Expert opinion on pharmacotherapy
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Novel compounds targeting various aspects of fibrogenesis have been developed consequent to the increasing knowledge of the pathogenetic mechanisms of the interstitial lung diseases (ILDs). The authors review the evolution of treatment approaches in the ILDs, informed by recent placebo-controlled trials, and discuss current clinical trials in which emerging pathogenetic mechanisms are targeted as novel therapeutic agents. ⋯ In IPF, significant treatment effects have been reported with pirfenidone, nintedanib and N-acetylcysteine. Combinations of these pleiotropic agents, along with future monotherapies, in 'oncological regimens' may hold the key to more effective IPF treatment. In disorders other than IPF, there is an ongoing need for the controlled evaluation of traditional anti-inflammatory and immunosuppressive therapies. 'Cohort enrichment' (the selective recruitment of patients most likely to progress) holds the key to the identification of worthwhile treatment benefits.
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Expert Opin Pharmacother · Jan 2013
Review Meta AnalysisSecond-line treatments for the management of advanced renal cell carcinoma: systematic review and meta-analysis.
A systematic review/meta-analysis was conducted to assess the effectiveness and safety of second-line treatments for advanced renal cell carcinoma (RCC), which includes the vascular endothelial growth factor inhibitor axitinib. ⋯ Results from the present study suggest that axitinib will be an important treatment option to extend PFS in the management of advanced RCC in the second-line setting. Ongoing research will define the optimal treatment algorithm leading to a patient-focused treatment strategy.
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The worldwide occurrence of burn injuries remains high despite efforts to reduce injury incidence through public awareness campaigns and improvements in living conditions. In 2004, almost 11 million people experienced burns severe enough to warrant medical treatment. Advances over the past several decades in aggressive resuscitation, nutrition, excision and grafting have reduced morbidity and mortality. Incorporation of pharmacotherapeutics into treatment regimens may further reduce complications of severe burn injuries. ⋯ Existing drugs offer promising advances in the care of burn injuries. Continued gains in the understanding of the molecular mechanisms driving the hypermetabolic response will enable the application of additional existing drugs to be broadened to further attenuate the hypermetabolic response.
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Expert Opin Pharmacother · Dec 2012
ReviewInotropes for the management of acute heart failure patients with renal dysfunction. Still an option?
Renal dysfunction is highly prevalent in patients with acute heart failure (AHF). These patients are more vulnerable in worsening of kidney function and have also higher mortality rates. ⋯ Inotropes may be indicated on a short-term basis and under close monitoring in AHF with renal dysfunction mostly in cases of low output heart failure that can provoke renal hypoperfusion. Dopamine administration with low dose of i.v. furosemide has been recently compared with high dose of i.v. furosemide alone, demonstrating lower rates of worsening renal function and electrolyte disturbances. Moreover, small clinical trials have shown that the novel inodilator levosimendan seems to be superior to dobutamine or placebo in improving renal function in patients with acutely decompensated heart failure. The impact of novel inotropes on kidney function is still unclear. Randomized clinical trials are required in order to identify the role of inotropes in the management and/or prevention of acute cardiorenal syndrome.
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Expert Opin Pharmacother · Nov 2012
ReviewRuxolitinib, an oral JAK1 and JAK2 inhibitor, in myelofibrosis.
Myelofibrosis (MF) is a debilitating hematologic malignancy characterized by progressive splenomegaly, burdensome symptoms, cytopenias and shortened survival. Chronic alterations in Janus-associated kinase-signal transducer and activator of transcription (JAK-STAT) signaling have been identified in the pathogenesis of MF, making this pathway a target for drug development. Ruxolitinib is the first JAK1 and JAK2 inhibitor to be approved by the US Food and Drug Administration. ⋯ Conventional MF treatments alleviate some MF symptoms but have limited efficacy, do not modify the natural history of the disease and are not approved for MF. The JAK1 and JAK2 inhibitor ruxolitinib has shown promising results in pre-clinical and clinical trials. In Phase III trials, ruxolitinib was shown to reduce splenomegaly and improve MF-related symptoms. Recent evidence also suggests that ruxolitinib may improve survival. The most common adverse events were anemia and thrombocytopenia, which were managed with dose adjustments (or red blood cell transfusions for anemia).