An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis

Background: Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT. Methods: 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint Was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion. Results: Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were! hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety. Conclusions: A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay. (C) 2004 Elsevier Ltd. All rights reserved.

Efficacy, safety and tolerability of terbinafine for Tinea capitis in children: Brazilian multicentric study with daily oral tablets for 1, 2 and 4 weeks

Background: Tinea capitis is a common skin disease seen predominantly in children. The standard therapies for this disease are griseofulvin and ketoconazole. Nevertheless, these drugs have drawbacks in that they are only fungistatic and require treatment for at least 6 weeks. Previous studies with oral terbinafine for the treatment of Tinea capitis have shown that this agent is effective when given for 4 weeks, comparable to an 8-week regimen with griseofulvin. To date there is no data on the use of oral terbinafine in Brazilian children. Objectives: To assess the efficacy, safety and tolerability of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of Tinea capitis in children. Patients and methods: One hundred and thirty-two children aged 1-14 years were enrolled in this study, but only 107 were considered for the final efficacy analysis. Diagnosis included clinical assessment and examination by Wood's light. Confirmation was obtained by direct microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was adjusted according to patient weight. Efficacy was evaluated both by clinical and mycological assessment. Safety and tolerability variables included data on adverse reaction and clinical laboratory evaluations. Results: Mycological evaluation in the follow-up visit at week 12 showed negative direct microscopy and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week, respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical cure with a significant difference compared to groups 1- and 2-week, 54.3 and 60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and 10.9% of patients in groups 1-, 2- and 4-week, respectively. Terbinafine was not associated with clinically relevant increases in liver function tests. Conclusions: Terbinafine is an effective, well tolerated and safe antifungal agent for the treatment of Tinea capitis m children. The shorter duration of treatment resulted in lower cure rates. However, it is important to note that depending on the severity of the disease, a 1-week-only treatment can also be effective in this indication.

Acute coronary syndrome associated with continuous 5-fluorouracil infusion in a patient with metastatic colorectal cancer-a case report with a discussion on this clinical dilemma

Introduction: 5-Fluorouracil (5-FU) is considered to be the backbone of colorectal cancer (CRC) systemic therapy since the great majority of recommended regimens include its administration. A clinical picture consisting of chest pain, sometimes cardiac enzyme elevation, electrocardiogram abnormalities consistent with myocardial ischemia, and normal coronary angiogram associated with 5-FU administration have been infrequently reported. The clinical dilemma is: Which chemotherapy regimen should we use in CRC patients with a previous acute coronary syndrome (ACS) associated with 5-FU? Case Report: We describe the case of a 55-year-old otherwise healthy woman with metastatic colon adenocarcinoma who presented an ACS probably secondary to arterial vasospasm while receiving continuous intravenous 5-FU infusion (mFOLFOX6 regimen). After the ACS, the patient was treated with raltitrexate plus oxaliplatin (TOMOX) and subsequently with irinotecan plus cetuximab with no other cardiac event. Conclusion: The risk of cardiotoxicity associated with 5-FU is low but real. The probable mechanism is arterial vasospasm, as suggested by our case report. Both the use of the TOMOX regimen and irinotecan plus cetuximab seems to be safe regimens to be considered in this clinical scenario. © 2009 Humana Press Inc.

Advances in sickle cell disease treatment: From drug discovery until the patient monitoring

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed. © 2011 Bentham Science Publishers Ltd.

Oncological Safety of Autologous Fat Grafting after Breast Conservative Treatment: A Prospective Evaluation

Autologous fat graft to the breast is a useful tool to correct defects after breast conservative treatment (BCT). Although this procedure gains popularity, little is known about the interaction between the fat graft and the prior oncological environment. Evidences of safety of this procedure in healthy breast and after post-mastectomy reconstruction exist. However, there is paucity of data among patients who underwent BCT which are hypothetically under a higher risk of local recurrence (LR). Fifty-nine patients, with prior BCT, underwent 75 autologous fat graft procedures using the Coleman's technique, between October 2005 and July 2008. Follow-up was made by clinical and radiologic examination at least once, after 6 months of the procedure. Mean age was 50 +/- 8.5 years, and mean follow-up was 34.4 +/- 15.3months. Mean time from oncological surgery to the first fat grafting procedure was 76.6 +/- 30.9months. Most of patients were at initial stage 0 (11.8%), I (33.8%), or IIA (23.7%). Immediate complication was observed in three cases (4%). Only three cases of true LR (4%) associated with the procedure were observed during the follow-up. Abnormal breast images were present in 20% of the postoperative mammograms, and in 8% of the cases, biopsy was warranted. Autologous fat graft is a safe procedure to correct breast defects after BCT, with low postoperative complications. Although it was not associated with increased risk of LR in the group of patients studied, prospective trials are needed to certify that it does not interfere in patient's oncological prognosis.

