Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Automated low flow pump system for the treatment of refractory ascites: A multi-center safety and efficacy study

BACKGROUND & AIMS: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. METHODS: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. RESULTS: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p <0.01]. Cirrhosis-related adverse events decreased along follow-up. CONCLUSIONS: The automated pump seems an efficacious tool to move out ascites from the peritoneal cavity to the bladder. Its safety is still moderate, but a broad use in different countries will improve the surgical technique as well as the medical surveillance. A prospective randomized clinical trial vs. large volume paracentesis is underway to confirm these preliminary results.

Differences in coping, self-efficacy, and external control beliefs between patients at-risk for psychosis and patients with first-episode psychosis

Patients with first-episode psychosis (FEP) often show dysfunctional coping patterns, low self-efficacy, and external control beliefs that are considered to be risk factors for the development of psychosis. Therefore, these factors should already be present in patients at-risk for psychosis (AR). We compared frequencies of deficits in coping strategies (Stress-Coping-Questionnaires, SVF-120/SVF-KJ), self-efficacy, and control beliefs (Competence and Control Beliefs Questionnaire, FKK) between AR (n=21) and FEP (n=22) patients using a cross-sectional design. Correlations among coping, self-efficacy, and control beliefs were assessed in both groups. The majority of AR and FEP patients demonstrated deficits in coping skills, self-efficacy, and control beliefs. However, AR patients more frequently reported a lack of positive coping strategies, low self-efficacy, and a fatalistic externalizing bias. In contrast, FEP patients were characterized by being overly self-confident. These findings suggest that dysfunctional coping, self-efficacy, and control beliefs are already evident in AR patients, though different from those in FEP patients. The pattern of deficits in AR patients closely resembles that of depressive patients, which may reflect high levels of depressiveness in AR patients. Apart from being worthwhile treatment targets, these coping and belief patterns are promising candidates for predicting outcome in AR patients, including the conversion to psychosis

Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat HIV/hepatitis C virus-coinfected patients

OBJECTIVES: The efficacy of current hepatitis C virus (HCV) triple therapy, including a protease inhibitor, is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and nonresponse to previous peginterferon-ribavirin. These patients have a low chance (only 30%) of achieving a sustained virological response (SVR) during triple therapy and cannot wait for next-generation anti-HCV drugs. In a pilot study, we investigated the efficacy of a lead-in therapy with silibinin before triple therapy in difficult-to-treat patients. METHODS: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented failure of previous peginterferon-ribavirin treatment. Intervention was lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days. Subsequently, peginterferon-ribavirin combined with telaprevir was initiated for 12 weeks, followed by peginterferon-ribavirin dual therapy until week 48 after initiation of triple therapy. The outcome measurements were HCV RNA after silibinin lead-in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24 after the end of treatment. RESULTS: We examined six HIV/HCV-coinfected patients (four infected with genotype 1a). All had fibrosis grade METAVIR ≥F3 and were on fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin therapy was 2.6 log10 IU/mL (range 2-3 log10 IU/mL). Five of the six patients were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple therapy. One experienced a viral breakthrough thereafter. Four of five patients (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week 24. CONCLUSIONS: A lead-in with silibinin before triple therapy is highly effective and increases the probability of HCV treatment success in difficult-to-treat HIV/HCV-coinfected patients with advanced liver fibrosis and previous failure of peginterferon-ribavirin.

Safety and efficacy of thrombolysis with intravenous alteplase in older stroke patients.

Stroke is a common cause of death and persisting disability worldwide, and thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. Older age is the most important non-modifiable risk factor for stroke, and demographic changes are also resulting in an increasingly ageing population. However, clinical trial evidence for the use of intravenous alteplase is limited for the older age group where stroke incidence is highest. In this article, the current evidence regarding the safety and efficacy of intravenous thrombolytic therapy in stroke patients aged ≥80 years is critically analysed and the gap in current knowledge highlighted. In summary, intravenous thrombolysis in stroke patients aged ≥80 years seems to be associated with less favourable clinical outcomes and higher mortality than in younger patients, which is consistent with the natural course in untreated patients. The risk of symptomatic intracranial haemorrhage does not appear to be significantly higher in the elderly group, suggesting that intracranial bleeding complications are unlikely to outweigh the potential benefit in this age group. Overall, withholding thrombolytic treatment in ischaemic stroke on the basis of advanced age alone is no longer justifiable.

Lack of efficacy of low-dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs.

Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.

