DEPRESSION AND ANXIETY, Issue 5 2008
Andrew G. Bulloch Ph.D.
Abstract Remission from the symptoms of depression is the optimal outcome for depression treatment. Many studies have assessed the frequency of treatment, but there are none that have estimated the frequency of treated remission in the general population. We addressed this issue in the population of Alberta using a brief Hamilton Depression Rating Scale (HAMD)-7 scale (recently validated against the HAMD-17 scale in a clinical setting) that has been proposed as a suitable indicator for remission in primary care. We used data from a survey conducted within the Alberta Depression Initiative in 2005 (n=3,345 adults), to produce a population-based estimate of the number of respondents taking antidepressant medication for depression. From this group we selected a subpopulation that did not screen positive when the MINI module for major depression was administered (i.e., who did not have an active episode). Non-remission in this subpopulation was assessed with a version of the HAMD-7 scale adapted for telephone administration by a nonclinician. Of the survey respondents, 189 reported taking antidepressant medication for depression. Of these, 115 were found not to have an active episode. However, 49.0% of this subpopulation was not in remission as evaluated by the HAMD-7. We estimate that 1.3% (95% confidence interval, 0.9,2.0%) of the population is in treated non-remission for depression. Our study indicates a substantial degree of non-remission from depression in individuals taking antidepressants in the general population. This suggests that, in addition to increasing the frequency of treatment, increasing the effectiveness of treatment can have an impact on population health. Depression and Anxiety 0:1,5, 2007. © 2007 Wiley-Liss, Inc. [source]

Outcome of suicidal patients with schizophrenia: results from a naturalistic study

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010
R. Schennach-Wolff
Schennach-Wolff R, Jäger M, Seemüller F, Obermeier M, Schmauss M, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkötter J, Heuser I, Maier W, Lemke MR, Rüther E, Klingberg S, Gastpar M, Möller H-J, Riedel M. Outcome of suicidal patients with schizophrenia: results from a naturalistic study. Objective:, Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. Method:, Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. Results:, Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. Conclusion:, Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission. [source]

Achieving symptomatic remission in out-patients with schizophrenia , a naturalistic study with quetiapine

ACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009
T. Wobrock
Objective:, Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12-week non-interventional study (NIS) with quetiapine was conducted in Germany. Method:, For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission. Results:, Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks' treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI-S) at baseline. Predictors of non-remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse. Conclusion:, This study demonstrated that the majority of schizophrenia out-patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission. [source]

ORIGINAL ARTICLE Clinical haemophilia: Remission of paroxysmal atrial fibrillation with iron reduction in haemophilia A

HAEMOPHILIA, Issue 5 2010
L. R. ZACHARSKI
Summary., Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12,15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing. [source]

Effectiveness and tolerability of paroxetine controlled release (CR) in the treatment of major depressive disorder: an open-label, prospective, multi-center trial in Korea

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2007
Chi-Un Pae
Abstract Objectives This study evaluated the effectiveness and tolerability of paroxetine controlled release (CR) for the treatment of Korean patients with major depressive disorder (MDD) in a naturalistic treatment setting. Methods One hundred and ninety patients with MDD were enrolled in this study. The Hamilton Depression Rating Scale-17 item (HAMD-17) and Clinical Global Impression-Severity (CGI-S) scores were measured at the baseline (day 0) and at weeks 1, 2, 4, and 8 (endpoint). The primary measure of effectiveness was a change in the mean HAMD-17 scores from the baseline to the endpoint. The secondary effectiveness measures included a decrease in the HAMD-17 scores of 50% or more at the endpoint compared with the baseline and a change in the mean CGI-S scores from the baseline to the endpoint. Remission was defined as a HAMD-17 score,,,7 at the endpoint. Results The HAMD-17 scores decreased by 56.5% (observed difference, OD,=,,13.3) (t,=,26.63, p,<,0.0001) from the baseline. The CGI-S scores also decreased by 50.0% (OD,=,,2.3) (t,=,24.47, p,<,0.0001). The response and remission rate at the endpoint was 64.2 and 48.4%, respectively. The adverse events were tolerable. No unexpected or serious side effects were observed. Conclusions Despite the methodological limitations, this study demonstrated that paroxetine CR is effective and tolerable for treating patients with MDD in an East Asian population. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: A pilot study