Safety of kidney transplantation using anti-HBc-positive donors

Background. Prospective studies evaluating the risk of hepatitis B virus (HBV) transmission in transplants of kidneys from hepatitis B core antibody (anti-HBc)-positive/ hepatitis B surface antibody (anti-HBs) negative donors are still lacking. The objective of this study was to assess the safety of kidney transplantation with the use of anti-HBc positive donors.Methods. This prospective case series study included 50 kidney transplant recipients from anti-HBc positive donors with or without anti-HBs positivity. Recipients were required to test positive for anti-HBs (titers >10 mUI/mL), regardless of anti-HBc status, and negative for hepatitis B surface antigen (HBsAg). Recipient and donor data were retrieved from medical records, databases, and organ procurement organization sheets. Liver function tests were performed at progressively increasing post-transplantation intervals. Complete serologic tests for HBV were performed before transplantation, 3 and 6 months after transplantation, and annually thereafter.Results. Six months after transplantation, all recipients were negative for HBsAg, HBeAg, anti-HBe, and anti-HBcIgM. No seroconversion was observed among the 20 patients who received kidneys from anti-HBc positive/anti-HBs negative donors. No patient showed elevated liver enzymes during follow-up.Conclusions. Kidney transplantation using organs from anti-HBeIgG positive donors (even when they are concurrently anti-HBs negative) in anti-HBs positive recipients is a safe procedure and may be considered as a way to expand the donor pool.

Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy

To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM-FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19-35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM-FC was initiated and administered once daily at 8 pm for 4-6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). A total of 49 patients were enrolled (mean age, 63 [range, 42-82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM-FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM-FC) was -5.0±3.6 mmHg. IOP decreased significantly (P<0.0001) from baseline (22.1±2.6 mmHg) to study end (17.1±3.9 mmHg) in the ITT population, with a mean IOP reduction of 22.3%. Most patients (n=33/45; 73.3%) achieved IOP ≤18 mmHg. Two patients experienced a total of four adverse events (AEs), including a patient who reported one serious AE (enterorrhagia) that was considered unrelated to treatment, and a patient who reported one event each of drug-related redness, pruritus, and foreign body sensation. Most patients (n=47/49; 95.9%) reported no AEs. TRAV/TIM-FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM-FC. TRAV/TIM-FC was well tolerated in this population.

Resolution of tremor fluoxetine-induced in an elderly patient

Aim: To report a possible case of tremor fluoxetine-induced treated as Parkinson’s disease in an elderly female patient noncompliant with the pharmacotherapy, with uncontrolled hypertension and using fluoxetine to treat depression. Presentation of Case: Patient complained of sleepiness in the morning, agitation, anxiety, insomnia and mental confusion. Her greatest concern was about bilateral hand tremors which, in her view became, worse after biperiden was prescribed. Therefore, she stopped taking it. The initial medication was: omeprazole, losartan, biperiden, fluoxetine, atenolol + chlorthalidone, acetylsalicylic acid, atorvastatin and diazepam. Pharmacotherapeutic follow up was performed in order to check the necessity, safety and effectiveness of treatment. Discussion: During the analysis of pharmacotherapy, the patient showed uncontrolled blood pressure and had difficulty complying with the treatment. Thus, in view of the complaints expressed by the patient, our first hypothesis was a possible serotonin syndrome related to fluoxetine use. We proposed a change in the fluoxetine regime and discontinuation of biperiden. As tremors persisted, we suggested the replacement of fluoxetine by sertraline, since a possible tremor fluoxetine-induced could explain the complaint. This approach solved the drug-related problem identified. Conclusion: Tremors reported by the patient was identified as an iatrogenic event related to fluoxetine, which was solved by management of serotonin-reuptake inhibitors.

Safety and efficacy of gemcitabine plus cisplatin combination in pretreated metastatic breast cancer patients

Metastatic breast cancers (MBC) previously treated with anthracyclines (A) and taxanes (T) have a complicated management. Gemcitabine (G)-cisplatin (C) combinations have been used as synergistic salvage therapy in MBC and are considered as another option for patients with important symptoms and aggressive visceral disease. We analyzed the safety and efficacy of GC in AT-pretreated MBC, as well as overall survival (OS) and time to progression (TTP). Forty-nine subjects received IV G 750 mg/m(2) and C 30 mg/m(2), both d1 and d8 every 3 weeks. Response evaluation was performed every second cycle and in the end of treatment. GC protocol was the first-line palliative chemotherapy in half of the cases, and median number of cycles/patient were 4(2-12). Lung (75.5%) was the most frequent site of metastasis. Most of the patients related clinical improvement with chemotherapy with minimal/mild tolerable collateral effects in 85.7% of cases. Following 34 months, mean OS/TTP was 13.12/6.6 months. Objective-responded patients (40.3%) were statistically associated with the improvement in symptoms after CT (P < 0.01), and OS was directly correlated with chemotherapy response (P < 0.01). HER-2 overexpression was a prognostic factor with reduced OS (P = 0.01). GC protocol was effective and tolerable in objective-responded patients.

