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A multivariate model for the prediction of relapse after outpatient treatment of decompensated chronic obstructive pulmonary disease.

PURPOSE: To develop and validate a multivariate model for predicting relapses after treatment of decompensated chronic obstructive pulmonary disease in an emergency department. METHODS: A 5-year survey was conducted, including training and validation periods. Stepwise logistic regression was used to develop a multivariate predictive model using clinical data obtained at the time of each visit. A relapse was defined as an unscheduled return to the emergency department within 48 hours. SITE: The study was conducted in the emergency department of the Albuquerque (New Mexico) Veterans Affairs Medical Center. SUBJECTS: The subjects were 289 patients with documented chronic obstructive pulmonary disease. MEASUREMENTS AND MAIN RESULTS: During the first 3 years, there were 705 visits in which the patient was treated and released from the emergency department. Relapse occurred 82 times (11.6%). Logistic regression showed that the following variables had an effect on the risk of relapse: the relapse rate for previous visits, a previous visit within 7 days, long-term home oxygen therapy, the number of doses of nebulized bronchodilators, the administration of aminophylline, and the use of antibiotics and prednisone at the time of discharge from the emergency department. During the next 2 years, the 48-hour relapse rate was 9.9% (47 of 476 discharges). When the model was fitted to these data, all of the original variables contributed to the prediction of relapse except antibiotic use and long-term home oxygen therapy. The logistic model was used to categorize each visit during the validation phase. The relapse rate for "high-risk" visits was significantly higher than that for "low-risk" visits (18.4% vs 6.1%). The method identified 57.4% of visits that ended in relapse at 48 hours. CONCLUSIONS: A multivariate model can be used to identify patients with a poor prognosis after the outpatient treatment of decompensated chronic obstructive pulmonary disease.

Ambulatory Care↗

Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group.

Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment.

Adolescent↗

Relapses in paucibacillary leprosy after MDT--a clinical study.

A study was undertaken in a field-based project to assess the incidence and clinical profile of relapses occurring in paucibacillary leprosy patients after adequate doses of multidrug therapy (MDT). Of the 1509 paucibacillary patients who had received not less than 6 doses of MDT (WHO regimen), 85 relapsed; a relapse rate of 5.63% (17.5/1000 person years at risk). These relapses included 12 cases with features of reversal reaction. Seventy-nine percent of the patients relapsed with skin lesions. The relapse rate was higher in borderline cases and in those with more lesions, and it was lower in those who had received dapsone for at least 6 months after cessation of MDT. Seventy-four percent of the relapses were detected between 7 and 24 months of follow up. We feel that uniform clinical criteria should be formulated for the diagnosis of relapse. Individualization of therapy, rather than adhering to a fixed duration of MDT, would be likely to achieve satisfactory cure rates and fewer relapses.

Drug Administration Schedule↗

The role of splenectomy in the treatment of relapsing thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a serious disorder of unknown etiology. Clinical findings are the result of vascular occlusions by platelet aggregates. Treatment with plasma exchange, often used in combination with corticosteroids, vincristine, aspirin, and dipyridamole, has reduced mortality to 20%. Relapses may occur even after long disease-free intervals. In this report we describe our experience with splenectomy in patients with relapsing TTP. Between July 1978 and March 1994, 16 patients with TTP were treated in our hospital. Five of the 13 patients surviving the first episode of TTP had relapses. Most relapses were treated as the first episode of TTP with plasma exchange with fresh-frozen plasma, followed by plasma infusions, corticosteroids, and vincristine. Sometimes aspirin and dipyridamole were added. Splenectomy was performed after five relapses in the first two patients and after two and three relapses in the other patients. Before splenectomy the disease-free interval varied from 3 weeks to 27 months and the incidence rate of relapses was 1.5 relapse/patient/year. None of the patients had relapses after splenectomy. The mean follow-up after splenectomy is 39 months with a range of 9-62 months. We conclude that patients with relapsing TTP can benefit from splenectomy, since it seems to increase disease-free intervals. Further investigation is necessary to understand the role of the spleen in the pathogenesis of TTP.

Adult↗

Clinical features and diagnosis of relapses in leprosy.

