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Biomedical subjects

Sheila A Doggrell

Publications and source records attributed to Sheila A Doggrell.

At least 55 records · Page 3Linked to original sources
PubMed2005

Fluoxetine--do the benefits outweigh the risks in adolescent major depression?

Major depressive disorder probably occurs in approximately 5% of adolescents. In these adolescents, selective serotonin re-uptake inhibitors (SSRIs), other than fluoxetine, have shown limited benefit and may increase the risk of suicide. In the Treatment for Adolescents with Depression Study, treatment with fluoxetine of adolescents diagnosed with major depressive disorder, or with the combination of fluoxetine and cognitive behavioural therapy, was superior to placebo. Cognitive behavioural therapy alone was not shown to be superior to placebo. Of the patients in the study, 27% had at least minimal suicidal ideation at baseline, and this reduced to 9% at the end of the treatment period, with the reduction being similar in each of the treatment groups. There were more suicide-related adverse events in the patients treated with fluoxetine (15 of 216) than in patients not treated with fluoxetine (9 of 223). There were no actual suicides. Although further investigation of any association between fluoxetine and suicidal tendencies is clearly required, at present, fluoxetine is the only SSRI for which benefit has been clearly shown, and the benefits seem to outweigh the risks. Thus, fluoxetine should generally be the first choice drug of clinicians if they decide that antidepressant drug treatment is indicated in adolescents with major depressive disorder.

Adolescent↗
PubMed2005

Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction.

Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70 years of age. In the first major trial of sildenafil in ED, at 24 weeks, improved erections were reported by 77 and 84% of men taking sildenafil 50 and 100mg, respectively. Subsequently, sildenafil has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED. Sildenafil is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects with sildenafil are headache, flushing and dyspepsia. Vardenafil is more potent and more selective than sildenafil at inhibiting phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the treatment of ED. The only advantage that vardenafil has over sildenafil is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action than sildenafil and vardenafil. Tadalafil is similarly effective as sildenafil in the treatment of ED. In comparison studies, tadalafil is preferred to sildenafil (50/100mg) by men with ED, possibly because of its longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may displace sildenafil as the drug of choice among men with ED.

Carbolines↗
PubMed2005

CLARITY about the use of clopidogrel in patients with acute coronary syndromes and myocardial infarction.

Clopidogrel was shown to have added benefits to aspirin in patients with acute coronary syndromes without ST-segment elevation in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. The cost in CURE was estimated to be US442 dollars greater in the clopidogrel group and the incremental cost-effectiveness ratio (incremental cost/life-year gained) was US6318 dollars. Clopidogrel has also recently been shown to have added benefits to aspirin in patients with myocardial infarction with ST-segment elevation in the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)--Thrombolysis in Myocardial Infarction (TIMI) 28 study. The primary efficacy composite end point in CLARITY was an occluded infarct-related artery, death from any cause prior to angiography, or recurrent myocardial infarction, and this end point occurred less in the clopidogrel group (15%, 262 of 1752 patients) than placebo group (21.7%, 377 of 1739 patients). This difference was predominantly due to a reduction in the occluded infarct-related artery, which occurred in less of the clopidogrel (11.7%) than placebo group (18.4%). There was also a reduction in urgent revascularisations in the clopidogrel group of CLARITY. Thus, clopidogrel is effective and cost effective in acute coronary syndromes, and is also beneficial in patients with myocardial infarction with ST-segment elevation.

Acute Disease↗
PubMed2005

Ximelagatran--recent comparisons with warfarin.

Recently, ximelagatran and warfarin have been compared for stroke prevention in the Stroke Prevention using an Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) V trial in patients with non-valvular atrial fibrillation, and for the treatment of deep vein thrombosis in the Thrombin Inhibitor in Venous Thromboembolism (THRIVE) trial. In a mean follow-up of 20 months in SPORTIF V, the primary end point of stroke or systemic embolic events occurred in 37 patients in the warfarin group (of 1962) and 51 in the ximelagatran group (1960 patients). There was no difference between the groups in major bleeding. The rates of elevated alanine aminotransferase were much higher in the ximelagatran group (6%) than in the warfarin group (0.8%). In THRIVE, the primary efficacy end point of recurrent venous thromboembolism occurred in 26/1240 ximelagatran patients and 24/1249 patients in the enoxaparin/warfarin group. The incidence of alanine aminotransferase levels greater than three times the upper limit of normal was much higher with ximelagatran than with enoxaparin/warfarin (9.6 and 2.0%, respectively). In conclusion, although the trials comparing ximelagatran with warfarin as prophylaxis for stroke in atrial fibrillation and in the treatment of venous thromboembolism show noninferiority, concerns about the hepatic safety of ximelagatran remain.

Journal Article↗
PubMed2005

Which drug combination for hormone-refractory prostate cancer?

