Drug Safety
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Academic medical centres face the need to care for patients with complex medical conditions, educate physicians-in-training and conduct research, all with increasingly constrained budgets. The adoption of new therapeutic technology presents challenges and opportunities in each of these areas. Severe sepsis remains a major cause of morbidity and mortality, especially in tertiary-care facilities. Recombinant human activated protein C reduces mortality in patients with severe sepsis, but trial data indicate that the benefit of the drug is confined to the more seriously ill patients, while the risk of bleeding complications can be considerable. The cost of the drug is approximately USD 6000-8000 per treated patient. Integration of this product into routine care has produced unique challenges concerning clinical decision making, safety and cost. ⋯ The BWH approach to activated protein C used an innovative multidisciplinary approach and computer-assisted order entry to guide clinical use of a new agent with substantial clinical efficacy, risks and costs. This approach provides a model for strategies to deal with other new and complex medical technologies.
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The prescription of known teratogenic medications requires a careful balance between allowing women access to medications that they might need and avoiding unnecessary exposure to these medications during pregnancy because of their devastating fetal effects. Isotretinoin, a potent human teratogen, is of particular concern because of its widespread use among reproductive-aged women and the dramatic increase in use from 1992 through 2000. A revised risk management system was implemented in 2002 because of concerns about the continued occurrence of isotretinoin-exposed pregnancies. ⋯ Although the companies cannot be legally compelled to use a consolidated approach, the use of a single registry for the originator's product and all generic brands would allow identification of duplicates and also avoid the confusion that is introduced by providing materials that not only look different, but also have different addresses, contact information and names for participation in follow-up surveys. This is particularly important because women might take more than one version of isotretinoin during a single course of therapy or might receive a different programme's materials from their doctor than from the pharmacy. Though the introduction of generic versions of isotretinoin further complicates risk management, the companies marketing isotretinoin have an opportunity to work together to demonstrate their commitment to both limit the occurrence of exposed pregnancies and conduct a meaningful evaluation of the occurrence of pregnancies exposed to isotretinoin.
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Depression is a serious condition, associated with considerable morbidity and mortality; selective serotonin reuptake inhibitors (SSRIs) were commonly used in its treatment in child and adolescent psychiatry until recently. In the wake of the recent UK Committee on Safety of Medicines (CSM) advice, we conducted a rapid review of current available information on SSRIs and suicidality (suicidal ideation, self-harm and suicide attempt) in children and adolescents from clinical trials and epidemiological studies. There is insufficient safety information from the randomised controlled trials to confirm a definite association between SSRIs and suicidality. ⋯ Local bodies of clinicians or peer groups should agree protocols and acceptable guidelines, taking into consideration the type of patients being assessed, the availability of nonpharmacological intervention, and the benefit-risk ratio of the pharmacological intervention. It is important that parents (and patients when possible) be given accurate information regarding the current controversy over SSRI prescribing. More research into the use of SSRIs in childhood depression is urgently required.
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Review Comparative Study
A benefit-risk assessment of inhaled long-acting beta2-agonists in the management of obstructive pulmonary disease.
The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. ⋯ There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.
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Review Comparative Study
Tolerability of treatments for postherpetic neuralgia.
Herpes zoster occurs in up to 20% of people infected with varicella-zoster virus, due to reactivation of the virus from latently infected sensory ganglia. Although pain is a typical feature of acute zoster, pain persisting for more than a month after resolution of the rash is less common and is termed postherpetic neuralgia (PHN). The pain associated with PHN is neuropathic in origin and is notoriously difficult to treat. ⋯ Although effective, the relatively common adverse effects of opioids and ketamine limit their usefulness in treating PHN. Topical treatment with 5% lidocaine patch or capsaicin is of benefit in some patients and is generally well tolerated. Intrathecal methyl prednisolone may be considered for intractable pain but efficacy and safety have not been confirmed.