Science.gov

Sample records for double anti-platelet therapy

  1. Future innovations in anti-platelet therapies

    PubMed Central

    Barrett, N E; Holbrook, L; Jones, S; Kaiser, W J; Moraes, L A; Rana, R; Sage, T; Stanley, R G; Tucker, K L; Wright, B; Gibbins, J M

    2008-01-01

    Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti-platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet-specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti-platelet agents. In this review, the mechanisms of platelet regulation and current anti-platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti-platelet drug development are discussed. PMID:18587441

  2. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  3. The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery.

    PubMed

    Alcock, Richard F; Naoum, Chris; Aliprandi-Costa, Bernadette; Hillis, Graham S; Brieger, David B

    2013-07-31

    Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised. The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed. We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk. Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management. Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Duration of dual anti-platelet therapy - State of the art after the DAPT and PEGASUS-TIMI 54 trials.

    PubMed

    Pirlet, Charles; Legrand, Victor; Nyssen, Astrid; Pierard, Luc; Gach, Olivier

    2017-06-01

    Dual anti-platelet therapy is prescribed in the setting of coronary heart disease for the prevention of stent thrombosis and acute thrombotic events. The optimal duration of dual anti-platelet therapy is still under debate as numerous trials have shown non-inferiority of a strategy of early cessation of one of the agents as compared to the standard practice whereas two larger trials have demonstrated benefit of prolonging dual anti-platelet therapy.

  5. Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics.

    PubMed

    Kumar, A Jaya; Kumari, M Meena; Arora, Nupur; Haritha, A

    2009-09-01

    The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision.

  6. Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics

    PubMed Central

    Kumar, A. Jaya; Kumari, M. Meena; Arora, Nupur; Haritha, A.

    2009-01-01

    The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision. PMID:20379408

  7. Pharmacogenomics of Anti-platelet Therapy: How much evidence is enough for clinical implementation?

    PubMed Central

    Perry, Christina G.; Shuldiner, Alan R.

    2013-01-01

    Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Those who carry loss-of-function variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamics, and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will the astute clinician be able to use pharmacogenetic information in conjunction with the history, physical exam, and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient. PMID:23697979

  8. Anti-platelet therapy is efficacious in treating endometriosis induced in mouse.

    PubMed

    Guo, Sun-Wei; Ding, Ding; Liu, Xishi

    2016-10-01

    In light of recent findings showing that platelets play important roles in the development of endometriosis in general and in fibrogenesis in particular, this study investigated the efficacy of Ozagrel, a TXA2 synthase inhibitor, in a murine model of endometriosis. In addition, another mouse experiment was conducted to evaluate the effect of timing of platelet depletion and of sequential depletion of platelets and macrophages on the development of endometriosis. It was found that both the Ozagrel treatment and different platelet depletion schemes resulted in significant reduction in lesion growth (all P-values <0.01) along with improved hyperalgesia in mice with induced endometriosis. They also significantly reduced the expression of markers of proliferation, angiogenesis, inflammation and fibrosis as well as decreased macrophage infiltration in endometriotic lesions (all P-values <0.05). Compared with untreated mice, pre-emptive depletion of platelets as well as platelet depletion after induction resulted in significant reduction in lesion weight (both P-values <0.001), while sequential depletion of platelets and macrophages yielded similar reduction. These results, in conjunction with other roles that platelets play in the development of endometriosis, strongly argue for the potential of anti-platelet therapy in treating endometriosis. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  9. Anti-platelets in diabetes management.

    PubMed

    Grantham, N M; Magliano, D J; Tai, G; Cohen, N; Shaw, J E

    2010-06-01

    This study aimed to determine the prevalence of anti-platelet use, and the extent to which contraindications to anti-platelet therapy prevent its use, in 726 diabetic patients attending a private clinic. Among those who reported a history of cardiovascular disease (CVD), 87.1% were on anti-platelet therapy. Of those without prior CVD but with at least one CVD risk factor, 59.8% were not on anti-platelet therapy, but only 7.1% of these had a contraindication to anti-platelet therapy. This study showed that high usage of anti-platelet therapy in diabetic patients with prior CVD is achievable, and that contraindications did not explain low use in those without prior CVD.

  10. Bleeding Risk Following Percutaneous Coronary Intervention in Patients with Diabetes Prescribed Dual Anti-platelet Therapy

    PubMed Central

    Grodzinsky, Anna; Arnold, Suzanne V.; Wang, Tracy Y.; Sharma, Praneet; Gosch, Kensey; Jones, Philip G.; Bhatt, Deepak L.; Steg, Philippe Gabriel; McGuire, Darren K.; Cohen, David J.; Spertus, John A.; Chhatriwalla, Adnan K.; Lind, Marcus; Graham, Garth; Kosiborod, Mikhail

    2017-01-01

    Background Patients with diabetes (DM) experience higher rates of in-stent restenosis and greater benefit from DES implant at the time of PCI, necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM receiving long-term DAPT is unknown. Methods Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. Results Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI (DM vs no DM: BARC =1: 78.0% vs 87.7%, p<0.001; BARC ≥ 2: 4.3% vs 5.3%, p=0.33). Following adjustment, patients with (vs. without DM) had a lower risk of BARC ≥1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83–0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. Conclusions In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from DES, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered. PMID:27914490

  11. Recurrent stent thrombosis in a patient with antiphospholipid syndrome and dual anti-platelet therapy non-responsiveness.

    PubMed

    Lee, You-Hong; Yang, Hyoung-Mo; Tahk, Seung-Jea; Hong, You-Sun; Park, Jin-Sun; Seo, Kyoung-Woo; Choi, Yong-Woo; Noh, Choong-Kyun

    2015-01-01

    Antiphospholipid syndrome (APS), the most common acquired hypercoagulable condition, is diagnosed by persistent presence of antiphospholipid antibodies and episodes of vascular thrombosis. It may be an important predisposing factor for stent thrombosis, resulting in poor outcomes. Also, anti-platelet therapy non-responsiveness is associated with stent thrombosis. We report a case of a 39-year-old man who after undergoing successful percutaneous coronary intervention for significant coronary artery disease suffered repeated stent thrombosis events leading to ST-segment elevation myocardial infarction. Eventually, he underwent coronary artery bypass surgery because of uncontrolled thrombosis and was diagnosed as having APS and dual antiplatelet therapy non-responsiveness.

  12. Assessment of the risk of haemorrhage and its control following minor oral surgical procedures in patients on anti-platelet therapy: a prospective study.

    PubMed

    Girotra, C; Padhye, M; Mandlik, G; Dabir, A; Gite, M; Dhonnar, R; Pandhi, V; Vandekar, M

    2014-01-01

    Controversy exists concerning the suspension or maintenance of anti-platelet drugs before elective surgical procedures. We assessed the association of the risk of prolonged postoperative bleeding with anti-platelet therapy by type of minor surgical procedure and the association between anti-platelet therapy and the level of hemostatic measures required. Five hundred and forty-six patients were included in the study group: those on aspirin (n = 310), clopidogrel (n = 97), and aspirin + clopidogrel dual therapy (n = 139); the control group comprised 575 healthy individuals. Cramer's V test was significant (P < 0.05) but showed a weak association between anti-platelet therapy and prolonged immediate postoperative bleeding. Compared to controls, the odds ratio revealed that the risk of prolonged bleeding in the immediate postoperative period was significantly higher with dual therapy, followed by clopidogrel and aspirin. Prolonged bleeding occurred in 22 patients in the study group and 20 in the control group, and was successfully controlled with local hemostatic measures. Fisher's exact test showed a significant association between dual therapy and higher levels of hemostatic measures (P = 0.004; P = 0.035). Prolonged bleeding in patients on anti-platelet therapy was independent of the type of minor surgical procedure. The greatest risk of prolonged bleeding was found in patients on dual therapy; this required higher levels of hemostatic measures. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Diffuse Alveolar Hemorrhage Associated With Low Molecular Weight Heparin and Dual Anti-platelet Therapy After Percutaneous Coronary Intervention.

    PubMed

    Yildirim, Fatma; Kara, İskender; Okuyan, Hızır; Abaci, Adnan; Turkoglu, Melda; Aygencel, Gülbin

    2016-01-19

    A 54-year-old man had undergone to percutaneous coronary intervention (PCI) and two stents were placed to left anterior coronary artery and circumflex artery. Low molecular weight heparin (LMWH) together with ticagrelor 90 mg twice a day and acetylsalicylic acid (Aspirin) were started after PCI due to high risk of stent trombosis. On the fourth day of patient's follow-up in the intensive care unit (ICU), bloody secretion was started from endotracheal tube. Hemoglobin dropping, bilateral infiltration on the chest X-ray and bleeding from lung were diagnosed as diffuse alveolar hemorrhage (DAH). Apart from LMWH and antiplatelet therapies with aspirin and ticagrelor, there were no other identified risk factors for DAH. As far as we know, our report is the first case of DAH caused by LMWH and dual anti-platelet therapy including ticagrelor. This article is protected by copyright. All rights reserved.

