Fish oil (n-3 fatty acids) in drug resistant epilepsy: a randomised placebo-controlled crossover study.

Backgroundn-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health.MethodsRandomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42 weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency.FindingsLow-dose fish oil (3 capsules/day, 1080 mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors.InterpretationIn this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080 mg/day) in drug resistant epilepsy.Trial registration numberNCT00871377

Advanced Data Analysis - Lecture Notes

Lecture notes for Advanced Data Analysis (ADA1 Stat 427/527 and ADA2 Stat 428/528), Department of Mathematics and Statistics, University of New Mexico, Fall 2016-Spring 2017. Additional material including RMarkdown templates for in-class and homework exercises, datasets, R code, and video lectures are available on the course websites: https://statacumen.com/teaching/ada1 and https://statacumen.com/teaching/ada2 . Contents I ADA1: Software 0 Introduction to R, Rstudio, and ggplot II ADA1: Summaries and displays, and one-, two-, and many-way tests of means 1 Summarizing and Displaying Data 2 Estimation in One-Sample Problems 3 Two-Sample Inferences 4 Checking Assumptions 5 One-Way Analysis of Variance III ADA1: Nonparametric, categorical, and regression methods 6 Nonparametric Methods 7 Categorical Data Analysis 8 Correlation and Regression IV ADA1: Additional topics 9 Introduction to the Bootstrap 10 Power and Sample size 11 Data Cleaning V ADA2: Review of ADA1 1 R statistical software and review VI ADA2: Introduction to multiple regression and model selection 2 Introduction to Multiple Linear Regression 3 A Taste of Model Selection for Multiple Regression VII ADA2: Experimental design and observational studies 4 One Factor Designs and Extensions 5 Paired Experiments and Randomized Block Experiments 6 A Short Discussion of Observational Studies VIII ADA2: ANCOVA and logistic regression 7 Analysis of Covariance: Comparing Regression Lines 8 Polynomial Regression 9 Discussion of Response Models with Factors and Predictors 10 Automated Model Selection for Multiple Regression 11 Logistic Regression IX ADA2: Multivariate Methods 12 An Introduction to Multivariate Methods 13 Principal Component Analysis 14 Cluster Analysis 15 Multivariate Analysis of Variance 16 Discriminant Analysis 17 Classificationhttps://digitalrepository.unm.edu/unm_oer/1002/thumbnail.jp

Predictors of Preterm Birth in New Mexico: outcomes from 377,770 pregnancies over fifteen years

Background: Preterm birth (PTB) is a significant health problem both in New Mexico and nationally. It accounts for significant infant morbidity and mortality and it poses an economic burden to both individuals and the state. The goal of this study is to elucidate maternal risk factors for PTB in New Mexico, a poor state with a unique ethnic background. By doing this we hope to be able to identify women at increased risk and invite further study into targeted interventions among these high risk populations. Methods: This was a cross-sectional analysis of 377,770 singleton live births in the state of New Mexico from 1991-2005. The medical risk factors tracked were pulmonary, renal, cardiac, diabetes, eclampsia, oligo/polyhydramnios, hypertensive disorders, cervical incompetence, previous preterm delivery, tocolysis and isoimmunization. Gestational age of less than 37 weeks was defined as PTB. Multiple gestations and congenital anomalies were excluded. The Kotelchuck Index was used as a measure for level of prenatal care described as inadequate, intermediate, adequate, and intensive. Multivariate logistic regression was conducted using SAS 9.1 statistical software. Results: Of the live births analyzed, 28,036 of these were preterm (7.4%). Overall the PTB rate has risen from 1991-2005 at a rate of 0.18 percent per year. This was statistically significant (p = \u3c0.00004). Among patients with medical risk factors, PTB rate had a direct inverse relationship with an intensive level of prenatal care. High risk patients with intensive care were less likely to have a PTB delivery with an odds ratio of 0.74 than similar patients with low levels of care. The nadir for risk of PTB is among women aged 25-29 with significant increases in risk among women \u3c15 and \u3e40 years of age. Other risk factors are unmarried status, education less than high school,tobacco/alcohol use, Black, Asian, and White Hispanic ethnicity and the presence of one or more medical risk factors. Statistically significant protective factors for PTB are age 25-29, education surpassing high school, and Native American race. Counties with rising adjusted PTB rates are Chaves, Dona Ana, Grant, Hidalgo, Lea, Lincoln, McKinley, Mora, Otero, Rio Arriba, San Juan and San Miguel. Counties with decreasing PTB rates are Sandoval and Santa Fe counties. Conclusion: Even adjusted for known risk factors PTB is still a significant problem in New Mexico. A lack of prenatal care was a significant predictor of PTB in high risk patients. Other predictors include the known risk factors of age \u3c15 and \u3e40, single, tobacco/alcohol use, being of low socioeconomic status and White Hispanic, Asian and Black ethnicities. Interestingly, Native American patients have a lower PTB rate compared to other groups, even though this group is traditionally one of low socioeconomic status in New Mexico

