Drugs
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Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. ⋯ Overall, ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline fosamil is a broad-spectrum parenteral cephalosporin with excellent in vitro activity against resistant Gram-positive pathogens, including MRSA, as well as many common Gram-negative organisms. It is a welcome treatment option for ABSSSI and CABP.
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Review
Delirium in critically ill patients: epidemiology, pathophysiology, diagnosis and management.
Delirium is commonly observed in critically ill patients and is associated with negative outcomes. The pathophysiology of delirium is not completely understood. However, alterations to neurotransmitters, especially acetylcholine and dopamine, inflammatory pathways and an aberrant stress response are proposed mechanisms leading to intensive care unit (ICU) delirium. ⋯ In addition, the combined use of sedation, ventilation, delirium and physical therapy protocols can reduce the frequency and severity of adverse outcomes and should become part of routine practice in the ICU, as should avoidance of deliriogenic medication such as anticholinergic drugs and benzodiazepines. Once delirium develops, symptomatic treatment with antipsychotics is recommended, with haloperidol being the drug of first choice. However, there is limited evidence on the safety and effectiveness of antipsychotics in ICU delirium.
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Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. ⋯ In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.
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Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. ⋯ Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.
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Corticosteroids are widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, in contrast to their use in mild-to-moderate asthma, they are much less effective in enhancing lung function and have little or no effect on controlling the underlying chronic inflammation. In most clinical trials in COPD patients, corticosteroids have shown little benefit as monotherapy, but have shown a greater clinical effect in combination with long-acting bronchodilators. ⋯ Of these, PI3Kδ, PDE4, p38 MAPK inhibitors and chemokine receptor antagonists are in clinical patient trials. Of importance, patient adverse effects associated with oral administration of these novel agents needs to be addressed in order to optimize therapy and patient compliance. Combinations of these drugs with corticosteroids may have additional benefits.