INFLAMMATORY BOWEL DISEASES, Issue 5 2009
Hien Q. Huynh MD
Abstract Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom-free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population. Methods: Eighteen eligible patients between the ages of 3,17 with mild to moderate acute UC received open-label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8. Results: Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI ,3) was achieved in 56% of children (n = 10); response (decrease in SCCAI ,2, but final score ,5) in 6% (n = 1); and no change or worsening in 39% (n = 7). Post-VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. Conclusions: Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%. (Inflamm Bowel Dis 2008) [source]

MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 5 2007
Juan L. Mendoza MD
Abstract Background: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). Methods: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. Results: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6,12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8,22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82,3.9; P = 0.14). Conclusions: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy. (Inflamm Bowel Dis 2007) [source]

Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel disease

INFLAMMATORY BOWEL DISEASES, Issue 2 2007
Siew C. Ng MRCP
Abstract Background: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. Methods: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5,10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). Results: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35,203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. Conclusion: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted. (Inflamm Bowel Dis 2007) [source]

Azathioprine Maintains first remission in newly diagnosed pediatric Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 9 2006
Gerald J. Jaspers
Abstract 6-Mercaptopurine (6-MP) maintains remission in pediatric Crohn's disease (CD). Azathioprine, a prodrug of 6-MP, is used for maintenance of remission of CD in Europe. We evaluated to what extent azathioprine is used in newly diagnosed pediatric CD patients and whether maintenance of remission differed between patients using azathioprine or not. Charts of children (diagnosed 1998-2003, follow-up , 18 mo) were reviewed. Active disease was defined as Pediatric Crohn's Disease Activity Index (PCDAI) greater than 10 or systemic corticosteroid use. Remission was defined as PCDAI 10 or less without use of corticosteroids. Eighty-eight children (55M/33F, age 12 ± 3 yr) were included. Seventy-two (82%) patients received azathioprine during the follow-up period (38 ± 17 mo). Patients diagnosed after 2000 received azathioprine significantly earlier during the course of disease compared with those diagnosed earlier (median, at 233 vs. 686 days; P < 0.05). At initial presentation, moderate-severe disease activity and prescription of corticosteroids were more prevalent in patients using azathioprine compared with nonazathioprine patients (75% vs. 52%; P < 0.05; and 89% vs. 58%; P < 0.005, respectively). Duration of corticosteroid use was longer in patients receiving azathioprine (232 vs. 168 days; P < 0.005). Median maintenance of first remission in patients who initially used corticosteroids, however, was longer in patients receiving azathioprine compared with nonazathioprine patients (PCDAI, 544 vs. 254 days, P = 0.08; corticosteroid free, 575 vs. 259 days, P < 0.05, respectively). We conclude that, since 2000, azathioprine is being introduced earlier in the treatment of newly diagnosed pediatric CD patients. The use of azathioprine is associated with prolonged maintenance of the first remission. [source]

Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: Results of a multicenter prospectively randomized study

