We assessed the safety of tacrolimus therapy for rheumatoid arthritis. Forty-two patients who started tacrolimus therapy between April 2005 and July 2006 were investigated retrospectively using data from their medical records up to June 2007. The cumulative treatment continuation rate was assessed by the Kaplan-Meier method. Fisher's exact test was used to compare gastrointestinal symptoms between different tacrolimus doses and between the presence and absence of each concomitant medication. The mean (+/-SD) observation period was 288 +/- 238 days. The cumulative treatment continuation rate was, respectively, 59.5% and 38.1% at 6 months and 1 year after the patients started treatment. Tacrolimus was discontinued in 28 patients, and was discontinued because of adverse reactions in 21 patients. Gastrointestinal symptoms were the most common adverse reactions (45.2% = 19/42 patients), followed by infections and hyperglycemia. Tacrolimus was discontinued in 9/19 patients with gastrointestinal symptoms, and was discontinued within 60 days of starting treatment in seven of them. Nausea and vomiting led to discontinuation in seven patients (within 60 days of starting treatment in six of them). The incidence of gastrointestinal symptoms was higher in patients receiving a daily dose >or=2 mg than in those receiving <2 mg/day. During treatment of rheumatoid arthritis by oral tacrolimus therapy, gastrointestinal symptoms were common, early, and dose-dependent. However, these symptoms were not severe and did not cause any serious safety problems.

We encountered a 62-year-old woman who had systemic sclerosis (SSc) complicated by idiopathic portal hypertension (IPH). She had a 10-year history of scleroderma and Raynaud's phenomenon. She also had pancytopenia, splenomegaly, and esophageal varices. Treatment with prednisolone and endoscopic variceal ligation resulted in improvement of her symptoms. According to our literature review, the prognosis of patients with SSc complicated by IPH is relatively poor. However, the factors that predict outcome of these patients have not been elucidated.

We encountered a 62-year-old woman who had systemic sclerosis (SSc) complicated by idiopathic portal hypertension (IPH). She had a 10-year history of scleroderma and Raynaud's phenomenon. She also had pancytopenia, splenomegaly, and esophageal varices. Treatment with prednisolone and endoscopic variceal ligation resulted in improvement of her symptoms. According to our literature review, the prognosis of patients with SSc complicated by IPH is relatively poor. However, the factors that predict outcome of these patients have not been elucidated.

Objective : To determine the feasibility of low-dose, intermittent administration of trimethoprim-sulfamethoxazole (TMP／SMX) for prophylaxis against pneumocystis pneumonia (PCP) in patients with systemic autoimmune diseases receiving mediumto high-dose glucocorticoid therapy. Methods : A randomized prospective study was performed. Patients who were scheduled to receive medium-to high-dose glucocorticoid therapy were selected and randomly allocated to one of two groups : one group received 1 tablet of TMP／SMX (TMP 80 mg and SMX 400 mg) daily and the other group received 1 tablet twice a week. The observation period was up to one year, or until the prophylactic therapy was discontinued because of steroid tapering or occurrence of adverse events (AEs). The endpoint was occurrence of PCP, and safety was also assessed. Results : Thirty-seven patients were enrolled in this study, with 19 patients assigned to the daily regimen and 18 to the twice weekly regimen. One patient in each group withdrew before starting treatment. None of the patients who entered this study developed PCP. Safety analysis showed fewer AEs with the twice weekly regimen than with the daily regimen (5 of 17 patients(29.4％)vs. 10 of 18 patients(55.6％), p＝0.176). Conclusion : From this pilot study, twice weekly TMP／SMX prophylaxis seems to be more tolerable than daily dosing in patients with systemic autoimmune diseases receiving mediumto high-dose glucocorticoid therapy. Since the number of patients was insufficient, further study is necessary to determine the optimal regimen for PCP prevention in these patients.

AimTo assess the effectiveness and safety of switching the antidepressant formulation from immediate-release (IR) to controlled-release (CR) paroxetine in patients with major depressive disorder (MDD).Patients and methodsA total of 113 outpatients with MDD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and treated with a stable dose of IR paroxetine for at least 6 months were enrolled. Patients were then switched to CR paroxetine for 8 weeks. Effectiveness was evaluated by scores on the Himorogi Self-Rating Depression/Anxiety Scales (HSDS/HSAS) and the Clinical Global Impression – Severity (CGI-S). Safety was evaluated based on the reported adverse drug reactions (ADRs). Medication satisfaction and preference were assessed based on questionnaire responses using Likert-type scales.ResultsThe overall patient HSDS/HSAS scores significantly improved after switching from IR to CR paroxetine (P<0.001). Furthermore, CR paroxetine was superior to IR paroxetine (P<0.001) according to the results of the CGI-S evaluation. ADRs were experienced by 14 (12.4%) patients, including dry mouth, nausea/vomiting, somnolence/drowsiness, and wakefulness/arousal during sleep. Satisfaction and preference for paroxetine improved after switching to the CR formulation (P<0.001; chi-square test).ConclusionThese results suggest that switching the treatment from IR to CR paroxetine could improve depressive symptoms and decrease ADRs. However, these results may have been caused by the psychological effect of drug switching. Hence, future studies with blinded evaluation methods are required to confirm and expand our findings.