Significant Differences In Remission Rates Research Articles

Risperidone versus risperidone plus sodium valproate for treatment of bipolar disorders: a randomized, double-blind clinical-trial.

Objective:This study compared the efficacy of risperidone monotherapy with risperidone plus valproate in bipolar I disorder, manic phase. Some studies showed the efficacy of risperidone monotherapy in the treatment of bipolar disorder, so we examined this effectiveness in this clinical-trial study.Method:This 7-week, randomized, single-blind study included 48 bipolar I inpatients manic phase without psychotic features divided in risperidone group (n = 23) and risperidone plus sodium valproate group (n = 25). According to clinical symptoms, 3 categories: complete remission, partial remission and no remission were mentioned in weekly follow-up. Remission rate compared with survival analysis.Results:The results showed a significant difference in remission rate between risperidone monotherapy and risperidone plus sodium valproate at the 1st, 2nd and the 3rd week (p = 0.012, 0.023, 0.027 respectively), It means the remission rate in risperidone plus valproate group was higher in the first three weeks, but at the end of the seventh week, the difference was not statistically significant. There was no significant difference between the two groups in the development of adverse effects.Conclusions:Risperidone can be effective and well tolerated in both acute manic episodes of bipolar mood disorders.

Periodontal Disease Bacteria Specific to Tonsil in IgA Nephropathy Patients Predicts the Remission by the Treatment

BackgroundImmunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse.Methods and FindingsWe made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy.ConclusionThis insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

Comorbidity, Measured By The Charlson Index, Has No Negative Impact On Remission In Patients With Chronic Myeloid Leukemia: Results Of The Randomized CML-Study IV

▪ BackgroundFive-year overall survival (OS) of chronic myeloid leukemia (CML) patients treated with imatinib exceeds 90%. With many tyrosine kinase inhibitors (TKI) available as treatment options for CML, the influence of TKI therapy on OS is difficult to define. Comorbidities can complicate randomized trials. Their influence on OS in CML has not been studied so far. AimsWe sought to evaluate the influence of comorbidities at diagnosis of CML on remission rates and OS of patients with Philadelphia and/or BCR-ABL positive chronic-phase CML. The CML-Study IV, a randomized five-arm trial designed to optimize imatinib therapy alone or in combination, used very few exclusion criteria as compared to other studies which typically excluded patients with severe illnesses. MethodsThe age-adjusted Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index (Charlson ME et al., 1987) and has been validated for long-term studies. The score weighs a) the severity of comorbidities (e.g. one point is allocated to myocardial infarction and diabetes, two points to non-active malignancies) and b) the age of patients (with one point for each decade above 40 years). The CCI at diagnosis was calculated for each randomized patient. For the analyses, patients were grouped into CCI 2, 3-4, 5-6, and ≥7. Performance status was measured by the Karnofsky Score (KS) and patients were grouped into 50-80, >80-<100, and 