  14. Management of type-2 diabetes with anti-platelet therapies: special reference to aspirin.

    PubMed

    Rao, Gundu H R

    2011-01-01

    Adult onset diabetes currently affects 380 million individuals worldwide and is expected to affect 380 million by 2025. Major defects contributing to this complex disease are insulin resistance and beta cell dysfunction. More than 80% of patients professing to type-2 diabetes are insulin resistant. Recent studies have shown that the Indian subcontinent ranks very high in the occurrence of Diabetes and Coronary artery disease (1, 2, 3). Patients with Type 2 diabetes carry an equivalent cardiovascular risk to that of a non-diabetic individual who has already experienced a coronary event. The risk of coronary artery disease in any given population seems to be 2-3 times higher in diabetics than non-diabetics. Inflammation, platelet activation, endothelial dysfunction and coagulation are the four processes, whose interplay determines the development of cardiovascular disease. In this article, we provide a brief overview on platelet physiology, vascular dysfunction, platelet hyper-function, and the role of platelet related clinical complications in diabetes mellitus and what is know about the management of this complex disease with anti-platelet drugs such as aspirin and Clopidogrel.

  15. Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (from the Patterns of Non-adherence to Anti-platelet Regimens In Stented Patients Registry).

    PubMed

    Schoos, Mikkel; Chandrasekhar, Jaya; Baber, Usman; Bhasin, Aarti; Sartori, Samantha; Aquino, Melissa; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Kini, Annapoorna; Kruckoff, Mitchell; Moliterno, David; Henry, Timothy D; Weisz, Giora; Gibson, C Michael; Iakovou, Ioannis; Colombo, Antonio; Steg, P Gabriel; Witzenbichler, Bernhard; Chieffo, Alaide; Cohen, David; Stuckey, Thomas; Ariti, Cono; Dangas, George; Pocock, Stuart; Mehran, Roxana

    2017-09-15

    Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation for <14 days. Of the study cohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology.

    PubMed

    Barillà, Francesco; Pelliccia, Francesco; Borzi, Mauro; Camici, Paolo; Cas, Livio Dei; Di Biase, Matteo; Indolfi, Ciro; Mercuro, Giuseppe; Montemurro, Vincenzo; Padeletti, Luigi; Filardi, Pasquale Perrone; Vizza, Carmine D; Romeo, Francesco

    2017-01-01

    Definition of the optimal duration of dual anti-platelet therapy (DAPT) is an important clinical issue, given the large number of patients having percutaneous coronary intervention (PCI), the costs and risks of pharmacologic therapy, the consequences of stent thrombosis, and the potential benefits of DAPT in preventing ischaemic outcomes beyond stent thrombosis. Nowadays, the rationale for a prolonged duration of DAPT should be not only the prevention of stent thrombosis, but also the prevention of ischaemic events unrelated to the coronary stenosis treated with index PCI. A higher predisposition to athero-thrombosis may persist for years after an acute myocardial infarction, and even stable patients with a history of prior myocardial infarction are at high risk for major adverse cardiovascular events. Recently, results of pre-specified post-hoc analyses of randomized clinical trials, including the PEGASUS-TIMI 54 trial, have shed light on strategies of DAPT in various clinical situations, and should impact the next rounds of international guidelines, and also routine practice. Accordingly, the 2015 to 2016 the Board of the Italian Society of Cardiology addressed newer recommendations on duration of DAPT based on most recent scientific information. The document states that physicians should decide duration of DAPT on an individual basis, taking into account ischaemic and bleeding risks of any given patient. Indeed, current controversy surrounding optimal duration of DAPT clearly reflects the fact that, nowadays, a one size fits all strategy cannot be reliably applied to patients treated with PCI. Indeed, patients usually have factors for both increased ischaemic and bleeding risks that must be carefully evaluated to assess the benefit/risk ratio of prolonged DAPT. Personalized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk/benefit to the patient according to changes in his/her clinical profile. Also, in order to

  17. Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

    PubMed Central

    Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian

    2017-01-01

    Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

  18. Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis.

    PubMed

    Massel, D; Little, S H

    2001-02-01

    The objective of this study was to compare the effectiveness and safety of adding dipyridamole or aspirin to warfarin among patients with prosthetic heart valves using meta-analytic techniques. Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimize this risk. An important issue is the effectiveness and safety of the latter strategy. A combined MEDLINE and manual search was made for relevant articles from 1966 to November 1999. Standard meta-analysis techniques were used. Ten studies involving 2,199 subjects met the inclusion criteria. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio [OR]: 0.41, p < 0.001) and total mortality (OR: 0.49, p < 0.001). The risk of major bleeding was increased when antiplatelet agents were added (OR: 1.50, p = 0.033). For major bleeding, the comparison of trials performed before and after 1990 (OR: 2.23 and 0.88, respectively) showed that the chi-square test for heterogeneity was significant (p = 0.025). The latter trials used low-dose aspirin, suggesting that the risk of bleeding may be lower with contemporary low-dose (100 mg daily) aspirin. Adding antiplatelet therapy, especially low-dose aspirin, to warfarin decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is slightly increased with antiplatelet therapy. Nonetheless, the risk of bleeding appears to have diminished with the lower doses of aspirin used in the more recent trials, resulting in a favorable risk-to-benefit profile.

  19. Anti-platelet antibodies in a natural animal model of sulphonamide-associated thrombocytopaenia.

    PubMed

    Lavergne, Sidonie N; Trepanier, Lauren A

    2007-12-01

    Delayed hypersensitivity (HS) reactions to sulphonamide antimicrobials occur in both humans and dogs with a similar clinical presentation, and may include thrombocytopaenia. Drug-dependent anti-platelet antibodies have been identified in humans with sulphonamide-associated thrombocytopaenia. Our purpose was to determine whether similar antibodies were present in dogs with sulphonamide-associated thrombocytopaenia. Flow cytometry was used to detect anti-platelet antibodies in sera from 32 dogs with sulphonamide HS, eight dogs that tolerated sulphonamide therapy without adverse reactions and nine healthy control dogs were used as controls. Anti-platelet antibodies were found more frequently, with significantly stronger fluorescence signals, in HS dogs (75%) compared to 'tolerant' dogs (38%), and in HS dogs with thrombocytopaenia (90%) compared to HS dogs with normal platelet counts (46%). Binding to platelets was enhanced in the presence of soluble sulphonamide in 42% of positive samples. Experiments with canine Glanzmann's platelets, and competition assays with fibrinogen fragments or anti-GP antibodies, did not support the hypothesis that these canine antibodies target the fibrinogen receptor. In conclusion, anti-platelet antibodies were identified in dogs with sulphonamide-associated thrombocytopaenia, which suggests a similar immunopathogenesis for this reaction in dogs as seen in humans. Further work in both species will determine whether these antibodies are pathogenic in vitro.

  20. Early Clinical Experience with a Polymer-Free Biolimus A9 Drug-Coated Stent in DES-Type Patients Who Are Poor Candidates for Prolonged Dual Anti-Platelet Therapy

    PubMed Central

    Kinnaird, Tim; Butt, Mehmood; Abdul, Fairoz; Yazji, Khaled; Hailan, Ahmed; Gallagher, Sean; Ossei-Gerning, Nicholas; Chase, Alexander; Choudhury, Anirban; Smith, David; Anderson, Richard

    2016-01-01

    Introduction Prolonged dual anti-platelet therapy (DAPT) may cause excess bleeding in certain patients. The biolimus-A9 drug-coated stent (BA9-DCS) has a rapid drug-elution profile allowing shortened DAPT. Data were gathered on the early experience implanting this stent in drug-eluting stent eligible patients deemed to be at high risk of bleeding. Background and Methods The demographics, procedural data and clinical outcomes were gathered prospectively for 249 patients treated with a BA9-DCS stent at 2 UK centres, and compared to a cohort of patients treated in the same period with drug-eluting stents (PCI-DES). Results Operator-defined BA9-DCS indications included warfarin therapy, age, and anaemia. Patients receiving a BA9-DCS were older (71.6±11.8 vs. 64.8±11.6yrs, p<0.001), more often female (38.2 vs. 26.8%, P<0.001), and more likely to have comorbidity including chronic kidney disease or poor LV function than PCI-DES patients. The baseline Mehran bleed risk score was also significantly higher in the BA9-DCS group (19.4±8.7 vs. 13.1±5.8, p<0.001). Of the BA9-DCS cohort, 95.5% of patients demonstrated disease fitting NICE criteria for DES placement. The number of lesions treated (1.81±1.1 vs. 1.58±0.92, p = 0.003), total lesion length (32.1±21.7 vs. 26.1±17.6mm, p<0.001), number of stents used (1.93±1.11 vs. 1.65±1.4, p = 0.007) and total stent length (37.5±20.8 vs. 32.4±20.3, p<0.01) were greater for BA9-DCS patients. DAPT was prescribed for 3.3±3.9 months for BA9-DCS patients and 11.3±2.4 months for PCI-DES patients (p<0.001). At follow up of 392±124 days despite the abbreviated DAPT course stent related event were infrequent with ischemia-driven restenosis PCI (2.8 vs. 3.4%, p = 0.838), and stent thrombosis (1.6 vs. 2.1%, p = 0.265) rates similar between the BA9-DCS ad PCI-DES groups. After propensity scoring all clinical end-points were similar between both cohorts. Conclusions This early experience using polymer-free BA9 drug-coated stents in

  1. IMPLEMENTATION OF PHARMACOGENETICS: THE UNIVERSITY OF MARYLAND PERSONALIZED ANTI-PLATELET PHARMACOGENETICS PROGRAM

    PubMed Central

    Shuldiner, Alan R.; Palmer, Kathleen; Pakyz, Ruth E.; Alestock, Tameka D.; Maloney, Kristin A.; O’Neill, Courtney; Bhatty, Shaun; Schub, Jamie; Overby, Casey Lynnette; Horenstein, Richard B.; Pollin, Toni I.; Kelemen, Mark D.; Beitelshees, Amber L.; Robinson, Shawn W.; Blitzer, Miriam G.; McArdle, Patrick F.; Brown, Lawrence; Jeng, Linda Jo Bone; Zhao, Richard Y.; Ambulos, Nicholas; Vesely, Mark R.

