Nefopam (Ajan®)

Ohne Zusammenfassung     

The comparison of Filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) as a first line peripheral blood stem cell mobilization strategy in autologous hematopoieitic stem cell transplantation: A single center experience from Turkey

Objectives and aimPatients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34⁺ mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT).Materials and methodsWe retrospectively analysed data of patients who underwent autoHSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients’ files. Patients who received Filgrastim (Neupogen®), biosimilar Filgrastim (Leucostim®, Group) and Lenograstim (Granocyte®) were evaluated mainly for total CD34⁺ cell count at the end of mobilization procedure.ResultsA total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3 × 10⁶ CD34⁺/kg was 2 in Neupogen® (min–max: 1–4) and Granocyte® (min–max: 1–3) groups and 1 (min–max: 1–2) in Leucostim® group. The median doses of G-CSF agents (μg/kg/day) in PBSC collection procedure were; 10.00 (min–max: 7.00–12.00) in the Neupogen® group, 8.00 (min–max: 7.25–9.00) in the Leucostim® group and 8.50 (6.00–9.50) in the Granocyte® group. There was no statistical significance among groups (p = 0.067). The number of total collected PB CD34⁺ cells (×10⁶/kg) was 7.64 (min–max: 4.09–13.86) in the Neupogen® group, 13.43 (min–max: 8.15–23.38) in the Leucostim® group and 5.45 (min–max: 4.28–9.40) in the Granocyte® group. The data showed that patients in the leucostim group had significantly higher PB CD34⁺ cells compared to patients in the Granocyte® group (p = 0.013).ConclusionLeucostim® was comparable to Neupogen® for PBSC mobilization in patients who underwent autoHSCT.     

Lurasidone (latuda®): an atypical antipsychotic

Lurasidone is a new atypical antipsychotic that has demonstrated positive effects on psychosis, mood, and cognition. This improved efficacy and safety profile for the treatment of schizophrenia. Its overall tolerability profile seems to be comparable to the other atypical antipsychotics. Perhaps its more potent blockade on the 5HT7 receptor will give it more of an advantage in treating the negative symptoms as well as improve cognitive and depressive symptoms associated with schizophrenia. Additionally, it does not appear to have any significant adverse impact on the metabolic profile, such as weight, glucose, or lipid metabolism. Lurasidone is also associated with good cardiovascular tolerability without widening of the QT interval. The use of this medication may be of particular interest in patients presenting with endocrine or cardiovascular abnormalities. The average price for a 30-day supply of lurasidone is $475.98.     

Buprenorphin (Temgesic®)—Pharmakologie und klinische Anwendung

Ohne Zusammenfassung     

Clarithromycin (Biaxin®) extended-release tablet: a therapeutic review

Clarithromycin (Biaxin^®) extended-release tablets, an advanced generation macrolide, were recently introduced into the USA for the treatment of acute exacerbations of chronic bronchitis, community-acquired pneumonia and acute maxillary sinusitis. The reformulation is intended to improve both patient compliance and tolerability. The extended-release tablets allow convenient once-daily dosing (1000 mg). The extended-release formulation has been shown to be equivalent to the immediate-release formulation concerning area under the plasma concentration time curve. In comparative clinical trials for acute exacerbations of chronic bronchitis, community-acquired pneumonia and acute maxillary sinusitis, clarithromycin extended-release tablets were equivalent to the immediate-release formulation concerning clinical efficacy and bacterial eradication, with improved gastrointestinal tolerability. Similar efficacy and gastrointestinal tolerability results were demonstrated in a recent comparative study of clarithromycin extended-release formulation and amoxicillin-clavulanate in patients with acute exacerbations of chronic bronchitis. Clarithromycin extended-release 1000 mg daily has also been shown to be equivalent to levofloxacin 500 mg daily for the treatment of community-acquired pneumonia in a recent study. The macrolide class of antimicrobials, including clarithromycin extended-release, continues to be a safe and efficacious choice for the out-patient management of community-acquired bacterial respiratory tract infections.     

Differential Effects of Oral Doxercalciferol (Hectorol®) or Paricalcitol (Zemplar®) in the Cyp27b1-Null Mouse Model of Uremia