100. Correlation analyses were performed by the chi-square test. Survival probabilities were calculated by Kaplan-Meier curves. Calculating cumulative incidences, the competing risks progression and/or death were considered. Cox models were estimated for the multivariate analysis to analyse the prognostic influence of the candidate factors age, sex, leukocytes, hemoglobin, EUTOS score, KS, and CCI on OS. Results1551 patients were randomized from 2002 to 2012, 1524 patients were evaluable. Median follow-up time was 67.5 months. Additional to CML, 521 index comorbidities were reported in 1519 patients resulting in the following CCI groups: i) CCI 2: 589 patients, ii) CCI 3 or 4: 599 patients, iii) CCI 5 or 6: 229 patients, and iv) CCI ≥ 7: 102 patients. Median value of the CCI was 3 (range: 2-12). The distribution of the CCI groups was not different between treatment arms. Most common comorbidities were diabetes (n=106), non-active cancer (n=102), chronic pulmonary disease (n=74), renal insufficiency (n=47), myocardial infarction (n=38), cerebrovascular disease (n=29), congestive heart failure (n=28), and peripheral vascular disease (n=28).Between patients with CCI 2, 3-4, 5-6, and ≥7 no significant differences in remission rates were found neither for time to complete cytogenetic remission (CCR) nor for time to major molecular remission (MMR). Median times to CCR were 12.9, 12.6, 13.7, and 13.1 months and to MMR 17.5, 15.9, 16.5, and 18.1 months, respectively. No differences were observed between the CCI groups for the cumulative incidences of progression. As expected, significant differences in OS according to CCI at diagnosis were observed (s. Fig. 1, p<0.001). Probabilities of OS at 8 years for patients with CCI 2, 3-4, 5-6, and ≥7 were 93.6%, 89.4%, 78.7%, and 45.2%. [Display omitted] We found a correlation between CCI and KS (p<0.001). In multivariate analysis CCI (p<0.001), KS (p=0.022), and EUTOS Score (p=0.012) were significant predictors of OS. Hazard ratios for the CCI group 3-4, 5-6, >7 (each vs. 2), were 1.695 (95%-confidence interval, CI 1.066-2.695), 3.231 (CI 1.942-5.376) and 6.495 (CI 3.817-11.111), respectively. Separating the CCI into an age-related part and a comorbidity-related part, the comorbidity-related part was still an important risk factor (Wald test, p=0.002). ConclusionsComorbidities of CML-patients do not seem to have an impact on the success of imatinib treatment. In CML-Study IV, even patients with a considerable comorbidity benefitted from imatinib as the chances to achieve MMR and CCR did not differ from those of healthier CML-patients. Our data also indicate that OS alone is not any more an appropriate measure for the effectiveness of a specific treatment for CML, as TKI have reduced the CML-related lethality to too low levels. Adjusting for comorbidity is essential for a valid comparison and interpretation of OS observed with different TKIs in CML-patients. Disclosures:Saussele:Pfizer: Honoraria; BMS: Honoraria, Research Funding, Travel, Travel Other; Novartis: Honoraria, Research Funding, Travel Other. Hehlmann:BMS: Consultancy, Research Funding; Novartis: Research Funding. Hochhaus:Novartis: Consultancy, Honoraria, Research Funding, Travel Other; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Ariad: Consultancy, Honoraria. Müller:Ariad: Honoraria; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau.

