Common sense dictates that one should choose tried and tested drugs with proven, concrete benefits that outweigh their adverse effects. Many new drugs are approved each year, often despite a lack of solid evidence that they are any better than existing treatments. Worse, some are approved despite being less effective or more harmful than current options. Massive promotion is used to ensure that such drugs achieve a positive image in the eyes of healthcare professionals and patients. Renowned "opinion leaders" intervene in their favour at conferences and in specialist media, and their opinions are further propagated by specialists in the field. Finally, campaigns in the lay media are used to highlight the target illness, encouraging patients to request a prescription. New data sometimes show that older, initially promising drugs are less effective or more harmful than first thought. For all these reasons, many drugs that are now present on the market are more harmful than beneficial and should be avoided. Unfortunately, negative assessment data and warnings are often drowned in the flood of promotion and advertising. Front-line healthcare professionals who are determined to act in their patients' best interests can find themselves swimming against a tide of specialist opinion, marketing authorisation, and reimbursement decisions. By leaving drugs that are more harmful than beneficial on the market and contenting themselves with simple half-measures, healthcare authorities are failing in their duty to protect patients. Prescrire, a journal funded solely by its subscribers, does not seek to do the work of health authorities, and does not have the means to do so. Prescrire's goal is simply to help healthcare professionals provide better care. The following text lists the principal drugs that we consider more harmful than beneficial, based on our reviews published between 2010 and 2012 in our French edition. These drugs should not be used. Patients and healthcare professionals should reassess ongoing treatments and, if necessary, replace these drugs with proven treatments. Without waiting for the authorities to remove them from the market in a timely manner, as the accumulation of data showing that they are more harmful than beneficial would require.

The therapeutic advances identified in 2012 were minimal, and 15 new drugs or indications are dangerous. The dearth of improvement in patient care contrasts with the sometimes disproportionately high prices agreed upon for drugs, especially in oncology. The few steps taken by health authorities that benefited patients, mainly by withdrawing or revoking reimbursement for drugs with an unfavourable harm-benefit balance, were insufficient in view of the constant pressure from the pharmaceutical industry to sell ever more drugs.

Patients with deep venous thrombosis are at a short-term risk of symptomatic or even life-threatening pulmonary embolism, and a long-term risk of post-thrombotic syndrome, characterised by lower-limb pain, varicose veins, oedema, and sometimes skin ulcers. What is the best choice of initial antithrombotic therapy following deep venous thrombosis or pulmonary embolism, in terms of mortality and short-term and long-term complications? How do the harm-benefit balances of the different options compare? To answer these questions, we reviewed the available literature using the standard Prescrire methodology. Unfractionated heparin has documented efficacy in reducing mortality and recurrent thromboembolic events in patients with pulmonary embolism or symptomatic proximal (above-knee) deep venous thrombosis. The authors of a systematic review selected 23 trials of low-molecular-weight heparin (LMWH) versus adjusted-dose unfractionated heparin in a total of 9587 patients. Deaths, recurrences and major bleeds were less frequent with LMWH than with unfractionated heparin. The results of other meta-analyses are similar, but all are undermined by a probable publication bias and methodological flaws. Compared to unfractionated heparin, LMWHs have the advantage of fixed-dose administration, once or twice daily, by subcutaneous injection. All available LMWHs seem to have similar efficacy. Those with the longest experience of use are enoxaparin, dalteparin and nadroparin. The harm-benefit balances of fondaparinux and rivaroxaban do not appear more favourable than that of an LMWH followed by an adjusted-dose vitamin K antagonist. A meta-analysis included 12 trials comparing thrombolysis with anticoagulation alone in 700 patients with deep venous thrombosis. Adding a thrombolytic drug did not reduce mortality or the incidence of pulmonary embolism, whereas it increased the incidence of bleeding. A meta-analysis of 13 trials failed to show that adding a thrombolytic drug to initial anticoagulant therapy reduced mortality or recurrences after pulmonary embolism. In the 5 trials that included patients with massive pulmonary embolism, thrombolytic therapy appeared to reduce mortality by about one-half (6% versus 13%). This difference is noteworthy, even if it did not reach the usual threshold of statistical significance. The results of the 6 trials involving patients with deep venous thrombosis, and those of 2 trials and 8 cohort studies in patients with pulmonary embolism at low risk of complications, suggest that outpatient management is acceptable in some cases. Clinical practice guidelines largely agree on the use of LMWH or fondaparinux as initial therapy for most patients with deep venous thrombosis or pulmonary embolism. Unfractionated heparin is generally recommended for patients with renal failure. Thrombolysis is recommended for massive pulmonary embolism and, in some guidelines, for iliofemoral venous thrombosis. In practice, initial treatment of deep venous thrombosis and pulmonary embolism should be based on LMWH in patients without renal failure. Thrombolytic agents may be useful in case of massive pulmonary embolism, but more evaluation is needed. Bleeding and heparin thrombocytopenia are the main adverse effects of these treatments.