1. The definition of relapse as "occurrence of new signs and symptoms of the disease during the period of surveillance or thereafter in a patient who successfully completes an adequate course of multidrug therapy" accommodates the current policy of releasing patients even when there are clinical and bacteriological signs of activity after fixed duration treatment. 2. The predisposing cause of relapse in the persistence of live M. leprae in various tissues in MB leprosy and in the nerve in PB leprosy. 3. The precipitating causes of relapse include (a) inadequate therapy due to miscategorization of MB cases as PB when there are solitary or few MB lesions since skin smear examinations for AFB are not routinely done in PB cases. (b) Previously sulphone treated LL cases inactive for more than two years are not included for MDT. Relapses commonly seen in NLEP units are in such cases. (c) Multiple skin and nerve lesions in PB leprosy. (d) Pregnancy and lactation. (e) Mental depression which downgrades immunity. (f) HIV infection. 4. There may be a change in type on relapsing, PB cases relapsing as MB and MB cases relapsing as PB. 5. Criteria for diagnosis of relapse are: increase in the extent of lesions, infiltration and erythema, fresh skin and nerve lesions, positive skin smears for AFB in previously negative cases; and in bacteriologically positive cases during surveillance, an increase in BI by two logs at any site over the previous BI in two successive examinations. 6. Relapses are but too often diagnosed as reversal reactions inspite of the absence of symptoms and signs of acute inflammation to the detriment of patients; a course of steroid therapy which is administered to these patients on the diagnosis of reversal reaction does not halt the progress of the disease especially in the nerve, resulting in disability.

Causality↗

ANCA and predicting relapse in systemic vasculitis.

We studied 60 patients with ANCA-positive systemic vasculitis (SV) to assess the prognostic significance of clinical and serological features at presentation, and the value of sequential monitoring of ANCA, C-reactive protein (CRP) and ESR levels as predictors of disease relapse. Patients were recruited at the time of diagnosis, treated with a standard protocol, and assessed monthly for one year. Clinical remission was achieved in 56/60 (93%), and ANCA became undetectable in 50/60 (83%) after treatment. During the one year follow-up period, disease relapses were seen in 23 (38%) patients. No specific associations were observed between initial disease presentation, initial ANCA level or ANCA antigenic specificity and relapse. However, 13/23 (57%) of relapses were preceded by a rise in ANCA a mean of 7.8 weeks earlier, while at the time of relapse 19/23 (83%) were ANCA-positive. Rises in CRP and ESR occurred in 23/60 (38%) and 14/43 (33%), respectively, but were less closely associated with relapse than ANCA. A sustained rise in ANCA was seen in six patients without relapse while clinical relapse occurred with a negative ANCA in four. Sequential ANCA monitoring at monthly intervals during disease remission is of value, at least during the first year, in the prediction and diagnosis of relapse in SV, and is superior to measurement of CRP or ESR.

Antibodies, Antineutrophil Cytoplasmic↗

Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is the only effective treatment for hematologic malignancies resistant to conventional chemotherapy. Until recently, no cure existed for patients who relapsed post-BMT. We present our long-term observations on remission induction, after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the feasibility of remission induction in allo-CT-resistant patients by activation of antileukemia effector cells with recombinant human interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of successful allo-CT (event-free survival, greater than 8 years) was made in a patient with resistant pre-B lymphoblastic leukemia who received infusions with graded increments of donor (female) peripheral blood lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse was noticed early post-BMT. The patient is currently without evidence of residual host (male) cells as determined by polymerase chain reaction (PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT, 10 were reinduced into complete remission. Four patients with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhIL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistent minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT.

Adolescent↗

[A study on relapse of schizophrenic patients--10-year-follow-up investigation after initial admission].