An exploratory study of the variables impacting preterm birth rates in New Mexico

BACKGROUND: Preterm birth (PTB) is a substantial health problem that accounts for significant infant morbidity and mortality and poses an economic burden to both individuals and the state of residence. The goal of this study was to identify maternal risk factors for PTB in New Mexico, a poor state with a unique ethnic background, in order to identify populations at increased risk that would benefit from intervention. METHODS: This was a cross-sectional retrospective exploratory analysis of 377,770 singleton live births in the state of New Mexico from 1991-2005. Gestational age of less than 37 weeks was defined as PTB. The Kotelchuck Index was used as a measure for level of prenatal care described as inadequate, intermediate, adequate, and intensive. RESULTS: Of the live births analyzed, 28,036 of these were preterm (7.4%). Overall the PTB rate rose at a rate of 0.18% per year from 1991-2005. Among patients with medical risk factors, the absence of prenatal care was associated with higher odds for PTB as compared to adequate prenatal care. Other risk factors were unmarried status, education less than high school, tobacco/alcohol use, black, Asian, and white Hispanic ethnicity, and the presence of one or more medical risk factors. Statistically significant protective factors for PTB were age 25-29, education surpassing high school, and Native American race. CONCLUSIONS: This study identified several factors that correlate with increased PTB in New Mexico, in particular ethnicity and level of prenatal care. The finding that Native American patients have a lower PTB rate compared to other groups, even though this group is traditionally one of low socioeconomic status in New Mexico, signifies that other factors yet to be identified affect PTB

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study

Abstract Background Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. Methods This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12–20 weeks, 26–28 weeks, 34–36 weeks, and 6–8 weeks postpartum. Vitamin D levels were measured at 12–20 weeks (N = 117) and 34–36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. Results We found that vitamin D levels at 12–20 weeks were inversely associated with BDI scores both at 12—20 and at 34–36 weeks’ gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. Conclusions In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. Trial registration https://clinicaltrials.gov/ Registration Number: NCT00711971http://deepblue.lib.umich.edu/bitstream/2027.42/134615/1/12884_2016_Article_988.pd

Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC

Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses:A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients

Peroxisomal alterations in Alzheimer’s disease

In Alzheimer’s disease (AD), lipid alterations are present early during disease progression. As some of these alterations point towards a peroxisomal dysfunction, we investigated peroxisomes in human postmortem brains obtained from the cohort-based, longitudinal Vienna-Transdanube Aging (VITA) study. Based on the neuropathological Braak staging for AD on one hemisphere, the patients were grouped into three cohorts of increasing severity (stages I–II, III–IV, and V–VI, respectively). Lipid analyses of cortical regions from the other hemisphere revealed accumulation of C22:0 and very long-chain fatty acids (VLCFA, C24:0 and C26:0), all substrates for peroxisomal β-oxidation, in cases with stages V–VI pathology compared with those modestly affected (stages I–II). Conversely, the level of plasmalogens, which need intact peroxisomes for their biosynthesis, was decreased in severely affected tissues, in agreement with a peroxisomal dysfunction. In addition, the peroxisomal volume density was increased in the soma of neurons in gyrus frontalis at advanced AD stages. Confocal laser microscopy demonstrated a loss of peroxisomes in neuronal processes with abnormally phosphorylated tau protein, implicating impaired trafficking as the cause of altered peroxisomal distribution. Besides the original Braak staging, the study design allowed a direct correlation between the biochemical findings and the amount of neurofibrillary tangles (NFT) and neuritic plaques, quantified in adjacent tissue sections. Interestingly, the decrease in plasmalogens and the increase in VLCFA and peroxisomal volume density in neuronal somata all showed a stronger association with NFT than with neuritic plaques. These results indicate substantial peroxisome-related alterations in AD, which may contribute to the progression of AD pathology

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)