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Biomedical subjects

Jordi Río

Publications and source records attributed to Jordi Río.

15 recordsLinked to original sources
PubMed2006

Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients.

OBJECTIVE: Many patients with multiple sclerosis (MS) are currently receiving treatment with interferon (IFN)-beta. Early identification of nonresponder patients is crucial to try different therapeutic approaches. We investigated various criteria of treatment response to assess which criterion better identifies patients with a poor response. METHODS: We studied relapsing-remitting MS (RRMS) patients treated with IFN-beta and followed them up for at least 2 years. Expanded Disability Status Score was scored every 3 months and relapses were recorded. We analyzed various criteria based on relapses, disability progression, or both. RESULTS: Three hundred ninety-three patients were included. After 2 years of treatment, we observed a proportion of nonresponders, ranging from 7 to 49% depending on the stringency of the criteria used. Criteria based in disability progression had higher sensitivity, specificity, and accuracy. The hazard ratio for the development of marked disability after 6 years of treatment was 39.6 (95% confidence interval, 16.6-94.4) among the patients who fulfilled the criterion based only in disability progression. INTERPRETATION: Criteria of response to IFN-beta therapy in RRMS using disability progression are more clinically relevant than those based only in relapse rate. This finding may be important for the counseling and care of RRMS patients treated with IFN-beta.

Adjuvants, Immunologic↗
PubMed2006

Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone.

BACKGROUND AND OBJECTIVE: Fatigue is one of the most limiting symptoms in multiple sclerosis (MS) and the mechanisms underlying its origin are poorly understood. Our aim was to test whether fatigue in MS is associated with endocrine markers. METHODS: We longitudinally studied 73 progressive MS patients. Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue Severity Scale (FSS). Given the longitudinal design of our study, patients were labelled as sustained fatigued when FSS scores were >5.0 at all time points, and as non-fatigued when FSS scores were < or = 5.0 at all time points. Serum levels of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol were measured at each time point. RESULTS: Twenty-nine patients scored >5.0 in the FSS at all time points, and 9 patients (12.3%) scored 5.0 at all time points. Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained fatigue when compared to patients without fatigue (P = 0.01 and P = 0.03 respectively). Analysis of DHEAS and DHEA over time showed significantly lower hormone levels in patients with fatigue [F(1,31) = 6.14, P=0.019 for DHEAS; F(1,32) = 6.63, P=0.015 for DHEA]. CONCLUSIONS: Fatigue in progressive MS could be related to low serum levels of DHEA and DHEAS. Our results suggest that these hormones should be considered as biological markers of fatigue in MS patients and that hormone replacement may thus be tested as an option to treat fatigue in MS patients.

Adult↗
PubMed2005

Interferon beta in relapsing-remitting multiple sclerosis. An eight years experience in a specialist multiple sclerosis centre.

BACKGROUND AND OBJECTIVE: Long-term observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data of our cohort of relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta (IFNbeta). METHODS: We analysed RRMS patients followed for at least 2 years. From 1995, we initiated therapy with IFNbeta. As they became available, patients were allocated to one of the IFNs at standard doses (IFNbeta-1b, IFNbeta-1a i.m. or IFNbeta-1a s.c.). Each patient was included in a follow-up protocol containing demographic and baseline clinical data. RESULTS: Between 1995 and 2004, 382 patients have completed at least 2 years of follow-up. Significant differences at entry were observed. Patients on IFNbeta-1b had a higher disease activity and disability at baseline than those on IFNbeta-1a i.m. or IFNbeta-1a s.c. A significant reduction in the relapse rate was observed for the three drugs (70% for IFNbeta-1b, 64% for IFNbeta-1a i.m. and 74% for IFNbeta-1a s.c.). We observed a sustained progression of disability in 11% of patients on IFNbeta-1b, 17% on IFNbeta-1a i.m. and 19% on IFNbeta-1a s.c.; and at four years of follow-up in 24% of patients on IFNbeta-1b, 23% on IFNbeta-1a i.m. and 35% on IFNbeta-1a s.c. No unexpected major adverse events were observed with any of the drugs. CONCLUSIONS: Interferon beta is safe and well tolerated. The various registered interferon beta drugs provide a comparable efficacy in a large non-selected cohort of RRMS patients.

Adjuvants, Immunologic↗
PubMed2005

[Long-term effect of neutralizing antibodies to interferon beta-1 b in patients with multiple sclerosis].

BACKGROUND AND OBJECTIVE: Our goal was to evaluate the relation between the presence of neutralizing antibodies (NABs) to interferon beta-1b in multiple sclerosis (MS) patients and the clinical evolution in the following years. PATIENTS AND METHOD: As we previously reported, we tested NABs in 68 patients treated with interferon beta-1b after 2 years of treatment. We prospectively followed this cohort every three months for a minimum period of 6 years collecting data about relapses, disability, secondary effects and dropouts. RESULTS: During the 6 year follow-up period, the annualized relapse rate did not differ between patients with and patients without NABs. A sustained progression was observed in 33% of positive patients and in 38% of patients without NABs. No differences were found in the proportion of patients who reached an EDSS score of 6. Secondary effects were similar in both groups. CONCLUSIONS: Although our results do not vouch for a negative effect of the presence of NABs on the clinical evolution of MS patients treated with interferon beta, further longitudinal studies to clarify the real effect of the presence of NABs in these patients are still much needed.