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 3 2005
Intravenöse Dexamethason-Cyclophosphamid-Pulstherapie im Vergleich zu einer oralen Methylprednisolon-Azathioprin-Therapie bei Patienten mit Pemphigus-Erkrankungen: Ergebnisse einer multizentrischen, prospektiven, randomisierten Studie
Azathioprin; Cyclophosphamid; Pemphigus; Pulstherapie Summary Background: Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22,patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. Patients and methods: The 11,patients of the M/A group were treated with daily doses of methylprednisolone (initially 2,mg/kg body weight) and azathioprine (2,,,2,5,mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11,patients consisted of intravenous administration of 100,mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500,mg) on day one. Pulses were initially repeated every 2,,,4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50,mg) was given daily for 6,months. Results: Within 24,months after treatment initiation, 5/11,patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3,patients) and 6/11,patients had a progression. In the M/A group, there were remissions in 9/11,patients (complete remissions after discontinuation of therapy in 3,patients) and progression in 1/11,patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Conclusion: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy. Zusammenfassung Hintergrund: Pemphiguserkrankungen sind potentiell lebensbedrohliche blasenbildende Autoimmunerkrankungen, die üblicherweise mit hochdosierten Kortikosteroiden in Kombination mit Immunsuppressiva behandelt werden. In einer multizentrischen, prospektiven, randomisierten Studie verglichen wir die Wirksamkeit und Nebenwirkungen einer Dexamethason-Cyclophosphamid (D/C)-Pulstherapie mit einer Methylprednisolon-Azathioprin (M/A)-Therapie bei 22,Patienten mit neu diagnostiziertem Pemphigus vulgaris und Pemphigus foliaceus. Patienten und Methoden: 11,Patienten der M/A-Gruppe wurden kontinuierlich oral mit Methylprednisolon (initial 2,mg/kg Körpergewicht/Tag) und Azathioprin (2,,,2,5,mg/kg Körpergewicht/Tag) behandelt; die Dosen wurden schrittweise reduziert. Die Therapie bei den 11,Patienten der D/C-Gruppe erfolgte durch intravenöse Gabe von 100,mg Dexamethason/Tag an 3 aufeinander folgenden Tagen und 500,mg Cyclophosphamid am ersten Tag. Die Pulstherapie wurde zunächst alle 2,,,4 Wochen, dann in längeren Abständen wiederholt. Im Intervall wurden 50,mg Cyclophosphamid/Tag oral für 6,Monate verabreicht. Ergebnisse: Innerhalb von 24,Monaten nach Therapiebeginn kam es bei 5 von 11,Patienten der D/C-Gruppe zu einer Remission (komplette Remission nach Absetzen der Therapie bei 3,Patienten); bei 6 der 11,Patienten verlief die Erkrankung progredient. In der M/A-Gruppe kam es bei 9 von 11,Patienten zu einer Remission (komplette Remission nach Absetzen der Therapie bei 3,Patienten) und bei einem Patienten zu einer Progression. In der M/A-Gruppe traten häufiger Rezidive nach Remission auf als in der D/C-Gruppe. Therapienebenwirkungen kamen in der M/A-Gruppe häufiger vor. Diese Unterschiede waren nicht signifikant (p > 0,05). Schlußfolgerungen: Aufgrund der hohen Anzahl von Progressionen bei Patienten der D/C-Gruppe können wir die positiven Ergebnisse früherer Berichte über die D/C-Pulstherapie nicht bestätigen. Dennoch scheint die D/C-Therapie, beim einzelnen Patienten einmal erfolgreich, seltener zu Rezidiven zu führen und möglicherweise auch besser verträglich zu sein als die M/A-Therapie. [source]

Remission and Resurgence of Anxiety-Like Behavior Across Protracted Withdrawal Stages in Ethanol-Dependent Rats