Several epidemiological studies, some of which included several thousand women, have shown a link between digoxin exposure and the risk of breast cancer. A cohort study of women with angina, identified in the Danish Prescription Registry, showed a statistically significant increase in the risk of breast cancer among women taking digoxin compared with those not taking digoxin. An increase in the risk of breast cancer of similar magnitude was observed in a case-control study based on Danish hospital registries. In both studies, the risk of breast cancer was increased by about one-third with digoxin (relative risk around 1.3). A causal link is plausible, given the oestrogen-like properties of digoxin. In practice, this risk must be taken into account, especially in patients at risk of breast cancer. Women should be informed of the increased risk of breast cancer before deciding whether the impact of digoxin on cardiac symptoms warrants taking this risk.

The time required for a skin wound to heal depends on its depth and on the distance between the wound edges. Very superficial wounds do not bleed and heal completely within about a week. When the dermis is damaged, repair begins at the wound edges. When these edges are close together, healing can take up to 3 weeks. The scar then continues to evolve for 12 to 18 months.

Healing of surgical and traumatic wounds mainly involves the clotting process, inflammation, cell proliferation and tissue remodelling. Healing time depends on the depth of the wound. In order to identify drugs that can slow the healing process, we reviewed comparative clinical trials, epidemiological studies and detailed case reports, using the standard Prescrire methodology. Delayed healing of surgical or traumatic wounds is associated with persistent bleeding, increased wound seepage and, in some cases, failed wound closure. Delayed wound healing can have severe and sometimes life-threatening consequences, including deep-seated infection, prolonged hospitalisation, repeat surgery to join or rejoin the wound edges, and delayed functional recovery of a transplanted organ. Delayed healing may be due to failure of one or several steps in the healing process, caused by metabolic, cardiovascular, infectious, immunological or drug-related disorders. The principal drugs that can slow wound healing are cytotoxic antineoplastic and immunosuppressive agents, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticoagulants. In practice, when wound healing is delayed, it is best to keep in mind that a drug may be the cause, and to consider withdrawing any drug or drugs known to have this effect, in order to allow the wounds to heal.

Currently, the only curative treatment for bone marrow fibrosis is haematopoietic stem cell transplantation, but it is only feasible in a minority of patients. Ruxolitinib (Jakavi, Novartis) inhibits Janus kinases, enzymes necessary for haematopoiesis. Many cases of bone marrow fibrosis appear to be due to mutations that interfere with the expression of these kinases. Clinical assessment of ruxolitinib is based on a randomised placebo-controlled trial in 309 patients in whom conventional treatments had failed, and on a randomised, unblinded trial versus standard management in 219 patients. The patients enrolled in the placebo-controlled trial had a poor prognosis. Mortality appeared to be lower in the ruxolitinib arm after 24 and 51 weeks, but not in the trial versus standard management. Ruxolitinib had a short-lived symptomatic effect, but almost all patients enrolled in a non-comparative study discontinued ruxolitinib because of inadequate efficacy or adverse effects. Discontinuation often led to symptom rebound. The primary endpoint in these trials was the reduction in spleen volume, a surrogate outcome measure. Ruxolitinib was effective on this endpoint, but it is unclear whether reduction in spleen volume correlates with symptoms. Ruxolitinib aggravates haematological disorders associated with bone marrow fibrosis (anaemia, thrombocytopenia) and also causes neurological disorders (headache, dizziness, confusion). In practice, ruxolitinib appears to have an unfavourable harm-benefit balance in most patients. It is therefore better to avoid using this drug. Additional clinical trials are needed in patients for whom haematopoietic stem cell transplantation is not feasible, especially those with a large, expanding spleen.