FRI0094 Outcomes of two years of remission steered treatment in early arthritis patients

ObjectivesTo evaluate the 2 year clinical outcomes of remission steered therapy in early arthritis patients in the IMPROVED study.Methods610 patients with early rheumatoid or undifferentiated arthritis (RA or UA) started...

Impact of Technique on Cushing Disease Outcome Using Strict Remission Criteria

Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery. A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement. Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031 and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008). Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

Complete Molecular Remission (CMR 4.5) of CML Is Induced Faster by Dose – Optimized Imatinib and Predicts Better Survival - Results From the Randomized CML-Study IV

AbstractAbstract 67Dose optimized imatinib (IM) at doses of 400– 800mg has been shown to induce faster and deeper cytogenetic and molecular – responses than standard IM (400mg/day). Since complete molecular remission (CMR 4.5) identifies a subgroup of patients who may stay in remission even after discontinuation of treatment, it was of interest to analyse whether CMR 4.5 is reached faster with dose optimized IM and whether CMR 4.5 correlates with survival.CMR 4 and CMR 4.5 are defined as ≤ 0.01% BCR-ABL IS or ≥ 4. log reduction and ≤ 0.0032% BCR-ABL IS or ≥ 4.5 log reduction, respectively, from IRIS baseline as determined by real-time PCR. CML-Study IV is a five arm randomized study of IM 400 mg vs IM 400 mg + IFN vs. IM 400 mg + Ara C vs. IM after IFN failure vs. IM 800 mg. In the IM 800 arm, a 6 weeks run in period at IM 400 mg was followed by a dose increase to 800 mg and then by a dose reduction according to tolerability. Grade 3 or 4 adverse effects (AE) were to be avoided. From July 2002 to March 2012 a total of 1551 patients with newly diagnosed chronic phase CML were randomized of whom 1525 were evaluable. Median age was 52 years, 88% were EUTOS low risk, 12% high risk, 36% were Euro score low risk, 52% intermediate and 12% high risk, 38% were Sokal low risk, 38% intermediate and 24% high risk. 113 patients were transplanted, 246 received 2nd generation TKI. 152 patients have died, 90 of CML or unknown reasons, 62 of not directly CML-related causes.After a median observation time of 67,5 months 6 years OS was 88.2% and PFS 85.6%. CCR, MMR, CMR 4 and CMR 4,5 were achieved significantly faster with dose optimized IM (400 – 800 mg). No significant differences in remission rates were observed between IM 400 mg and the combination arms IM 400 mg + IFN and IM 400 mg + Ara C, whereas IM after IFN failure thus far yielded significantly slower response rates. After 4 years CCR rates were for IM 400, IM 400 + IFN, IM 400 + Ara C, IM 400 after IFN, and IM 800, 80%, 75%, 73%, 59% and 80%, respectively, MMR rates 84%, 77%, 82%, 61% and 88%, CMR 4 rates 57%, 55%, 55%, 40% and 65%, and CMR 4.5 rates 40%,42%, 42%, 28% and 52%, respectively. CMR 4 was reached after a median of 27 months with IM 800 and 41.5 months with IM 400. CMR 4.5 was reached after a median of 41.5 months with IM 800 and 63 months with IM 400. EUTOS low risk patients reached all remissions faster than EUTOS high risk patients. The differences of CMR 4 rates between IM 800 and IM 400 at 3 years were 13% and at 4 years 8%, and of CMR 4.5 rates at 3 years 10% and at 4 years 13%. Grade 3 and 4 AE were not different between IM 400 and dose optimized IM 800.Independent of treatment approach, CMR 4 and more clearly CMR 4.5 at 3 years predicted better OS and PFS, if compared with patients without CMR 4 or CMR 4.5, respectively. CMR 4 and 4.5 were stable. After a median duration of CMR 4 of 3.7 years only 4 of 792 patients with CMR 4 have progressed. Life expectancy with CMR 4 and 4.5 was identical to that of the age matched population.We conclude that dose optimized IM induces CMR 4.5 faster than IM 400 and that CMR 4 and CMR 4.5 at 3 years are associated with a survival advantage. Dose optimized IM may provide an improved therapeutic basis for unmaintained treatment discontinuation in patients with CML. Disclosures:Hehlmann:Novartis: Research Funding. Müller:Novartis, BMS: Consultancy, Honoraria, Research Funding. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Hochhaus:Novartis, BMS, MSD, Ariad, Pfizer: Consultancy Other, Honoraria, Research Funding.

Endoscopic Transsphenoidal Surgery for Cushing Disease

The efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing disease has not been clearly established. To assess efficacy of a pure endoscopic approach for treatment of Cushing disease and determine predictors of remission. A prospectively acquired database of 61 patients undergoing ETS was reviewed. Remission was defined as postoperative morning serum cortisol of <5 μg/dL or normal or decreased 24-hour urine-free cortisol level in follow-up. Overall, hypercortisolemia resolved in 58 of 61 patients (95%) by discharge. Tumor size did not predict resolution of hypercortisolemia at discharge (microadenomas [97%], magnetic resonance imaging-negative Cushing [100%], macroadenomas [87%]). At 2- to 3-month evaluations, 45 of 49 patients (91.8%) were in remission. Fifty patients were followed for at least 12 months (mean, 28 months; range, 12-72). Forty-two (84%) achieved remission from a single ETS. In these patients, there was no significant difference in remission rates between microadenomas (93%), magnetic resonance imaging-negative (70%), and macroadenomas (77%). Patients with history of previous surgery (n = 14, 23%) were 9 times less likely to achieve follow-up remission (P = .021). In-house cortisol level of <5.7 μg/dL provided the best prediction of follow-up remission (sensitivity 88.6%, specificity 83.3%). Postoperative diabetes insipidus occurred transiently in 7 patients (9%) and permanently in 3 (5%). One patient experienced postoperative cerebrospinal fluid leak that resolved with further surgery. ETS for Cushing disease provides high rates of remission with low rates of complications regardless of size. Although patients with a history of previous surgery are less likely to achieve remission, the majority can still achieve remission following treatment.

BMI Guidelines for Bariatric Surgery in Diabetes: How Low Can We Go?