    2014-01-01

    Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within five hours along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine. PMID:24616408

  2. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    PubMed

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies.

  3. Anti-platelet effects of yuzu extract and its component.

    PubMed

    Yu, Hye Yon; Park, Se Won; Chung, Ill Min; Jung, Yi-Sook

    2011-12-01

    In this study, we investigated whether the methanolic extract of yuzu (yuzu ME) and its components hesperidin and naringin, have anti-platelet activities. Yuzu ME and hesperidin inhibited collagen-, arachidonic acid (AA)-, ADP- and thrombin-induced rat platelet aggregation in vitro and ex vivo. Naringin also inhibited platelet aggregation induced by collagen, AA, or thrombin, but not aggregation induced by ADP. The oral administration of yuzu ME or hesperidin prolonged mouse tail vein bleeding time in a dose-dependent manner in vivo. These results suggest that yuzu ME and hesperidin have anti-platelet activity, and that intake of yuzu, which includes various flavonoids such as hesperidin, may be beneficial for individuals at high risk of cardiovascular diseases.

  4. Implementation of pharmacogenetics: the University of Maryland Personalized Anti-platelet Pharmacogenetics Program.

    PubMed

    Shuldiner, Alan R; Palmer, Kathleen; Pakyz, Ruth E; Alestock, Tameka D; Maloney, Kristin A; O'Neill, Courtney; Bhatty, Shaun; Schub, Jamie; Overby, Casey Lynnette; Horenstein, Richard B; Pollin, Toni I; Kelemen, Mark D; Beitelshees, Amber L; Robinson, Shawn W; Blitzer, Miriam G; McArdle, Patrick F; Brown, Lawrence; Jeng, Linda Jo Bone; Zhao, Richard Y; Ambulos, Nicholas; Vesely, Mark R

    2014-03-01

    Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients' are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within 5 hr along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine. © 2014 Wiley Periodicals, Inc.

  5. An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study.

    PubMed

    Holmes, Chris E; Ramos-Nino, Maria E; Littenberg, Benjamin

    2010-06-15

    Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System. Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; P = .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; P = .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy. Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal.

  6. An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study

    PubMed Central

    2010-01-01

    Background Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. Methods We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System. Results Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; P = .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; P = .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy. Conclusions Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal. PMID:20546622

  7. [Recurrent idiopathic cerebral infarction in a 5-year-old boy, with emphasis on the importance of platelet aggregation analysis for appropriate selection of anti-platelet drugs].

    PubMed

    Sugiyama, Nobuyoshi; Matsuda, Shin-ichi; Shimizu, Mie; Obara, Saori; Ikegami, Mariko; Yokoyama, Jyun-ichi; Miyashita, Yoshihiro; Takizawa, Shyunya; Takagi, Shigeharu

    2009-01-01

    We present a 5-year-old boy with recurrent idiopathic cerebral infarction in which analysis of platelet hyperaggregability was useful in choosing appropriate anti-platelet drugs. The patient presented with gait disturbance at the age of 5 years and 1 month. Brain MRI demonstrated multiple infarctions in the right thalamus and left cerebellum. There were no apparent underlying diseases including hematological, cardiac and vascular abnormalities. He was diagnosed as idiopathic cerebral infarction. First, we administered ticlopidine and he remained stable with persistent mild intention tremor in the left upper extremity for 4 months. Then he developed the second stroke at the age of 5 years and 5 months, and multiple infarctions in the right celebellum and cerebellar vermis were demonstrated. On platelet aggregation analysis, adenosine diphosphate (ADP)-induced aggregation was inhibited, probably due to ticlopidine administration. Collagen- and epinephrine-induced platelet aggregation showed hyperaggregation, so we started to administer cilostazol, which inhibits only epinephrine-induced hyperaggregation. We also added aspirin, which inhibits collagen-induced hyperaggregation. The combination of anti-platelet drugs inhibited epinephrine-, collagen- and ADP-induced hyperaggregation in this patient. He has been stable on the triple combination of anti-platelet drugs without further episodes of cerebral infarction or transient ischemic attack for 4 years to date. Appropriate selection of anti-platelet therapy was achieved by the simple and repeatable platelet aggregation analyses, which must be considered even in pediatric patients with cerebral infarction.

  8. Molecular spectroscopic and thermodynamic studies on the interaction of anti-platelet drug ticlopidine with calf thymus DNA.

    PubMed

    Afrin, Shumaila; Rahman, Yusra; Sarwar, Tarique; Husain, Mohammed Amir; Ali, Abad; Shamsuzzaman; Tabish, Mohammad

    2017-11-05

    Ticlopidine is an anti-platelet drug which belongs to the thienopyridine structural family and exerts its effect by functioning as an ADP receptor inhibitor. Ticlopidine inhibits the expression of TarO gene in S. aureus and may provide protection against MRSA. Groove binding agents are known to disrupt the transcription factor DNA complex and consequently inhibit gene expression. Understanding the mechanism of interaction of ticlopidine with DNA can prove useful in the development of a rational drug designing system. At present, there is no such study on the interaction of anti-platelet drugs with nucleic acids. A series of biophysical experiments were performed to ascertain the binding mode between ticlopidine and calf thymus DNA. UV-visible and fluorescence spectroscopic experiments confirmed the formation of a complex between ticlopidine and calf thymus DNA. Moreover, the values of binding constant were found to be in the range of 10(3)M(-1), which is indicative of groove binding between ticlopidine and calf thymus DNA. These results were further confirmed by studying the effect of denaturation on double stranded DNA, iodide quenching, viscometric studies, thermal melting profile as well as CD spectral analysis. The thermodynamic profile of the interaction was also determined using isothermal titration calorimetric studies. The reaction was found to be endothermic and the parameters obtained were found to be consistent with those of known groove binders. In silico molecular docking studies further corroborated well with the experimental results. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Anti-platelet aggregation activities of different fractions in leaves of Apocynum venetum L.

    PubMed

    Kasimu, Rena; Fan, Zhenzhen; Wang, Xinling; Hu, Junping; Wang, Peng; Wang, Jinhui

    2015-06-20

    Ethnopharmacological relevance Apocynum venetum: is widely used in Uygur and traditional Chinese medicine. Modern pharmaceutical studies have shown that leaves of A. venetum have effects of liver protection, antidepressant and regulation of blood pressure. However, it is unclear that which components have pharmacological activities. The aim was to study chemical constituents of A. venetum and its anti-platelet aggregation activity. Nephelometery was applied to evaluate anti-platelet aggregation activity of multi-components of A. venetum. Systematic separation components were characterized by HPLC analysis method, and in vitro screening active components by anti-platelet aggregation study. Ethyl acetate fraction (L-III) and L-III-4 have better anti-platelet aggregation activity than other fractions. The results indicated that isoquercitrin, hyperoside and other flavonoids have anti-platelet aggregation activity in A. venetum. Our studies provide basis on the endeavors of screening chemicals with that anti-platelet aggregation activity in leaves of A. venetum. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs

    PubMed Central

    Wright, Bernice; Spencer, Jeremy P.E.; Lovegrove, Julie A.; Gibbins, Jonathan M.

    2013-01-01

    Flavonoids are low-molecular weight, aromatic compounds derived from fruits, vegetables, and other plant components. The consumption of these phytochemicals has been reported to be associated with reduced cardiovascular disease (CVD) risk, attributed to their anti-inflammatory, anti-proliferative, and anti-thrombotic actions. Flavonoids exert these effects by a number of mechanisms which include attenuation of kinase activity mediated at the cell-receptor level and/or within cells, and are characterized as broad-spectrum kinase inhibitors. Therefore, flavonoid therapy for CVD is potentially complex; the use of these compounds as molecular templates for the design of selective and potent small-molecule inhibitors may be a simpler approach to treat this condition. Flavonoids as templates for drug design are, however, poorly exploited despite the development of analogues based on the flavonol, isoflavonone, and isoflavanone subgroups. Further exploitation of this family of compounds is warranted due to a structural diversity that presents great scope for creating novel kinase inhibitors. The use of computational methodologies to define the flavonoid pharmacophore together with biological investigations of their effects on kinase activity, in appropriate cellular systems, is the current approach to characterize key structural features that will inform drug design. This focussed review highlights the potential of flavonoids to guide the design of clinically safer, more selective, and potent small-molecule inhibitors of cell signalling, applicable to anti-platelet therapy. PMID:23024269

  11. Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs.