Effects of overt self-­talk on team partners’ other-efficacy and performance in a golf putting task

Introduction According to Lent and Lopez’ (2002) tripartite view of efficacy beliefs, members of a team form beliefs about the efficacy of their team partners. This other-efficacy belief can influence individual performance as shown by Dunlop, Beatty, and Beauchamp (2011) in their experimental study using manipulated performance feedback to alter other-efficacy beliefs. Participants holding favorable other-efficacy beliefs outperformed those with lower other--‐efficacy beliefs. Antecedents of such other-efficacy beliefs are amongst others perceptions regarding motivation and psychological factors of the partner (Jackson, Knapp, & Beauchamp, 2008). Overt self-talk could be interpreted as the manifestation of such motivational or psychological factors. In line with this assumption, in an experimental study using dubbed videos of the same segment of a tennis match, Van Raalte, Brewer, Cornelius, and Petitpas (2006) found that players were perceived more favorably (e.g., more concentrated, and of higher ability levels) when shown with dubbed positive self-talk as compared to dubbed negative or no dubbed self--‐talk. Objectives The aim of the study was to examine the possible effects of a confederate’s overt self-talk on participants’ other-efficacy beliefs and performance in a team setting. Method In a laboratory experiment (between-subjects, pre-post-test design, matched by pretest performance) 89 undergraduate students (female = 35, M = 20.81 years, SD = 2.34) participated in a golf putting task together with a confederate (same gender groups). Depending on the experimental condition (positive, negative, or no self-talk), the confederate commented his or her putts according to a self-talk script. Bogus performance feedback assured that the performance of the confederate was held constant. Performance was measured as the distance to the center of the target, other-efficacy by a questionnaire. Results The data collection has just finished and the results of repeated measures analyses of variance will be presented and discussed at the congress. We expect to find higher other-efficacy beliefs and better individual performance in the positive self-talk condition. References Dunlop, W.L., Beatty, D.J., & Beauchamp, M.R. (2011). Examining the influence of other-efficacy and self-efficacy on personal performance. Journal of Sport & Exercise Psychology, 33, 586-593. Jackson, B., Knapp, P., & Beauchamp, M.R. (2008). Origins and consequences of tripartite efficacy beliefs within elite athlete dyads. Journal of Sport and Exercise Psychology, 30, 512-540. Lent, R.W., & Lopez, F.G. (2002). Cognitive ties that bind: A tripartite view of efficacy beliefs in growth--‐promoting relationships. Journal of Social and Clinical Psychology, 21, 256-286. Van Raalte, J.L., Brewer, B.W, Cornelius, A.E., & Petitpas, A.J. (2006). Self-presentational effects of self-talk on perceptions of tennis players. Hellenic Journal of Psychology, 3, 134-149.

Individual group efficacy beliefs and performance motivation: A mediational approach

Introduction: According to the theoretical model of Cranach, Ochsenbein, and Valach (1986) understanding group actions needs consideration of aspects at both the group level and the level of individual members. For example individual action units constituting group actions are motivated at the individual level while potentially being affected by characteristics of the group. Theoretically, group efficacy beliefs could be a part of this motivational process as they are an individual’s cognitive contents about group-level abilities to perform well in a specific task. Positive relations between group level efficacy-beliefs and group performance have been reported and Bandura and Locke (2003) argue that this relationship is being mediated by motivational processes and goal setting. The aims of this study were a) to examine the effects of group characteristics on individual performance motivation and b) to test if those are mediated by individual group efficacy beliefs. Methods: Forty-seven students (M=22.83 years, SD=2.83, 34% women) of the university of Berne participated in this scenario based experiment. Data were collected on two collection points. Subjects were provided information about fictive team members with whom they had to perform a group triathlon. Three values (low, medium, high) of the other team members’ abilities to perform in their parts of the triathlon (swimming and biking respectively) were combined in a 3x3 full factorial design (Anderson, 1982) yielding nine groups. Subjects were asked how confident they were that the teams would perform well in the task (individual group efficacy beliefs), and to provide information about their motivation to perform at their best in the respective group contexts (performance motivation). Multilevel modeling (Mplus) was used to estimate the effects of the factors swim and bike, and the context-varying covariate individual group efficacy beliefs on performance motivation. Further analyses were undertaken to test if the effects of group contexts on performance motivation are mediated by individual group efficacy beliefs. Results: Significant effects were reported for both the group characteristics (βswim = 7.86; βbike = 8.57; both p < .001) and the individual group efficacy beliefs (βigeb; .40, p < .001) on performance motivation. The subsequent mediation model indicated that the effects of group characteristics on performance motivation were partly mediated by the individual group efficacy beliefs of the subjects with significant mediation effects for both factors swim and bike. Discussion/Conclusion: The results of the study provide further support for the motivational character of efficacy beliefs and point out a mechanism by which team characteristics influence performance relevant factors at the level of individual team members. The study indicates that high team abilities lead to augmented performance motivation, adding a psychological advantage to teams already high on task relevant abilities. Future investigations will be aiming at possibilities to keep individual performance motivation high in groups with low task relevant abilities. One possibility could be the formulation of individual task goals. References: Anderson, N. H. (1982). Methods of information integration theory. New York: Academic Press. Bandura, A. & Locke, E. A. (2003). Negative self-efficacy and goal effects revisited. Journal of Applied Psychology, 88, 87-99. Cranach, M. von, Ochsenbein, G. & Valach, L. (1986). The group as a self-active system: Outline of a theory of group action. European Journal of Social Psychology, 16, 193-229.

