Atorvastatin added to interferon beta for relapsing multiple sclerosis: a randomized controlled trial

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3months, they were randomized 1:1 to receive atorvastatin 40mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95% CI 0.36-3.56; p=0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p=0.02). In conclusion, atorvastatin 40mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month perio

Association of alcohol craving and proximal outcomes of a residential treatment program for patients with alcohol use disorders

Background: Alcohol craving is an essential construct in research and treatment of alcohol use disorders (AUD). Craving is mostly investigated in association with concurrent variables or distal treatment outcomes at follow-up. Objectives: The aim of this study is to examine craving at admission and its relevance for essential proximal outcomes at discharge from AUD treatment such as positive alcohol expectancy, abstinent-related self-efficacy, and substance-related coping, as well as patients’ demographic and AUD characteristics. Methods: In total, 36 patients were recruited within an inpatient treatment AUD program. Results: An association between craving and positive alcohol expectancies at discharge was found in the regression model even when the respective expectancies, age, gender, and severity of alcohol dependence at admission were controlled for (F(2,29)1⁄432.71, p50.001). Craving explained 2.3% of the variance of change in positive alcohol expectancy. Conclusion: The results suggest a low predictive value of craving for positive alcohol expectancy. In addition, we found significant associations between the craving and the severity of AUD and alcohol consumption before admission. Future studies should include proximal outcomes related to treatment efficacy as well as distal outcomes

Schweizer Studie zur Validierung der deutschen Mannheimer Craving Scale (MaCS)

Aim: In the research and treatment of Substance Use Disorders (SUDs), craving for alcohol, nicotine, and drugs is an important concept associated with addictive processes, including relapse after treatment. The 12-item Mannheimer Craving Scale (MaCS) has been proved to be an economic, reliable, and valid self-rating instrument across several substances in German samples. The aim of this study was to examine its psychometric characteristics in a Swiss German sample. Method: Overall, 166 patients were recruited from an inpatient SUD treatment program at the University Hospital of Psychiatry in Bern, Switzerland. Results: The internal consistency was high and the test-retest reliability was satisfactory. The total scale and three specific analogue craving measures were highly correlated. Principal component analysis extracted two factors, explaining 62 % of the total variance, and these factors were confirmed through confirmatory factor analysis. However, the two factors correlated highly, and several items loaded on both factors, so that the factor structure was inconclusive. Conclusions: The psychometric characteristics of the MaCS in a Swiss German sample are as good as those characteristics of the German version, suggesting that it is a valid and reliable measure. The MaCS factor structure must be examined on a larger sample that integrates a broader range of SUDs and their severities.Ziel: Für das Verständnis von Störungen durch Substanzkonsum ist subjektiv wahrgenommener Suchtdruck (engl. craving) ein wichtiges psychologisches Konzept. Die zwölf Items umfassende Mannheimer Craving Scale (MaCS) erwies sich in deutschen Stichproben von Patienten mit Konsumstörungen unterschiedlicher psychotroper Substanzen als ökonomische, reliable und valide Selbstbeurteilungsskala allgemeinen Suchtdrucks. Das Ziel dieser Studie ist, deren psychometrische Eigenschaften in einem deutschschweizerischen Patientenkollektiv zu überprüfen. Methode: In der Universitätsklinik für Psychiatrie und Psychotherapie Bern wurde in zwei stationären Programmen für den qualifizierten Entzug von Suchtmitteln bei 166 Patienten mit vorwiegend Alkoholkonsumstörungen als primäre Konsumstörung, aber auch anderen primären oder komorbiden Konsumstörungen neben soziodemographischen und klinischen Merkmalen zusätzlich Daten mit der MaCS erhoben. Ergebnisse: Die interne Konsistenz der MaCS war hoch (Eintritt: Cronbach’s α = .91; Austritt: α = .88) und die Retest-Reliabilität befriedigend (rtt = .65). Die explorative Hauptkomponentenanalyse extrahierte zwei Faktoren, die 61.74 % der Gesamtvarianz erklärten (Faktor 1 „obsessions“: 49.98 %; Faktor 2 „compulsions“: 11.76 %) und die in der konfirmatorischen Faktoranalyse bestätigt werden konnte (CFI = .949; RMSEA = 0.740; χ2 (50) = 95.27, p < .001). Die beiden Faktoren korrelierten allerdings stark miteinander (r = .86) und mehrere Items luden auf beiden Faktoren so hoch, dass die Zwei-Faktorstruktur nicht schlüssig war und auch eine Ein-Faktorenlösung gültig wäre (CFI = .913; RMSEA = 0.096; χ2 (50) = 128.36, p < .001). Mit einer Ausnahme unterscheidet sich das Ausmass von Suchtdruck nicht zwischen den Substanzklassen. Wie erwartet war der Suchtdruck bei Alkohol als Hauptsubstanzkonsumstörung deutlich niedriger als bei Drogen (Heroin, Kokain, Cannabis u. a.; U = 1154, z = –2.34, p = .009; diskrimiante Validität). Der Gesamtscore der MaCS korrelierte hoch mit den Antworten auf den visuellen Analogskalen zu Häufigkeit und Intensität von Suchtdruck (von r = 49 bis r = .51; p < .001) und moderat mit dem DSM-5 Item zur Erfassung von Craving (r = 41; p < 001; konvergente Validität). Schlussfolgerung: Die psychometrischen Eigenschaften der MaCS sind in Deutschland und der Schweiz sehr ähnlich, so dass für beide Länder ein valides und reliabels Instrument zu allgemeinem Suchtdruck vorliegt. Die Faktorenstruktur muss jedoch noch in einer grösseren Stichprobe mit einem breiteren Spektrum an Substanzkonsumstörungen geprüft werden