Background/Aims: Kidney disease patients experience declining calcitriol levels and develop secondary hyperparathyroidism (SHPT). Animal models of uremia based on 5/6 nephrectomy (NTX) do not consistently reproduce this calcitriol deficiency. We developed an animal model, the NTX Cyp27b1-null mouse, which completely lacks endogenous calcitriol, and examined the suitability of this model for evaluation of treatment with vitamin D analogs in uremia. Methods: NTX was performed at 2 months of age. One week post-NTX, animals were treated for 4 weeks with vehicle; doxercalciferol at 30, 100 or 300 pg/g body weight (b.w.); or paricalcitol at 100, 300 or 1,000 pg/g b.w. by gavage 3 times per week. Results: Serum blood urea nitrogen and creatinine were elevated. Vehicle-treated NTX null mice had hypocalcemia and SHPT. Doxercalciferol at 100 or 300 pg/g b.w. normalized serum calcium and parathyroid hormone (PTH) levels. Paricalcitol at 300 or 1,000 pg/g normalized serum calcium, but PTH levels remained elevated. Osteomalacia was corrected by 100 pg/g b.w. of doxercalciferol or 1,000 pg/g b.w. of paricalcitol. The highest dose of doxercalciferol, but not of paricalcitol, significantly reduced osteitis fibrosa. Conclusion: Our results reveal the differential efficacy of doxercalciferol and paricalcitol in this novel animal model incorporating both calcitriol deficiency and renal insufficiency.     

Peginterferon–α2a (40 kDa) (Pegasys®) for hepatitis B

Chronic hepatitis B virus is a serious and life threatening disease afflicting 350 million people worldwide, despite the availability of effective vaccines. Thus far, current monotherapy with conventional interferon-α, lamivudine and adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional interferon-α needs to be administered subcutaneously three-times weekly and is associated with frequent adverse events. Although nucleoside/nucleotide analogs such as lamivudine and adefovir dipivoxil are well tolerated and can normalize serum alanine aminotransaminase rapidly, 1-year therapy with either lamivudine or adefovir dipivoxil results in low hepatitis B e antigen seroconversion rates. In hepatitis B e antigen-negative patients, most would relapse after lamivudine has been discontinued. Peginterferon-α2a, an immunomodulatory agent, is a new drug that has just completed Phase III clinical trials for the treatment of both hepatitis B e antigen-positive and -negative chronic hepatitis B virus infection. The advantage of peginterferon-α2a in achieving sustained virologic response over nucleoside/nucleotide analogs is particularly obvious in the hepatitis B e antigen-negative group. In both studies, sustained off-treatment response is superior to the use of monotherapy with lamivudine, and concomitant use of lamivudine and pegnterferon-α2a does not have advantages over the use of peginterferon-α2a alone. These recent data put peginterferon-α2a as the antihepatitis B virus therapy of choice, especially in young and motivated patients with chronic hepatitis B virus infection. However, despite the superiority of peginterferon-α2a over currently licensed nucleoside/nucleotide analogs, more research needs to be conducted in order to find the most optimal treatment regimen in our fight against chronic hepatitis B virus infection.     

Reproducibility of thrombelastometry (ROTEM®): point-of-care versus hospital laboratory performance

Thrombelastometry (ROTEM?) has gained wide acceptance in detecting and tailoring acquired hemostatic changes in adults and children. We investigated in this observational trial whether the reproducibility of this point-of-care testing was influenced by performance at the bedside or in the hospital laboratory. In addition, difference in time of performance between both measurements was compared. Perioperative blood samples obtained during major pediatric surgery were run in duplicate on two different ROTEM? devices located in the OR and in the hospital laboratory. The Bland-Altman test was used to compare differences of both measurements. ROTEM? measurements of 90 blood samples obtained from 24 children showed no overall clinically meaningful differences, whether they were performed bedside or in the hospital laboratory. Minor differences were found for the InTEM clot formation time (CFT) showing a mean bias of 10.79 seconds. Time saving was 11 minutes (8-16 minutes) if ROTEM? measurements were performed bedside (p < 0.001). In conclusion, there were minimal effects on ROTEM? measurements irrespective of whether they were performed in the hospital laboratory or at the bedside by a single trained staff member, while the latter saved valuable time.     

Laronidase (Aldurazyme®): enzyme replacement therapy for mucopolysaccharidosis type I

Background: Laronidase (Aldurazyme^®) is a recombinant formulation of α-L-iduronidase, the enzyme deficient in mucopolysaccharidosis type I (MPS-I); a disorder associated with skeletal dysplasia, restricted joint movement, short stature, obstructive pulmonary disease, cardiac valvular problems and cognitive impairment (in the severe and intermediate variants). Objective: To describe MPS-I and review data on the safety and efficacy of laronidase. Results: Laronidase is safe and effective in stabilizing or improving pulmonary function and physical endurance. As intravenously administered enzyme is unable to correct CNS disease, hematopoietic stem cell transplantation remains the primary treatment for Hurler's syndrome despite the morbidity and mortality risks. Conclusions: Palliative care remains part of the treatment. Long-term studies are required to ascertain the effect of enzyme therapy on survival and its effectiveness in modifying the disease course and reducing morbidity. Intrathecal administration is under investigation for patients with signs of cord compression secondary to glycosaminoglycan accumulation within the dura matter. The cost of therapy remains a concern.     

