Potentially Inappropriate Medication Use is Associated with Clinical Outcomes in Critically Ill Elderly Patients with Neurological Injury

Background

Limited data suggest that potentially inappropriate medications (PIMs) impact outcomes in critically ill elderly patients. No data are available on the association between PIM use as well as drug burden index (DBI), which is a measure of PIM use, and clinical outcomes in neurocritical care elderly patients. This study evaluates whether PIM use and a higher DBI are associated with poor clinical outcomes in neurocritical care elderly patients.

Methods

PIMs were retrospectively identified in critically ill elderly patients admitted to the neuroscience intensive care unit (NSICU) from March to July 2011. DBI was calculated based on PIM doses. Relationships with clinical outcomes were evaluated.

Results

PIMs were prescribed to a majority (81.3 %) of the 112 patients. Opioids were most commonly associated with a decrease in Richmond Agitation Sedation Scale (RASS) scores (56 % of PIM doses). Time to recovery was significantly longer in patients with a higher PIM burden (≤2 PIMs: 8 h, >2 PIMs: 29 h; p = 0.02). There was a significantly longer NSICU and hospital length of stay (9 vs 2; 15 vs 5 days; p < 0.0001) as well as a lower Glasgow Coma Scale score upon discharge (14 vs 15, p = 0.02) in patients with a higher DBI after 72 h of hospitalization. There was no difference in mortality.

Conclusions

PIM use and higher DBI scores were associated with poor clinical outcomes and longer lengths of stay. Further studies are needed to determine the impact of PIMs and DBI on mortality in neurocritical care elderly patients.     

Stroke,IL-1ra,IL1RN,Infection and Outcome

Background

Infection is a common phenomenon following stroke, and adversely affects outcome. Previous studies suggest that interleukin-1 receptor antagonist (IL-1ra) and single nucleotide polymorphisms (SNPs) in the IL1RN gene might influence the risk of post-stroke infection and outcome. In this study, we addressed the effects of the rs4251961 SNP in IL1RN on infection risk and outcome.

Methods

Subjects with acute ischemic stroke were enrolled within 72 h of symptom onset and followed up to 1 year. Plasma IL-1ra was measured at multiple time points and outcome assessed at 1, 3, 6, and 12 months. Active surveillance for infection occurred while subjects were hospitalized. Subjects were genotyped for the IL1RN rs4251961 polymorphism.

Results

In the population of 113 subjects for this study, those with the minor C allele of rs4251961 polymorphism in IL1RN were more likely to be Caucasian, hypertensive, and to be afflicted with coronary heart disease. Higher plasma IL-1ra was associated with an increased risk of infection (other than pneumonia), and the minor C allele of rs4251961 was independently associated with a decreased risk of infection (other than pneumonia). Initial plasma IL-1ra was not predictive of long-term outcome, but patients with the minor C allele of rs4251961 were more likely to experience good (modified Rankin Score <2) long-term outcome.

Conclusions

These data indicate that IL-1ra and IL1RN may influence the risk of infection after stroke, but this influence seems limited to infections other than pneumonia. Further studies are needed to better understand the complexities of immune regulation on infection and outcome after stroke.     

Adipose derived stem cells and nerve regeneration

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.     

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon–fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied. Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC₅₀ = 112.8 μM), as evaluated with Annexin‐V‐Alexa 508 in combination with BOBO‐1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH‐DA, increased significantly in fetal ovaries exposed to ¼ LC₅₀ (28.2 μM, a noncytotoxic and relevant occupational exposure concentration) and LC₅₀ PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells‐oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.