Adjuvants, Immunologic↗
PubMed2005

Plasma osteopontin levels in multiple sclerosis.

Osteopontin (OPN) is a pleiotropic integrin binding protein with functions in cell-mediated immunity, inflammation, tissue repair, and cell survival. Recent studies have shown that OPN may play an important role in the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis (MS). Here, we investigated the plasma levels of OPN in 221 MS patients and 36 healthy controls using an enzyme-linked immunoassay. The MS group comprised of 71 patients with primary and transitional progressive MS (PP/TP-MS), 35 patients with secondary progressive MS (SPMS), and 115 patients with relapsing-remitting MS (RRMS)[46 patients during clinical remission, 26 patients during relapse, and 43 patients treated with interferon-beta (IFNbeta)]. Levels of OPN in plasma were elevated in SPMS patients compared with healthy controls, RRMS patients in remission, and PP/TP-MS patients. Patients with RRMS during relapse presented higher OPN levels than patients with RRMS during clinical remission. When MS patients were classified based on progression of neurological disability, an inverse relation between levels of OPN and disability progression was observed only in patients with relapsing MS. In RRMS patients receiving therapy with IFNbeta, OPN plasma levels were similar to RRMS patients during remission. These findings suggest that OPN is involved in both acute and chronic disease activity, thus expanding the role of OPN in MS pathogenesis suggested by previous studies. Furthermore, the different profiles of OPN levels found in acute relapses and chronic progression and its apparent lack of influence in primary progressive MS phenotypes raise interesting questions on the actual role of OPN in the pathogenesis of MS.

Adult↗
PubMed2005

Factors related with treatment adherence to interferon beta and glatiramer acetate therapy in multiple sclerosis.

BACKGROUND: Awareness of the factors influencing discontinuation of immunomodulatory drugs (IMD) treatment in multiple sclerosis (MS) can help to find approaches to patient management with the aim of establishing more specific indications and also attaining more optimal patient selection in future clinical trials. OBJECTIVE: To identify the causes that influence adhesion to IMD therapy within the clinical practice in a large cohort of patients with MS. PATIENTS AND METHODS: We have studied all MS patients who have initiated IMD in our hospital. All patients took part in training sessions where treatment expectations and side effects were explained and they received training in the administration technique. Reasons for stopping therapy were recorded during follow-up. RESULTS: We studied 632 MS patients (mean follow-up was 47.1 (28.7) months). At the time of analysis, 107/632 patients (17%) were no longer receiving IMD. Almost half of the patients who stopped IMD (52/107) did so within the first two years on therapy. Fifty-six patients stopped IMD because of lack of efficacy. Only 27 patients (4.3%) discontinued treatment for reasons other than inefficacy or side effects. The proportion of patients with secondary progressive MS that stopped IMD therapy was 30%, while only 13.5% of the patients with relapsing remitting MS stopped therapy (P < 0.0001). Expanded Disability Status Scale (EDSS) score at entry was the main factor that predicted interruption of therapy. CONCLUSIONS: The proportion of patients interrupting IMD in our centre is low, possibly due to individualized care. Higher EDSS, mainly in the first two years of treatment, is the main factor related with interruption. Close follow-up of these patients would be useful in avoiding early discontinuation of therapy.

Adjuvants, Immunologic↗
PubMed2005

Interferon-beta 1b in the treatment of multiple sclerosis.

Ever since IFN-beta1b was first approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) in the US and Europe, other disease-modifying drugs have become available. Phase III clinical trials have shown the efficacy of IFN-beta1b in the treatment of RRMS and secondary progressive MS in that it can reduce the annual relapse rate as well as magnetic resonance imaging parameters of activity and progression. There is mounting evidence that the best time to initiate treatment is early in the course of the disease, and available data suggest that efficacy is sustained for at least 5 years. IFN-beta1b is safe and well tolerated, although there are adverse events such as the flu-like complex and skin reactions. In the face of a proportion of RRMS patients experiencing a poor response to the drug, other therapeutic approaches need to be considered.

Humans↗
PubMed2004

Specificity of Barkhof criteria in predicting conversion to multiple sclerosis when applied to clinically isolated brainstem syndromes.

