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Item does not contain fulltext, OBJECTIVES: (1) To assess real-time patterns of fatigue; (2) to assess the association between a real-time fatigue score and 3 commonly used questionnaires (Checklist Individual Strength [CIS] fatigue subscale, Modified Fatigue Impact Scale (MFIS), and Fatigue Severity Scale [FSS]); and (3) to establish factors that confound the association between the real-time fatigue score and the conventional fatigue questionnaires in patients with multiple sclerosis (MS). DESIGN: Cross-sectional study. SETTING: MS-specialized outpatient facility. PARTICIPANTS: Ambulant patients with MS (N=165) experiencing severe self-reported fatigue. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A real-time fatigue score was assessed by sending participants 4 text messages on a particular day (How fatigued do you feel at this moment?; score range, 0-10). Latent class growth mixed modeling was used to determine diurnal patterns of fatigue. Regression analyses were used to assess the association between the mean real-time fatigue score and the CIS fatigue subscale, MFIS, and FSS. Significant associations were tested for candidate confounders (eg, disease severity, work status, sleepiness). RESULTS: Four significantly different fatigue profiles were identified by the real-time fatigue score, namely a stable high (n=79), increasing (n=57), stable low (n=16), and decreasing (n=13). The conventional questionnaires correlated poorly (r<.300) with the real-time fatigue score. The Epworth Sleepiness Scale significantly reduced the regression coefficient between the real-time fatigue score and conventional questionnaires, ranging from 15.4% to 35%. CONCLUSIONS: Perceived fatigue showed 4 different diurnal patterns in patients with MS. Severity of sleepiness is an important confounder to take into account in the assessment of fatigue.

Item does not contain fulltext, OBJECTIVES: (1) To assess real-time patterns of fatigue; (2) to assess the association between a real-time fatigue score and 3 commonly used questionnaires (Checklist Individual Strength [CIS] fatigue subscale, Modified Fatigue Impact Scale (MFIS), and Fatigue Severity Scale [FSS]); and (3) to establish factors that confound the association between the real-time fatigue score and the conventional fatigue questionnaires in patients with multiple sclerosis (MS). DESIGN: Cross-sectional study. SETTING: MS-specialized outpatient facility. PARTICIPANTS: Ambulant patients with MS (N=165) experiencing severe self-reported fatigue. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A real-time fatigue score was assessed by sending participants 4 text messages on a particular day (How fatigued do you feel at this moment?; score range, 0-10). Latent class growth mixed modeling was used to determine diurnal patterns of fatigue. Regression analyses were used to assess the association between the mean real-time fatigue score and the CIS fatigue subscale, MFIS, and FSS. Significant associations were tested for candidate confounders (eg, disease severity, work status, sleepiness). RESULTS: Four significantly different fatigue profiles were identified by the real-time fatigue score, namely a stable high (n=79), increasing (n=57), stable low (n=16), and decreasing (n=13). The conventional questionnaires correlated poorly (r<.300) with the real-time fatigue score. The Epworth Sleepiness Scale significantly reduced the regression coefficient between the real-time fatigue score and conventional questionnaires, ranging from 15.4% to 35%. CONCLUSIONS: Perceived fatigue showed 4 different diurnal patterns in patients with MS. Severity of sleepiness is an important confounder to take into account in the assessment of fatigue.

Item does not contain fulltext

Item does not contain fulltext

Contains fulltext : 95629.pdf (publisher's version ) (Open Access), BACKGROUND: Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to those in phase III trials. METHODS: A prospective, International Conference on Harmonization (ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)-supported study in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs' severity (mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were compared with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the patients experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial, we found statistically significantly lower incidences for most of the common AEs: headache, muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular events in study month 22, both AEs were assessed as not related to INFb-1a. CONCLUSION: Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatment-related AEs, most of these being mild. Our data externally validate the favorable phase III safety profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially hazardous AEs of IM INFb-1a.

Contains fulltext : 97839.pdf (publisher's version ) (Open Access), BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months.Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care.In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA. METHODS/DESIGN: The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiate

Contains fulltext : 95629.pdf (publisher's version ) (Open Access), BACKGROUND: Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to those in phase III trials. METHODS: A prospective, International Conference on Harmonization (ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)-supported study in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs' severity (mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were compared with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the patients experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial, we found statistically significantly lower incidences for most of the common AEs: headache, muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular events in study month 22, both AEs were assessed as not related to INFb-1a. CONCLUSION: Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatment-related AEs, most of these being mild. Our data externally validate the favorable phase III safety profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially hazardous AEs of IM INFb-1a.

Contains fulltext : 97839.pdf (publisher's version ) (Open Access), BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months.Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care.In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA. METHODS/DESIGN: The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiate

Contains fulltext : 97839.pdf (Publisher’s version ) (Open Access), BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months.Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care.In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA. METHODS/DESIGN: The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiate

Cytoplasmic linker protein (CLIP)-170, CLIP-115, and the dynactin subunit p150(Glued) are structurally related proteins, which associate specifically with the ends of growing microtubules (MTs). Here, we show that down-regulation of CLIP-170 by RNA interference results in a strongly reduced accumulation of dynactin at the MT tips. The NH(2) terminus of p150(Glued) binds directly to the COOH terminus of