Duration Of Treatment In Patients Research Articles

Optimal treatment duration for patients with HCV genotype 1 infection

The rapidity of viral disappearance on antiviral treatment of chronic hepatitis C with peginterferon/ribavirin correlates with the cure rate. The earlier the virus becomes undetectable, the higher are the response rates. This observation is the basis of response-guided therapy. Viral clearance within the first 4 weeks of treatment is called a rapid virologic response (RVR). The rate of RVR varies among various populations, with the highest one observed in Asian patients and the lowest in African-Americans. In patients infected with genotypes 1 and 4 who experience a RVR treatment with peginterferon/ribavirin can be shortened to just 24 weeks without losing efficacy (sustained virologic rate in RVR are >80%). In contrast, patients with a slow decline in viral load (> 2 log drop after 12 weeks with still detectable virus) may benefit from treatment extension to 72 weeks. Prolonged treatment reduces relapse rates but has no significant effect on cure rates. The data in patients with genotypes 2 and 3 are less clear, mostly because these genotypes are much easier to cure and a benefit is hard to detect. Nevertheless in patients with RVR and low baseline viral load treatment can be safely shortened to 16 weeks. The recently described polymorphism in the region of the IL28B gene may help to select patients for abbreviated or extended treatment schedules.

Efficacy and safety of regimens of capecitabine-based chemotherapy in the treatment of advanced breast cancer

To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer. Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles. Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01). The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

Impact of HCV Protease-Inhibitor-Based Triple Therapy for Chronic HCV Genotype 1 Infection

Boceprevir and telaprevir are the first HCV protease inhibitors to be approved for the treatment of chronic hepatitis C genotype 1 infection. These drugs must be used in combination with pegylated interferon plus ribavirin (P/R) to maximize efficacy and prevent the emergence of resistance-associated variants (RAVs). In randomized, placebo-controlled international studies in treatment-naive and previously treated HCV patients, treatment with either boceprevir- or telaprevir-based triple therapy regimens significantly increased sustained virological response rates compared with placebo plus P/R. Protease inhibitors have the potential, not only to significantly increase cure rates among patients with genotype 1 infection, but also to reduce the duration of treatment for patients who have an extended rapid virological response. Boceprevir is associated with an increased incidence of anaemia and dysgeusia and telaprevir is associated with an increased incidence of rash and anaemia. The emergence of RAVs was associated with an increased risk of virological failure in clinical studies. Although these new drugs bring significant promise, it remains unclear if all genotype 1 patients will need triple therapy. Here, we review some of the complexities uncovered and controversies highlighted by the introduction of HCV protease inhibitors.

Shortening of treatment duration in patients with chronic hepatitis C genotype 2 and 3 - impact of ribavirin dose - a randomized multicentre trial

BackgroundChronic hepatitis C (CHC) Patients, infected with genotype (GT) 2 or 3 are treated with Peg-IFN and ribavirin (RBV) (800 mg/day) for 24 weeks. Treatment duration can be shortened to 12-16 weeks if a higher dose of RBV (1.000/1.200 mg/day) was used without considerable loss of responsiveness or increased risk of relapse. Previously we have shown that in patients with CHC, GT 2/3 RBV can be reduced to 400 mg/day if administered for 24 weeks without an increase in relapse rates. Therefore we investigated the efficacy of a reduced RBV dosage of 400 mg/day with shorter treatment duration (16 weeks).MethodsTreatment naïve patients with CHC, GT 2/3 were randomized to receive 180 μg peginterferonα2a/week in combination with either 800 (group C) or 400 mg/d (group D) for 16 weeks. The primary endpoint was SVR.Results12 months after the first patient was randomized a inferior outcome of group D as compared to group C was noted, therefore the study was terminated. At study termination 89 patients were enrolled (group C: 31, D: 51). The SVR rate was statistically different in the two study groups with 51.6% in group C and 28.4% in group D (p = 0.038). Patients with low viral load had higher SVR rates (C: 67%, D: 33%) than those with high viral load (C: 33%, D: 21%).ConclusionBoth treatment duration and the dose of RBV play a major role to optimize outcome of patients with GT3. If one intends to shorten the treatment weight based RBV dose should be used, if lower RBV doses are used patients should be treated for at least 24 weeks as. A treatment regimen with a reduced RBV dosage and shortened treatment duration is associated with low SVR rates due to high relapse rates.Trial registrationNCT01258101

