Early Therapy

Abstract: Objective. Delay of disease-modifying anti-rheumatic drug (DMARD) therapy is a major contributing factor for poor outcome in rheumatoid arthritis (RA). Although early therapy has been shown to be particularly effective, there is still uncertainty about the optimal time point of DMARD introduction. We wanted to test if a therapeutic window of opportunity may exist within the first few months of the disease. Methods. In this case-control parallel-group study, 20 very early RA (VERA) patients with median disease duration of 3 months were age and gender matched to a group of 20 late early RA (LERA) patients with median disease duration of 12 months until first DMARD initiation. Follow-up time was 36 months. Primary outcome measures were the disease activity score (DAS28) and radiological joint destruction using the Larsen method. Results. Already after 3 months of DMARD therapy we found a significant difference of improvement in favour of the VERA patients in the DAS28. This trend continued over the study period. At study end the DAS28 showed an improvement of 2.8±1.5 in the VERA vs 1.7±1.2 in the LERA group (P c < 0.05). The Larsen scores showed a statistically significant retardation of progression in the VERA compared with the LERA. Conclusion. Our results indicate that there is a window of opportunity for highly successful treatment of RA in the first year, and especially within the first 3 months of therapy. Thus, early diagnosis and therapy may be the crucial step in achieving optimal control of disease progression and prognosis in RA.

Abstract: AIMS To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 × 10 9 /l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential. Key messages MAS is a rare complication of childhood rheumatic disease It is a potentially fulminant disorder, which may occur as part of the initial presentation of the rheumatic disease An infective trigger may herald the onset of this complication in predisposed patients Differentiation from a disease flare may be difficult, but is critical to ensure optimal outcome An early and dramatic fall in platelet count is characteristic, with changes in WBC and haemoglobin being more variable early and common Elevation in transaminases and coagulation abnormalities may not be present at onset of MAS Bone marrow examination is supportive, but false negative reports occur as a result of sampling errors or the subtle nature of the disease Multisystem involvement is a poor prognostic sign

Abstract: Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain’s dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

Abstract: Background: The relapsing form of neuromyelitis optica (NMO) is characterized by recurrent optic neuritis and myelitis, usually leading to severe, permanent, relapse-related neurologic impairment (e.g., blindness, paraplegia) within 5 years. Aggressive therapy aimed at relapse prevention initiated soon after disease onset may be expected to have a relatively greater impact on early relapse-related disability in NMO than in typical MS. Early prediction of a relapsing course and subsequent disease severity would facilitate design and implementation of clinical trials of such therapies. Methods: A database of clinical and laboratory features of patients with NMO (n = 80) was used to develop potentially useful models predictive of a relapsing disease course and of subsequent disease severity as measured by survival. Results: Predictors of a relapsing course were longer interattack interval between the first two clinical events (rate ratio [RR] = 2.16; per month increase), older age at onset (RR = 1.08; per year increase), female sex (RR = 10.0, female vs male), and less severe motor impairment with the sentinel myelitis event (RR = 0.48; per severity scale point increase). A history of other autoimmune disease (RR = 4.15; presence vs absence), higher attack frequency during the first 2 years of disease (RR = 1.21; per attack), and better motor recovery following the index myelitis event (RR = 1.84; per point increase) were associated with mortality due to relapsing NMO. Conclusions: These predictive models identify several clinical features, each available at diagnosis or early in the disease course, that predict relapsing disease and survival. These results may be useful to identify patients at high risk for severe, relapsing neuromyelitis optica in order to initiate early therapy for relapse prevention and to design clinical trials to study such interventions.