Prescrire International最新文献

Five meta-analyses of double-blind randomised comparative clinical trials have shown a small but statistically significant increase in the risk of type 2 diabetes in statin users. The relative risk was about 1.1. One add- itional case of diabetes occurred for approximately every 255 patients treated with a statin for 4 years. The risk is dose-dependent. It was observed with all the statins studied, including pravastatin, simvastatin, atorvastatin and rosuvastatin. In practice, the risk of diabetes is not a reason for choosing one statin rather than another. When statin ther- apy is justified, pravastatin and simva- statin remain the statins of choice.

In a randomised trial, reducing the systolic blood pressure target to around 120 mmHg led to a reduction in all-cause mortality compared to a tar- get of around 135 mmHg: after about 3 years, 3.3% of patients in the "inten- sive" treatment group had died versus 4.5% in the "standard" treatment group. The trial was not blinded, however.The patients included were aged 50 years or older, at high risk of cardiovascular events, often overweight but not dia- betic, and had no history of stroke or symptomatic heart failure. This survival benefit was accompan- ied by a twofold increase in serious adverse effects, in particular renal effects, and cannot be extrapolated to the majority of hypertensive patients.

Ideally, health professionals would have all the necessary information at their disposal for making healthcare decisions, but in reality they lack a great deal of clinically relevant data. Some of these missing data simply cannot, or cannot yet, exist. In other cases, the data are missing because the healthcare professional was unable to find them even though they are available, because they have not been generated even though they could have been, because they have not been published, or because they have been concealed. In most cases, when data on medi- cal interventions are suspected or known to be missing, this can be taken into account by assuming that the supposed benefits of the interven- tion are overestimated, while its harms are underestimated. When several drugs appear to have a similar harm-benefit balance, it is better to choose those for which fewer data are missing, or those which have the longest clinical use.

About twenty benzodiazepines and related drugs, such as zolpidem and zopiclone, are used to treat sleep dis- orders and anxiety, and also as anti- convulsants.Their short-term adverse effects include confusion and cogni- tive disorders that regress only slow- ly after treatment withdrawal, especial- ly in elderly patients. Questions have been raised as to persistent cognitive effects in case of long-term benzo- diazepine exposure. A case-control study of 1796 patients over 66 years of age showed that benzodiazepine exposure 5 to 10 years previously was statistically significant- ly more frequent among those who developed Alzheimer's disease. Five other epidemiological studies provided similar results. However, some studies showed no relation with the duration of exposure or the cumu- lative dose; this is an argument against a causal relationship between benzodiazepine use and dementia. These studies provide only weak evidence and thus fail to establish a causal relationship. In addition, early symptoms of dementia can cause anx- iety, which may lead to benzodiazepine prescription in the period preceding diagnosis.The results of these studies do not, however, rule out a long-term risk of persistent cognitive impair- ment. In practice, the known adverse effects of benzodiazepines are a suf- ficient reason to avoid these drugs, especially in elderly patients. The pos- sibility of irreversible cognitive impair- ment is another reason not to pre- scribe them.

Malaria remains a major public health problem in most tropical coun- tries. Plasmodium falciparum infection can be life-threatening, especially in children. Insecticide-treated bed nets have been shown to reduce deaths due to malaria among young children. A malaria vaccine (RTS,S/AS01E) containing two adjuvants has been assessed for its ability to prevent P. falciparum malaria among young children living in endemic areas. The clinical data have been analysed by the European Medicines Agency (EMA) in conjunction with the World Health Organization (WHO). Efficacy has been evaluated in sub-Saharan African countries. Two trials including a total of more than 16 000 children aged 6 weeks to 17 months compared the malaria vac- cine with a rabies vaccine or a menin- gococcal vaccine. Most of the children were healthy, had ready access to healthcare, and were protected with bed nets. In these trials, three injections of the malaria vaccine one month apart did not reduce overall mortality or malaria mortality in low-mortality settings. In the year following vaccina- tion, the risk of malaria episodes was reduced by about 30% among children aged 6 to 12 weeks and by about 50% among those aged 5 to 17 months.The incidence of severe malaria was only reduced in the older age group. Vac- cine efficacy waned rapidly over time, even with a booster dose at 18 months. During clinical trials, reactions at the injection site and systemic reac- tions were more frequent with the malaria vaccine than with the compara- tor vaccines. Febrile seizures during the days following vaccination were 2 to 5 times more frequent with the malaria vaccine among children aged 5 to 17 months. The malaria vaccine may also carry a risk of meningitis, as well as a risk of pneumonia among HIV-infected children and premature infants.

Standard post-surgical (adjuvant) chemotherapy for ovarian cancer is based on a platinum salt, and may be repeated if relapse occurs more than six months after the end of chemo- therapy. Olaparib inhibits enzymes involved in DNA repair. It is claimed to have an antitumour effect, especially in the presence of deleterious BRCA muta- tions. Olaparib has been authorised in the EU for continuous single-agent therapy after the end of platinum-based chemotherapy in patients with "plati- num-sensitive" BRCA-positive ovarian cancer who have already received at least two lines of platinum-based che- motherapy and entered complete or partial remission after the last course of treatment. Clinical evaluation of olaparib is based on a randomised, double-blind, placebo-controlled trial in 265 patients who were recruited regardless of their BRCA status. After a median follow-up of 37 months, patients treated with olaparib showed no survival advan- tage, whether or not their tumour harboured BRCA mutations. The time to radiological progression was pro- longed by several months. An inher- ently unreliable post hoc analysis suggested that olaparib delayed the need for further chemotherapy. Olaparib exposes these patients in remission to frequent adverse effects, including nausea, vomiting, and impaired haematopoiesis. Olaparib can also cause life-threatening myelo- dysplastic syndrome, acute myeloid leukaemia, and haemorrhage. Olaparib is metabolised in the liver, mainly by cytochrome P450 isoenzymes CYP3A4 and CYP3A5. It is also a P-glycoprotein substrate and is likely to inhibit CYP3A4, P-glycopro- tein and other carrier proteins. Multiple pharmacokinetic interactions are also likely. Treatment with olaparib requires patients to take eight capsules twice a day, between meals. In practice, in early 2016, expectations of patients with ovarian cancer who have received at least two lines of chemotherapy are high, as they have short life expectancy and no sat- isfactory treatment options. Yet treat- ment with olaparib after the end of platinum-based chemotherapy still has an unfavourable harm-benefit bal- ance: patients derive no proven ben- efit, but adverse effects are frequent and sometimes fatal.