Reducing Cost and Intravenous Duration of Nicardipine in Intracerebral Hemorrhage Patients via an Interdisciplinary Approach.

BACKGROUND: The mainstay of acute management of intracerebral hemorrhage (ICH) is blood pressure reduction. Intravenous (IV) nicardipine is an effective but costly intervention for blood pressure reduction in the intensive care unit (ICU). Earlier transition to oral (PO) antihypertensive agents may reduce ICU length of stay (LOS) and associated costs. We sought to study the effectiveness of an interdisciplinary intervention to start earlier transition to PO antihypertensives. METHODS: From July 2011 to July 2012, patients with ICH who received IV nicardipine were reviewed and screened for eligibility by an interdisciplinary team including physicians and pharmacists. These patients were compared to a control group 1 year prior to this intervention. The duration of nicardipine treatment (median hours), estimated costs, and ICU LOS were measured. RESULTS: A total of 35 patients and 44 controls were studied. The median hours of IV nicardipine use were significantly decreased from a baseline mean of 118 to 30 hours (P < .001); total cost savings per year was $433,566 ($18,475 per patient). The average LOS remained similar (8.4 versus 8.9 days, P < .990). In a follow-up study 1 year later, after the intervention was no longer used, a sample of 21 consecutive patients was reviewed and the duration of IV nicardipine treatment had increased to a mean of 96 hours. CONCLUSION: A physician and pharmacist-led project to initiate oral antihyperintensive medications earlier was successful in reducing the duration of IV nicardipine treatment in patients with ICH while leading to substantial cost savings.

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural differentiation, but also in imbalanced neuronal excitability and accelerated drug export.

Use Patterns and Unlabeled Uses of Target-Specific Oral Anticoagulants: A Single-Center Experience.

Background: Target-specific oral anticoagulants (TSOAs) have advantages and disadvantages over warfarin, and they differ by indication, dosage adjustment, and drug interactions. Objective: The purpose of this retrospective cohort study is to determine use patterns and unlabeled uses of TSOAs. Methods: From July 1, 2012, to April 30, 2014, orders for warfarin, dabigatran, rivaroxaban, or apixaban in a tertiary medical center were included. Electronic medical records were reviewed to collect information regarding characteristics of the patients receiving these medications. Unlabeled use was defined as an indication or dose not approved by the US Food and Drug Administration. The percentage of orders for each study drug per month and the percentage of orders for each TSOA that contained an unlabeled use were calculated. Results: Of a total of 869 orders, 140 (16.1%) were for TSOAs (13 dabigatran, 97 rivaroxaban, and 30 apixaban orders). Compared with the first 4 months of the study period, the monthly percentage of orders for a TSOA increased by 2.5-fold in the last 4 months. Of the 3 TSOAs, only orders for dabigatran decreased (5.6% in July 2012 vs 0% in April 2014). Of the 140 TSOA orders, 28 (20.0 %) were unlabeled uses (3 unlabeled indications and 25 unlabeled dose), which included 16 unlabeled renally adjusted doses. The percentage of unlabeled uses did not significantly differ by TSOA. Conclusion: The use of TSOAs has increased and unlabeled uses are common. These data provide opportunities for quality improvement in the use of TSOA in clinical practice.

Comparison of MS inflammatory activity in women using continuous versus cyclic combined oral contraceptives.

