Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Specific risk factors for Clostridium difficile-associated diarrhea: a prospective, multicenter, case control evaluation.

BACKGROUND: Clostridium difficile is a toxin-producing bacterium that is responsible for toxicity to the colonic mucosa, causing inflammation, necrosis, and, in some extreme cases, intestinal dilation and perforation. C difficile-associated diarrhea (CDAD) occurs when patients have a reduction in their natural gastrointestinal flora that allows for the proliferation of and toxin production by C difficile. METHODS: Using a multicenter, prospective observational case control study, we assessed and quantified risk factors associated with the development of diarrhea caused by Clostridium difficile, with particular attention to antibiotic use. All hospitalized patients with diarrhea requiring a C difficile toxin test as part of their routine clinical workup were considered for study inclusion. Patients with a negative specimen (controls) were considered for enrollment if matched (by age, sex, length of stay, and institution) to a case. Variables associated with CDAD were identified using univariate analysis. Significant factors were then entered into multivariate logistic regression analysis to identify independent factors. RESULTS: There were no significant differences in antibiotic use between cases and controls. Patient severity, classified by Horn's Index, was significantly different between cases and controls (P = .0022). No other significant variables were identified. CONCLUSION: The severity of illness of the cases was classified as more severe than the controls, but no significant differences in antibiotic use were identified between the groups. The negative C difficile toxin studies on the well-matched control patients indicate a different etiology of diarrhea (such as antibiotic-associated diarrhea), which may have developed in the presence of similar antibiotic use as the cases.