Efficacy and safety of perioperative pregabalin for post‐operative pain: a meta‐analysis of randomized‐controlled trials

We calculated in a meta-analysis the effect size for the reduction of post-operative pain and post-operative analgesic drugs, which can be obtained by the perioperative administration of pregabalin. Three end-points of efficacy were analysed: early (6 h-7 days) post-operative pain at rest (17 studies) and during movement (seven studies), and the amount of analgesic drugs in the studies that obtained identical results for pain at rest (12 studies). Reported adverse effects were also analysed. The daily dose of pregabalin ranged from 50 to 750 mg/day. The duration of treatment in patients assessed for pain ranged from a single administration to 2 weeks. Pregabalin administration reduced the amount of post-operative analgesic drugs (30.8% of non-overlapping values - odds ratio=0.43). There was no effect with 150, and 300 or 600 mg/day provided identical results. Pregabalin increased the risk of dizziness or light-headedness and of visual disturbances, and decreased the occurrence of post-operative nausea and vomiting (PONV) in patients who did not receive anti-PONV prophylaxis. The administration of pregabalin during a short perioperative period provides additional analgesia in the short term, but at the cost of additional adverse effects. The lowest effective dose was 225-300 mg/day.

P03-94 - Collaborative study of compliance in psychotic patients with risperidone long-acting injection (RLAI) in the last 5 years

IntroductionCompliance is essential to achieve the best results in serious mental illness like schizophrenia.ObjectivesIt was expected that the use of second-generation oral antipsychotics with less extrapyramidal side effect profile would improve the compliance, but the results do not support these expectations except in the case of risperidone long-acting injection.AimsThe aim of this study is to assess the degree of compliance in outpatients who were started treatment with RLAI while they were hospitalized for an acute psychotic episode in psychiatric unit.MethodsA retrospective study was conducted by reviewing medical records of hospitalized patients for psychotic episodes over the past 5 years in three hospitals in Mallorca (Balearic Islands, Spain) -Hospital de Manacor, Hospital son Llatzer and Hospital de Inca). Due to computerization of medical records, we knew the degree of compliance with treatment and outcome in outpatient clinics. We designed a case report data (CRD) to assess specific variables in our study that was completed for each patient.ResultsThe mean duration of treatment in patients who continue with RLAI was 38.8 months. Overall. 69.5% continued with the treatment after 5 years. The patients who continued treatment were rehospitalazed 20% less than the ones who discontinued.ConclusionsThe compliance with RLAI in outpatients was high even in patients with substances abuse. The patients who remain on treatment from hospital discharge have less readmissions. The most common dosis of RLAI is 50 mg. Lack of insight was the most frequent cause of discontinuation.

Successful Treatment of Recurrent Triple-Negative Breast Cancer with Combination of Targeted Therapies

We present an interesting case of a 56-year-old female diagnosed with invasive high-grade triple-negative breast cancer, who developed diffuse liver metastases following lumpectomy and combination chemotherapy with docetaxel, doxorubicin and cyclophosphamide, re-excision and radiation therapy. Restaging CT and PET scans revealed massive involvement of the liver. She was treated with a combination of gene targeted and cytotoxic chemotherapy including capecitabine, erlotinib, bevacizumab and phenylbutyrate. She tested weakly positive for HER-2 despite prior negative FISH, which prompted us to add trastuzumab to her regimen. Baseline CT revealed five liver tumors—the sum of the products of the two largest perpendicular diameters was 110 cm2. Follow-up CT after three months of treatment revealed 62% decrease in total tumor load. More than 50% decrease in tumor size persisted on two follow-up CT scans, confirming partial response. She developed progressive disease after 15 months of treatment. A group of 16 women, including this patient, diagnosed with triple negative breast cancer with distant metastases were treated by our team with a combination of gene targeted therapy and chemotherapy. Six percent of patients obtained partial response, 25% minor response, 31% stable disease, and 38% progressive disease. The median duration of treatment in patients who relapsed after the second-, third- and fourth- to seventh-lines of chemotherapy was 59 weeks, 22 weeks and 17 weeks, respectively. Comparison of results obtained with cytotoxic chemotherapy revealed that MDT in the second- and third-lines was only nine and four weeks, respectively. In conclusion, this case report indicates that it is possible to obtain durable objective response of recurrent TNBC with a combination of gene targeted agents.