The benefit of weight loss on glycemic control in type 2 diabetes is well known; weight management is foundational to good diabetes care. Intensive lifestyle intervention, which produces modest (5–10%) weight loss can produce durable (demonstrated up to 4 years) improvement in HbA1c and some cardiovascular risk factors (1,2). As for bariatric surgery, a recent systematic review and meta-analysis (3) of 621 bariatric surgery studies (>135,000 patients) reported that diabetes “improved or resolved” in 84%. Thus, there is a growing appreciation for the role of bariatric surgery as a tool in diabetes management. The appreciation that bariatric surgery might yield remission of diabetes stimulated the American Diabetes Association (ADA) to convene a consensus committee to define the terms “partial remission,” “complete remission,” and “durable remission\x{201d} (4). This is an important step because slight variation in definition can yield significant differences in remission rates (5). If we are to be able to develop evidence to support recommendations for this procedure in diabetes, we must be able to compare results across studies. Surgery for obesity has typically been reserved for patients with more severe obesity, and current guidelines (6) for the diagnosis and management of obesity indicate bariatric surgical procedures for patients with BMI ≥40 kg/m2 or for patients with a serious comorbidity (such as type 2 diabetes) and BMI ≥35 kg/m2. These BMI cut points are drawn from observations of large populations that show …

P352 Need for infliximab dose intensification in patients with Crohn's disease and ulcerative colitis

ation, endoscopic remission and need of colectomy. Results: Eighty-two patients (30 male; median age 39 years, IQR 32-48) have been enrolled. Main indications for ADA treatment were steroid-dependency (45%), steroid-resistance (23%) and extraintestinal manifestations (15%). Most of patients (78%) received previous infliximab treatment. Median partial Mayo score at baseline was 6 (IQR 4-7). ADA induction regimen was 160/80 mg (88%) or 80/40 mg (12%) and maintenance treatment was 40 mg every other week for a median time of 11 months (IQR 4-17). During follow up 30% of patients required dose-escalation. Clinical remission at 4, 12, 24 and 54 weeks was achieved in 13/82 (16%), 20/78 (27%), 26/75 (35%) and 24/60 (42%) patients, respectively. Sustained clinical remission at 12, 24 and 54 weeks was achieved in 10/60 (17%) patients. Thirty-three of 55 patients (60%) receiving corticosteroids at baseline were able to discontinue them. Forty-seven patients underwent baseline and follow-up endoscopy after a median of 11 months (IQR 3-13). Endoscopic remission was achieved in 21/47 patients (45%). During the study period, 18 patients (22%) underwent colectomy after a median of 5.5 months (IQR 2-14). No significant differences in remission rates at 4, 12, 24 and 54 weeks and colectomy rates were observed between anti-TNF alpha naive and non-naive patients. Conclusions: In this large “real-life” experience ADA appeared to be effective in active UC. One fourth of patients achieved clinical remission within three months. In patients receiving scheduled maintenance treatment for one year the remission rate was about 40%. Although ADA shows a steroid-sparing effect, the probability of colectomy for treatment failure is high.

Effects of Race and Ethnicity on Depression Treatment Outcomes: The CO-MED Trial

The investigators examined whether outcomes differ by race-ethnicity for patients with major depressive disorder in acute- (12 weeks) and continuation-phase (weeks 12-28) treatment with one of two antidepressant combinations or one selective serotonin reuptake inhibitor. This single-blind, seven-month prospective, randomized trial enrolled 352 non-Hispanic white (59%), 169 black (28%), and 79 white Hispanic (13%) participants from six primary and nine psychiatric care U.S. sites. Patients had nonpsychotic chronic or recurrent major depressive disorder (or both) of at least moderate severity. Escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine were delivered according to measurement-based care. The primary outcome was remission (last two consecutive 16-item Quick Inventory of Depressive Symptomatology-Self-Report ratings <8 and <6); secondary outcomes included side effects, adverse events, quality of life, function, and attrition. Black participants had greater baseline psychiatric and medical comorbidity. Baseline depression severity did not significantly differ between groups. In both phases more blacks than those in other groups exited the trial early. There were only minor differences in side effects, no significant differences in remission rates, and no significant differences between groups in other outcomes for each treatment. Despite differences in sociodemographic characteristics and comorbidities, when measurement-based care was used, members of different minority groups had similar outcomes when treated with one antidepressant or a combination of two antidepressants. Black participants had the highest attrition rate, an important issue to address in clinical care.