Ten year prognosis of schizophrenic patients after their initial admission was studied. The subjects of the present investigation were 106 schizophrenic patients who fulfilled the criteria for schizophrenia of DSM-III-R and were initially admitted to a hospital between January 1979 and December 1984. They were classified into following five groups: 1) a discontinuing group (39 patients who could not be followed up because of changing the hospital or ceasing outpatient treatment), 2) an unrelapsing group (29 patients who had no relapse in continuing medication), 3) an A group (13 patients who relapsed in spite of continuing medication), 4) a B group (22 patients who relapsed only after discontinuing medication), and 5) a C group (3 patients who relapsed in continuing medication as well as after discontinuing medication). These groups were compared in multiple domains such as age at onset, age on initial admission, duration from onset to initial admission, etc. The average age at onset was significantly older in the unrelapsing group (29.0 years) than in the A group (22.1 years) (p < 0.05). The average age on initial admission was significantly older in the unrelapsing group (35.2 years) than in the A group (25.0 years) (p < 0.01). Furthermore the average duration from onset to initial admission was significantly longer in the unrelapsing group (70.9 months) than in the A group (23.8 months) (p < 0.05). Assuming theoretical groups considered in points of tendency of relapse and the effect of neuroleptics on the prevention in each patient, as well as theoretical subgroups considered in points of biological pathology and nonbiological pathology as factors of relapse, the following two subgroups were abstracted from the groups of this study: a subgroup with a high effect of medication on the prevention of relapse and the other with a low effect. There were significant differences in the average age at onset, age on initial admission, duration from onset to initial admission, and duration of initial admission between these two subgroups. These different onset pattern suggest that the effect of medication on relapse is different among patients. Our results indicate existence of a group of schizophrenic patients whose relapse can not be prevented by current neuroleptic therapy.

Adult↗

Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation.

Relapse remains a significant problem after allogeneic bone marrow transplantation (BMT). For patients with relapsed chronic myelogenous leukemia (CML), infusions of donor mononuclear cells (MNC) provide a potent graft-versus-leukemia (GVL) reaction inducing complete remissions in the majority of patients. Little is known about the efficacy of donor MNC infusions for patients who relapse with other diseases. We have studied the GVL effects of donor MNC in eight patients with relapsed acute leukemia or myelodysplasia (MDS). One patient with relapsed MDS achieved complete remission and another patient had a transient response. Five of six non-responders died of progressive leukemia and one non-responder died of complications during second BMT. Three patients developed grade I-II acute GVHD responsive to immunosuppression. These data, and review of the literature, suggest that GVL induction with donor MNC infusions is less effective for patients with relapsed acute leukemia than for patients with relapsed CML; too few patients with relapsed MDS have been treated to draw definite conclusions. However, some patients respond, and given the high mortality associated with alternative procedures such as second BMT, donor MNC infusions are a reasonable approach for relapsed acute leukemia and MDS after allogeneic BMT.

Acute Disease↗

Autologous bone marrow transplantation for patients with acute myeloblastic leukemia in relapse after autologous blood stem cell transplantation.

Leukemic relapse remains the most frequent reason for treatment failure in patients with acute myeloblastic leukemia (AML) treated with autologous blood stem cell transplantation (ABSCT). The aim of this study was to evaluate the possible role of autologous bone marrow transplant (ABMT) in patients with AML who relapse after ABSCT. Eighteen consecutive patients were enrolled in the study. At ABMT, 17 patients were in untreated relapse and one was in third complete remission (CR). The preparative regimen was BAVC, and consisted of BCNU 800 mg/m2 on day -6, M-AMSA 150 mg/m2/day on days -5 to -3, VP-16 150 mg/m2/day on days -5 to -3 and Ara-C 300 mg/m2/day on days -5 to -3. There were two regimen-related deaths (11%). Thirteen out of 17 patients in untreated relapse before ABMT achieved CR (76%). The cumulative risk of relapse was 58 +/- 13% at 3 years. Seven patients are in CR between 7+ and 53+ months, with a disease-free survival (DFS) probability of 36 +/- 12% at 3 years. The probability of DFS after ABMT was clearly higher in those patients relapsing later than 7 months after the first autograft (52%) than in patients relapsing earlier (20%)(P = 0.02). In a significant proportion of patients, remission duration was clearly longer after ABMT than ABSCT. We conclude that BAVC conditioning followed by ABMT is associated with a low treatment-related toxicity and results in prolonged DFS in a substantial number of AML patients who relapse after ABSCT. Until better therapeutic options become available, ABMT in untreated relapse is a useful alternative in this group of very poor-risk patients.

Acute Disease↗

Gender differences in relapse situations.