Phase 3 Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin Lymphoma (EXTEND): End of Study Results.

AbstractAbstract 2833 Introduction:No therapy with reliable, durable efficacy exists for patients with aggressive non-Hodgkin lymphoma (aNHL) who relapse following at least two lines of therapy. Pixantrone dimaleate (PIX) is a novel aza-anthracenedione, structurally similar to anthracyclines and mitoxantrone, and forms stable DNA adducts. Unlike anthracyclines and mitoxantrone, PIX does not bind iron, minimally promotes reactive oxygen species formation, and is substantially less cardiotoxic in preclinical models. On the basis of promising early clinical activity and acceptable safety, we conducted a phase 3 trial with PIX in patients with aNHL and ≥2 relapses. Patients and Methods:This randomized, multicenter, controlled, open-label study enrolled patients with aNHL (de novo or transformed) with ≥1 prior anthracycline-containing regimen and ≥2 relapses. Patients were randomized to PIX 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle, for up to 6 cycles, or to investigator's choice of single-agent comparator (COMP): vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or, in the US only, gemcitabine or rituximab. Both groups were followed for 18 months after last treatment. The primary endpoint, CR/CRu rate in ITT population, was assessed by an independent assessment panel. Other efficacy endpoints were overall response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Final end-of-study results are reported here. Results:Planned enrollment was set at 320 patients; however, due to slow accrual, a total of 140 patients were randomized (n=70 per group) to this study. Median number of treatment cycles for PIX group was 4 vs 3 for COMP. Median duration of treatment for patients in the PIX group was about one month longer than in the COMP group (3.8 vs 2.6 months). The end-of-study CR/CRu rate was 24% (16% CR, 8%CRu) for PIX vs 7% (no CRs, 7% CRu only) for COMP (P = 0.009); ORR (CR/CRu/PR) was 40% vs 14% (P = 0.001). After treatment ended, 3 patients in the PIX group achieved CR with no subsequent therapy. Two of the 3 patients converted from SD to CR and 1 from PR to CRu. Median CR/CRu duration was 9.6 months for PIX vs 4.0 months for COMP (P = 0.081). For survival endpoints, there was a 40% improvement in PFS with a median of 5.3 months vs 2.6 months (HR = 0.60, log-rank P = 0.005) and a 21% improvement in OS with a median of 10.2 months for PIX vs 7.6 months for COMP (HR = 0.79, log-rank P = 0.251). Exploratory subgroup analyses of CR/CRu and ORR were consistently higher for PIX patients and suggest stronger efficacy with the subgroups sex (female), <3 prior regimens, no prior rituximab, and ≥1 yr from 1st to 2nd line therapy. During treatment, neutropenia and leukopenia were the most common (≥10%) grade 3/4 adverse events and the incidence of febrile neutropenia was 7.4% for PIX vs 3% for COMP. Percentage of patients with cardiac disorder SAEs was 8.8% for PIX vs 4.5% for COMP. There were 11 grade 1/2 and 2 grade 3 LVEF events for PIX vs 7 grade 1/2 for COMP. Conclusions:In this phase 3 study, patients treated with PIX achieved superior efficacy when compared with other agents, as assessed by CR/CRu rate, ORR, and PFS, and had a positive trend in OS. Pixantrone had a tolerable safety profile in heavily pretreated patients with relapsed aggressive NHL. Disclosures:Pettengell:Cell Therapeutics, Inc: Honoraria. Coiffier:Cell Therapeutics, Inc: Advisory Board. Schiller:Sunesis: Consultancy; Celgene, Genzyme, Millenium, CTI, Antisoma, Novartis: Research Funding. Rizzieri:Cell Therapeutics, Inc: Membership on an entity's Board of Directors or advisory committees. Cernohous:Cell Therapeutics, Inc: Employment. Wang:Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment, Membership on an entity's Board of Directors or advisory committees; DiaKine Therapeutics, Inc: Membership on an entity's Board of Directors or advisory committees.