ALCOHOLISM, Issue 9 2007
Yu Zhao
Background:, Alcohol dependence is a chronic disorder in which withdrawal symptoms often persist after detoxification. The purpose of the present experiment was to characterize susceptibility to stress and anxiogenic stimuli in rats over an extended time period following ethanol withdrawal. Methods:, Male Wistar rats were made dependent via ethanol vapor exposure. The rats were then tested in the elevated plus-maze during acute ethanol withdrawal (ACW, ,8 hour), early "protracted" withdrawal (EPW, 2 weeks), or late "protracted" withdrawal (LPW, 6, 12 weeks) following brief restraint or no stress. Principal components analysis was used to identify constructs underlying plus-maze behavior. Results:, Three factors characterized plus-maze performance: anxiety, locomotor activity, and risk assessment/decision making. Spontaneous anxiety-like behavior was increased during ACW, decreased to levels of ethanol-naïve controls during EPW, but markedly resurged during LPW. Withdrawal did not alter sensitivity to the anxiety-like effects of restraint stress. All ethanol-dependent rats showed locomotor hypoactivity that, in contrast to anxiety, remained stable throughout all withdrawal stages. Neither ethanol withdrawal nor restraint stress altered mean "risk assessment/decision making" scores, though ethanol withdrawal altered the emission of "risk assessment/decision making" behavior in relation to anxiety-like behavior and behavioral activation state. Conclusions:, The findings illustrate and model the spontaneous, severe, and long-lasting nature of behavioral abnormalities that accompany withdrawal from chronic, intermittent ethanol intoxication. The dynamic remission and resurgence in symptoms of negative affect (i.e., behavioral signs of anxiety) during "protracted" withdrawal may complicate recovery from alcoholism. [source]

Application of a Quality of Life Measure, the Life Situation Survey (LSS), to Alcohol-Dependent Subjects in Relapse and Remission

ALCOHOLISM, Issue 11 2000
J. H. Foster
Background: Recent studies have shown that quality of life (QOL) is improved significantly when subjects do not relapse to heavy drinking, and QOL deteriorates significantly on prolonged relapse. This article further investigates these relationships using a QOL index, the Life Situation Survey (LSS). Methods: Eighty-two DSM-IV alcohol-dependent subjects admitted for alcohol detoxification were studied at baseline and 12 week follow-up. Sociodemographic data were collected, and severity of alcohol dependence (SADQ) and General Health Questionnaire (GHQ-12) were baseline indices only. The main outcome measure, the LSS, was administered at both time points. Results: Two subjects were lost to follow-up and one died during the study period. Thus, the relapse/nonrelapse analysis related to 79 subjects. Fifty subjects (63%) had relapsed to heavy drinking at 3 months follow-up. There was a significant correlation between LSS and GHQ-12 scores. Significant changes occurred in total LSS scores as a result of relapse and nonrelapse. The improvement in LSS scores associated with nonrelapse was larger than the deterioration that accompanied relapse. In those subjects who did not relapse to heavy drinking, the mean follow-up score remained in the poor/borderline LSS range. Remission from heavy drinking was accompanied by significant improvements in appetite, sleep, and self-esteem. Relapse to heavy drinking coincided with a significant deterioration in mood/affect, public support, and work/life role scores. Conclusion: QOL as assessed by the LSS in recently detoxified alcoholics is impaired significantly. In the nonrelapse group, there was a significant improvement in LSS scores after 3 months. Relapse was accompanied by a smaller deterioration in LSS scores. The LSS can play an important role in monitoring the clinical care and progress of alcohol-dependent subjects. [source]

The use of exclusive enteral nutrition for induction of remission in children with Crohn's disease demonstrates that disease phenotype does not influence clinical remission

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
E. BUCHANAN
Summary Background, Exclusive enteral nutrition (EEN) achieves variable remission rates in patients with Crohn's disease (CD). Aim, To describe our experience of treating CD with an 8-week course of primary EEN and to study factors affecting treatment outcome. Methods, All CD patients treated with EEN in our centre between 2004 and 2007 were included in the study. Remission was determined by a combination of clinical parameters. Disease phenotype was assigned using published classifications. Inflammatory markers and anthropometry (Z -scores) were calculated before and after treatment. Results, A total of 114 children were treated (four were excluded). Median age at diagnosis was 11.6 years. Fifty-seven (51.8%) were fed orally whilst 53 (48.2%) were fed by tube. Eighty-eight (80%) achieved remission with consequent reductions in erythrocyte sedimentation rate and C-reactive protein (P < 0.001). Patients in remission had comparative improvements in weight (,1.04 cf. ,0.40) and BMI Z -scores (,0.98 cf. ,0.03) by the end of treatment (P < 0.001). Individuals with isolated terminal ileal disease (n = 4) had lower remission rates than other locations (P = 0.02). No other significant differences in remission rates for any other disease locations were found. Conclusions, Exclusive enteral nutrition induces clinical remission, normalization of inflammatory markers and improves weight/BMI Z -scores in most patients. This study demonstrates that disease phenotype should not influence clinicians when commencing patients on EEN. [source]