    PubMed

    Wright, Bernice; Spencer, Jeremy P E; Lovegrove, Julie A; Gibbins, Jonathan M

    2013-01-01

    Flavonoids are low-molecular weight, aromatic compounds derived from fruits, vegetables, and other plant components. The consumption of these phytochemicals has been reported to be associated with reduced cardiovascular disease (CVD) risk, attributed to their anti-inflammatory, anti-proliferative, and anti-thrombotic actions. Flavonoids exert these effects by a number of mechanisms which include attenuation of kinase activity mediated at the cell-receptor level and/or within cells, and are characterized as broad-spectrum kinase inhibitors. Therefore, flavonoid therapy for CVD is potentially complex; the use of these compounds as molecular templates for the design of selective and potent small-molecule inhibitors may be a simpler approach to treat this condition. Flavonoids as templates for drug design are, however, poorly exploited despite the development of analogues based on the flavonol, isoflavonone, and isoflavanone subgroups. Further exploitation of this family of compounds is warranted due to a structural diversity that presents great scope for creating novel kinase inhibitors. The use of computational methodologies to define the flavonoid pharmacophore together with biological investigations of their effects on kinase activity, in appropriate cellular systems, is the current approach to characterize key structural features that will inform drug design. This focussed review highlights the potential of flavonoids to guide the design of clinically safer, more selective, and potent small-molecule inhibitors of cell signalling, applicable to anti-platelet therapy.

  12. Synthesis and Anti-Platelet Activity of Thiosulfonate Derivatives Containing a Quinone Moiety

    PubMed Central

    Bolibrukh, Khrystyna; Polovkovych, Svyatoslav; Khoumeri, Omar; Halenova, Tetyana; Nikolaeva, Irina; Savchuk, Olexiy; Terme, Thierry; Vanelle, Patrice; Lubenets, Vira; Novikov, Volodymyr

    2015-01-01

    Thiosulfonate derivatives based on quinones were synthesized for studying “structure-activity relationship” compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed. PMID:26839819

  13. Anti-platelet aggregation triterpene saponins from the galls of Sapindus mukorossi.

    PubMed

    Huang, Hui-Chi; Tsai, Wei-Jern; Liaw, Chia-Ching; Wu, Shih-Hsiung; Wu, Yang-Chang; Kuo, Yao-Haur

    2007-09-01

    Bioassay-directed fractionation of an ethanolic extract of the galls of Sapindus mukorossi has resulted in the isolation of two new tirucallane-type triterpenoid saponins, sapinmusaponins Q (1) and R (2), along with three known oleanane-type triterpenoid saponins (3-5). Their structures were elucidated on the basis of spectroscopic analysis and chemical hydrolysis. Biological evaluation showed that both sapinmusaponins Q and R demonstrated more potent anti-platelet aggregation activity than aspirin.

  14. Clinical outcomes, health resource use, and cost in patients with early versus late dual or triple anti-platelet treatment for acute coronary syndrome.

    PubMed

    Friedman, Howard; Mollon, Patrick; Lian, Jean; Navaratnam, Prakash

    2013-08-01

    Acute coronary syndrome (ACS) guidelines recommend early dual anti-platelet therapy (thienopyridines + acetylsalicylic acid [aspirin]). However, triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors [GRIs]) has shown benefit in clinical trials. This study assessed real-world ACS treatment patterns and outcomes in the acute care setting. A retrospective analysis of patients admitted to hospital with ACS (index event) from January 2007 to December 2009 was conducted (Thomson's MarketScan Hospital Drug Database). Eligible patients were ≥18 years of age, of either sex, and had primary admission and discharge diagnoses of ACS. Cohorts were defined by anti-platelet treatment and then by the timing of treatment initiation (early initiation: within ≤2 days of admission; late initiation: ≥2 days post-admission). Patient characteristics, clinical outcomes, resource utilization, and costs were assessed using descriptive statistics. A total of 249,907 eligible patients were placed into four treatment cohorts (aspirin assumed for all patients): aspirin only; clopidogrel only (dual therapy); GRI only (dual therapy); and clopidogrel + GRI (triple therapy). Patients in the 'clopidogrel-only' cohort were more likely to be older, female, and have more co-morbidities than those in other cohorts; stroke (6.2 %) and re-hospitalization (15.4 %) rates were higher than in the 'GRI-only' and 'triple therapy' cohorts. The GRI-only cohort had higher major bleeding rates (3.3 %), mortality (7.6 %), and costs ($US21,975 [year 2010 values]) than the clopidogrel-only and triple-therapy cohorts. Late initiation cohorts were more likely to be older, female, and have more co-morbidities than early initiation cohorts. Major bleeding was more likely with GRI-only patients (regardless of initiation timing) than with other cohorts. Late-treated clopidogrel-only patients had higher rates of stroke (6.9 %), ACS-related re-admissions (6.1 %), and all

  15. Pharmacological studies on the antispasmodic, bronchodilator and anti-platelet activities of Abies webbiana.

    PubMed

    Yasin, Mamoona; Hussain Janbaz, Khalid; Imran, Imran; Gilani, Anwar-ul-Hassan; Bashir, Samra

    2014-08-01

    This study evaluated the antispasmodic, bronchodilator and anti-platelet activities of Abies webbiana to rationalize some of its folk uses in gut and airways disorders and inflammation. The crude extract of A. webbiana (Aw.Cr) caused a complete relaxation of both spontaneous and K(+) (80 mM)-induced contractions in isolated rabbit jejunum in a concentration-dependent manner. Aw.Cr shifted the Ca(++) concentration-response curves (CRCs) to the right, in a fashion similar to verapamil, confirming its Ca(++) channel blocking (CCB) effect. In isolated rabbit tracheal preparations, it caused relaxation of carbachol (1 μM) and K(+) (80 mM)-induced contractions comparable to verapamil suggesting that the bronchodilatory effect may possibly be mediated through CCB activity. Aw.Cr was found to be the inhibitor of both ADP- and epinephrine-induced aggregation of human platelets thereby suggesting therapeutic potential in this plant against thrombo-embolic conditions. The exhibited anti-platelet effect was observed at low doses against epinephrine as compared to ADP. This study confirmed the presence of spasmolytic activity in Abies webbiana through possible blockade of Ca(++) channels providing evidence for its folkloric use in gut and respiratory disorders in addition to anti-platelet activity. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Engineering and characterization of a chimeric anti-platelet glycoprotein Ibalpha monoclonal antibody and preparation of its Fab fragment.

    PubMed

    Yang, Jianfeng; Ji, Shundong; Dong, Ningzheng; Zhao, Yiming; Ruan, Changgeng

    2010-04-01

    Glycoprotein Ibalpha (GPIbalpha) is a platelet-specific membrane protein. It mediates platelet adhesion to collagen exposed at the vascular injury site by binding to von Willebrand factor (VWF) in plasma. This process is crucial for arterial thrombus formation. Blocking interaction between GPIbalpha and VWF may prevent platelet adhesion and thrombus formation. We previously generated a high affinity monoclonal antibody against human platelet GPIbalpha, SZ2, which inhibits both ristocetin- and botrocetin-induced platelet aggregation in vitro. To convert SZ2 into mouse/human chimeric antibody for anti-platelet therapy in humans, in this study, we constructed a mouse/human chimeric antibody derived from the hybridoma cells producing murine antibody against platelet glycoprotein Ibalpha, conducted its expression in dihydrofolate reductase-deficient Chinese hamster ovary (CHO) cells, and prepared its chimeric Fab fragment. Results from ELISA and Western blot analysis showed that the chimeric antibody was secreted from the cells and that the heavy and light chains were assembled correctly. Flow cytometry analysis confirmed specific binding of the chimeric antibody to the GPIb-expressing CHO cells. In vitro functional studies revealed that the chimeric antibody and its Fab fragment prevented platelet adhesion to VWF under high shear stress and inhibited ristocetin-induced platelet aggregation in a dose-dependent manner. These results demonstrated that the chimeric antibody was successfully engineered and suggested that the Fab fragment of chimeric antibody against GPIbalpha is a promising therapeutic antibody more suitable for prevention and treatment of human arterial thrombosis.

  17. [Anti-platelet aggregation bioassay based quality control for XST capsules].

    PubMed

    Han, Bing; Mao, Xin; Han, Shu-xian; Chen, Ying; Xiang, Yan-hua; Ge, Yi-meng; Liao, Fu-long; You, Yun

    2015-12-01

    A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules.

  18. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

    PubMed

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-08-24

    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo(L-Pro-L-Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Evaluation of Anti-Platelet Aggregation Effect of Some Allium Species

    PubMed Central

    Lorigooini, Zahra; Ayatollahi, Seyed Abdolmajid; Amidi, Salimeh; Kobarfard, Farzad

    2015-01-01

    Epidemiologic studies show that the cardiovascular diseases are associated with multiple factors such as raised serum total cholesterol, increased LDL, increased platelet aggregation, hypertension and smoking. In-vitro studies have confirmed the ability of some plants of Allium species to reduce these parameters. Therefore, we evaluated anti-platelet aggregation effect of some Allium species (Allium ampeloprasum, A. hirtifolium, A. haemanthoides, A. vavillovi, A. atroviolaceum, A. jesdianum, A. shelkovnikovii) using arachidonic acid (AA) and adenosine diphosphate (ADP) as platelet aggregation inducers. The screening results for methanolic extract of Allium species showed that the maximum effect of anti-platelet aggregation was related to A. atroviolaceum. This extract inhibited the in-vitro platelet aggregation induced by AA and ADP with IC50 values of 0.4881 (0.4826-0.4937) mg/ml and 0.4945 (0.4137-0.5911) mg/ml respectively. These results support the hypothesis that the dietary intake of Allium could be beneficial for prevention of cardiovascular diseases. PMID:26664390

  20. Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies.