Antidepressant monotherapy: A claims database analysis of treatment changes and treatment duration

Background: The basic principles of pharmacotherapy for depression are consistent among most US and western European guidelines. All recommend ≥6 months of antidepressant therapy and propose several alternatives in cases of inappropriate response. Objectives: The aims of this analysis were to describe antidepressant treatment changes and treatment duration in patients undergoing treatment for a new episode of depression and to identify risk factors for treatment changes and treatment discontinuation. Methods: For this claims database analysis, adults and children treated with antidepressants for a new episode of depression in the time period from 2004 to 2006 were identified using the IMS LifeLink Health Plan Database. Treatment changes (defined as switches to an antidepressant or antipsychotic; combination with an antidepressant; or augmentation with lithium, an anticonvulsant, or an atypical antipsychotic) were described. Antidepressant treatment duration was assessed and described per treatment change. Risk factors for treatment change or discontinuation were identified using multivariate logistic regression (treatment change) or Cox regression (treatment duration). Results: Of 134,287 patients identified using the database (mean [SD] age, 39.1 [14.9] years; 68.1% women), 31,123 (23.2%) had a treatment change, most commonly an antidepressant switch (12,735 [9.5%]) or combination (12,214 [9.1%]). Antipsychotics were introduced in <5% of patients. The median overall treatment duration (111 days) was shorter than that recommended in the guidelines (≥6 months). Index antidepressant class was significantly associated with treatment change (higher for tricyclic antidepressants [TCAs] [odds ratio (OR) = 1.59 (95% CI, 1.48–1.70)]; lower for selective serotonin reuptake inhibitors [OR = 0.87 (95% CI, 0.84–0.91)]) and duration (increased risk for early discontinuation for TCAs [hazard ratio (HR) = 1.36 (95% CI, 1.30–1.44)]; lower risk for late discontinuation for serotonin-norepinephrine reuptake inhibitors [HR = 0.81 (95% CI, 0.79–0.84)]). Indicators of depression severity or complexity (prescription by a mental health specialist, previous use of psychotropics, previous psychiatric hospitalization, and presence of psychosomatic comorbidities) were associated with a higher risk for treatment change and inconsistently associated with treatment duration. Two health plans were associated with increased risk for discontinuation (Medicaid, HR = 1.35 [95% CI, 1.28–1.42]; Medicare, HR = 1.38 [95% CI, 1.12–1.71]). Combination and augmentation strategies were associated with a lower risk for treatment discontinuation (combination, HR = 0.83 [95% CI, 0.81–0.86]; augmentation, HR = 0.75 [95% CI, 0.73–0.77]). Overall treatment duration was <30 days in 31,177 patients (26.2%) and >6 months in 54,502 (37.5%). Conclusions: In this claims database analysis, changes in antidepressant treatment involved 23.2% of patients. The median overall treatment duration was shorter than recommended by guidelines due to a quarter of patients having early treatment discontinuation.

Holiday Treatment Breaks May Adversely Predict for Loss of Tumor Control

An emerging body of literature has stressed the importance of radiation prescription compliance and overall duration of treatment in patients undergoing definitive radiotherapy. Holiday breaks represent a barrier to prescription compliance. Unstudied are those patients whose course of external beam radiotherapy (EBRT) spans the entire winter holiday season, including Thanksgiving, Christmas, and New Years Day. The purpose of this study was to examine overall prescription compliance and use radiobiologic principles to calculate the potential impact on local tumor control (LCT).

What is the optimum duration of anticoagulation for the management of patients with idiopathic deep venous thrombosis and pulmonary embolism?

Anticoagulant therapy is highly effective in preventing recurrent events in patients with venous thrombo-embolism (VTE). For patients with ‘secondary’ or ‘provoked’ VTE affecting isolated calf veins or upper limb, there is general agreement that six weeks to three months of anticoagulation is adequate. Those with ‘provoked’ iliofemoral deep vein thrombosis (DVT) or pulmonary embolism (PE) are usually treated for three or six months. The duration of treatment in patients with idiopathic VTE, however, is controversial. Some experts recommend long-term anticoagulation after the first episode of VTE, whereas others, including ourselves, advocate only three months of anticoagulation.