Clinical trial: cyclophosphamide pulse therapy , a promising therapeutic alternative in refractory Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009
K. J. SCHMIDT
Summary Background, In severe steroid-refractory Crohn's disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients. Aim, To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD. Methods, Fifteen patients with steroid-refractory (n = 13) or steroid-dependent (n = 2) CD received 2,6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open-label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2). Results, Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid-free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245,550) to 100 (26,538) at week 8. Remission lasted 16 months (median, range 4,40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects. Conclusions, Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid-refractory/-dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD. [source]

Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007
M. LAZZERINI
Summary Background Anti-tumour necrosis factor- , antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor- , suppressive properties. Aim To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. Methods Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5,2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. Results Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). Conclusions Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension. [source]

Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2006
C. SCHMIDT
Summary Background In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. Aim To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. Methods Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. Results Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1,45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. Conclusions In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy. [source]

Trial of trefoil factor 3 enemas, in combination with oral 5-aminosalicylic acid, for the treatment of mild-to-moderate left-sided ulcerative colitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2005
A. Mahmood
Background :,Current treatment of ulcerative colitis is imperfect. Trefoil peptides are known to stimulate repair in many models of injury, including animal models of colitis. Aim :,To assess the efficacy of trefoil factor family-3 enema treatment in a clinical trial. Methods :,A total of 16 patients with mild-to-moderate left sided ulcerative colitis were recruited into a double-blind randomized placebo-controlled study. Patients taking steroids or with proctitis only were excluded. Patients received 75 mL enemas containing either human recombinant trefoil factor family-3 (10 mg/mL) or saline alone once a day for 14 days. All patients also received an oral dose-increment of 1.2 g of mesalazine daily above their normal usage. Patients were assessed at 0, 2, 4 and 12 weeks. Remission was defined as Ulcerative Colitis Disease Activity Index of 0 or 1 with no blood in stool. Individual clinical improvement was defined as a Ulcerative Colitis Disease Activity Index reduction of >3. Data was analysed using chi-square test and anova. Results :,Median Ulcerative Colitis Disease Activity Index at entry were 8.5 (trefoil factor family-3 group) and 8 (placebo group). Analysed on an intention-to-treat basis, only one patient went into remission (in trefoil factor family-3 group at day 28). Clinical improvement was seen in two trefoil factor family-3 and three placebo patients on day 14 and two patients in each group on day 28. Conclusion :,Increasing the dose of 5-aminosalicylic acid was moderately effective in reducing the Ulcerative Colitis Disease Activity Index but was insufficient to induce remission. Trefoil factor family-3 enemas were well-tolerated but did not provide additional benefit above that of adding additional 5-aminosalicylic acid alone. [source]

An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2002
J. M. Sabate
Summary Background : Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-,, is a new potent therapy for active Crohn's disease, but induces short-lived improvements. Aim : To evaluate the efficacy of thalidomide, a drug with anti-tumour necrosis factor-, activity, for the maintenance of infliximab-induced response in refractory Crohn's disease. Methods : Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 ± 10 days after they had responded to infliximab (5 mg/kg infusions). Results : The median follow-up period was 238 days (range, 10,458 days) from the initiation of thalidomide and 265 days (range, 10,537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170,525), 119 (range, 24,503) and 35 (range, ,,60,360) before infliximab, at the initiation of thalidomide and at the end of follow-up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan,Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side-effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient. Conclusions : Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease. [source]

Remission of acute psychotic anxious depression in a patient with Parkinson's disease after treatment with quetiapine,

MOVEMENT DISORDERS, Issue 16 2009
Silva Link MD
[source]

Successful Treatment of Pediatric Psoriasis with Indigo naturalis Composite Ointment