Patients with metastatic hormone-refractory prostate cancer have a progressive disease with a median survival of approximately 11 months, and currently no treatment offers a survival advantage. The standard drug treatment is a corticosteroid and chemotherapy with mitoxantrone. In a comparison of docetaxel every 3 weeks and prednisone, versus mitoxantrone and prednisone, with a follow-up of approximately 21 months, there were less deaths in the docetaxel group than in the mitoxantrone group (166 of 335 patients and 201 of 337 patients, respectively). Docetaxel also prolonged the duration of survival compared with mitoxantrone (18.9 and 16.5 months, respectively). When given with prednisone, docetaxel was also shown to reduce pain and serum prostate specific antigen levels and improve quality of life compared with mitoxantrone/prednisone. In another trial in hormone-resistant prostate cancer patients, which compared docetaxel and estramustine with mitoxantrone and prednisone during a median follow-up of 32 months, there were fewer deaths with docetaxel/estramustine than with mitoxantrone/prednisone, which were 217 of 338 and 235 of 336 patients, respectively. Median survival was also longer in the docetaxel and estramustine group than in the mitoxantrone/prednisone group (17.5 and 15.6 months, respectively). In conclusion, two combinations (docetaxel/prednisone and docetaxel/estramustine) have been shown to be superior to mitoxantrone/prednisone in hormone-refractory prostate cancer and both should be considered for use. With the present information, there is little to distinguish between these combinations.

Antineoplastic Agents, Hormonal↗
PubMed2005

Has the controversy over the use of calcium channel blockers in coronary artery disease been resolved?

Calcium channel blockers are used in the treatment of hypertension and angina. The negative findings on cardiovascular outcomes with some short-acting formulations of calcium channel blockers, described in the 1990s, have led to a much reduced use of calcium channel blockers in general. A Coronary disease Trial Investigating Outcome with Nifedipine (ACTION) investigated the effects of the long-acting gastrointestinal therapeutic system (GITS) formulation of nifedipine in patients with stable symptomatic coronary artery disease. There was less new overt heart failure in the nifedipine GITS group (117 of 3825 patients) than in the placebo group (158 of 3840), and coronary angiography and coronary bypass surgery were also lower in the nifedipine GITS than placebo group. Peripheral revascularisation was slightly higher in the nifedipine GITS (187/3825) than the placebo group (144/3840). The Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial compared a calcium channel blocker (amlodipine) and angiotensin-converting enzyme inhibitor (enalapril) in normotensive patients with coronary artery disease. The primary outcome of cardiovascular events occurred in 151 (23.1%), 110 (16.6%) and 136 (20.2%) of placebo, amlodipine and enalapril patients, respectively, with the only significant difference being a reduction with amlodipine compared with placebo. This reduction mainly represented a reduction in coronary revascularisation and hospitalisation for angina with amlodipine compared with placebo. These results suggest that calcium channel blockers are safe and beneficial in the treatment of coronary artery disease.

Calcium Channel Blockers↗
PubMed2005

Recent important trials of pharmacotherapy in Parkinson's disease.

Parkinson's disease (PD) affects approximately 1% of individuals > 60 years. Of these PD patients approximately 40% suffer dementia in later life. Levodopa is commonly used in the treatment of PD. Experimental evidence suggests that the dopamine synthesised from levodopa may contribute to the further degeneration of dopaminergic neurons. The results of the clinical outcome part of the Earlier Versus Later Levodopa Therapy in PD study suggest that levodopa slows the progression of PD. In contrast, the single photon emission-computed tomography imaging substudy was not conclusive but suggested that levodopa hastened the progression of PD. Thus, further studies of the effects of levodopa on the progression of PD are needed before it can be proved that levodopa does not have a detrimental effect on dopaminergic neurons. In a clinical trial of the anticholinesterase rivastigmine, a small improvement was observed in some patients suffering from dementia associated with PD. This small benefit has to be balanced against cholinergic side effects and a possible loss of efficacy of antimuscarinic agents used for motor control in PD.

Antiparkinson Agents↗
PubMed2005

Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent ulcer bleeding.

Although low-dose aspirin is commonly used as the antiplatelet agent to prevent ischaemic events such as myocardial infarction and stroke, clopidogrel is probably superior at preventing ischaemic events. For patients who cannot tolerate aspirin, adding a proton pump inhibitor or substituting clopidogrel are options. Patients with endoscopy-confirmed ulcer healing were assigned to clopidogrel 75 mg/day or aspirin 80 mg/day and esomeprazole 20 mg b.i.d. for 12 months. There were 14 confirmed cases of recurrent ulcer bleeding, with 13 being from the 161 patients taking clopidogrel and 1 from the 159 patients taking aspirin plus esomeprazole. This trial has clearly shown that the combination of aspirin and esomeprazole is superior to clopidogrel in preventing recurrent ulcer bleeding. A more interesting study may have been to compare the effects of aspirin and clopidogrel in the presence of esomeprazole in patients with a history of ulcers.

