Objective: We performed a systematic review and meta-analysis to explore the risk of an aortic aneurysm or aortic dissection following fluoroquinolone administration. Methods: PubMed, Cochrane library, ClinicalTrials.gov, Embase and Google Scholar were systematically reviewed for controlled studies including adult patients exposed to fluoroquinolones with a primary outcome of aortic aneurysm or aortic dissection. Results: The meta-analysis was conducted by pooling the effect estimates of four controlled observational studies (one case-control, one case-crossover and two cohort studies). Fluoroquinolone administration more than doubled the risk to develop aortic aneurysm or aortic dissection within 60 days following fluoroquinolone exposure (adjusted Relative Risk [RR] (95% confidence interval [CI]) = 2.14 (1.93 - 2.36); I2 = 15.8%). The quality of the finding was rated as moderate. : The risk increase for aortic aneurysm alone was found to be significant (adjusted RR (95% CI) = 2.23 (2.01 - 2.45); I2 = 0%) while the risk increase for aortic dissection alone was not found to be significant (adjusted RR = 1.88 (0.11 - 3.65); I2 = 74%). : In subgroup analysis, the risk increase for aortic aneurysm or aortic dissection appeared to be higher in females compared to males (RR = 1.87 (1.24 - 2.51); I2 = 0% versus RR = 1.58 (1.25 - 1.92); I2 = 0%, respectively) and higher in older patients compared to younger patients (RR = 1.72 (1.37 - 2.07); I2 = 0% versus RR = 1.47 (0.91 - 2.04); I2 = 0%, respectively). : Subgroup analysis of two studies which measured the duration-response analysis found that as the duration of fluoroquinolone therapy increased from 3 to 14 days to greater than 14 days, there was an increased risk of aortic aneurysm or dissection. Conclusion: The findings of this meta-analysis confirm the positive association between fluoroquinolones and the development of aortic aneurysm or dissection. The data tend to show that this association may be majorly driven by aortic aneurysm. Additionally, some risk factors appear to prevail including prolonged fluoroquinolone treatment and older age.

Dementia affects more than 40 million people worldwide. When it is accompanied by psychosis, symptom management is especially challenging. Although no drug has been approved by the US Food and Drug Administration (FDA) for psychosis in patients with dementia, atypical antipsychotics are used off-label in severe cases in patients who do not respond to non-pharmacological interventions. However, antipsychotic use in elderly patients with dementia-related psychosis (DRP) is associated with adverse reactions including motor function disorders, cognitive impairment, cerebrovascular events, and increased risk of death. In 2017, the US FDA granted breakthrough therapy designation to the new antipsychotic pimavanserin for the treatment of DRP. Topline result of the pivotal phase III HARMONY (NCT03325556) trial suggests that pimavanserin reduces the relapse of psychosis by 2.8-folds compared to placebo. This favorable result may open path for the potential approval of pimavanserin in DRP. In this review, we discuss the pharmacological activity, clinical efficacy and safety of pimavanserin as a novel atypical antipsychotic with potentials to address the unmet needs of older adults with DRP.

Dementia represents a global health challenge due to the increase in elderly population worldwide. In addition to memory loss, dementia often results in severe behavioral and psychological changes where pharmacological treatments might be considered in addition to nonpharmacological strategies for optimal symptomatic control. Risperidone, the second oldest atypical antipsychotic, has been widely used off-label to treat behavioral and psychological symptoms of dementia (BPSD), including agitation, aggression, and psychosis. Several studies have indicated that risperidone offers a modest and statistically significant effectiveness in the clinical setting. However, in the past decade, safety concerns emerged due to increased risk for cerebrovascular adverse events and death following the use of risperidone in the elderly population. Clinical guidelines suggest that, in severe dementia where an older adult is threatening to harm himself or others, pharmacological treatments might be considered when nonpharmacological treatments fail. Risperidone was approved for BPSD in some countries (Australia, Canada, United Kingdom and New Zealand) but not in the United States. This article reviews risperidone's pharmacological activity, clinical effectiveness and safety, marketing approval, and off-label use in BPSD.

Nearly all bacterial species express two or more chaperonin genes. Recent data indicate that type I chaperonins may be key players in bacterial infections. This is partly due to the well-known contribution of chaperonins in cellular proteostasis, the latter being compromised during bacterial host infection. In addition to their protein-folding activity, it has been revealed that certain chaperonins also exhibit moonlighting functions that can contribute in different ways to bacterial pathogenicity. Examples range from inducing adhesion molecules in Chlamydophila pneumoniae to supporting intracellular survival in Mycobacterium tuberculosis and Leishmania donovani, to inducing cytokines in Helicobacter pylori to promoting antimicrobial resistance in Escherichia coli, amongst others. This article provides a thorough reviews of our current understanding of the different mechanisms involving type I chaperonins during bacteria-host interactions, and suggests new areas to be explored and the potential of finding new targets for fighting bacterial infections.