Prescrire international
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Prescrire international · Jun 2006
Comparative StudyCinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data?
(1) Patients who require dialysis for chronic renal failure develop phosphocalcium metabolic disorders that often lead to secondary hyperparathyroidism. Standard treatment consists of a phosphate chelator and vitamin D, along with the use of an appropriate calcium concentration in the dialysis bath, but is difficult to manage. (2) Parathyroid cancer is a rare malignancy frequently associated with hypercalcaemia. (3) Cinacalcet is a calcimimetic agent that reduces the parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. ⋯ Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction. Cinacalcet is a powerful CYP 2D6 inhibitor and is also metabolised by isoenzymes CYP 3A4 and CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of phosphate chelator and vitamin D therapy (especially as an alternative to surgery) or in parathyroid cancer.
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Prescrire international · Jun 2006
Comparative StudyAdjuvant chemotherapy of colon cancer: lymph node involvement without metastases.
(1) The standard treatment for colon cancer is surgical excision, but without additional treatment nearly 50% of surgically treated patients die from relapse and metastatic disease progression. Adjuvant chemotherapy is designed to reduce the risk of post-surgical relapse. (2) The standard adjuvant chemotherapy is a combination of fluorouracil + folinic acid administered intravenously for 6 months (de Gramont protocol). (3) In patients with stage III disease (corresponding to Dukes stage C: lymph node involvement but no metastases), the 5-year survival rate after a 6-month course of fluorouracil + folinic acid is significantly higher than with placebo (63% versus 51%). The efficacy of this treatment has not been established in patients with stage II disease (no lymph node involvement or metastases), for whom the overall 5-year survival rate is about 80%. (4) In one trial a combination of oxaliplatin + fluorouracil + folinic acid (FOLFOX 4 protocol) failed to increase the overall 3-year survival rate more than the fluorouracil + folinic acid combination. It increased the event-free survival rate (72.2% versus 65.3%) but had more severe adverse effects, including: neuropathies (in about 12% of patients), neutropenia (41%), and gastrointestinal disturbances (5% to 10% of patients had nausea, vomiting and diarrhoea). (5) Capecitabine, a fluorouracil precursor, does not appear to be more effective than fluorouracil, but it does provide an alternative oral treatment with a slightly different profile of adverse effects (more frequent erythrodysesthesia, etc.). (6) In practice, adjuvant treatment with fluorouracil + folinic acid should be offered to patients with surgically treated stage-III colonic cancer.
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Prescrire international · Apr 2006
Comparative StudyBuprenorphine replacement therapy: a confirmed benefit.
(1) The aim of replacement therapy for heroin addiction is to suppress craving for other opiates and to prevent opiate withdrawal symptoms. (2) In France, methadone was the first drug to be licensed for this use, in 1995, with very strict prescribing and dispensing conditions. Buprenorphine was approved in 1996, and was subject to less restrictive conditions. (3) In 2003 in France, an estimated 80 000 people were receiving replacement therapy with buprenorphine and 14 000 with methadone. (4) A meta-analysis of 13 comparative trials involving a total of 2544 patients showed that buprenorphine 6 to 12 mg initially reduced both opiate and benzodiazepine use, whereas doses of 2 to 4 mg had no marked impact on heroin use. This meta-analysis concluded that buprenorphine and methadone had similar efficacy in clinical trials in which the dose was adjusted to outcome. ⋯ Injection carries a risk of infections; other potential long-term effects are poorly understood. Compared with methadone users, and regardless of the substances involved, buprenorphine users appear more likely to self-inject. (9) The consequences of sniffing crushed buprenorphine tablets have not been studied. (10) Deaths have been reported following buprenorphine overdose, but they appear to be less frequent than with methadone (0.2 and 0.7 deaths per 1000 users, respectively in 1998). (11) Approaches designed to help patients stop self-injecting have not been tested in comparative trials. Prescriptions of methadone syrup or an injection opiate may be worth trying when all other measures fail.
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Prescrire international · Feb 2006
Antiviral drugs in influenza: an adjunct to vaccination in some situations.
(1) Influenza is a common acute respiratory disease due to a virus that causes annual seasonal epidemics. Three major pandemics occurred in the 20th century, in 1918-1919, 1957 and 1968, mainly due to genetic variants of type A influenza virus. (2) In temperate regions the incidence of hospitalisation increases during annual influenza epidemics. More than 90% of deaths linked to influenza involve people over 65 years of age. (3) The clinical manifestations of influenza virus infection are non specific. ⋯ Under these conditions, treatment should be started within 48 hours after contact with a person who has flu-like symptoms during a seasonal epidemic; residents in institutions in which influenza cases occur may also qualify for preventive treatment. Other preventive measures should also be used, including immediate vaccination, case isolation, use of face masks, and more frequent hand washing. (16) During seasonal influenza epidemics due to viral strains against which the current vaccine is of limited effectiveness, the utility, target populations and optimal duration of preventive antiviral treatment must be determined by examining the groups most at risk and the severity of complications. (17) Most flu-like syndromes are not due to the influenza virus, and the preventive effect of antiviral drugs on complications in persons at risk has not yet been demonstrated. (18) In practice, antiviral drugs are not an alternative to influenza vaccination, but may be a useful adjunct in some situations. It is best to limit their use to short-term prophylaxis of vulnerable persons in situations where the risk of contracting influenza virus infection is high.
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(1) Nicorandil, a vasodilator marketed for symptomatic relief of angina pectoris, is known to cause mouth ulcers, which can sometimes be very large. (2) Cases of anal ulceration have also been reported, associated with pain and, sometimes, a bloody discharge. These anal ulcerations heal very slowly (several weeks) after nicorandil withdrawal.