Effects of Race and Ethnicity on Depression Treatment Outcomes: The CO-MED Trial

Objective: The investigators examined whether outcomes differ by race-ethnicity for patients with major depressive disorder in acute- (12 weeks) and continuation-phase (weeks 12–28) treatment with one of two antidepressant combinations or one selective serotonin reuptake inhibitor. Methods: This single-blind, seven-month prospective, randomized trial enrolled 352 non-Hispanic white (59%), 169 black (28%), and 79 white Hispanic (13%) participants from six primary and nine psychiatric care U.S. sites. Patients had nonpsychotic chronic or recurrent major depressive disorder (or both) of at least moderate severity. Escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine were delivered according to measurement-based care. The primary outcome was remission (last two consecutive 16-item Quick Inventory of Depressive Symptomatology-Self-Report ratings <8 and <6); secondary outcomes included side effects, adverse events, quality of life, function, and attrition. Results: Black participants had greater baseline psychiatric and medical comorbidity. Baseline depression severity did not significantly differ between groups. In both phases more blacks than those in other groups exited the trial early. There were only minor differences in side effects, no significant differences in remission rates, and no significant differences between groups in other outcomes for each treatment. Conclusions: Despite differences in sociodemographic characteristics and comorbidities, when measurement-based care was used, members of different minority groups had similar outcomes when treated with one antidepressant or a combination of two antidepressants. Black participants had the highest attrition rate, an important issue to address in clinical care. (Psychiatric Services 62:1167–1179, 2011)

Prognostic Impact of Helicobacter pylori Infection and Eradication Therapy in Gastric Mucosa-associated Lymphoid Tissue Lymphoma

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection and H. pylori eradication is used as its first-line therapy. However, controversies exist about the prognostic value of H. pylori infection in these patients. We evaluated the prognostic impact of H. pylori infection and eradication therapy in gastric MALT lymphoma. A total of 292 patients diagnosed with MALT lymphoma since 2000 were analysed. MALT lymphoma was diagnosed with tissue biopsy and H. pylori infection was diagnosed with hematoxylin-eosin and additional Warthin-Starry stains on tissue sections. Clinical variables such as bone marrow (BM) involvement, multiorgan involvement, tumor stage at diagnosis, and remission were obtained with retrospective review of electronic medical records. Non-gastric MALT lymphoma patients showed higher multiorgan involvement rates (26.6% vs. 9.6%, P<0.001) and higher proportion of stage ≥ 3 (27.7% vs. 16.7%, P=0.029) than gastric cases. Regarding gastric MALT lymphoma, patients with H. pylori infection at diagnosis showed significantly less BM (2.1% vs. 21.8%, P<0.001) and multiorgan involvement rates (6.3% vs. 18.2%, P=0.011) than those without infection. But there was no significant difference in remission rates between them. In contrast, those with successful H. pylori eradication therapy showed significantly higher remission rates (81.0% vs. 30.8%, P<0.001) than those with failure. Non-gastric MALT lymphoma patients showed worse prognosis compared to gastric cases. As for remission rates in patients with gastric MALT lymphoma, successful H. pylori eradication therapy could be a good prognostic factor even if H. pylori infection was present at diagnosis.

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Relapse remains the major cause of treatment failure in pediatric acute myeloid leukemia (AML). We analyzed the clinical characteristics, treatment response to relapse treatment and overall survival (OS) of 379 children with AML relapse treated according to three consecutive frontline protocols of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87/-93/-98). Of 313 treated patients with data on remission status, 198 children (63%) achieved a second complete remission (CR2). There were no significant differences in remission rates and OS for the intensive reinduction treatment schedules used. The 5-year OS rate was 23% for the total group and 29% for patients treated with curative intent. OS rates increased with study periods from 18 to 34% (P(log rank)=0.012), whereas the proportion of patients receiving only palliative treatment decreased from 23 to 11% (P(CMH)=0.005). Late relapse, no allogeneic stem cell transplantation (SCT) in CR1, age <10 years and favorable cytogenetics were independent favorable prognostic factors for survival. Achievement of CR2 was the most important prognostic factor (OS 44 vs 3%; P(log rank)<0.0001). Overall, one-third of children with relapsed AML can be cured today. SCT in CR2 is recommended for most patients, although its impact on CR2 is discussed.

Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials

Objectives To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential...

Clinical Outcome of Patients with Follicular Lymphoma and Bulky Disease After Rituximab-CHOP Immunochemotherapy with and without Consolidating Radiotherapy.

