelin (Zoladex), a gonadotropin-releasing hormone analogue, reduces plasma/serum estrogen levels in pre- or perimenopausal women (to postmenopausal levels), and is indicated in hormone receptor-positive early breast cancer in this population group. Adjuvant goserelin monotherapy has similar efficacy to adjuvant chemotherapy in pre- or perimenopausal women with early, hormone receptor-positive breast cancer. Furthermore, the addition of goserelin to adjuvant chemotherapy appeared to offer an advantage over chemotherapy alone in younger patients. Fewer patients remained amenorrheic after goserelin therapy than after chemotherapy. Complete endocrine blockade provided by the addition of tamoxifen to therapy including goserelin appears to improve outcomes. Thus, goserelin offers a valuable addition to the currently available options for treating pre- or perimenopausal women with hormone therapy-responsive early breast cancer, particularly for women wishing to regain ovarian function after treatment.

Antineoplastic Agents, Hormonal↗

PubMed2005

Losartan: a review of its use in stroke risk reduction in patients with hypertension and left ventricular hypertrophy.

Losartan (Cozaar) is an angiotensin AT1 receptor antagonist. It is approved in numerous countries for the treatment of hypertension and has been approved in the UK, the US and several European countries for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan is recommended for use alone or with hydrochlorothiazide, but it can also be administered with other antihypertensive medications. In patients with hypertension, losartan effectively lowers blood pressure and also leads to regression of LVH. In the large, well designed LIFE (Losartan Intervention For Endpoint reduction in hypertension) study in patients with hypertension and LVH, losartan was more effective than atenolol in reducing the composite primary endpoint of cardiovascular (CV) mortality, stroke or myocardial infarction (MI). This was mainly due to a significant 25% reduction in the risk of stroke in the losartan group. Losartan recipients also had a significantly lower incidence of new-onset diabetes mellitus compared with atenolol recipients. Similar benefits were observed in several patient subgroups from the LIFE study, but not in the subgroup of Black patients. Losartan is well tolerated and is a cost effective alternative to atenolol in the setting of stroke reduction. Comparative data on clinical outcomes in hypertensive patients for losartan versus other antihypertensive agents would be of interest. Nonetheless, in addition to its established antihypertensive and end organ effects, the LIFE study indicates that, with the possible exception of Black patients, losartan can reduce the risk of stroke in patients with hypertension and LVH.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Intramuscular olanzapine: a review of its use in the management of acute agitation.

Intramuscular olanzapine (Zyprexa) is a rapid-acting atypical antipsychotic drug that is also indicated for use in patients with agitation associated with schizophrenia or bipolar mania, the focus of this review. Evidence from three well designed trials indicates that this formulation of olanzapine is at least as effective as intramuscular haloperidol or lorazepam in the treatment of patients with acute agitation associated with schizophrenia or bipolar mania, and has a faster onset of action. Although transient reductions in blood pressure and heart rate may occur in some patients administered intramuscular olanzapine, preliminary evidence of a general lack of clinical effect on the corrected QT (QTc) interval and a low incidence of extrapyramidal symptoms (EPS) is promising. The parenteral formulation of olanzapine appears to offer an effective, fast-acting and generally well tolerated alternative in the treatment of this significant behavioural problem.

Acute Disease↗

PubMed2005

Intranasal sumatriptan: in adolescents with migraine.

Sumatriptan, a serotonin 5-HT(1B/1D) agonist, constricts cranial blood vessels and inhibits neuroinflammatory processes. A single dose of sumatriptan 10 mg (approved European dosage) was significantly more effective than placebo in achieving headache relief at 1 hour post-dose in a well designed study. Headache relief occurred in significantly more adolescents administered a single dose of intranasal sumatriptan 20 mg (at 1 and 2 hours) and 5 mg (at 2 hours) than placebo (pooled data from two studies). Sustained headache relief (1-24 and 2-24 hours) occurred in significantly more recipients of a single dose of intranasal sumatriptan 20mg and 5mg than placebo (pooled data from two studies). Intranasal sumatriptan was generally well tolerated in adolescent migraineurs (in single-episode studies or long term in multiple-episode studies). Taste disturbance occurred more often with intranasal sumatriptan than with placebo [Chart: see text].

Administration, Intranasal↗