    PubMed

    de Roos, Baukje; Zhang, Xuguang; Rodriguez Gutierrez, Guillermo; Wood, Sharon; Rucklidge, Garry J; Reid, Martin D; Duncan, Gary J; Cantlay, Louise L; Duthie, Garry G; O'Kennedy, Niamh

    2011-10-01

    Platelets play a key role in haemostasis and wound healing, contributing to formation of vascular plugs. They are also involved in formation of atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are associated with a lower risk of cardiovascular disease. Components in these diets may have anti-platelet functions contributing to their health benefits. We studied the effects of alperujo extract, an olive oil production waste product containing the majority of polyphenols found in olive fruits, through measurement of effects on platelet aggregation and activation in isolated human platelets, and through identification of changes in the platelet proteome. Alperujo extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p = 0.02) induced platelet activation as measured by the flow cytometry using the antibody for p-selectin (CD62p), but it did not affect the conformation of the fibrinogen receptor as measured by flow cytometry using the antibodies for anti-fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen- and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible for this effect. Proteomic analysis identified nine proteins that were differentially regulated by the alperujo extract upon ADP-induced platelet aggregation. These proteins represent important mechanisms that may underlie the anti-platelet effects of this extract: regulation of platelet structure and aggregation, coagulation and apoptosis, and signalling by integrin αIIb/β3. Alperujo extract may protect against platelet activation, platelet adhesion and possibly have anti-inflammatory properties.

  1. Vasorelaxant and anti-platelet aggregation effects of aqueous Ocimum basilicum extract.

    PubMed

    Amrani, Souliman; Harnafi, Hicham; Gadi, Dounia; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Aziz, Mohammed; Martin-Nizard, Françoise; Bosca, Lisardo

    2009-08-17

    In this work the endothelium-dependant vasorelaxant and anti-platelet aggregation activities of an aqueous extract from Ocimum basilicum were studied. The vasorelaxant effect was undertaken in thoracic aorta from three experimental groups of rats: one of them (NCG) fed with standard diet, the second (HCG) with hypercholesterolemic diet (HCD) and the third (BTG) with hypercholesterolemic diet together with an intragastric administration of Ocimum basilicum extract at a dose of 0.5 g/kg body weight for a period of 10 weeks. The in vitro anti-platelet aggregation of Ocimum basilicum extract was studied using thrombin (0.5 U/ml) and ADP (5 microM) as agonists. The results show that the HCD statistically decreases vascular relaxation in HCG compared to NCG (p<0.001) and increases the vascular responses to phenylephrine (p<0.02). Ocimum basilicum extract exerts a significant vasorelaxant effect at 10(-5) M (p<0.01) and 10(-4) M carbachol (p=0.001). The plant extract also tends to suppress the elevated contractions induced by HCD (p=0.05). The extract inhibits ADP-induced platelet aggregation by 13%, 28.2%, 30.5%, 44.7% and 53% at a dose of 1, 2, 3, 4 and 5 g/l, respectively. Thrombin-induced platelet activation was also reduced by 15%, 23%, 40%, 38.4%, and 42% at the same doses of extract described above. The use of Ocimum basilicum as medicinal plant could be beneficial for cardiovascular system.

  2. Comparison of cytotoxic and anti-platelet activities of polyphenolic extracts from Arnica montana flowers and Juglans regia husks.

    PubMed

    Rywaniak, Joanna; Luzak, Boguslawa; Podsedek, Anna; Dudzinska, Dominika; Rozalski, Marcin; Watala, Cezary

    2015-01-01

    Polyphenolic compounds of plant origin are well known to be beneficial to human health: they exert protective effects on haemostasis and have a particular influence on blood platelets. However, the anti-platelet properties of polyphenolic compounds observed so far have not been weighed against their potential cytotoxic action against platelets. The aim of this study was to demonstrate that anti-platelet and cytotoxic effects on blood platelets may interfere and therefore, may often lead to confusion when evaluating the properties of plant extracts or other agents towards blood platelets. The anti-platelet and cytotoxic in vitro effects of plant extracts obtained from the husks of walnuts (J. regia) and flowers of arnica (A. montana) on platelet reactivity and viability were examined. Platelet function was assessed using standard methods (flow cytometry: P-selectin expression, activation of GPIIbIIIa complex, vasodilator-stimulated phosphoprotein, VASP index; turbidimetric and impedance aggregometry) and newly set assays (flow cytometric monitoring of platelet cytotoxicity). The results reveal that none of the studied plant extracts demonstrated cytotoxicity towards blood platelets. The phenolic acid-rich extract of A. montana (7.5 and 15 µg/ml) significantly reduced the ADP-induced aggregation in both whole blood and PRP, and decreased the platelet reactivity index (PRI; VASP phosphorylation) in whole blood, while showing excellent antioxidant capacity. The extract of J. regia husks significantly reduced ADP-induced platelet aggregation in whole blood when applied at 7.5 µg/ml, and only slightly decreased the PRI at 15 µg/ml. Both examined extracts suppressed platelet hyper-reactivity, and such influence did not interfere with cytotoxic effects of the extracts. Thus, its high polyphenol content, excellent antioxidant capacity and distinct anti-platelet properties, in combination with its lack of toxicity, make the extract of A. montana flowers a possible

  3. Studies on the nature of anti-platelet aggregatory factors in the seeds of the Amazonian Herb Guarana (Paullinia cupana).

    PubMed

    Subbiah, M T Ravi; Yunker, R

    2008-03-01

    Guarana (Paullinia cupana) is a popular herb native to the Amazon Basin and used extensively in soft drinks in Brazil, other Latin American countries, and more recently in the United States. Extracts derived from the dried seeds of guarana possess strong anti-platelet aggregatory properties. In this study, an active fraction containing this activity was purified and analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) techniques. It was noted that this fraction contains catechins, epicatechins, and their dimers, with a small amount of caffeine. It is suggested that complexes containing caffeine and catechins (and their dimers) might be responsible for anti-platelet aggregatory activity in guarana seeds and might offer health benefits towards decreasing risk of thrombosis and cardiovascular disease.

  4. Mechanism of the anti-platelet effect of natural bioactive compounds: role of peroxisome proliferator-activated receptors activation.

    PubMed

    Fuentes, Eduardo; Fuentes, Francisco; Palomo, Iván

    2014-01-01

    Platelets are crucial mediators of the acute complications of atherosclerosis causing life-threatening ischemic events throughout plaque development. The inhibition of the platelet function has been used for a long time in an effort to prevent and treat cardiovascular diseases. However, morbidity and mortality figures indicate that current anti-platelet strategies are far from a panacea. In this context, a large number of natural bioactive compounds (NBCs) (polyphenols, terpenoids, alkaloids and fatty acids, among others) have been reported with apparent inhibitory activity on human platelets and each constituent may possess multiple targets. In this sense, the article describes how the mechanism of anti-platelet action by NBCs peroxisome proliferator-activated receptors agonists is mediated by inhibition of protein kinase-α, cyclooxygenase-1, thromboxane A2, cytosolic calcium, and indirect stimulation of protein kinase A (increased in cyclic adenosine monophosphate levels) and protein kinase G (increased in cyclic guanosine monophosphate levels).

  5. A novel ranacyclin-like peptide with anti-platelet activity identified from skin secretions of the frog Amolops loloensis.

    PubMed

    Hao, Xue; Tang, Xiaopeng; Luo, Lei; Wang, Yuming; Lai, Ren; Lu, Qiumin

    2016-01-15

    Albeit many bioactive peptides have been reported from amphibian skins, no anti-platelet peptide has been identified till to date. Here, an anti-platelet peptide, namely Zongdian platelet inhibitor (ZDPI), with the molecular weight of 1798.6 Da, was purified and characterized from skin secretions of the frog, Amolops loloensis. The amino acid sequence of ZDPI was determined as FRGCWLKNYSPRGCL-NH2 by combination methods of Edman degradation, mass spectrometry analysis and carboxypeptidase Y treatment revealing that it is composed of 15 amino acid residues with two cysteines formed an intra-molecular disulfide bridge and C-terminal amidation. cDNA encoding ZDPI precursor was cloned from skin cDNA library of A. loloensis. The precursor is composed of 63 amino acid (aa) residues including the predicted signal peptide (22 aa), an acidic spacer peptide (19 aa), and mature ZDPI. BLAST search indicates that ZDPI belongs to antimicrobial peptide family of ranacyclin, peptide leucine arginine or odorranain. It was found to inhibit ADP-induced platelet aggregation in a dose-dependent manner. At the concentration of 32 μg/ml, ZDPI completely inhibited platelet aggregation induced by ADP. To the best of our knowledge, this is the first report about an anti-platelet peptide from amphibian skin secretions. Considering its strong inhibitory ability on platelets and simple structure, ZDPI might be an excellent candidate or template to develop anti-thrombosis agent. In addition, the discovery of anti-platelet peptide in the frog skin increases biological function spectrum of amphibian skin peptides.