Preventing airborne infection with an intranasal cellulose powder formulation (Nasaleze Travel®)

A total of 52 volunteers were recruited to take part in a dual-centered, randomized, blinded study so investigators could determine whether the level of airborne infection could be significantly reduced in patients randomly assigned to treatment with either Nasaleze cellulose extract alone or a combination of Nasaleze cellulose and powdered garlic extract (PGE). One puff into each nostril was recommended, and volunteers who developed an infection while traveling were told to use at least 3 puffs per nostril until symptoms were reduced. This study took place over an 8-wk period across Finland and the United Kingdom between November 2006 and March 2007. Volunteers were instructed to use a 5-point scale to assess their health and to record infectious episodes and symptoms in a daily diary. The activetreatment group (Nasaleze cellulose with PGE) experienced significantly fewer infections than the control group (20 vs 57; P<.001) and far fewer days on which an infection was obviously present (126 d in the active group vs 240 d in the control group; P<.05). Consequently, volunteers in the active group were less likely to pick up an airborne infection when PGE was added to this novel cellulose extract. Volunteers in the control group were much more likely to report more than 1 infectious episode over the treatment period or to endure longer periods of infection. The investigators concluded that the combination Nasaleze Travel formulation significantly reduced the number of airborne infections to which volunteers were exposed while traveling.     

Prophylactic botulinum type A toxin complex (Dysport®) for migraine without aura

(Headache 2011;51:52‐63) Objective.— To evaluate the efficacy, safety, and optimum dose of a highly purified Clostridium botulinum type A toxin‐hemagglutinin complex (Dysport) for migraine prophylaxis. Background.— Botulinum toxin type‐A has demonstrated good efficacy in several open‐label studies of patients with migraine, involving either individualized or standardized protocols, although data from placebo‐controlled trials have been conflicting. Methods.— A 12‐week, double‐blind, randomized trial of Dysport (120 or 240 units) vs placebo was conducted in 6 centers in Thailand to evaluate the efficacy, safety, and optimum dose of botulinum toxin type‐A (Dysport) for migraine prophylaxis. A total of 128 patients with migraine without aura were enrolled. The primary end point was the change in the mean number of migraine attacks per 4‐week period from the pre‐treatment period to 8‐12 weeks post injection. Secondary efficacy measures included the change in the mean total intensity score from the pre‐treatment period to 8‐12 weeks, the investigator and patient global assessments of change at each visit compared with pre‐treatment, and Migraine Disability Assessment and Short Form‐36 scores. Results.— Change in number of migraine attacks from pre‐treatment to weeks 8‐12 was not significantly different. There was a greater improvement in total intensity score at weeks 8‐12 with Dysport‐240 (not significant), and interim visit data showed that this was significant at weeks 0‐4 (P = .03 Dysport‐240 vs placebo). The mean duration of headache during weeks 0‐4 was lower with Dysport‐240 (P = .04 vs placebo). Improvements in patient and investigator global assessments of change between weeks 0‐4 and 8‐12 were significant for the Dysport‐240 group (both P < .05 vs placebo). Conclusions.— Limitations in study design and assessment tools employed may have contributed to the inconclusive nature of the primary end point data. Dysport‐240 showed significant benefit over placebo at some end points and further trials with more appropriate outcome measures are required to evaluate effectively this treatment.     

Usefulness of gray-scale contrast-enhanced ultrasonography (SonoVue®) in diagnosing hepatic alveolar echinococcosis

Hepatic alveolar echinococcosis (HAE) is a parasitic infection with an infiltrative growth pattern that has the appearance of a hepatic malignant tumor. Ultrasound (US) has been used for screening of HAE in epidemic areas. However, it has been very difficult to evaluate the clear boundary and microvessel perfusion of the lesions. The aim of this study was to demonstrate the characteristic imaging and clinical significance of HAE lesions by contrast-enhanced ultrasonography (CEUS). Seventeen patients with 19 HAE lesions were examined in sequence with US, color Doppler flow imaging (CDFI) and then CEUS before any treatment. All the data were compared before surgery. Examined by fundamental US, 47.4% of HAE lesions showed irregular hyperechoic substantive areas and 52.6% appeared as having a mixed echotype with irregular anechoic areas in the central portion of the lesions. The CDFI method indicated no blood flow signals inside any of the 19 lesions. By CEUS, all 19 lesions displayed circular rim enhancement in the peripheral segments and absent enhancement within the central areas of the lesions (a “black hole” effect). As a result, the lesions’ margins were clear, irregular and distinct. In general, the sizes of all the HAE lesions observed by CEUS were larger than those obtained by fundamental US. Therefore, CEUS is a simple imaging method and can be a helpful tool for more accurate sizing of HAE lesions and their surrounding invasion range and the proper cut-off margin when radical hepatectomy is needed.     

