Assessing cardiometabolic parameter monitoring in inpatients taking a second-generation antipsychotic: The CAMI-SGA study - a cross-sectional study.

OBJECTIVES: This study aims to determine the proportion of initial cardiometabolic assessment and its predicting factors in adults with schizophrenia, bipolar disorder or other related diagnoses for whom a second-generation antipsychotic was prescribed in the hospital setting. DESIGN: Cross-sectional study. SETTING: The psychiatry unit of a Canadian tertiary care teaching hospital in Montreal, Canada. PARTICIPANTS: 402 patients with aforementioned disorders who initiated, restarted or switched to one of the following antipsychotics: clozapine, olanzapine, risperidone, paliperidone or quetiapine, between 2013 and 2016. PRIMARY OUTCOME MEASURES: We assessed the proportion of cardiometabolic parameters monitored. SECONDARY OUTCOME MEASURES: We identified predictors that influence the monitoring of cardiometabolic parameters and we assessed the proportion of adequate interventions following the screening of uncontrolled blood pressure and fasting glucose or glycated haemoglobin (HbA1c) results. RESULTS: Only 37.3% of patients received monitoring for at least three cardiometabolic parameters. Blood pressure was assessed in 99.8% of patients; lipid profile in 24.4%; fasting glucose or HbA1c in 33.3% and weight or body mass index in 97.8% of patients while waist circumference was assessed in 4.5% of patients. For patients with abnormal blood pressure and glycaemic values, 42.3% and 41.2% subsequent interventions were done, respectively. The study highlighted the psychiatric diagnosis (substance induced disorder OR 0.06 95% CI 0.00 to 0.44), the presence of a court-ordered treatment (OR 0.79 95% CI 0.35 to 1.79) and the treating psychiatrist (up to OR 34.0 95% CI 16.2 to 140.7) as predictors of cardiometabolic monitoring. CONCLUSIONS: This study reports suboptimal baseline cardiometabolic monitoring of patients taking an antipsychotic in a Canadian hospital. Optimising collaboration within a multidisciplinary team may increase cardiometabolic monitoring.

Absence of apolipoprotein E protects mice from cerebral malaria.

Cerebral malaria claims the life of millions of people each year, particularly those of children, and is a major global public health problem. Thus, the identification of novel malaria biomarkers that could be utilized as diagnostic or therapeutic targets is becoming increasingly important. Using a proteomic approach, we previously identified unique biomarkers in the sera of malaria-infected individuals, including apolipoprotein E (ApoE). ApoE is the dominant apolipoprotein in the brain and has been implicated in several neurological disorders; therefore, we were interested in the potential role of ApoE in cerebral malaria. Here we report the first demonstration that cerebral malaria is markedly attenuated in ApoE(-/-) mice. The protection provided by the absence of ApoE was associated with decreased sequestration of parasites and T cells within the brain, and was determined to be independent from the involvement of ApoE receptors and from the altered lipid metabolism associated with the knock-out mice. Importantly, we demonstrated that treatment of mice with the ApoE antagonist heparin octasaccharide significantly decreased the incidence of cerebral malaria. Overall, our study indicates that the reduction of ApoE could be utilized in the development of therapeutic treatments aimed at mitigating the neuropathology of cerebral malaria.

Iron prevents the development of experimental cerebral malaria by attenuating CXCR3-mediated T cell chemotaxis.

Cerebral malaria is a severe neurological complication of Plasmodium falciparum infection. Previous studies have suggested that iron overload can suppress the generation of a cytotoxic immune response; however, the effect of iron on experimental cerebral malaria (ECM) is yet unknown. Here we determined that the incidence of ECM was markedly reduced in mice treated with iron dextran. Protection was concomitant with a significant decrease in the sequestration of CD4+ and CD8+ T cells within the brain. CD4+ T cells demonstrated markedly decreased CXCR3 expression and had reduced IFNγ-responsiveness, as indicated by mitigated expression of IFNγR2 and T-bet. Additional analysis of the splenic cell populations indicated that parenteral iron supplementation was also associated with a decrease in NK cells and increase in regulatory T cells. Altogether, these results suggest that iron is able to inhibit ECM pathology by attenuating the capacity of T cells to migrate to the brain.

A new animal model of spontaneous autoimmune peripheral polyneuropathy: implications for Guillain-Barré syndrome.

BACKGROUND: Spontaneous autoimmune peripheral neuropathy including Guillain-Barré Syndrome (GBS) represents as one of the serious emergencies in neurology. Although pathological changes have been well documented, molecular and cellular mechanisms of GBS are still under-explored, partially due to short of appropriate animal models. The field lacks of spontaneous and translatable models for mechanistic investigations. As GBS is preceded often by viral or bacterial infection, a condition can enhance co-stimulatory activity; we sought to investigate the critical role of T cell co-stimulation in this autoimmune disease. RESULTS: Our previous study reported that transgene-derived constitutive expression of co-stimulator B7.2 on antigen presenting cells of the nervous tissues drove spontaneous neurological disorders. Depletion of CD4+ T cells in L31 mice accelerated the onset and increased the prevalence of the disease. In the current study, we further demonstrated that L31/CD4-/- mice exhibited both motor and sensory deficits, including weakness and paresis of limbs, numbness to mechanical stimuli and hypersensitivity to thermal stimulation. Pathological changes were characterized by massive infiltration of macrophages and CD8+ T cells, demyelination and axonal damage in peripheral nerves, while changes in spinal cords could be secondary to the PNS damage. In symptomatic L31/CD4-/- mice, the disruption of the blood neural barriers was observed mainly in peripheral nerves. Interestingly, the infiltration of immune cells was initiated in pre-symptomatic L31/CD4-/- mice, prior to the disease onset, in the DRG and spinal roots where the blood nerve barrier is virtually absent. CONCLUSIONS: L31/CD4-/- mice mimic most parts of clinical and pathological signatures of GBS in human; thus providing an unconventional opportunity to experimentally explore the critical events that lead to spontaneous, autoimmune demyelinating disease of the peripheral nervous system.