PEDIATRIC DERMATOLOGY, Issue 5 2006
Yin-Ku Lin M.D.
Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis. [source]

Intravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndrome

PEDIATRICS INTERNATIONAL, Issue 1 2003
ZELAL B
AbstractBackground: Steroid dependency is a major problem seen after therapy for idiopathic nephrotic syndrome in childhood. Although there is consensus about the usage of cyclophosphamide (CYC) in frequent relapsers, there is still a controversy concerning its usage in steroid-dependent nephrotic syndrome (SDNS). Methods: In the present study, nineteen children with SDNS were treated with CYC: ten via the intravenous (i.v.) route, and nine via the oral route. Remission was then maintained with prednisolone. Oral CYC therapy consisted of CYC at a dose of 2 mg/kg per day for 12 weeks. Intravenous (i.v.) CYC therapy consisted of CYC 500 mg/m2 per month (with intravenous 3500 cc/m2 per 24 h one-third saline hydration) for 6 months. Results: The cumulative dose of CYC was 168 mg/kg in the oral group and 132 mg/kg in the IV group. Daily oral CYC dose was 1.96~0.31 mg/kg, whereas i.v. CYC dose was 0.73~0.03 mg/kg. Long-term complications and side-effects such as alopecia, infection and hemorrhagic cystitis were not observed in the i.v. CYC treated group. In the long term, the dosage of prednisolone that held remission after CYC, the annualized relapse rates and the subsequent relapse time were significantly better in the i.v. CYC group, and the number of patients in remission for 2 years was significantly higher in the i.v. treated group (P<0.05). Conclusion: In SDNS, i.v. CYC has a long lasting effect with lower annualized relapse rates and longer subsequent relapse time with a lower steroid dosage required to maintain remission than oral CYC. The results of the present study showed the safety of the i.v. route, and it is the preferable treatment in noncompliant patients for its long lasting remission and simple and inexpensive follow up. [source]

Age-Related Pregnancy Results and Further Examination of Bitches after Aglepristone Treatment of Pyometra

REPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2010
P Jurka
Contents The cystic endometrial hyperplasia and pyometra complex is one of the most common uterine diseases in bitches. The appearance of pharmacological preparations containing anti-progestagens created new possibilities for pyometra treatment. The aim of this study was to evaluate the curative effect of the anti-progestagen aglepristone treatment of pyometra in bitches of different ages. Twenty four bitches of different breeds, aged from 0.8 to 9.5 years (21,48 kg) exhibiting clinical pyometra symptoms (two groups , I , 5 years, n = 14 and II >5 years, n = 10) were evaluated. Information about the general reproductive health was collected up to 54 months after anti-progestagen treatment. Remission of clinical symptoms and return of blood chemistry results and total leucocyte count to referential values were achieved in all cases within 14 days of treatment. Bitches were naturally mated at the first, and when unsuccessful, the second oestrus after treatment. In group I, no recurrence of pyometra symptoms was observed during following cycle(s). Eight bitches (57.1%) had a full-term pregnancy and the number of newborn pups ranged from 1 to 12. None of the bitches from the group II became pregnant. In conclusion, the basic indication for conservative pharmacological treatment of pyometra is preserving female fertility and obtaining offspring. The important conditions for successful aglepristone treatment are: the young age (up to 5 years) and the lack of detectible ovarian cysts. It seems necessary to mate bitches in the first or second oestrus after finishing treatment. The efficacy of treatment can be measured by the after-treatment pregnancy rate. [source]

Apparent Remission of a Solitary Metastatic Pulmonary Lesion in a Liver Transplant Recipient Treated with Sorafenib

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
M. Yeganeh
Hepatocellular carcinoma (HCC) remains a significant disease worldwide and its incidence is expected to increase. In selected patients, liver transplantation offers a 5-year patient survival between 48% and 75%. However, HCC recurrence occurs in approximately 20% of transplant recipients. No therapy has proven efficacious in decreasing the risk of recurrence after transplantation. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced HCC that have no history of liver transplantation. We report complete remission of HCC in a 54-year-old man who developed biopsy-proven lung metastasis after liver transplantation treated with sorafenib. [source]