Duración del tratamiento antibiótico en la infección intraabdominal

The duration of antibiotic treatment in patients with an infectious process is based on empirical considerations and those with intraabdominal infections are no exception. Therefore, the recommended duration of antibiotic therapy in intraabdominal infection is controversial and no consensus has been reached due to the lack of controlled studies that would provide sufficient scientific evidence. Excessive duration of antibiotic therapy can increase the risk of developing bacterial resistance as well as treatment-associated costs. These considerations have led to the exploration of "short-term treatment" strategies, lasting 3-5 days, with encouraging results. However, the development of biomarkers such as procalcitonin opens the door to individualized treatment that might allow the duration of antibiotic treatment in intraabdominal and other infections to be individually tailed to patient response.

Temozolomide Treatment for Aggressive Pituitary Tumors: Correlation of Clinical Outcome with O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation and Expression

The typically indolent behavior of pituitary tumors is juxtaposed with high rates of tumor cell invasion into adjacent dural structures, and occasional aggressive behavior. Although clinically significant invasion and malignant transformation remain uncommon, there are limited treatment options available for the management of these aggressive tumors. Recently, case reports have described efficacy of temozolomide for the treatment of aggressive pituitary tumors. Seven patients with aggressive pituitary tumors have been treated with temozolomide. We compared O(6)-methylguanine methyltransferase (MGMT) promoter methylation and MGMT expression in 14 surgical specimens from these seven patients and correlated these molecular features with the clinical response to temozolomide. Significant tumor regression was seen in two patients (29%), a 20% reduction in tumor volume with subsequent stable tumor size was noted in one patient, arrest of tumor growth occurred in three patients, and progressive metastatic disease developed during treatment in one patient. The DNA promoter site for MGMT was unmethylated in all 14 adequate specimens, and variable MGMT expression was seen in all 14 cases. There was no correlation between MGMT expression and clinical outcomes. We conclude that medical therapy with temozolomide can be helpful in the management of life-threatening pituitary tumors that have failed to respond to conventional treatments. The optimal duration of treatment in patients with stabilization or reduction of tumor size has not been established, and long-term follow up studies are needed.

Rabeprazole Is Effective in Treating Laryngopharyngeal Reflux in a Randomized Placebo-Controlled Trial

There is controversy about the efficacy of treating patients with laryngopharyngeal reflux (LPR) using proton pump inhibitors (PPIs). We assessed the effects of high doses of the PPI rabeprazole in patients with LPR. Patients with LPR symptoms were assigned randomly to receive rabeprazole (20 mg, twice daily, n = 42) or placebo (n = 40) for 12 weeks. All patients completed symptom questionnaires; these provided demographic information and the reflux symptom index before, during, and 6 weeks after cessation of treatment. Videolaryngostroboscopy was used to document the laryngeal findings and determine the reflux finding score. Twenty-four patients (57.1%) in the rabeprazole group and 27 patients (67.5%) in the placebo group had pH-documented LPR. The total reflux symptom index score decreased significantly in the group given rabeprazole, compared with patients given placebo, at weeks 6 and 12, but not at week 18. However, there were no significant differences in reflux finding scores between the rabeprazole and placebo groups at any of the time points. Twelve weeks of treatment with rabeprazole (20 mg, twice daily) significantly improved reflux symptoms, compared with placebo, in patients with LPR. Relapse of symptoms was observed 6 weeks after stopping PPI therapy, indicating the requirement for longer treatment duration in patients with LPR.

The effect of anti-TNF agent on oxidation status in patients with ankylosing spondylitis

The aim of this study was to comparatively evaluate oxidative status of ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor (TNF) or non-steroid anti-inflammatory drugs (NSAID). Forty-seven patients with AS and 27 healthy controls were enrolled. Of these, 23 were on anti-TNF (group 1) and 24 on NSAIDs (group 2). Groups 1 and 2 were consisted of matched patients with respect to age, gender, body mass index, disease duration, C-reactive protein, erythrocyte sedimentation rate, total cholesterol, and Bath Ankylosing Spondylitis Disease Activity Index. Mean duration of treatment for patients in group 1 was 12.6 +/- 6.8 months. Serum total antioxidative status (TAS) and total oxidative status (TOS) levels were determined using new automated methods. Oxidative stress index (OSI) was calculated. The groups' carotid intima-media thicknesses (IMT-C) were also measured using ultrasonography. Group 1 had the highest TAS and lowest TOS levels. The TOS levels of group 1 was lower than the control, while group 2 being higher than controls. The difference in TOS levels between group 1 and group 2 was statistically significant (p = 0.040). OSI values were highest in group 2 and lowest in group 1. There was no significant correlation between oxidant/antioxidant parameters and IMT-C for group 1 (r = -0.30, p = 0.198 for OSI; r = 0.22, p = 0.366 for TAS; r = -0.22, p = 0.361 for TOS). This is the first study to evaluate total oxidative/antioxidative status in patients with AS on anti-TNF agent. These results clearly indicate positive effects of anti-TNF treatment on oxidative status of AS patients. The limited effects of NSAIDs compared with controls may be due to excess impaired oxidative status in the patients in this study.