Gender differences in variables relating to alcohol treatment are receiving increased attention. Most reports indicate gender differences in both intrapersonal, interpersonal and environmental trans-situational variables that relate specifically to women's drinking. This study investigates gender differences in the immediate relapse situation itself. These differences are then examined in the context of trans-situational (i.e. across time) affective and cognitive variables and social support. This report is part of a larger study designed to replicate Marlatt's taxonomy of high risk situations for relapse, and to examine alternative methods of describing relapse situations. Three hundred subjects (169 men, 131 women) were recruited from six different inpatient and outpatient programs. Subjects were asked to identify their last relapse before entering the index treatment. Details of the drinking episode itself were also obtained, e.g. number of drinking days in episode, drinking to intoxication, presence of others. Measures of state and trait affect, expectancies, and social support were also collected. There were no gender differences in Marlatt's taxonomy, or in drinking topography during relapse. At baseline, women reported drinking less, and drinking less often than men. However, women drank to intoxication more often than men. Surprisingly, men relapsed alone more often than did women. Men and women report relapsing frequently with same sex friends, and women showed a tendency to relapse in the presence of romantic partners. Men also tend to report more positive mood states during relapse than women, which is congruent with the finding that women report more depression. Severity of drinking pattern was found to be an important confounding variable in these analyses. It is suggested that gender differences found in individuals in treatment for alcohol problems may reflect societal differences between men and women, and that taking these differences into account in designing treatment programs may improve outcomes.

Adult↗

Risk of relapse in leprosy after fixed-duration multidrug therapy.

Between 1986 and 1995, 8307 leprosy patients have completed fixed-duration multidrug therapy (FD-MDT) and were followed annually for possible relapse. The mean relapse rate for multibacillary (MB) leprosy is 0.15/1000 person-years (py) and for paucibacillary (PB) 0.55/1000 py. There is no difference in the relapse rates between patients with or without chemotherapy before FD-MDT. In MB patients, the five relapses occurred between 4 and 7 years; in PB patients, five relapses occurred at 4-5 years after FD-MDT. Six additional PB relapses self-reported 1-4 years after the 5-year surveillance period and were not included in the relapse rates. Most PB patients relapsed into MB due to wrong classification and insufficient therapy. For the known 62 irregular MB patients the cumulative relapse rate is 6.5%.

Anti-Infective Agents↗

Pharmacological prevention of relapse.

Relapse is the "return of a disease after partial recovery", and is a major feature of schizophrenia disorder. It can be defined in terms of need for change in treatment, including rehospitalization or crisis intervention, the re-emergence of florid psychotic features, or gross social decompensation. Relapse is best viewed as continuum of severity rather than as discrete "attacks". Factors influencing relapse include major life events and the family constellation. Antipsychotic drugs protect against the latter but not the former, and relapse may be mediated by non-specific arousal mechanisms. The efficacy of drug treatment in postponing rather than preventing relapse is well established. The interval between relapses is prolonged at least two-fold, but in the long run most patients relapse. Unwanted effects of antipsychotic drugs can be a burden to patients, impairing quality of life. In particular, movement disorders and subjective dysphoria may be marked, as may compliance. Of these EPS, tardive dyskinesia is the most serious on long term use. Non-EPS long term effects include weight gain and endocrine changes. Depot medication has advantages over oral medication in the more ill, less compliant patients. Side effects may, however, be more marked. The greatest pain is in improved compliance but the regular supervision of the patient is also helpful. Pharmacokinetic issues are poorly understood. High and mega-dose strategies have been advocated. High doses may be needed in some patients, but megadoses are rarely justified and may be hazardous. Low dose and intermittent therapy have been evaluated but are not as successful as hoped. Some less ill patients may benefit. These schedules depend on the identification of prodromata of relapse which is not always easy, nor are relapses necessarily preceded by prodromata. Newer drugs are being developed rapidly in the search for a safer clozapine, the only antipsychotic with definitely enhanced efficacy. Other drugs which have been re-evaluated include the benzodiazepines. However, the area of greatest priority in research is that of interactions, particularly potentiation, between drug and non-drug treatments.

Antipsychotic Agents↗

Late relapsing childhood lymphoblastic leukemia.

Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can truly be confident of cure, if ever.

Adult↗

Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis.