  6. Novel uses for anti-platelet agents as anti-inflammatory drugs

    PubMed Central

    Pitchford, S C

    2007-01-01

    An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well-characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non-atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti-platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases. PMID:17603547

  7. Anti-platelet effects of different phenolic compounds from Yucca schidigera Roezl. bark.

    PubMed

    Olas, Beata; Wachowicz, Barbara; Stochmal, Anna; Oleszek, Wieslaw

    2002-05-01

    Resveratrol (3,4',5-trihydroxystilbene) has been reported to have a variety of anti-inflammatory, anti-carcinogenic, anti-fungal and anti-platelet effects. It occurs naturally in different medicinal plants. Recently, resveratrol and other related phenolic compounds including trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene and yuccaols A and C were isolated from the bark of Yucca schidigera. The aim of the present study was to evaluate in vitro the effects of these compounds on platelet aggregation induced by thrombin and ADP. Pretreatment of platelets with resveratrol or other tested phenolics (1-25 microg/ml) slightly reduced platelet aggregation stimulated by 5 microM ADP (P < 0.05) or 10 microM ADP (P < 0.005). The comparison of the inhibitory effects of tested compound in thrombin-induced platelet aggregation revealed that phenolic showed even stronger antiplatelet actions than resveratrol. These compounds also had an inhibitory effect on the thrombin-induced enzymatic platelet lipid peroxidation determined as the level of thiobarbituric acid reactive substances.

  8. Lupus vulgaris responding to double antituberculous therapy.

    PubMed

    Heller, G L; Pavlidakey, G P; Hashimoto, K; Greenberg, M; Rosenberg, M

    1984-11-01

    A patient with a 3 by 4 cm ulcerated lesion on the nose and upper lip in whom previous antibiotics and antifungal treatments for a "mixed infection" were of no avail is presented. Her history revealed that she has had pulmonary and pharyngeal tuberculosis and subsequently scrofuloderma of cervical lymph nodes. She eventually responded well to isoniazid, rifampin, and pyridoxine therapy.

  9. Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

    PubMed Central

    Karpatkin, S; Nardi, M A; Hymes, K B

    1995-01-01

    Human immunodeficiency virus 1-related idiopathic thrombocytopenic purpura (HIV-1-ITP) patients have a 4-fold increased percentage of CD5+ B cells and a 4.8-fold increased percentage of serum immune complexes precipitated by polyethylene glycol (PEG-ICs) compared to control subjects, as reported previously. Since CD5+ B cells produce predominantly IgM rheumatoid factor (RF) vs. Fc of IgG and PEG-ICs contain high levels of IgM, we looked for the presence of RF in the immune complexes of HIV-1-ITP patients. PEG-ICs were adsorbed to protein A and dissociated with acid, and IgM and IgG were purified by gel filtration and affinity chromatography. Solid-phase ELISA was used to measure antibody specificity vs. platelets, Fc, and HIV-1 gp120, p24, and CD4. Dissociated IgG antibody reacted with platelets, HIV-1 gp120, p24, and CD4, but not with Fc. Serum IgG did not react with platelets or Fc but did react with HIV-1 gp120, p24, and CD4. Both PEG-IC IgM and serum IgM reacted with Fc as well as the other four antigens. Control IgM and IgG were unreactive. Isolated IgM from PEG-ICs relocated approximately 50% of the IgG preincubated with IgM to the Vo region of a G200 gel-filtration column. Anti-platelet IgG but not IgM could be affinity-purified from fixed platelets. Both F(ab')2 fragments of anti-platelet IgG and the total PEG-IC bound to platelets in a saturation-dependent manner. F(ab')2 of anti-platelet IgG inhibited 50% binding of PEG-IC to platelets at an F(ab')2/complex ratio of 3:1 (wt/wt). Scatchard analysis revealed two classes of binding sites: high-affinity Kd values of 0.8-1.8 nM and lower-affinity Kd values of 6.6-12.3 nM with respective numbers of binding sites of 44,000-57,000 and 122,000-256,000 (n = 4). Anti-platelet IgG of 6/6 patients precipitated GPIIIa from platelet lysates of surface 125I-labeled platelets. Platelet count correlated inversely with anti-platelet IgG (r = -0.73; P < 0.01; n = 27). Thus, PEG-ICs of HIV-1-ITP patients contain IgM RF, which

  10. New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity.

    PubMed

    de Candia, Modesto; Marini, Elisabetta; Zaetta, Giorgia; Cellamare, Saverio; Di Stilo, Antonella; Altomare, Cosimo D

    2015-05-25

    A number of new nitric oxide (NO)-precursors were synthesized by grafting nitrate-containing moieties on the structures of the benzyloxy isonipecotanilide derivatives 1 and 2 already reported as moderately potent antiplatelet agents. Various nitrooxy (ONO2)-alkyl side chains were covalently linked to the piperidine nitrogen of the parent compounds through carbamate and amide linkage, and the synthesis of a benzyl nitrate analog (15) of compound 1 was also achieved. The in vitro vasodilatory activities, as well as platelet anti-aggregatory effects, of the newly synthesized organic nitrates were assessed. The (ONO2)methyl carbamate-based derivative 5a and the benzyl nitrate analog 15, which on the other hand retain activity as inhibitors of ADP-induced platelet aggregation, exhibited strong NO-mediated vasodilatory effects on pre-contracted rat aorta strips, with EC50 values in the low nanomolar range (13 and 29 nM, respectively). Experiments carried out with the selectively inhibited soluble guanylate cyclase (sGC), which is the key enzyme of the NO-mediated pathway leading to vascular smooth muscle relaxation, confirmed the involvement of NO in the observed vasodilation. The nitrate derivatives proved to be stable in acidic aqueous solution and at pH 7.4. In human serum, unlike 5a, which showed not to undergo enzyme-catalyzed decomposition, the other tested (ONO2)-alkyl carbamate-based compounds (5b and 5e) and benzyl nitrate 15 underwent a faster degradation. However, their decomposition rates in serum were quite slow (t½>2.6 h), which suggests that nitrate moiety is poorly metabolized in blood plasma and that much of the in vitro anti-platelet activity has to be attributed to the intact (ONO2)-containing molecules.

  11. Double suicide gene therapy using human neural stem cells against glioblastoma: double safety measures.

    PubMed

    Lee, Ji Yeoun; Lee, Do-Hun; Kim, Hyung A; Choi, Seung-Ah; Lee, Hong Jun; Park, Chul-Kee; Phi, Ji Hoon; Wang, Kyu-Chang; Kim, Seung U; Kim, Seung-Ki

    2014-01-01

    With recent advancements in stem cell-based gene therapy, concerns about safety have grown. Stem cell-based gene therapies may pose the risk of immunological problems and oncogenesis. We investigated the feasibility of treating glioblastomas with neural stem cells [(NSCs), HB1.F3 cells] expressing double prodrug enzymes [cytosine deaminase (CD) and tyrosine kinase (TK)] to eliminate the NSCs following treatment for safety purposes. First, the in vitro and in vivo therapeutic efficacies of NSCs engineered with double prodrug enzymes (HB1.F3-CD.TK cells) were compared to cells expressing a single prodrug enzyme (HB1.F3-CD). Second, the degree of safety achieved by NSC elimination was compared with an in vitro viability assay of the NSCs after treatment with the double prodrugs. We further compared the differences in in vivo proliferation of control, single prodrug enzyme and double prodrug enzyme expressing NSCs. HB1.F3-CD.TK cells showed a better or comparable treatment outcome than HB1.F3-CD cells in vitro and in vivo. For safety, HB1.F3-CD.TK cells showed the least viability in vitro after treatment with prodrugs compared to HB1.F3 and HB1.F3-CD cells. Additionally, the in vivo proliferation among the injected NSCs found in the tumor was the smallest for HB1.F3-CD.TK cells. Double-prodrug enzyme-directed gene therapy shows good therapeutic efficacy as well as efficient eradication of the NSCs to ensure safety for clinical applications of stem cell-based gene therapies.

  12. Investigation of standardized administration of anti-platelet drugs and its effect on the prognosis of patients with coronary heart disease.

    PubMed

    Ding, Chao; Zhang, Jianhua; Li, Rongcheng; Wang, Jiacai; Hu, Yongcang; Chen, Yanyan; Li, Xiannan; Xu, Yan

    2017-10-01

    The aim of the present study was to explore the effect of adherence to standardized administration of anti-platelet drugs on the prognosis of patients with coronary heart disease. A total of 144 patients newly diagnosed with coronary heart disease at Lu'an Shili Hospital of Anhui Province (Lu'an, China) between June 2010 and June 2012 were followed up. Kaplan-Meier curves and the Cox regression model were used to evaluate the effects of standardized administration of anti-platelet drugs on primary and secondary end-point events. Of the patients with coronary heart disease, 109 (76%) patients took standard anti-platelet drugs following discharge. Kaplan-Meier curve and Cox regression analysis showed that standardized administration of anti-platelet drugs reduced the risk of primary end-point events (including all-cause mortality, non-lethal myocardial infarction and stroke) of patients with coronary heart disease [hazard ratio (HR)=0.307; 95% confidence interval (CI): 0.099-0.953; P=0.041) and all-cause mortality (HR=0.162; 95% CI: 0.029-0.890; P=0.036); however, standardized administration had no predictive value with regard to secondary end-point events. Standardized administration of anti-platelet drugs obviously reduced the risk of primary end-point events in patients with coronary heart disease, and further analysis showed that only all-cause mortality exhibited a statistically significant reduction.