Acute Generalized Erythrodermic Pustular Psoriasis Associated with Bupropion/Naltrexone (Contrave®)

Background

We report a case of erythrodermic pustular psoriasis associated with initiation of bupropion/naltrexone (Contrave®; Orexigen Therapeutics, La Jolla, CA) in a patient with no history of psoriasis.

INGN 201 (Advexin®): adenoviral p53 gene therapy for cancer

Mutations in the p53 gene are the most frequent genetic alterations in human tumours, occurring in ～ 50% of all cancers. The p53 protein is pivotal in maintaining genetic integrity after DNA damage, and alterations in the p53 pathway, including mutations in the p53 gene, greatly increase the probability of tumour formation. Gene therapy using adenoviral p53 has emerged as a novel treatment option, with the potential to be safe and effective in a wide range of cancer types. INGN 201 (Ad5CMV-p53, Advexin^®), a replication-impaired adenoviral vector that carries the p53 gene, has been evaluated in both preclinical and clinical trials. Results show that Advexin is a well-tolerated and efficacious treatment for numerous cancers, both as monotherapy and in combination with radiation and/or chemotherapy agents. In addition, there is now data to support the use of Advexin in cancer immunotherapy.     

影响filgrastim动员正常供者CD34+细胞产率的因素

背景:为了保证为同种移植收集足够的CD34+细胞,一些供外周血祖细胞(PBPC)的正常供者需进行几天的单采。使用动员剂前以简单的临床或血液学参数为基础,能够识别供者对动员剂反应差的关系将会有实用价值。研究设计与方法:119名用粒细胞集落刺激因子(filgrastim)后的第4～6灭进行单采PBTC的供者,从单采的第一天开始,作者分析了他     

Moxifloxacin (Avelox®): a novel fluoroquinolone with a broad spectrum of activity

Moxifloxacin (Avelox^®) is a recently-developed fluoroquinolone that has a broad spectrum of antimicrobial activity, including typical respiratory pathogens, atypical and intracellular respiratory pathogens, Gram-negative pathogens and many anerobes. This spectrum of activity makes moxifloxacin particularly suitable for the therapy of community-acquired respiratory tract infections. It also has enhanced activity against specific bacteria, such as Mycobacteria spp. and Legionella. Moxifloxacin has pharmacologic characteristics that support once-daily dosing regimens and dual routes of excretion that require little or no adjustment for renal or hepatic insufficiency. The drug has maintained an excellent safety profile based upon broad global usage, and no adverse events have occurred that were unanticipated. Streptococcus pneumoniae, which are resistant to earlier fluoroquinolones, are less likely to be resistant to moxifloxacin.     

Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization?

BACKGROUND: In clinical trials in patients receiving myelosuppressive chemotherapy, 10-11 days of prophylaxis with filgrastim has been found to reduce the incidence of febrile neutropenia. In clinical practice, however, many patients receive shorter courses of therapy, even though the effectiveness of this regimen is unknown. OBJECTIVE: To examine the relationship between duration of filgrastim prophylaxis and risk of hospitalization in patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL), breast cancer, or lung cancer. METHODS: Using a large, automated, US healthcare claims database, we identified all adults who received chemotherapy for NHL, breast cancer, or lung cancer between 1998 and 2002. For these patients, we identified their first course of chemotherapy and each unique cycle within that course. We then focused attention on all patient cycles in which filgrastim was administered on or before cycle day 5 (filgrastim prophylaxis). Pooling all such cycles, we examined the relationship between duration of filgrastim prophylaxis and risk of hospitalization for neutropenia or infection and risk of hospitalization for any reason, using generalized estimating equations. RESULTS: Mean +/- SD duration of filgrastim prophylaxis was 6.5 +/- 3.1 days across 332 cycles for 133 NHL patients, 6.1 +/- 2.9 days across 482 cycles for 205 breast cancer patients, and 4.3 +/- 3.1 days across 522 cycles for 260 lung cancer patients. In multivariate analyses, risk of hospitalization for neutropenia or infection was found to decline with each additional day of filgrastim prophylaxis for patients with NHL (OR 0.81; p = 0.003), breast cancer (OR 0.77; p = 0.001), and lung cancer (OR 0.91; p = 0.084). Risk reductions with each additional day of prophylaxis ranged from 15% to 19% for patients with NHL, 17% to 23% for those with breast cancer, and 8% to 9% for those with lung cancer. Similar reductions in risk were noted for all-cause hospitalization. CONCLUSIONS: Among patients with NHL, breast cancer, or lung cancer, shorter courses of filgrastim prophylaxis may increase the risk of hospitalization.