Prescrire international
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Prescrire international · Aug 2005
Ischaemic stroke: acute-phase drug therapy. Mostly aspirin and heparin.
(1) In the acute phase of ischaemic stroke, antiplatelet or anticoagulant treatments reduce the risk of recurrence and pulmonary embolism, but carry a risk of haemorrhagic transformation. (2) Aspirin has been tested in several placebo-controlled trials and has a positive risk-benefit balance, preventing about 5 deaths per 1000 patients with ischaemic stroke. Aspirin must be given as soon as computed tomography has ruled out intracerebral haemorrhage, unless thrombolytic treatment is planned. (3) Heparin has as many potential benefits as risks: it tends to be beneficial at low doses but harmful at high doses. Low-dose heparin therapy appears to be justified, especially for patients with emboligenic heart disease, tight carotid stenosis, or at risk of pulmonary embolism. ⋯ Few clinical trials have evaluated the use of antihypertensive drugs in this setting and there is little evidence of benefit. One trial showed that a sudden drop in blood pressure led to neurological aggravation. Antihypertensive drugs should only be used in stroke patients with severe hypertension or cardiac complications. (7) Cerebral oedema is an important cause of death after stroke: treatments (especially mannitol, mechanical ventilation and neurosurgery) have been poorly evaluated. (8) Other treatments recommended only for patients with persistent complications include oxygen therapy, antibiotics, paracetamol, insulin, and anticonvulsants. (9) A controversial meta-analysis suggested that management by a specialised multidisciplinary team reduced the mid-term risk of death and disability in comparison with management in a non specialised unit.
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Prescrire international · Aug 2005
Comparative StudyPioglitazone, rosiglitazone, and rosiglitazone + metformin: new drugs. Glitazone + oral antidiabetic combination: inadequately evaluated.
(1) When single-agent therapy provides inadequate glycaemic control for patients with type 2 diabetes, most guidelines recommend metformin in combination with a glucose-lowering sulphonylurea as standard treatment, despite the lack of any proven impact on morbidity or mortality. Other options include switching to insulin or abandoning the target of strict glycaemic control. (2) Pioglitazone and rosiglitazone are approved for use in combination with a glucose-lowering sulphonylurea when metformin is poorly tolerated or contraindicated, and in combination with metformin in overweight patients. (3) A fixed-dose combination containing 1 or 2 mg of rosiglitazone plus 500 mg of metformin (hydrochloride) was launched onto the French market in October 2004. (4) The indication for rosiglitazone was extended to include its use as triple-agent therapy in combination with metformin and a glucose-lowering sulphonylurea. (5) No clinical trials assessing effects on mortality or morbidity have evaluated rosiglitazone or pioglitazone in combination with other oral antidiabetic drugs. (6) Several trials have compared the glucose-lowering effects of dual-agent therapy using rosiglitazone or pioglitazone plus a glucose-lowering sulphonylurea or metformin versus dual-agent therapy with metformin and a glucose-lowering sulphonylurea. (7) These clinical trials indicate that in terms of HbA1c level, dual-agent therapy based on rosiglitazone or pioglitazone is about as effective as combination therapy with metformin plus a glucose-lowering sulphonylurea. (8) The main known adverse effect of pioglitazone and rosiglitazone is water-sodium retention, which can provoke oedema and haemodilution anaemia, and can aggravate or reveal heart failure. (9) Pioglitazone has a positive effect on the lipid profile, whereas rosiglitazone increases the LDL-cholesterol level. (10) Dual-agent therapy with pioglitazone and a sulphonylurea causes more weight gain than metformin plus a sulphonylurea. (11) Several trials have assessed triple-agent regimens containing a glitazone. ⋯ The glycated haemoglobin level fell by 0.3% to 1.1% (in absolute values), depending on the trial and the dosage, but at a cost of the usual adverse effects such as weight gain, anaemia and oedema. Three unblinded trials have compared oral triple-agent regimens containing glitazone versus insulin plus metformin, alone or in combination with a glucose-lowering sulphonylurea; the treatment including glitazone was no more effective in terms of the glycated haemoglobin level, but was associated with an increase in adverse effects and dropouts. (12) Given the limited clinical data available in early 2005, pioglitazone and rosiglitazone have no place in the management of type 2 diabetes.
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Prescrire international · Jun 2005
Comparative StudyChickenpox vaccines: new drugs. A favourable risk-benefit balance in some situations.
(1) Chickenpox is generally mild. Most severe cases of chickenpox occur in immunocompromised patients, adults, and pregnant women (and their foetuses). (2) Two live attenuated chickenpox vaccines derived from the same strain of varicella virus (Oka) are marketed in France, under the trade names Varilrix and Varivax. (3) They have not been adequately evaluated in immunocompromised children. (4) The impact of routine vaccination of women of child-bearing age on complications of chickenpox during pregnancy has not been studied. (5) Immunogenicity studies in several thousand immunocompetent children aged from 1 to 12 years show that the vaccine is almost always immunogenic after a single injection. Other comparative studies in adolescents and adults show that two injections are needed, at least two months apart. (6) A double-blind placebo-controlled trial including 513 immunocompetent children showed that Varilrix prevented 88% of cases of chickenpox after a median follow-up of 29 months, but no data on severe chickenpox were reported. ⋯ There seems to be no increase in the risk of herpes zoster in vaccinated children nor is there any firm evidence that chickenpox vaccination increases the incidence of herpes zoster in the general population. (11) Little information is available on vaccination during pregnancy. As a precaution, however, pregnant women should not be vaccinated. (12) Mass vaccination does not appear to be justified: chickenpox is generally mild during childhood, and several questions concerning the effects of the vaccine remain unanswered. (13) Chickenpox vaccination should be restricted to specific groups of non immune immunocompetent adults who are in a position to transmit chickenpox to immunodeficient contacts (e.g. health care personnel and kindergarten staff); adults who have been in contact with a case of chickenpox within the past three days; and children awaiting transplantation. The potential benefits and risks of vaccinating immunocompromised patients should be assessed on a case by case basis.
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Prescrire international · Jun 2005
Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in children.
(1) Codeine, either used alone or in combination with paracetamol, is the standard step-2 opiate analgesic for children from the age of one year. (2) An oral solution of tramadol, another step-2 opiate analgesic, was recently approved in France for the treatment of children at least three years of age. (3) The only clinical trials of tramadol in this age group focused on short-term treatment of postoperative pain. Tramadol has not been compared with codeine, ibuprofen, or correctly dosed paracetamol (step-1 analgesic). Tramadol has been compared with diclofenac, a nonsteroidal antiinflammatory drug, in a trial that included patients over 11 years of age (including adults), but the results of this trial are uninformative because patients were not blinded and no separate paediatric subgroup analysis was carried out. (4) The adverse effects of tramadol in children appear to be mild but frequent (especially vomiting). (5) As with codeine, deaths have been reported following accidental overdose with oral tramadol in children. (6) There is no justification for prescribing such a potentially harmful drug with poorly documented efficacy.