Cannabis use and premorbid functioning as predictors of poorer neurocognition in schizophrenia spectrum disorder

BackgroundEvidence of associations between neurocognitive function and cannabis use in schizophrenia is inconclusive. However, direct measures of cannabis intake and premorbid function are rarely explored in this context. We investigated the relation between cannabis use, determined by its presence in urine, and neurocognitive functioning in schizophrenia controlling for the potential bias of premorbid functioning.MethodsNaturalistic study of 364 patients with schizophrenia spectrum disorder from catchment areas in Oslo, Norway. Hierarchical multiple regression analyses were used to assess the relationship between cannabis in urine and measures of neurocognitive functioning, with adjustment for confounders, including premorbid functioning.ResultsCannabis was detected in the urine of 21 patients, who had significant dysfunction in several neurocognitive domains independent of a current diagnosis of cannabis abuse. However, level of premorbid functioning explained the associations for all measures.ConclusionDifferences in premorbid functioning may explain apparent differences in neurocognitive function between schizophrenia spectrum patients using cannabis or not. The findings suggest that illness-related traits present early in life can affect both later cannabis use and neurocognition, probably by complex mechanisms.     

Residual small artery impairment in hypertensive patients with normal albumin–creatinine ratio

Objectives Previous studies have suggested that urine albumin excretion (UAE) mirrors generalized vascular damage; however, it is unclear to which degree UAE mirrors small artery impairment. Design We enrolled 67 patients with uncomplicated essential hypertension (EH) during stable antihypertensive therapy. F-R_min, ACR on three non-consecutive morning urine samples, pulse wave velocity (PWV), and 24-h ambulatory blood pressure (ABPM) were measured. Results ACR was low (0.39 and 0.30–0.60), but abnormal small artery structure defined as F-R_min?>_?mean?+?2 standard deviations of normotensive value (1.99?+?1?mmHg min/(ml/100?ml)) was present in 45% (n?=?30). The mean F-R_min was 2.89?±?0.09?mmHg min/(ml/100?ml). ACR correlated significantly to PWV (r^2?=^?0.11; p?<?0.05) and pulse pressure (r^2?=^?0.15; p?<?0.001), but not F-R_min and (r^2?=^?0.05, p?=?0.07). Conclusions Abnormal microvascular structure was present even in EH patients with low UAE. ACR correlated to arterial stiffness and not to small artery structure; therefore, UEA did not reflect microvascular damage in this population. ACR and F-R_min thus reflect two distinct types of subclinical organ damage in hypertension.     

Ficolin-2 recognizes DNA and participates in the clearance of dying host cells

Ficolin-2 is a serum opsonin, which has been shown to be a pattern recognition molecule in the lectin complement activation pathway. Because innate immune mechanisms are involved in maintaining tissue homeostasis we hypothesized that Ficolin-2 also participate in the clearance of dying host cells. We found that Ficolin-2 binds to late apoptotic cells, as well as to apoptotic bodies and necrotic cells, but not to early apoptotic cells. We demonstrated that Ficolin-2 binds DNA in a calcium dependent manner and that DNA inhibits the binding to late apoptotic and necrotic cells, suggesting that DNA on permeable dying cells is a plausible ligand. Reconstituting serum deficient of Ficolin-2, C1q and mannose-binding lectin with Ficolin-2 augmented deposition of complement C4 on necrotic cells. Opsonization leads to an enhanced attachment/uptake of necrotic cells by macrophages. In conclusion dying host cells expose ligands with the capacity of binding Ficolin-2, which in turn leads to increased attachment and engulfment. Binding of Ficolin-2 to DNA points at nucleic acid exposed by permeable late apoptotic and necrotic cells as one of the ligands for Ficolin-2. Ficolin-2 may therefore be a scavenger molecule participating in the removal of host cells and maintenance of tissue homeostasis.     

Improved Pharmacy Department Workflow with New Method of Order Entry for Single-Agent,High-Dose Methotrexate

Purpose:

To determine whether a process change impacted the proportion of orders for single-agent, high-dose methotrexate entered by chemotherapy pharmacists instead of general pharmacy staff. Coordination of antiemetic premedication and leucovorin rescue with the new method of order entry was evaluated.

Methods:

Adults treated with single-agent, high-dose methotrexate were identified retrospectively. Order entry of methotrexate and ancillary medications was examined to determine whether the old or new method was used and whether it was performed by a chemotherapy pharmacist. The fundamental difference between the old and new methods for order entry is use of the “unscheduled” frequency of medication administration to replace the administration frequency of “once” with a specified date and time. Timing of antiemetic premedication and leucovorin rescue relative to methotrexate administration were tallied for the new method. Chi-square analysis was performed for the primary objective. Observational statistics were performed otherwise.

Results:

The number of evaluable encounters identified was 158. A chemotherapy pharmacist entered a greater proportion of orders when the new method was utilized (P < .0001). The proportion of orders entered by a chemotherapy pharmacist increased during the hours of 0700 and 2259 with the new method. Appropriate coordination of antiemetic and leucovorin administration was documented for 96% and 100% of cases with the new method of order entry.

Conclusion:

The proportion of orders for single-agent, high-dose methotrexate entered by a chemotherapy pharmacist was significantly greater with the use of the new method. Administration of antiemetic premedication and leucovorin rescue were appropriately coordinated with the use of the new method for order entry of single-agent, high-dose methotrexate.