Is continuous antibiotic prophylaxis in children with vesicoureteral reflux really ineffective in preventing pyelonephritis?

Sirs, Although long-term antibiotic prophylaxis (AP) has been used for patients with vesicoureteral reflux (VUR) in order to prevent urinary tract infections for many years, recent randomized controlled trials (RCTs) revealed that AP with sulfametoxazole/trimethoprim (SMX/TMP) or nitrofurantoin was ineffective in reducing the rate of recurrence of pyelonephritis in children with low grade VUR and was associated with an increased risk of resistant infections [1– 3]. On the other hand, because of the increase in organisms resistant to SMX/TMP, conventional AP using low-dose cephalosporins, such as cefaclor (CCL), has been favored by many pediatric nephrologists and urologists in Japan for more than 10 years. Although we previously reported the efficacy and safety of the strategies of AP using low doses of CCL for children with VUR in this journal, since then there has been a paucity of evidence for the agent [4]. To investigate whether long-term use of CCL could effectively reduce the risk of recurrent pyelonephritis in comparison with SMX/TMP, we therefore reviewed retrospective data from children with VUR, including grade IV or V, in our hospital. Two hundred and forty-two children (168 male, 74 female) with VUR who had been diagnosed by voiding cystourethrography after acute pyelonephritis and had received AP (CCL or SMX/TMP) for more than 6 months in Saitama Children’s Medical Center from April 1994 to December 2008 were enrolled in this study. The VUR grade was based on the maximum grade on either side of the urinary collecting system (grade I, 7; II, 41; III, 64; IV, 82; V, 48). Of the 242 patients, 184 (76%) had received AP with CCL (5–10 mg/kg per day), while the remaining 58 (24%) had received SMX/TMP (5–10 mg/kg per day SMX and 1–2 mg/kg per day TMP). The choice of antibiotics and the duration of AP depended on the decisions of different physicians. The children’s ages at the first episode of acute pyelonephritis varied from 0.5 months to 127 months (median 4 months). The mean duration of treatment for patients who had received AP was 21±13.5 months. Forty patients (17%) developed breakthrough infections (total 70 episodes) during a total of 5,028 months of treatment (one recurrent pyelonephritis in approximately 72 months). Of these 40 patients, 29 (73%) had high grade VUR (grade IV or V). Table 1 shows the demographic characteristics of the patients who received AP with CCL or SMX/TMP. Although there were no significant differences between the two groups in terms of the gender ratio, the duration of treatment, VUR laterality, or VUR grade, the predicted months for one recurrent episode of pyelonephritis per patient was significantly longer for children on CCL than for those on SMX/TMP (P<0.05). However, children who had received AP with low doses of CCL were more likely to have had breakthrough infections of cephalosporinresistant bacteria other than Escherichia coli, such as Pediatr Nephrol (2009) 24:1431–1432 DOI 10.1007/s00467-009-1161-6

Elevated D-dimer levels predict recurrence in patients with idiopathic venous thromboembolism: a meta-analysis.

The evidence on the optimal duration of treatment in patients with an idiopathic venous thromboembolic event (VTE) is inconclusive. d-dimer testing to predict recurrent VTE has been evaluated in several studies. We performed a meta-analysis of studies of patients with idiopathic VTE treated with oral anticoagulation therapy (OAT) to assess the prognostic value of elevated D-dimer levels 1 month after discontinuation of OAT for VTE recurrence. The MEDLINE, EMBASE and Cochrane databases were searched to identify relevant studies. Studies were eligible for inclusion if they included patients with idiopathic VTE and in addition reported results for this group separately, had measured D-dimer approximately 1 month after discontinuation of OAT and had reported on recurrence of VTE. A random-effects model was used to pool study results. Data from four studies (1539 patients) were included in the current analysis. All studies reported on the number of recurrent events in the normal and elevated D-dimer groups. Overall, 125 of 751 patients (16.6%) with elevated D-dimer levels experienced recurrent VTE during the period of follow-up compared with 57 of 788 patients (7.2%) with normal D-dimer levels. Elevated D-dimer levels were significantly associated with recurrent VTE (odds ratio , 2.36; 95% CI, 1.65 to 3.36). Elevated d-dimer levels measured 1 month after discontinuation of OAT identify patients with idiopathic VTE at higher risk of recurrence.