  13. Bioassay-guided isolation and identification of anti-platelet-active compounds from the root of Ashitaba (Angelica keiskei Koidz.).

    PubMed

    Son, Dong Ju; Park, Ye Oak; Yu, Chengguang; Lee, Sung Eun; Park, Young Hyun

    2014-01-01

    Platelet aggregation is fundamental to a wide range of physiological and pathological processes, including the induction of thrombosis and arteriosclerosis. Anti-platelet activity of a crude methanol extract and solvent fractions of Ashitaba roots (Angelica keiskei Koidz.) was evaluated using a turbidimetric method using washed rabbit platelets. We identified the anti-platelet activities of two chalcones, 4-hydroxyderricin and xanthoangelol, isolated from the ethyl acetate-soluble fraction of Ashitaba roots by using a bioassay-guided isolation method. 4-Hydroxyderricin and xanthoangelol effectively inhibited platelet aggregation induced by collagen (IC50 of 41.9 and 35.9 μM, respectively), platelet-activating factor (IC50 of 46.1 and 42.3 μM, respectively) and phorbol 12-myristate 13-acetate (IC50 of 16.5 and 45.9 μM, respectively). These compounds did not inhibit thrombin-induced platelet aggregation (IC50 of>80 μM). The results suggest that the chalcones 4-hydroxyderricin and xanthoangelol may be potent anti-thrombotic components of A. keiskei Koidz.

  14. A Novel Direct Factor Xa Inhibitory Peptide with Anti-Platelet Aggregation Activity from Agkistrodon acutus Venom Hydrolysates

    PubMed Central

    Chen, Meimei; Ye, Xiaohui; Ming, Xin; Chen, Yahui; Wang, Ying; Su, Xingli; Su, Wen; Kong, Yi

    2015-01-01

    Snake venom is a natural substance that contains numerous bioactive proteins and peptides, nearly all of which have been identified over the last several decades. In this study, we subjected snake venom to enzymatic hydrolysis to identify previously unreported bioactive peptides. The novel peptide ACH-11 with the sequence LTFPRIVFVLG was identified with both FXa inhibition and anti-platelet aggregation activities. ACH-11 inhibited the catalytic function of FXa towards its substrate S-2222 via a mixed model with a Ki value of 9.02 μM and inhibited platelet aggregation induced by ADP and U46619 in a dose-dependent manner. Furthermore, ACH-11 exhibited potent antithrombotic activity in vivo. It reduced paralysis and death in an acute pulmonary thrombosis model by 90% and attenuated thrombosis weight in an arterio-venous shunt thrombosis model by 57.91%, both at a dose of 3 mg/kg. Additionally, a tail cutting bleeding time assay revealed that ACH-11 did not prolong bleeding time in mice at a dose of 3 mg/kg. Together, our results reveal that ACH-11 is a novel antithrombotic peptide exhibiting both FXa inhibition and anti-platelet aggregation activities, with a low bleeding risk. We believe that it could be a candidate or lead compound for new antithrombotic drug development. PMID:26035670

  15. [Metabolomics study of anti-platelet effect of Radix Paeoniae Rubra and Radix Paeoniae Alba by UPLC-MS].

    PubMed

    Yang, Qiwei; Yang, Li; Xiong, Aizhen; Wang, Rui; Wang, Zhengtao

    2011-03-01

    To study the anti-platelet effect and influence of Radix Paeoniae Rubra and Radix Paeoniae Alba on rat's endogenous metabolites by animal experiment and UPLC-MS based metabolomic method. After administration of 80% ethanol extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba for 6 d, the serum samples were analyzed by ultra-performance liquid chromatography- mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) to find out the potential biomarker. Both of the extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba have good effects of inhibition on platelet coacervation, and the effect of Radix Paeoniae Alba is better than that of Radix Paeoniae Rubra. Malic acid, alpha-acetone dicarboxylic acid, leukotrieneA4 (LTA4), prostaglandinE2 (PGE2) and prostaglandin F2alpha (PGF2alpha) are proved to be significant expressed biomarkers. Metabolomics is helpful for the further research of the mechanism of anti-platelet action of Radix Paeoniae Rubra and Radix Paeoniae Alba.

  16. Herpetic keratoconjunctivitis: Therapy with synthetic double-stranded RNA

    USGS Publications Warehouse

    Friedman, I.; Evans, C.; Meighan, C.W.; Foote, L.J.; Aiello, P.V.; Park, J.H.; Baron, S.

    1968-01-01

    A study was undertaken in rabbits to determine how late in the course of keratoconjunctivitis caused by herpes simplex recovery could be effected by an inducer of interferon. Interferon was induced by means of synthetic double-stranded RNA copolymer formed with polynosinic acid : polycytidilic acid RNA. Therapy promotes recovery from severe and fully established keratoconjunctivitis for which treatment was begun as late as 3 days after virus inoculation. No drug toxicity was observed in the therapeutic dose range. These findings further support the proposed role of the interferon mechanism in the natural recovery of already established viral infection. They also suggest the usefulness of interferon inducers in viral infections of man.

  17. Comparative anti-platelet and antioxidant properties of polyphenol-rich extracts from: berries of Aronia melanocarpa, seeds of grape and bark of Yucca schidigera in vitro.

    PubMed

    Olas, Beata; Wachowicz, Barbara; Tomczak, Anna; Erler, Joachim; Stochmal, Anna; Oleszek, Wieslaw

    2008-02-01

    The aim of the present study was to investigate and compare the anti-platelet action of extracts from three different plants: bark of Yucca schidigera, seeds of grape and berries of Aronia melanocarpa (chokeberry). Anti-platelet action of tested extracts was compared with action of well characterized antioxidative and anti-platelet commercial monomeric polyphenol-resveratrol. The effects of extracts on platelet adhesion to collagen, collagen-induced platelet aggregation and on the production of O2-* in resting platelets and platelets stimulated by a strong platelet agonist-thrombin were studied. The in vitro experiments have shown that all three tested extracts (5-50 microg/ml) rich in polyphenols reduce platelet adhesion, aggregation and generation of O2-* in blood platelets. Comparative studies indicate that all three plant extracts were found to be more reactive in reduction of platelet processes than the solution of pure resveratrol. The tested extracts due to their anti-platelet effects may play an important role as components of human diet in prevention of cardiovascular or inflammatory diseases, where blood platelets are involved.

  18. Vancomycin-induced Immune Thrombocytopenia Proven by the Detection of Vancomycin-dependent Anti-platelet Antibody with Flow Cytometry

    PubMed Central

    Yamanouchi, Jun; Hato, Takaaki; Shiraishi, Sanshiro; Takeuchi, Kazuto; Yakushijin, Yoshihiro; Yasukawa, Masaki

    2016-01-01

    Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal bleeding, which was quickly resolved after effective platelet transfusion following the cessation of vancomycin administration. This report suggests that the flow cytometric test is useful for the differential diagnosis of thrombocytopenia and platelet transfusion should be performed after the cessation of vancomycin administration. PMID:27746445

  19. Mechanism of platelet functional changes and effects of anti-platelet agents on in vivo hemostasis under different gravity conditions.

    PubMed

    Li, Suping; Shi, Quanwei; Liu, Guanglei; Zhang, Weilin; Wang, Zhicheng; Wang, Yuedan; Dai, Kesheng

    2010-05-01

    Serious thrombotic and hemorrhagic problems or even fatalities evoked by either microgravity or hypergravity occur commonly in the world. We recently reported that platelet functions are inhibited in microgravity environments and activated under high-G conditions, which reveals the pathogenesis for gravity change-related hemorrhagic and thrombotic diseases. However, the mechanisms of platelet functional variations under different gravity conditions remain unclear. In this study we show that the amount of filamin A coimmunoprecipitated with GPIbalpha was enhanced in platelets exposed to modeled microgravity and, in contrast, was reduced in 8 G-exposed platelets. Hypergravity induced actin filament formation and redistribution, whereas actin filaments were reduced in platelets treated with modeled microgravity. Furthermore, intracellular Ca2+ levels were elevated by hypergravity. Pretreatment of platelets with the cell-permeable Ca2+ chelator BAPTA-AM had no effect on cytoskeleton reorganization induced by hypergravity but significantly reduced platelet aggregation induced by ristocetin/hypergravity. Two anti-platelet agents, aspirin and tirofiban, effectively reversed the shortened tail bleeding time and reduced the death rate of mice exposed to hypergravity. Furthermore, the increased P-selectin surface expression was obviously reduced in platelets from mice treated with aspirin/hypergravity compared with those from mice treated with hypergravity alone. These data suggest that the actin cytoskeleton reorganization and intracellular Ca2+ level play key roles in the regulation of platelet functions in different gravitational environments. The results with anti-platelet agents not only further confirm the activation of platelets in vivo but also suggest a therapeutic potential for hypergravity-induced thrombotic diseases.