BACKGROUND: Barkhof criteria have been adopted to demonstrate dissemination in space in the new multiple sclerosis diagnostic criteria because of their high specificity for predicting conversion to multiple sclerosis. One of the 4 Barkhof criteria is the presence of an infratentorial lesion. In clinically isolated syndromes (CIS) of the brainstem (CISB), the infratentorial criterion does not demonstrate dissemination in space, raising the possibility that the criteria may be less specific in CISB, as compared with specificity in other CIS, in which all 4 criteria demonstrate dissemination in space. OBJECTIVE: To compare the validity indices of Barkhof criteria in CISB with those in other CIS. DESIGN: Inception cohort with median follow-up of 34 months for CISB and 40 months for other CIS. SETTING: Institutional ambulatory referral center. PATIENTS: A sample of 51 patients with CISB and 102 patients with other CIS (46 with myelitis and 56 with optic neuritis) was analyzed. Barkhof criteria, with a cutoff of 3 of 4, were applied to magnetic resonance imaging performed at baseline. Four combinations each containing 3 parameters were also applied, with a cutoff of 2 of 3. MAIN OUTCOME MEASURE: Specificity of unmodified Barkhof criteria and of the 4 combinations to predict conversion to clinically definite multiple sclerosis. RESULTS: The specificity of the criteria in CISB was 61% against 73% in other CIS. The combinations that retained the infratentorial lesion parameter had lower specificities in the CISB group; in analysis of the group with other CIS, no such differences were found. CONCLUSION: The infratentorial lesion criterion is responsible for the lower specificity of Barkhof criteria in CISB.

Adolescent↗
PubMed2004

Clinical impact of intravenous methylprednisolone in attacks of multiple sclerosis.

BACKGROUND: Intravenous methylprednisolone (IVMP) has been shown to hasten recovery from attacks of multiple sclerosis (MS) without altering the long term evolution of the condition; however, there is little evidence available to suggest which patients are more likely to benefit from IVMP treatment. OBJECTIVE: To measure clinical change after IVMP treatment and to identify predictors of good outcome. METHODS: Retrospective open-label study of medical records from 51 patients with clinically isolated syndromes or relapsing-remitting MS treated with IVMP for an acute attack (54 attacks). RESULTS: A measurable neurological improvement was observed at one month in 44% of these attacks; the only predictor of Expanded Disability Status Scale (EDSS) change at one month was the severity of the attack. CONCLUSION: Attack severity predicts good response to IVMP when measured by means of EDSS.

Adult↗
PubMed2003

Unconventional therapy in multiple sclerosis.

BACKGROUND: The use of unconventional therapies is growing in western countries. Few studies on their frequency and rationale among multiple sclerosis (MS) patients have been carried out in Europe. OBJECTIVE: To assess the frequency of use of unconventional therapies among MS patients and to explore associated clinical variables. METHODS: Structured questionnaires were given to 380 consecutive patients seen at two hospital-based MS clinics in Barcelona. Clinical and demographical data were recorded at the same time. The questionnaire inquired about demographical features, education, income, use of unconventional therapies for MS and satisfaction with conventional medicine both in general and specifically in MS. RESULTS: The response rate was 50.78%. Forty-one per cent of patients admitted using unconventional therapies during the previous year. Low levels of satisfaction with conventional medicine in general and for MS, and higher Expanded Disability Status Scale (EDSS) scores (EDSS mean: 4.43 in users versus 3.48 in nonusers) were significantly associated with use of unconventional therapies. CONCLUSION: Use of unconventional therapies is not rare among MS patients, and it is associated with high disability levels and dissatisfaction with conventional medicine.

Adult↗
PubMed2002

Assessment of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta: implications for clinical trials.

Clinical trials with interferons in relapsing-remitting multiple sclerosis have shown a modest effect on disability using fixed definitions of treatment failure to measure disease progression. However, in the course of the disease, treatment failure may be influenced by interrater variability and frequent remissions. Thus, the purpose of this study was to assess the clinical usefulness of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta. We studied 252 patients with a follow-up of more than 2 years. We used four different criteria of treatment failure with increasing stringency (1 Expanded Disability Status Scale [EDSS] point increase confirmed at 3 months, 1 EDSS point increase confirmed at 6 months, 1.5 EDSS points increase confirmed at 3 months, and 1.5 EDSS points increase confirmed at 6 months). We divided treatment failure into permanent treatment failure and transient treatment failure. We considered permanent treatment failure when treatment failure was confirmed on the last two scheduled visits and transient treatment failure when treatment failure was not confirmed on these visits at different time points (9, 12, 18, and 24 months). We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the different criteria of treatment failure to identify patients who achieved a high degree of disability after 4 years of follow-up. Regardless of the stringency of treatment failure definitions, a variable proportion of patients with treatment failure had transient treatment failure depending on the criterion applied. Patients with transient treatment failure had a significantly lower EDSS at entry compared with those with permanent treatment failure or no treatment failure. The number of relapses in patients with transient treatment failure did not differ from that of patients with permanent treatment failure. The criterion of confirmed 1 EDSS point increase at 6 months showed the best sensitivity (76.5%), with satisfactory specificity (89%). Our study shows that a large proportion of patients treated with interferon experience transient treatment failure that may affect outcome interpretation in clinical trials. Using a more strict criterion, as extending time to confirmation of EDSS deterioration, and longer follow-up may reduce this proportion of patients with transient treatment failure and improve the validity of the results attained in clinical trials.

Adjuvants, Immunologic↗