Mitoxantrone has been approved by the FDA for worsening relapsing remitting and secondary progressive Multiple Sclerosis. However the benefits of this agent in reducing disease progression and relapse rate cannot be sustained in the long-term, as treatment is limited by the potential for cumulative cardiotoxicity. We report our experience utilising Glatiramer Acetate as maintenance immuno-modulatory treatment following initial immunosuppression with Mitoxantrone in a consecutive series of 27 patients with very active relapsing remitting disease, eight of whom had experienced continuing relapse activity on first-line treatment. Duration of treatment with Mitoxantrone and thereby cumulative dose were reduced as our experience with the combination increased.No unanticipated side effects of combination treatment were encountered over a follow-up period of 66 months. A single patient developed therapy related acute leukaemia (TRAL) 9 months after completion of Mitoxantrone.A sustained 90% reduction in annualised relapse rate (p < 0.001) has been observed. Disability is stable or improved in all patients a mean of 36 (16-66) months from initiation of treatment. Early suppression of relapse activity with Mitoxantrone has been maintained at a mean of 22 months from last dose of this agent. Only two relapses have occurred in the cohort since withdrawal of Mitoxantrone, occurring in the two patients who had previously been treated with Glatiramer Acetate. In 9 of the first 10 patients treated, imaged a mean of 27 months after withdrawal of Mitoxantrone, no enhancing lesions were identified on MRI brain scans. Glatiramer Acetate appears a safe and effective option for continuing disease modification in patients with relapsing remitting multiple sclerosis treated with Mitoxantrone. The treatment protocol utilised in later patients in this series appears to have the potential to limit exposure to this agent.

Adolescent↗

Hypopyon uveitis and relapsing polychondritis: a report of 2 patients and review of autoimmune hypopyon uveitis.

OBJECTIVE: To report hypopyon uveitis as an ophthalmic finding associated with relapsing polychondritis. DESIGN: Interventional case reports. PARTICIPANTS: Two patients with hypopyon uveitis as a manifestation of relapsing polychondritis. METHODS: Complete ocular and systemic examinations as well as chart reviews were performed for 2 patients with hypopyon uveitis as a manifestation of relapsing polychondritis at presentation. MAIN OUTCOME MEASUREMENTS: Clinical observation and response to treatment in 2 patients with hypopyon uveitis secondary to relapsing polychondritis. RESULTS: A 70-year-old white male had unilateral hypopyon uveitis accompanied by a migratory polyarthralgia at presentation. Fifteen months later, he sought treatment for chondritis of the right auricle and was diagnosed with relapsing polychondritis. A 42-year-old white female with known relapsing polychondritis had bilateral hypopyon uveitis at presentation during a systemic relapse. Both patients had resolution of the hypopyon with topical and systemic steroids. CONCLUSIONS: Relapsing polychondritis should be considered in the differential diagnosis of sterile hypopyon uveitis. Steroids and systemic immunosuppression can be used to treat the uveitis.

Adult↗

The effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in multiple sclerosis.

We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis. Following a double blind trial designed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded. The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3). The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups. This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment.

Administration, Oral↗

Relapses and progression of disability in multiple sclerosis.

BACKGROUND: The influence of the patterns of onset of multiple sclerosis and relapses of the disease on the time course of irreversible disability is controversial. METHODS: In 1844 patients with multiple sclerosis who were followed for a mean (+/- SD) of 11 +/- 10 years, we determined the time of the clinical onset of the disease, the initial course (relapsing-remitting or progressive) and the subsequent course (relapsing-remitting, secondary progressive, or primary progressive), the times of relapses, the time to the onset of irreversible disability, and the time course of progressive, irreversible disability. We used three scores on the Kurtzke Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability) as measures of the severity and progression of disability: a score of 4 (limited walking ability but able to walk for more than 500 m without aid or rest), a score of 6 (ability to walk with unilateral support no more than 100 m without rest), and a score of 7 (ability to walk no more than 10 m without rest while leaning against a wall or holding onto furniture for support). We used Kaplan-Meier analyses to determine the influence of relapses on the time to the onset of irreversible disability. RESULTS: The median times from the onset of multiple sclerosis to the assignment of a score of 4, a score of 6, and a score of 7 on the disability scale were longer among the 1562 patients with a relapsing-remitting onset of disease (11.4, 23.1, and 33.1 years, respectively) than among the 282 patients who had progressive disease from the onset (0.0, 7.1, and 13.4 years, respectively; P<0.001 for all comparisons). In contrast, the times from the assignment of a score of 4 to a score of 6 were similar in the two groups (5.7 and 5.4 years, P=0.74). The time course of progressive, irreversible disease among patients with the primary progressive type of multiple sclerosis was not affected by the presence or absence of superimposed relapses. CONCLUSIONS: Among patients with multiple sclerosis, relapses do not significantly influence the progression of irreversible disability.

Adolescent↗