BACKGROUND: Many women with multiple sclerosis (MS) report fluctuating symptoms across their menstrual cycle. Oral contraceptives (OCs) alter hormonal levels across the menstrual cycle. While cyclic OCs administer hormones for 21 days, followed by a week of placebo, continuous OCs can administer continuous doses of hormones for up to 3 months. Previous studies have suggested that OC use is associated with lower MS-related inflammation. We hypothesized that due to reduced hormonal fluctuations, women with MS might experience less inflammatory activity (clinical relapses+MRI) on continuous OCs than on cyclic OCs. METHODS: We performed a retrospective analysis of prospectively collected data. For women with MS aged 18-50 seen at the UCSF Center for MS and Neuroinflammation, we extracted data on OC use from the Electronic Medical Records (EMR). All variables were confirmed using manual clinical chart review. We identified 19 women with relapsing forms of MS on continuous OCs and matched them (2:1 when possible) to women on cyclic OCs for OC formulation, age, MS duration and DMT type. Inflammatory activity in the two groups was then compared using log-rank tests (time to new relapse, new T2-weighted lesion formation, and gadolinium-enhancing lesion formation) and t-tests (annualized relapse rate). We also performed subgroup analyses in women with at least 1 year (N = 28) and 2 years (N = 21) of clinical observation. A power calculation was performed. RESULTS: There was no difference in time to relapse (p = 0.50) between continuous and cycling OC users. However, continuous OC users showed a statistical trend to longer time to T2 lesion formation (p = 0.09) and longer time to contrast-enhancing lesion formation (p = 0.05). In patients with at least 1 year of observation, there was a significant difference in time to T2 lesion formation (p = 0.03) and time to contrast-enhancing lesion formation (p = 0.02). CONCLUSION: In this exploratory study, women on continuous OCs showed a trend towards less inflammatory activity on MRI relative to women on cyclic OCs. This difference was not reflected in relapse rates. We estimate that 342 patients would be required for an adequately powered cohort study to evaluate such an effect. Our findings provide reassurance that for women using continuous OCs to alleviate menstrual fluctuations in symptoms, there is not an increase in MS-related inflammatory activity.

Before-After Study of an Electronic Order Set for Reversal of Vitamin K Antagonist-Associated Intracerebral Hemorrhage.

BACKGROUND: Vitamin K antagonist (VKA)-associated intracerebral hemorrhages (ICHs) are more likely to expand and are associated with higher mortality than primary ICH. Prompt reversal of anticoagulant effect with prothrombin complex concentrate (PCC) may promote hemostasis and decrease hematoma expansion. The aim of this study was to evaluate the impact of an electronic order set designed to standardize and facilitate more timely reversal of coagulopathy in VKA-associated ICH. METHODS: We identified all adults who received PCC for VKA-associated ICH from June 2012 to June 2015 at University of California San Francisco Medical Center, which included a period before and after an electronic order set became available in 2014. We abstracted baseline demographics and clinical data from electronic health records. The primary outcome was time from radiographic identification of ICH to administration of PCC. RESULTS: Thirty-one patients received PCC for VKA-associated ICH, including 17 patients before and 14 patients after the order set became available. Baseline demographics and clinical features were similar. Order set use was associated with a significant decrease in the time from identification of ICH on imaging to the administration of PCC (median 83 vs 45 minutes; P = .02), more accurate dosing (29.4% vs 92.9%; P < .01), and a shorter time from the PCC order to follow-up international normalized ratio (INR) testing (median 164 vs 85 minutes, P = .001). CONCLUSION: An electronic order set for administering PCC for VKA-associated ICH was associated with significantly faster time to PCC administration and increased dosing accuracy.

Rituximab before and during pregnancy: A systematic review, and a case series in MS and NMOSD.

OBJECTIVE: To evaluate the safety of rituximab treatment before and during pregnancy in women with MS and neuromyelitis optica spectrum disorders (NMOSDs) who may be at risk of relapses by performing a systematic literature review combined with a retrospective single-center case series. METHODS: Studies were systematically identified in the PubMed, Google Scholar, and EMBASE using the key terms "pregnancy" and "rituximab"; 22 articles were included for review (>17,000 screened). Then, patients with MS and NMOSD from 1 center (University of California, San Francisco) exposed to rituximab before conception were identified through medical record review. RESULTS: Systematic review: We identified 102 pregnancies with rituximab use within 6 months of conception: 78 resulted in live births and 12 in spontaneous abortions. Of 54 live births with reported gestational age, 31 occurred at term (37 weeks+) and 2 before 32 weeks. When checked, B-cell counts were low in 39% of newborns and normalized within 6 months. Case series: we identified 11 pregnancies (1 ongoing) in 10 women (7 MS and 3 NMOSD) treated with rituximab within 6 months of conception. All completed pregnancies resulted in term live births of healthy newborns (1 lost to follow-up at term). No maternal relapses occurred before/during pregnancy; 1 occurred postpartum (NMOSD). CONCLUSION: No major safety signal was observed with rituximab use within 6 months of conception. Beyond the need for monitoring neonatal B cells, these observations support prospectively monitoring a larger patient cohort to determine whether rituximab may safely protect women with MS and NMOSD who are planning a pregnancy against relapses.