Amaia Ugarte

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

One‐year psychosocial functioning in patients in the early vs. late stage of bipolar disorder

Rosa AR, González‐Ortega I, González‐Pinto A, Echeburúa E, Comes M, Martínez‐Àran A, Ugarte A, Fernández M, Vieta E. One‐year psychosocial functioning in patients in the early vs. late stage of bipolar disorder.

Antimalarials may influence the risk of malignancy in systemic lupus erythematosus

Background: Recent studies suggest that antimalarials have antineoplastic properties. Objective: To investigate whether antimalarials decrease the risk of cancer in systemic lupus erythematosus (SLE). Methods: An observational prospective cohort study was carried out. 235 patients were included in the study at the time of diagnosis (American College of Rheumatology criteria). The end point was the diagnosis of cancer. Kaplan–Meier cancer-free survival curves for patients treated and not treated with antimalarials were compared. A Cox proportional hazards model was fitted, with cancer as the dependent variable. Age at diagnosis, gender, treatment with azathioprine, cyclophosphamide and methotrexate, smoking, Systemic Lupus International Collaborating Clinics (SLICC) Damage Index 6 months after diagnosis, year of diagnosis and treatment with antimalarials were entered as independent variables. Results: 209 (89%) patients were women. 233 (99%) patients were white. Mean (SD) age at diagnosis was 37 (16) years. Median (range) follow-up was 10 (1–31) years. 156 (66%) patients had ever received antimalarials. 2/156 (1.3%) ever-treated patients compared with 11/79 (13%) never-treated patients had cancer (p<0.001). Cumulative cancer-free survival in treated and not treated patients was 0.98 and 0.73, respectively (p<0.001). Adjusted hazard ratio for cancer among malaria drug users compared with non-users was 0.15 (95% CI 0.02 to 0.99). Conclusions: This study launches the hypothesis of a protective action of antimalarials against cancer in patients with SLE. This effect should be confirmed in larger multicentre studies.

Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus

OBJECTIVE The aim of this study was to analyse the relationship between glucocorticoids and damage accrual in SLE. METHODS We report an observational cohort study including 230 patients with SLE enrolled at diagnosis with 5 years of follow-up. Damage was calculated using the SLICC damage index. Glucocorticoid-related damage was defined as avascular osteonecrosis, osteoporotic fractures, diabetes mellitus or cataracts. Prednisone doses were calculated at the end of the fourth year of follow-up (prednisone-4). A categorical prednisone-4 variable was constructed: no prednisone, ≤7.5 mg/day (low dose), >7.5 mg/day (medium-high dose). The relationship between methylprednisolone pulses and damage was also tested. RESULTS By the fifth year, 188 patients (82%) had been treated with prednisone. Eighty-seven patients (37.8%) had accrued damage at 5 years. Patients with damage at year 5 had received a higher mean daily prednisone-4 dose (10.4 vs 6 mg/day, P < 0.001). The mean daily prednisone-4 dose was higher in patients accruing glucocorticoid-attributable damage (11 vs 7 mg/day, P = 0.04). Patients taking medium-high doses of prednisone-4 had a higher risk of accruing damage than those taking no prednisone [adjusted odds ratio (OR) 5.39, 95% CI 1.59, 18.27]. Patients taking medium-high doses of prednisone-4 were more likely to develop glucocorticoid-related damage than those on no prednisone (adjusted OR 9.9, 95% CI 1.1, 84). No differences were seen between patients on low doses and those on no prednisone. The cumulative dose of i.v. methylprednisolone-4 was not associated with global or glucocorticoid-related damage. CONCLUSION Prednisone causes damage in SLE. Doses <7.5 mg/day and methylprednisolone pulses are not associated with damage accrual.

Comparison of high versus low–medium prednisone doses for the treatment of systemic lupus erythematosus patients with high activity at diagnosis

OBJECTIVE To compare the efficacy and safety of high vs. low-moderate oral doses of prednisone to treat patients with highly active lupus at diagnosis. PATIENTS AND METHODS Patients from the Lupus-Cruces cohort with an SLEDAI score ≥6 at diagnosis and treated with regimes containing low-medium prednisone doses (≤30 mg/day) were identified (group M). They were matched by sex and SLEDAI score with historical patients treated with high doses (>30 mg/day) at diagnosis (group H). Patients with proliferative nephritis were excluded. The difference in SLEDAI scores between baseline (SLEDAI-0) and year one (SLEDAI-1) was the efficacy variable. Damage at 5 years was calculated using the SLICC damage index (SDI) and regarded as the safety variable. Glucocorticoid related damage was considered in the presence of cataracts, osteonecrosis, osteoporotic fractures and/or diabetes mellitus. RESULTS 30 patients were included in each group. Patients in group H received 5-fold higher doses of prednisone, less hydroxychloroquine and less methyl-prednisolone pulses. SLEDAI improvement was similar in both groups. Patients in group H were more likely to accrue new damage (adjusted HR 3.85 (95% CI 1.03-14.2)). No patients in group M suffered glucocorticoid-related damage, vs. 5 patients in group H (p=0.02). The average daily prednisone dose during the first year predicted accrual of new damage (adjusted HR 1.03, 95% CI 1.0-1.07, p=0.056) and accrual of glucocorticoid-related damage (adjusted HR 1.06, 95% CI 1.01-1.13, p=0.03). Likewise, average doses of prednisone >7.5mg/day were an independent predictor of new damage (adjusted HR 4.8, 95% CI 1.2-19.1). CONCLUSION Prednisone doses ≤30 mg/day are similarly effective and safer than higher doses for treating active lupus.