Journal Article↗
PubMed2005

Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration.

Age-related macular degeneration is the leading cause of irreversible visual loss in the industrialised world. Angiogenesis underlies the neovascularisation, and vascular endothelial growth factor (VEGF) is an angiogenesis growth factor. In the VEGF Inhibition Study in Ocular Neovascularisation-1 (VISION-1) trial, pegaptanib (an aptamer inhibitor of VEGF) was tested in neovascular age-related macular degeneration. The 1186 patients received a sham injection or intravitreous injection of pegaptanib (0.3, 1.0 or 3.0 mg) every 6 weeks over a period of 48 weeks. The primary end point was the proportion of patients who lost < 15 letters of visual acuity between baseline and 54 weeks, and this occurred in 164/296 patients (55%) who received the sham injection. A higher percentage of patients maintained this visual acuity if they were treated with pegaptanib 0.3 mg (54/206 patients, 70%). There was no evidence that pegaptanib 1 or 3 mg was more effective than 0.3 mg. There was no excess of systemic adverse effects with pegaptanib, but ocular adverse effects occurred more commonly with pegaptanib than with sham injection; vitreous floaters (33 versus 8%), vitreous opacities (18 versus 10%) and anterior chamber inflammation (14 versus 6%). Although these results represent a new, beneficial and relatively safe approach to age-related macular degeneration, the progression was not halted or reversed, and further improvement to treatment for this condition should be sought.

Angiogenesis Inhibitors↗
PubMed2005

Relating statin therapy to C-reactive protein levels.

Inflammation is pivotal in atherosclerosis, and C-reactive protein (CRP) is an inflammatory marker that predicts cardiovascular events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial compared the standard lowering of low-density lipoprotein (LDL)-cholesterol with pravastatin 40 mg/day, with the intense lowering of LDL-cholesterol with atorvastatin 80 mg/day on atheroma volume in patients with coronary artery disease, and showed that the atheroma progressed by 2.7% in the pravastatin group, and remained unchanged in the atorvastatin group. At 18 months follow-up, the CRP levels were reduced from a baseline level of 2.8 mg/l to 1.8 mg/l by atorvastatin, whereas pravastatin had little effect, and there was a good correlation between both the ultrasonographic progression of disease and the reduction in CRP levels. The Pravastatin or Atorvastatin Evaluation and Infection Therapy--Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial compared the long-term effects of the standard lowering of LDL-cholesterol with pravastatin, with the intense lowering of LDL-cholesterol with atorvastatin in patients with an acute coronary syndrome. The primary end point was the first of death, myocardial infarction, unstable angina requiring hospitalisation, revascularisation or stroke, and, at the end of 2 years, was greater in the pravastatin than the atorvastatin group (26.3 versus 22.4%, respectively). Patients with CRP levels of 2 mg/l had lower rates of recurrent myocardial infarction or death from coronary causes than patients with higher levels. Further analysis should be undertaken to assess cardiovascular risk at different levels of CRP, including assessing cardiovascular risk at different levels in men and women. Definitive results about the importance of lowering CRP levels are not likely to be obtained until the results of the Justification for Use of Statins in Primary Prevention, an Intervention Trial in Evaluating Rosuvastatin (JUPITER) study are published.

Journal Article↗
PubMed2005

Bradykinin B2 receptors--a target in diabetic nephropathy.

Diabetic nephropathy is the leading cause of chronic renal failure in westernized countries. The polymorphism in angiotensin-converting enzyme (ACE), which leads to higher than normal levels of this enzyme, is a predictor of nephropathy in patients with diabetes. As increasing the levels of ACE by approximately 50% in this polymorphism is only calculated to increase the levels of angiotensin II by < 5%, whereas the levels of bradykinin will decrease by 20%, bradykinin may be nephroprotective. In diabetic mice without bradykinin B2 receptors, the only parameter that is altered compared with the diabetic mouse, is that the nephropathy is worse. Thus, in diabetic mice without a bradykinin receptor (Bdrb2(-/-)Ins2(+/C96Y)), compared with diabetic mice (Bdrb2(+/+)/Ins2(+/C96Y)), there is a greater kidney weight, increased urinary albumin output, and glomeruli mesangial sclerosis. In addition to reducing the levels of angiotensin II, vasopeptidase inhibitors increase the level of bradykinin. A vasopeptidase inhibitor (AVE7688) has been shown to prevent nephropathy developing and to ameliorate it once it has developed in Zucker diabetic rats. The nephroprotective effects (reduced albumin secretion and reduced kidney damage) of AVE7688 in Zucker diabetic rats were partially prevented by the bradykinin B2 receptor antagonist icatibant. These data establish that stimulation of bradykinin B2 receptors is a target in diabetic nephropathy.

Animals↗