Group abilities, individual group-efficacy beliefs and performance motivation: A mediation analysis

Introduction Research has shown that individuals infer their group-efficacy beliefs from the groups’ abilities to perform in specific tasks. Group abilities also seem to affect team members’ performance motivation adding a psychological advantage to teams already high on task relevant abilities. In a recent study we found the effect of group abilities on individual performance motivation to be partially mediated by the team members’ individual group-efficacy beliefs which is an example of how attributes on a group-level can be affecting individual-level parameters. Objectives The study aimed at testing the possibility to reduce the direct and mediated effects of low group abilities on performance motivation by augmenting the visibility of individual contributions to group performances via the inclusion of a separate ranking on individual performances. Method Forty-seven students (M=22.83 years, SD=2.83, 34% women) of the University of Bern participated in the study. At three collection points (t1-3) subjects were provided information about fictive team members with whom they had to imagine performing a group triathlon. Three values (low, medium, high) of the other team members’ abilities to perform in their parts of the triathlon (swimming and biking) were combined in a 3x3 full factorial design yielding nine groups with different ability profiles. At t1 subjects were asked to rate their confidence that the teams would perform well in the triathlon task, at t2 and t3 subjects were asked how motivated they were to perform at their best in the respective groups. At t3 the presence of an individual performance ranking was mentioned in the cover story. Mixed linear models (SPSS) and structural equation models for complex survey data (Mplus) were specified to estimate the effects of the individual performance rankings on the relationship between group-efficacy beliefs and performance motivation. Results A significant interaction effect for individual group-efficacy beliefs and the triathlon condition on performance motivation was found; the effect of group-efficacy beliefs on performance motivation being smaller with individual performance rankings available. The partial mediation of group attributes on performance motivation by group-efficacy beliefs disappeared with the announcement of individual performance rankings. Conclusion In teams low in task relevant abilities the disadvantageous effect of group-efficacy beliefs on performance motivation might be reduced by providing means of evaluating individual performances apart from a group’s overall performance. While it is believed that a common group goal is a core criterion for a well performing sport group future studies should also aim at the possible benefit of individualized goal setting in groups.

Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis.

INTRODUCTION Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index. METHODS The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography. RESULTS A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008). CONCLUSION The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.

Group abilities, individual group-efficacy beliefs and performance motivation: A mediation analysis

Introduction Research has shown that individuals infer their group-efficacy beliefs from the groups’ abilities to perform in specific tasks. Group abilities also seem to affect team members’ performance motivation adding a psychological advantage to teams already high on task relevant abilities. In a recent study we found the effect of group abilities on individual performance motivation to be partially mediated by the team members’ individual group-efficacy beliefs which is an example of how attributes on a group-level can be affecting individual-level parameters. Objectives The study aimed at testing the possibility to reduce the direct and mediated effects of low group abilities on performance motivation by augmenting the visibility of individual contributions to group performances via the inclusion of a separate ranking on individual performances. Method Forty-seven students (M=22.83 years, SD=2.83, 34% women) of the University of Bern participated in the study. At three collection points (t1-3) subjects were provided information about fictive team members with whom they had to imagine performing a group triathlon. Three values (low, medium, high) of the other team members’ abilities to perform in their parts of the triathlon (swimming and biking) were combined in a 3x3 full factorial design yielding nine groups with different ability profiles. At t1 subjects were asked to rate their confidence that the teams would perform well in the triathlon task, at t2 and t3 subjects were asked how motivated they were to perform at their best in the respective groups. At t3 the presence of an individual performance ranking was mentioned in the cover story. Mixed linear models (SPSS) and structural equation models for complex survey data (Mplus) were specified to estimate the effects of the individual performance rankings on the relationship between group-efficacy beliefs and performance motivation. Results A significant interaction effect for individual group-efficacy beliefs and the triathlon condition on performance motivation was found; the effect of group-efficacy beliefs on performance motivation being smaller with individual performance rankings available. The partial mediation of group attributes on performance motivation by group-efficacy beliefs disappeared with the announcement of individual performance rankings. Conclusion In teams low in task relevant abilities the disadvantageous effect of group-efficacy beliefs on performance motivation might be reduced by providing means of evaluating individual performances apart from a group’s overall performance. While it is believed that a common group goal is a core criterion for a well performing sport group future studies should also aim at the possible benefit of individualized goal setting in groups.