Abstract 2722Poster Board II-698 Background:As the clinical management of patients with bulky disease remains challenging, many centres apply involved-field radiotherapy (IF-RT) after completion of immunochemotherapy. This strategy remains controversial. Patients and Methods:To evaluate the benefit of consolidating IF-RT in addition to immunochemotherapy, we retrospectively analyzed relapse patterns and survival of patients presenting with bulky follicular lymphoma (FL). Bulky disease was defined as abdominal/ mediastinal lymphoma mass >7.5 cm and/ or peripheral lymphoma mass >5 cm. All patients were treated within a prospective randomized trial on 126 patients with FL with six cycles of standard CHOP-chemotherapy in combination with 1, 3 or 6 cycles of Rituximab, followed by consolidating IF-RT in patients with bulky disease. 42 eligible patients with bulky disease were identified and form the foundation of this analysis, of which 26 were irradiated and 16 were not, violating the protocol. Results:With the exception of number of affected nodal regions, there was no significant difference between the irradiated and the non-irradiated group with regards to presenting characteristics (p > .05). Among all patients, bulks were located below the diaphragm in 91%. A second tumour bulk was present in 9 patients (22%). Female to male ratio was 1.3:1, and the median age at diagnosis was 54 years (range 23–73). According to FLIPI, 10% were classified as low risk (0–1), 45% as intermediate risk (2), and 45% as high risk (3–5). B symptoms were absent in 69%. Eleven patients (26 %) had received one course of Rituximab, 17 (41%) three courses and 14 (33%) six courses. There was no significant difference between the irradiated and the non-irradiated group with regards to previous exposure to immunochemotherapy (p = .628). After a median follow-up of 60 months, a total of 21 patients (50%) had progressed or relapsed and 9 patients (21%) had died. With the exception of one patient who died from congestive heart failure following chemotherapy-related cardiomyopathy, the main cause of death was disease progression or relapse. Highly malignant transformation into diffuse large B-cell lymphoma was observed in 5 cases. In the irradiated group, relapse occurred in 12 of 26 patients. Half of these relapses were located within the original bulk or within the bulk plus a new location, and 50% at a new location altogether; 42% occurred within the previously irradiated area. In the non-irradiated group, 9 of 16 patients relapsed. The corresponding rates regarding relapse location were 67% for original plus new location and 33% for new location only. There was no statistically significant difference between exposure to radiotherapy after immunochemotherapy and the likelihood of a relapse per se (p = .751) or at a specific location (p = .66). At the last follow-up, 31% of irradiated patients had achieved CR and 23% PR. Among the non-irradiated group, the corresponding rates were 25% and 19%. There was no significant difference in remission rates at any staging examination throughout the clinical trial between the two treatment groups (p > .05). 6-year progression-free- and overall survival rates were 52% and 80% after IF-RT and 48% and 73% without IF-RT (p = 1.00, p = .68 respectively). Conclusion:In this analysis, there was no difference in relapse rate, relapse location, PFS and OS between patients with bulky FL treated with and without consolidating IF-RT. Although patient numbers are limited, this is the first analysis of its kind conducted in the Rituximab era. Disclosures:No relevant conflicts of interest to declare.

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

Exclusive enteral nutrition (EEN) achieves variable remission rates in patients with Crohn's disease (CD). To describe our experience of treating CD with an 8-week course of primary EEN and to study factors affecting treatment outcome. 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. 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. 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.

A comparison of a standard-dose prednisone regimen and mycophenolate mofetil combined with a lower prednisone dose in chinese adults with idiopathic nephrotic syndrome who were carriers of hepatitis B surface antigen: A prospective cohort study