Helicobacter pylori Eradication Therapy Success Regarding Different Treatment Period Based on Clarithromycin or Metronidazole Triple‐Therapy Regimens

The study compares the eradication success of standard first-line triple therapies of different durations (7, 10, and 14 days). A total of 592 naive Helicobacter pylori-positive patients were randomized to receive pantoprazole, amoxicillin, and clarithromycin or metronidazole for 14 days (PACl14 or PAM14), 10 days (PACl10 or PAM10), or 7 days (PACl7 or PAM7). H. pylori eradication was assessed by histological, microbiological, and rapid urease examination. The intention-to-treat (ITT) and per-protocol (PP) analyses have shown no overall statistically significant differences between the eradication success of PACl and PAM treatment groups (ITT p = .308, PP p = .167). Longer treatment duration has yielded statistically significant increase in eradication success for clarithromycin (ITT p = .004; PP p = .004) and metronidazole (ITT p = .010; PP p = .034) based regimens. Namely, PACl10, PACl14, and PAM14 protocols resulted in eradication success exceeding 80% in ITT and 90% in PP analysis. Primary resistance to clarithromycin and metronidazole equals 8.2% and 32.9%, respectively. Prolonging the metronidazole-based treatment duration in patients with resistant strains resulted in statistically significant higher eradication success. For all antimicrobial combinations, 14 days protocols have led to a significant increase of H. pylori eradication success when compared to 10 and 7 days, respectively. Prolonging the treatment duration can overcome the negative effect of metronidazole resistance. Only PAM14, PACl10 protocols achieved ITT success > 80% and should be recommended as the first line eradication treatment in Croatia.

Effective use of imatinib-mesylate in the treatment of relapsed chronic myeloid leukemia after allogeneic transplantation

Effective use of imatinib-mesylate in the treatment of relapsed chronic myeloid leukemia after allogeneic transplantation

216: Incidence of Flushing Decreases Over Time During Long-Term Therapy with a Novel Combination of Niacin Extended-Release with Simvastatin

Synopsis: Current evidence-based guidelines identify niacin as an important adjunct intervention, along with a statin, in high-risk patients with multiple lipid abnormalities. Perceptions regarding niacin-induced flushing limit its use. To date, however, no study has examined the extent to which patients who flush upon initiation of niacin continue to do so with continued therapy. Purpose: In this 52-week study (OCEANS), the incidence of flushing was evaluated over the duration of treatment in patients who experienced flushing during the initial 12 weeks of therapy with a novel, proprietary, niacin extendedrelease (NER) and simvastatin combination (NER/S). Methods: Patients were randomized to a variable titration schedule of NER/S, attaining a maximum dose of 2000/40 mg/day at 13 weeks. Total treatment duration was 24 to 52 weeks. Only patients who flushed during weeks 1–12 and completed a flushing log for weeks 1–12 and either weeks 13–24 or 41–52 were included in this post-hoc analysis. Concomitant treatment with aspirin/NSAIDS was allowed, though not mandated. Results: Flushing during the first 12 weeks of therapy occurred in 351 of 509 (71%) of patients. Of these patients, 45.8% (108 out of 236) did not experience flushing during weeks 13–24 although the dose of NER/S was increased to 2000/40 mg/day at the beginning of week 13 for 50% of patients. Further, 62.5% (75 out of 120) of patients did not experience flushing during weeks 41–52 [Figure]. Notably, 92% of the total flushing episodes in each titration group were rated as mild or moderate in intensity over the 52-week study. Conclusions: The majority of patients who experienced flushing during the initial 12 weeks of NER/S did not continue to experience flushing over the long-term despite continuing to receive NER/S. These results suggest that concerns with flushing over the long-term may be addressed and tolerance to NER-related flushing commonly occurs.