Remission of epilepsy after two drug failures in children: A prospective study,

ANNALS OF NEUROLOGY, Issue 5 2009
Anne T. Berg PhD
Objective Determine the probability of a more than 1-year remission after failure of a second drug in children prospectively followed from initial diagnosis of epilepsy and then from time of second drug failure. Identify prognostic factors for remission after second drug failure. Methods Of 613 children, 128 did not respond favorably to 2 drugs, had a trial of at least a third drug (median, 3), and were followed for more than 1 year (median, 10.1 years) since second drug failure. Product limit and proportional hazards techniques were used to analyze predictors of any 1-year remission (Rem1) and 1- and 3-year remission at last contact (Rem1/3-LC). Results Seventy-three patients (57%) had a remission. Repeated remissions and relapses were common. Only 48 (37.5%) achieved Rem1-LC and 28 (23%) Rem3-LC. Idiopathic epilepsy (Rem1: rate ratio [RR], 3.64, p < 0.0001; Rem1-LC: RR, 2.57, p = 0.008) and seizure frequency (Rem1: RR, 0.76, p = 0.003; Rem1-LC: RR, 0.82, p = 0.04 per increase in category) were the most robust predictors. Symptomatic cause was the only correlate of Rem3-LC. Remission before second drug failure did not predict remission after second drug failure. Interpretation Remission after second drug failure is common but often temporary. Children who have not responded to two appropriate drugs should be carefully evaluated to maximize therapy and possibly considered for more aggressive treatments. Ann Neurol 2009;65:510,519 [source]

Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug,free remission in rheumatoid arthritis: Results from two large early arthritis cohorts

ARTHRITIS & RHEUMATISM, Issue 8 2009
Diane van der Woude
Objective Remission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease-modifying antirheumatic drug (DMARD),free sustained remission after treatment with conventional therapy. Methods Remission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD-free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD-free remission by the patient's rheumatologist. Predictive factors were identified by Cox regression analysis. Results Sustained DMARD-free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD-free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM-RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti,cyclic citrullinated peptide 2 and IgM-RF) as independent predictors. Conclusion Sustained DMARD-free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD-free remission. [source]

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease-modifying antirheumatic drugs: A clinical and imaging comparative study

ARTHRITIS & RHEUMATISM, Issue 7 2009
Benazir Saleem
Objective For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis. Methods One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n = 50) or DMARDs (n = 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1,5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity. Results In patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P = 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission. Conclusion In RA patients with disease in remission, imaging-detected synovitis persists, with power Doppler activity seen in ,48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging-detected synovitis. [source]

Predicting the course of juvenile dermatomyositis: Significance of early clinical and laboratory features

ARTHRITIS & RHEUMATISM, Issue 11 2008
Elizabeth Stringer
Objective Juvenile dermatomyositis (DM) is a rare chronic inflammatory disease of childhood. The clinical course of juvenile DM appears to be variable, and little is known about predictors of the disease course. The aims of this study were to describe the clinical course of juvenile DM and to determine whether early clinical and laboratory features can be used to predict the time to remission and/or the disease course. Methods Clinical and laboratory data from a cohort of 84 patients with juvenile DM were prospectively entered into a database (1990,2005). Remission was defined as a clinical state of no active skin rash, weakness, or elevated muscle enzyme levels for 6 months off medication. The disease course was defined as monophasic, polyphasic, or chronic. Data were reviewed at the time of diagnosis and at 3 months and 6 months after the diagnosis to determine predictors of the time to remission and/or the disease course. Results The median time to remission was 4.67 years. Sixty percent of patients had a chronic course, 37% a monophasic course, and 3% a polyphasic course. The presence of rash (most strongly indicated by Gottron's papules) at 3 months was the earliest predictor of a longer time to remission (relative risk [RR] 0.55 [95% confidence interval (95% CI) 0.37,0.81], P = 0.002). At 6 months, the presence of nailfold abnormalities and rash also predicted a longer time to remission (RR 0.35 [95% CI 0.14,0.74], P = 0.003). We were unable to determine a prediction model of disease course. Conclusion The majority of patients in our cohort had a chronic disease course. The persistence of Gottron's papules and nailfold abnormalities early in the disease course was associated with a longer time to remission. [source]