Periodontal Manifestations and Ambulatorial Management in a Patient With Sturge Weber Syndrome

Sturge-Weber syndrome is a nonhereditary congenital condition characterized by leptomeningeal and facial skin angiomatous malformation following the trigeminal nerve path. The intraoral angiomatosis are presented in 40% of cases and results in an important periodontal alteration, increasing the risk of bleeding during dental procedures. A 43-year-old male patient presented with port wine stain on the right side of the face, the entire hard and soft palates, the alveolar ridge, and buccal mucosa, and had an excessive accumulation of calcified masses in both supragingival and subgingival sites, with swelling and generalized inflammation throughout the gingiva and alveolar mucosa. He reported not having sanitized the area for years for fear of bleeding. Periodontal management, to remove calculus and to control gingivitis initiated in the supragingival region and gradually reaching the subgingival region to control oral microbiota, was performed with mild bleeding. The redness of the staining greatly diminished with time and the extreme halitosis of the patient also improved sharply leading to a dramatic improvement in quality of life. Ambulatory care is a feasible alternative for periodontal management that within safety limits for bleeding risks reduces the operational cost.

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety.

Esophageal Dilation in Eosinophilic Esophagitis: Effectiveness, Safety, and Impact on the Underlying Inflammation

Esophageal dilation often leads to long-lasting relief of dysphagia in eosinophilic esophagitis (EoE). The aim of this study was to define the effectiveness, safety, and patient acceptance of esophageal dilation in EoE. In addition, we examined the influence of dilation on the underlying esophageal inflammation.

Safety of diagnostic balloon occlusion in normal coronary arteries

Diagnostic coronary balloon occlusion (CBO) is mandatory for collateral function assessment, during angioscopy and optical coherence imaging, and when using certain coronary protection devices against emboli. Thus far, the safety of diagnostic CBO regarding procedural and long-term complications in normal coronary arteries has not been studied. In 316 patients, diagnostic CBO was performed for collateral function measurement in 426 angiographically normal vessels. The angioplasty balloon was inflated for 60 to 120 seconds using inflation pressures of 1 to 3 atm, followed by control angiography during and after CBO. Patients were divided into groups with entirely normal (n = 133) and partially normal (n = 183) vessels. Primary end points were procedural and long-term complications. De novo stenosis development was assessed by quantitative coronary angiography in 35% of the patients. Secondary end points were cardiac events at 5 years of follow-up. Procedural complications occurred in 1 patient (0.2%). In 150 repeat angiographic procedures in 92 patients (follow-up duration 10 +/- 15 months), quantitative coronary angiography revealed no difference in percentage diameter narrowing between baseline and follow-up (4.1% vs 3.9%, p = 0.69). During follow-up periods of 14 and 72 months, respectively, a new stenotic lesion was detected in 1 patient in each group (1.3%). Major cardiac events and percutaneous coronary intervention for stable angina were less frequent in the group with entirely normal than with partially normal vessels (0.8% vs 5.5%, p = 0.02, and 0.8% vs 18%, p <0.0001). In conclusion, low-inflation pressure diagnostic CBO in angiographically normal coronary arteries bears a minimal risk for procedural and long-term complications and can therefore be regarded as a safe procedure.

Do new biologics meet the unmet medical need in rheumatoid arthritis? Safety and efficacy of abatacept following B-cell depletion

Sir, anti TNF-α agents (aTNFs) are the most commonly prescribed biological agents in RA. More recently abatacept (ABA), a T-cell costimulation modulator, and rituximab (RTX), a monoclonal antibody directed against CD20, have become available. Observational studies suggest that switching to a new drug class may be more effective in uncontrolled RA than switching to a class of biologics to which the patient had unsuccessfully been exposed [1]. Information about the efficacy and safety of cycling strategies through third-line biologics is lacking. This study aimed to analyse the effectiveness and safety of switching patients to ABA as the third biological class after failure of aTNF plus RTX. The Swiss Clinical Quality Management (SCQM) programme for RA is a longitudinal population-based cohort, which has been approved by the local ethics committees of all participating centres [2]. For this analysis, we collected all the …