Background: When receiving immunosuppressive therapy, patients with idiopathic nephrotic syndrome who are also carriers of hepatitis B virus (HBV) surface antigen (HBsAg) are at risk for reactivation of HBV.Objective: This study compared the effectiveness and tolerability of a standard-dose prednisone regimen with those of the combination of mycophenolate mofetil (MMF) and a lower prednisone dose for the treatment of idiopathic nephrotic syndrome characterized by minimal-change nephropathy or slight mesangial proliferative glomerulonephritis in Chinese adults who were also carriers of HBsAg, a combination here termed MSNS-HBV.Methods: This was a prospective, open-label cohort study in Chinese adults with MSNS-HBV. Patients were self-assigned to 1 of 2 treatment groups: the standard prednisone regimen of 1 mg/kg daily or oral MMF 0.5 to 1.0 g BID combined with the lower pred-nisone dose of 0.5 mg/kg daily. The planned duration of treatment was 36 weeks, with an additional 60 weeks of follow-up. The primary outcome measures were rates of complete remission of idiopathic nephrotic syndrome (a decrease in daily proteinuria to within the normal range [<0.3 g]) and rates of HBV reactivation (detectable serum HBV DNA). Secondary outcome measures included relapse rates (>1+ albuminuria on dipstick urinalysis on 3 consecutive days), alanine ami-notransferase (ALT) elevations (>50 U/L), use of la-mivudine 100 mg/d (added if HBV DNA titers reached ≥105 copies/mL), and adverse effects.Results: The intent-to-treat population included 41 patients (22 prednisone, 19 MMF). In patients who completed the study, rates of complete remission after 24 weeks of treatment were 78.9% (15/19) in the prednisone group and 76.5% (13/17) in the MMF group; 2 and 3 patients in the respective groups had a partial remission, and 2 and 1 patient had no response. HBV reactivation occurred in 63.6% (14/22) and 36.8% (7/19) of patients (P = 0.047). The only significant difference in the study was in the probability of HBV reactivation between groups (P = 0.043, log-rank test). During follow-up, at least 1 relapse occurred in 46.7% (7/15) and 30.8% (4/13) of patients. Elevations in ALT were observed in 36.4% (8/22) and 26.3% (5/19) of patients, and the addition of lamivu-dine was required in 40.9% (9/22) and 21.1% (4/19) of patients. The most frequent adverse effects in both groups were infections (27.3% and 26.3%), followed by gastrointestinal symptoms (13.6% and 21.1%). Two MMF patients developed leukopenia. One patient in the prednisone group discontinued treatment because of severe hepatitis, and 1 patient in the MMF group discontinued because of severe pulmonary infection.Conclusions: Among the adult Chinese patients with MSNS-HBV who completed this study, there were no significant differences in remission rates of idiopathic nephrotic syndrome between the standard prednisone regimen and the combination of MMF and a reduced prednisone dose. Rates of HBV reactivation, however, were significantly lower in the combination-therapy group.

Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's disease

Crohn's disease may be refractory to conventional treatments including corticosteroids and immunosuppressives. Recent studies suggest TNF-alpha blocking agents may be effective in maintaining remission in Crohn's disease. To conduct a systematic review of the evidence for the effectiveness of TNF-alpha blocking agents in the maintenance of remission in patients with Crohn's disease. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the IBD/FBD Review Group Specialized Trials Register were searched for relevant studies published between 1966-2007. Manual searches of references from potentially relevant papers were performed to identify additional studies. Experts in the field and study authors were contacted to identify unpublished data. Randomized controlled trials involving patients > 18 years with Crohn's disease who had a clinical response or clinical remission with a TNF-alpha blocking agent, or patients with Crohn's disease in remission but unable to wean corticosteroids, who were then randomized to maintenance of remission with a TNF-alpha blocking agent or placebo Two independent authors performed data extraction and assessment of the methodological quality of each trial. Outcome measures reported in the primary studies included clinical remission, clinical response, and steroid-sparing effects. Nine studies met all inclusion criteria. Four different anti-TNF-alpha agents were evaluated (infliximab in 3 studies, CDP571 in 3 studies, adalimumab in 2 studies, and certolizumab in 1 study). There is evidence from three randomized controlled trials that infliximab maintains clinical remission (RR 2.50; 95% CI 1.64 to 3.80), maintains clinical response (RR 1.66; 95% CI 1.00 to 2.76), has corticosteroid-sparing effects (RR 3.13; 95% CI 1.25 to 7.81), and maintains fistula healing (RR 1.87; 95% CI 1.15 to 3.04) in patients with Crohn's disease with a response to infliximab induction therapy. There were no significant differences in remission rates between infliximab doses of 5 mg/kg or 10 mg/kg. There is evidence from two randomized controlled trials that adalimumab maintains clinical remission (RR 2.86; 95% CI 2.01 to 4.02), maintains clinical response (RR 2.69; 95% CI 1.88 to 3.86), and has corticosteroid-sparing effects (RR 2.81, 95% CI 1.46 to 5.43) in patients with Crohn's disease who have responded or entered remission with adalimumab induction therapy. There were no significant differences in remission rates between adalimumab 40 mg weekly or every other week. There is evidence from one randomized controlled trial that certolizumab pegol maintains clinical remission (RR 1.68; 95% CI 1.30 to 2.16) and maintains clinical response (RR 1.74; 95% CI 1.41 to 2.13) in patients who have responded to certolizumab induction therapy. There is no evidence to support the use of CDP571 for the maintenance of remission in Crohn's disease. Infliximab 5 mg/kg or 10 mg/kg, given every 8 weeks, is effective for the maintenance of remission and maintenance of fistula healing in patients who have responded to infliximab induction therapy. Adalimumab 40 mg weekly or every other week is effective for the maintenance of remission in patients who have responded to adalimumab induction therapy. Certolizumab pegol 400 mg every 4 weeks is effective for the maintenance of remission in patients who have responded to certolizumab induction therapy. No comparative trials have evaluated the relative efficacy of these agents. Adverse events are similar in the infliximab, adalimumab, and certolizumab groups compared with placebo, but study size and duration generally are insufficient to allow an adequate assessment of serious adverse events associated with long-term use.

The clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review

To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS). Electronic databases from inception to February 2006, bibliographies of studies, and experts in the field. Studies were selected, quality assessed and data were extracted using recognised methods agreed a priori. Meta-analysis was undertaken where appropriate using the random effects model. Where data allowed, subgroup analysis was undertaken according to renal histopathology. Two systematic reviews and 11 trials were included in the clinical effectiveness review; however, the quality of reporting and methodology of the included studies was generally poor. No economic evaluations were identified. No statistically significant difference in remission rates was found between cyclophosphamide plus prednisone and prednisone alone for all children or those with focal segmental glomerulosclerosis (FSGS), also the time to response was statistically significantly less with cyclophosphamide (38.4 days versus 95.5 days). Remission rates were not statistically significantly different between intravenous and oral cyclophosphamide. Vomiting was common with intravenous cyclophosphamide, while pneumonia and alopecia occurred in the oral group. Ciclosporin statistically significantly increased the number of children with complete remission compared with placebo or supportive treatment, but not for the FSGS subgroup, adverse effects including infection and hypertension differed little between groups. No differences were found between azathioprine and placebo, with about 13% of each group having remission. Complete or partial remission occurred in six out of seven patients on the 18-month methylprednisolone regimen and three out of five patients on the 6-month regimen, for both groups renal function improved and adverse events such as hypertension and frequent infections occurred. Intravenous dexamethasone and methylprednisolone produced similar complete remission rates, partial remission rates, median time to response (about 10 days) and total number of adverse events, with hypertension as the most common. Six-hour urinary albumin and urinary albumin to creatinine ratio decreased statistically significantly with high-dose but not low-dose enalapril. Tuna fish oil was not associated with any statistically significant improvements in proteinuria, creatinine clearance, serum creatinine or lipid profiles compared with placebo. A very limited literature was found on costs associated with SRNS in children. The pharmaceutical cost of treatment varied considerably: an 8-week course of cyclophosphamide cost less than 6 pounds, while a course of ciclosporin cost almost 900 pounds per year. Treatment with tacrolimus, an alternative to ciclosporin, was estimated to cost in excess of 3400 pounds per year. Healthcare medical management costs were estimated; varying by treatment strategy, they ranged from 250 pounds to 930 pounds per year in patients not experiencing complications. Other longer term costs may also be incurred. Lack of data meant that cost-effectiveness modelling was not feasible. The clinical effectiveness literature on treatments for idiopathic SRNS in children is very limited. The available evidence suggests a beneficial effect of ciclosporin on remission rates and of cyclophosphamide on time to remission; however, the strength of the conclusions drawn is limited by the poor quality of the included studies. The other treatments included in this review were each evaluated by only one study, and none found a statistically significant effect. There is insufficient evidence to determine whether or not there is a clinically significant difference. The available data on costs and outcomes are sparse and do not permit the reliable modelling of the cost-effectiveness of treatments for SRNS at present. A modelling framework is suggested, should more relevant data become available. A well-designed adequately powered randomised controlled trial comparing ciclosporin with other treatments in children with SRNS without genetic mutation is required.

Keeping Our Eyes on STAR*D

Keeping Our Eyes on STAR*D