Can positive family factors be protective against the development of psychosis

Genetic and environmental factors are both involved in the aetiology of psychotic disorders. The aim of this study was to assess if positive and negative environmental factors, together with psychotic family antecedents, are associated with the recent development of psychosis. We also investigated the interactions between family history of psychosis and positive and negative family environment. The sample comprised 110 children and adolescents, who had suffered a first psychotic episode and 98 healthy controls. All subjects were interviewed about their socioeconomic status, family history of psychosis and family environment (Family Environment Scale, FES). Early onset psychosis was significantly associated with a family history of psychosis. Family environment was perceived as more negative and less positive among patients than among controls. A negative family environment increased the risk of psychosis independently of the family history of psychosis. However, there was a significant protective effect of a positive family environment for persons with a family history of psychosis. This effect was not seen in subjects without a family history of psychosis. Therefore, our results support the importance of considering both family history of psychosis and family environment in the early stages of psychosis.

Severe multiorganic flare of systemic lupus erythematosus successfully treated with rituximab and cyclophosphamide avoiding high doses of prednisone

Both acute pancreatitis and diffuse alveolar haemorrhage are rare conditions associated with systemic lupus erythematosus (SLE). In this case report, a 23-year-old female with SLE was diagnosed with lupus-associated pancreatitis and, within a few days and despite initial therapy with pulse methyl-prednisolone, subsequently suffered an acute respiratory failure due to a diffuse alveolar haemorrhage. The patient was admitted to the intensive care unit and treatment was intensified with cyclophosphamide and rituximab, which shortly induced the complete remission of SLE with resolution of both clinical conditions. She completed treatment with six pulses of cyclophosphamide followed by azathioprine, hydroxychloroquine and prednisone at initial doses of 20 mg/d with rapid tapering to 5 mg/d, without relapse of the disease during the following year. This case can illustrate that, even in severe, life-threatening SLE flares, it is possible to avoid high-dose prednisone, which has been associated with severe side effects, including infections. Acute pancreatitis and diffuse alveolar haemorrhage are rare conditions caused by SLE. DAH can be a life-threatening complication, with an early mortality of at least 50%. When facing such severe SLE activity, there is a general tendency to use high doses of prednisone as the initial therapy, maintaining such high doses for long periods of time, even after the clinical situation has subsided. We report a case of a young woman with SLE, suffering from acute pancreatitis and diffuse alveolar haemorrhage, who was successfully treated with pulse methyl-prednisolone, hydroxychloroquine, cyclophosphamide and rituximab, combined with medium doses of prednisone.

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study

AIMS This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.

Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: An observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts

OBJECTIVE To compare the clinical course of patients with class III, IV and V lupus nephritis (LN) treated at Hospital Universitario Cruces (CC) and at Bordeaux University Hospital (BC). METHODS The Lupus-Cruces nephritis protocol combines pulses of 125mg of methyl-prednisolone with each fortnightly pulse of cyclophosphamide and prednisone ≤30mg/day with tapering over 12-14weeks until 2.5-5mg/day. The BC followed international lupus nephritis guidelines, combining high-dose prednisone and either mycophenolate mofetil or cyclophosphamide, followed by maintenance therapy with low dose prednisone and immunosuppressive drugs. The main outcomes were complete renal remission (CR) and glucocorticoid toxicity. RESULTS 44 patients from BC and 29 from CC were included. The mean maximum prednisone dose was 42.5 (BC) vs. 21mg/day (CC), p<0.001. The average 6-month prednisone dose was 21 (BC) vs. 8.3mg/d (CC), p<0.001.The mean number of methyl-prednisolone pulses was 3 (BC) vs. 9.3 (CC), p<0.001. HCQ was used by 64% (BC) vs. 100% (CC), p<0.001. CR rates were 30% (BC) vs. 69% (CC), p=0.001, and 42% (BC) vs. 86% (CC), p<0.001, at 6 and 12months, respectively. Patients from the CC more frequently achieved CR (adjusted HR 3.8, 95%CI 2.05-7-09). The number of pulses of methyl-prednisolone were associated with CR (adjusted HR 1.09, 95%CI 1.03-1.15). Patients in the CC had a lower risk of GC-related side effects (adjusted HR 0.19, 95%CI 0.04-0.89). CONCLUSION The Lupus-Cruces nephritis protocol improves the outcome of LN. Repeated methyl-prednisolone pulses help reduce the dose of oral glucocorticoids and enhance clinical response.

Manic and depressive symptoms and insight in first episode psychosis

Insight impairment is common early in the course of psychosis. Most studies have focused on the relationship between insight and depression, although manic symptoms are also frequent in psychoses. The main aim of this study was to examine the relationship between insight dimensions and manic and depressive symptoms in first-episode psychosis. A group of inpatients in their first psychotic episodes (n=124) were evaluated using the Scale to Assess Unawareness of Mental Disorder, Young Mania Rating Scale and Hamilton Depression Rating Scale. To study the effect of clinical, manic and depressive symptoms on insight, awareness of mental disorder, awareness of the achieved effects of medication, and awareness of the social consequences of having a mental disorder were modelled using ordinal logistic regression techniques. Results showed that greater awareness of mental disorder was significantly related to higher age at first episode together with higher scores for negative and depressive symptoms. The opposite was found to be true in presentations with a higher severity of disease and manic symptoms. The model fitting unawareness of the achieved effects of medication identified the same significant variables, except in the case of negative symptoms. Finally, the model assessing the social consequences of having a mental disorder showed unawareness to be greater when manic symptoms and disease severity were high.