Association between craving and attention deficit/hyperactivity disorder symptoms among patients with alcohol use disorders

Adult Alcohol Use Disorders (AUD) patients with Attention Deficit/Hyperactivity Disorder (ADHD) symptoms may suffer more from craving than patients who only have AUD. However, craving may be even more strongly related to withdrawal and psychiatric symptoms; therefore, the association between craving and ADHD may be misinterpreted. The purpose of this study is to examine the association between craving and ADHD symptoms among AUD patients in more detail

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD

Personalized structural image analysis in patients with temporal lobe epilepsy

Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further personalized image analysis and surgical therapy. The goal of this study was to compare morphometric data analysis in 37 patients with temporal lobe epilepsies with expert-based image analysis, pre-informed by seizure semiology and ictal scalp EEG. Automated image analysis identified abnormalities exceeding expert-determined structural epileptogenic lesions in 86% of datasets. If EEG lateralization and expert MRI readings were congruent, automated analysis detected abnormalities consistent on a lobar and hemispheric level in 82% of datasets. However, in 25% of patients EEG lateralization and expert readings were inconsistent. Automated analysis localized to the site of resection in 60% of datasets in patients who underwent successful epilepsy surgery. Morphometric abnormalities beyond the mesiotemporal structures contributed to subtype characterisation. We conclude that subject-specific morphometric information is in agreement with expert image analysis and scalp EEG in the majority of cases. However, automated image analysis may provide non-invasive additional information in cases with equivocal radiological and neurophysiological findings

Publisher Correction: Personalized structural image analysis in patients with temporal lobe epilepsy.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper

Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial

BACKGROUND Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. OBJECTIVES To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS). METHODS In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study. RESULTS 27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51). All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated. CONCLUSIONS Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months

Atorvastatin added to interferon beta for relapsing multiple sclerosis: a randomized controlled trial

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3 months, they were randomized 1:1 to receive atorvastatin 40 mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95 % CI 0.36-3.56; p = 0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p = 0.02). In conclusion, atorvastatin 40 mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month period

Overview of published clinical studies evaluating the combination of statins and IFNB in RRMS.

<p>n, number; IFNB, interferon beta; t.i.w., three times per week; d, day; e.o.d., every other day.</p