Long-term management of vulval lichen sclerosus in adult women

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2010
J. BRADFORD
Background:, Adult vulval lichen sclerosus (VLS) is usually a lifelong disease with an estimated remission rate after treatment of only 16% [Arch Dermatol 2004; 140 (6): 709]. Although superpotent topical corticosteroid (TCS) is the validated gold standard treatment to induce remission, little data are available on how remission should be maintained. Aims:, We present a retrospective chart review of 129 adult patients with VLS who have been under surveillance by the authors for a minimum duration of three years. Methods:, Remission was maintained in most patients with low-to-moderate potency TCS. All subjects' symptoms, signs, treatment regimes and response to treatment including compliance, symptom remission, disease progression with scarring, squamous cell carcinoma and side effects were recorded. Data were compared for the compliant and non-compliant groups. Fischer's exact test was used to identify significant differences. Results:, The mean age at presentation was 53.6 years and mean duration of follow-up was 6.2 years. Compliance was excellent: 84 (65%) of patients' self-reporting as being fully compliant. Symptom remission was achieved in 98% of compliant and 75% of non-compliant patients (P = 0.001) Progression of disease with scarring was not encountered in any of the compliant patients, but was seen in 35% of non-compliant patients (P = 0.0001). One patient had squamous cell carcinoma on first presentation. Carcinoma subsequently occurred in none of the compliant patients, and in five partly compliant patients (P = 0.004). Mild, reversible corticosteroid side effects were encountered in 7% of patients. Conclusions:, Long-term treatment of adult VLS with individualised regimes using moderate potency TCS is safe and effective. Patients require long-term follow-up. [source]

Airway limitation and exercise intolerance in well-regulated myasthenia gravis patients

ACTA NEUROLOGICA SCANDINAVICA, Issue 2010
A. Elsais
Elsais A, Johansen B, Kerty E. Airway limitation and exercise intolerance in well-regulated myasthenia gravis patients. Acta Neurol Scand: 2010: 122 (Suppl. 190): 12,17. © 2010 John Wiley & Sons A/S. Objectives,,, Myasthenia gravis (MG) is an autoimmune disease of neuromuscular synapses, characterized by muscular weakness and reduced endurance. Remission can be obtained in many patients. However, some of these patients complain of fatigue. The aim of this study was to assess exercise capacity and lung function in well-regulated MG patients. Patients and methods,,, Ten otherwise healthy MG patients and 10 matched controls underwent dynamic spirometry, and a ramped symptom-limited bicycle exercise test. Spirometric variables included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV). Exercise variables included maximal oxygen uptake (VO2 max), anaerobic threshold (VO2 AT) maximum work load (W), maximum ventilation (VE max), and limiting symptom. Results,,, Myasthenia gravis patients had significantly lower FEV1/FVC ratio than controls. This was more marked in patients on acetylcholine esterase inhibitors. On the contrary, patients not using acetylcholine esterase inhibitors had a significantly lower exercise endurance time. Conclusion,,, Well-regulated MG patients, especially those using pyridostigmine, tend to have an airway obstruction. The modest airway limitation might be a contributing factor to their fatigue. Patients who are not using acetylcholinesterase inhibitor seem to have diminished exercise endurance in spite of their clinically complete remission. [source]

Childhood Leukemia Survivors Generally Do Well: Radiation Most Problematic Factor for Those in Long-Term Remission

CA: A CANCER JOURNAL FOR CLINICIANS, Issue 6 2003
Article first published online: 31 DEC 200
No abstract is available for this article. [source]