  20. Influence of low-dose proton pump inhibitors administered concomitantly or separately on the anti-platelet function of clopidogrel.

    PubMed

    Furuta, Takahisa; Sugimoto, Mitsushige; Kodaira, Chise; Nishino, Masafumi; Yamade, Mihoko; Uotani, Takahiro; Sahara, Shu; Ichikawa, Hitomi; Kagami, Takuma; Iwaizumi, Moriya; Hamaya, Yasushi; Osawa, Satoshi; Sugimoto, Ken; Umemura, Kazuo

    2017-04-01

    Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75 mg in the morning alone, or with omeprazole 10 mg, esomeprazole 10 mg, lansoprazole 15 mg, or rabeprazole 10 mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4 h after the last clopidogrel dose on Day 7 of each regimen. IPA by clopidogrel with rabeprazole administered at lunchtime, approximately 4 h after clopidogrel, was also measured. Mean IPAs in those concomitantly receiving omeprazole, esomeprazole, lansoprazole or rabeprazole (47.2 ± 21.1%, 43.2 ± 20.2%, 46.4 ± 18.8%, and 47.3 ± 19.2%, respectively) were significantly decreased compared with those receiving clopidogrel alone (56.0%) (all ps < 0.001). This decrease was observed when PPIs were administered separately in the evening. However, IPA by clopidogrel with rabeprazole administered at lunchtime was 51.6%, which was markedly similar to that of clopidogrel alone (p = 0.114). All tested PPIs reduce the efficacy of clopidogrel when administered concomitantly. Our preliminary data suggest that administration of rabeprazole 4 h following clopidogrel may minimize potential drug-drug interactions.

  1. The Effect of Desmopressin on the Amount of Bleeding in Patients Undergoing Coronary Artery Bypass Graft Surgery with a Cardiopulmonary Bypass Pump After Taking Anti-Platelet Medicine

    PubMed Central

    Mirmansoori, Ali; Farzi, Farnoush; Sedighinejad, Abbas; Imantalab, Vali; mohammadzadeh, Ali; Atrkar Roushan, Zahra; Ghazanfar Tehran, Samaneh; Nemati, Maryam; Dehghan, Afsaneh

    2016-01-01

    Background Coronary artery bypass grafting (CABG) is a common surgical intervention at the end-stages of coronary artery occlusion disease. Despite the effectiveness of CABG, it may have particular complications, such as bleeding during and after surgery. So far, there have been many drugs used to reduce bleeding. Objectives This study aimed at investigating the effects of desmopressin on the amount of bleeding in patients undergoing CABG with a cardiopulmonary bypass pump (CPBP) who were taking anti-platelet medicine. Methods One hundred patients scheduled for elective CABG with a CPBP were included in a prospective, placebo-controlled, double-blinded clinical trial study. They were randomly divided into two groups. One group received desmopressin (40 μg) and the other group received a placebo (isotonic saline). Seven patients were excluded from the study, and 47 and 46 patients participated in the desmopressin and control groups, respectively. The methods of monitoring and the anesthetic techniques were similar in both groups, and all surgeries were performed by one surgeon. Variables including age, gender, pump time, aortic clamp time, duration of surgery, complications (e.g., nausea and vomiting, blood pressure changes), the necessity to receive blood products, and coagulation tests (prothrombin time, partial thromboplastin time, international normalized ratio, and bleeding time) were assessed. Data were statistically analyzed with SPSS software version 17. Results There was no significant difference between the groups regarding age, gender, pump time, clamp time, duration of surgery, complications, and the changes in hemoglobin and coagulation test measurements (P > 0.05). No significant difference was noted between the groups regarding the rate of bleeding after surgery (359.3 ± 266.2 in group D vs. 406.3 ± 341.6 in group P (control group); P = 0.208). However, the platelet changes after surgery in both groups were significantly different. The analysis

  2. The effect of rituximab on anti-platelet autoantibody levels in patients with immune thrombocytopenia.

    PubMed

    Arnold, Donald M; Vrbensky, John R; Karim, Nadia; Smith, James W; Liu, Yang; Ivetic, Nikola; Kelton, John G; Nazy, Ishac

    2017-07-01

    Rituximab is an effective therapy resulting in a platelet count improvement in 60% of patients with immune thrombocytopenia (ITP). Rituximab depletes B cells; thus, a reduction in platelet autoantibody levels would be anticipated in patients who achieve a clinical response to this treatment. The objectives of this study were to determine whether rituximab was associated with a reduction in platelet autoantibody levels, and to correlate the loss of autoantibodies with the achievement of a treatment response. We performed a case-control study nested within a previous randomized controlled trial of standard therapy plus adjuvant rituximab or placebo. We measured platelet-bound anti-glycoprotein (GP) IIbIIIa and anti-GPIbIX using the antigen capture test. Of 55 evaluable patients, 25 (45%) had a detectable platelet autoantibody at baseline. Rituximab was associated with a significant reduction in anti-GPIIbIIIa levels (P = 0·02) but not anti-GPIbIX levels (P = 0·51) compared with placebo. Neither the presence of an autoantibody at baseline nor the loss of the autoantibody after treatment was associated with a response to rituximab. The subset of patients with persistent autoantibodies after treatment failed to achieve a platelet count response, suggesting that persistence of platelet autoantibodies can be a marker of disease severity. © 2017 John Wiley & Sons Ltd.

  3. Single vs double antiplatelet therapy in acute coronary syndrome: Predictors of bleeding after coronary artery bypass grafting

    PubMed Central

    Tarzia, Vincenzo; Bortolussi, Giacomo; Buratto, Edward; Paolini, Carla; Dal Lin, Carlo; Rizzoli, Giulio; Bottio, Tomaso; Gerosa, Gino

    2015-01-01

    AIM: To investigate the contribution of anti-platelet therapy and derangements of pre-operative classical coagulation and thromboelastometry parameters to major bleeding post-coronary artery bypass grafting (CABG). METHODS: Two groups of CABG patients were studied: Group A, treated with aspirin alone (n = 50), and Group B treated with aspirin and clopidogrel (n = 50). Both had similar preoperative, clinical, biologic characteristics and operative management. Classic coagulation parameters and rotational thromboelastometry (ROTEM) profiles were determined preoperatively for both groups and the same heparin treatment was administered. ROTEM profiles (INTEM and EXTEM assays) were analyzed, both for traditional parameters, and thrombin generation potential, expressed by area-under-curve (AUC). RESULTS: There was no significant difference between rates of major bleeding between patients treated with aspirin alone, compared with those treated with aspirin and clopidogrel (12% vs 16%, P = 0.77). In the 14 cases of major bleeding, pre-operative classic coagulation and traditional ROTEM parameters were comparable. Conversely we observed that the AUC in the EXTEM test was significantly lower in bleeders (5030 ± 1115 Ohm*min) than non-bleeders (6568 ± 548 Ohm*min) (P < 0.0001). CONCLUSION: We observed that patients with a low AUC value were at a significantly higher risk of bleeding compared to patients with higher AUC, regardless of antiplatelet treatment. This suggests that thrombin generation potential, irrespective of the degree of platelet inhibition, correlates with surgical bleeding. PMID:26413234

  4. Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery

    NASA Astrophysics Data System (ADS)

    Pandey, Ambarish; Sarangi, Sasmit; Chien, Kelly; Sengupta, Poulomi; Papa, Anne-Laure; Basu, Sudipta; Sengupta, Shiladitya

    2014-11-01

    Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics.

  5. Clinical and laboratory characteristics associated with a high optical density anti-platelet factor 4 ELISA test.

    PubMed

    Lu, Benjamin Y; Kudlowitz, David; Gardner, Lawrence B

    2015-01-01

    Diagnosing heparin-induced thrombocytopenia, a potentially catastrophic immune-mediated disorder, continues to pose significant challenges for clinicians, as both clinical and laboratory tools lack specificity. There is mounting evidence supporting a positive correlation between definitive heparin-induced thrombocytopenia and optical density (OD) positivity from the widely available anti-platelet factor 4 enzyme-linked immunosorbent assays (PF4 ELISAs). However, the clinical features distinguishing these patients remain poorly understood. To better characterize this group, we conducted a case-controlled, retrospective chart review of patients from two large, urban academic institutions who underwent a PF4 ELISA at a central laboratory. Associations between OD and 18 clinical characteristics were calculated using the Fisher's exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. In total, 184 negative patients (OD <0.7), and 121 positive patients (OD >0.7), including 74 low-positive patients (0.7< OD <1.4) and 47 high-positive patients (OD >1.4) were identified. Several clinical variables were significantly different in the negative group compared with the positive group, including hospital day (P<0.001), previous admission within the past 3 months (P<0.001), and the presence of a new thrombus (P=0.003). However, many of these variables were not different between the negative and low-positive group, and were only distinct between the negative and high-positive group. When the low-positive and high-positive groups were compared, only the 4T score was significantly different (P=0.003). These data indicate that those with OD >1.4 form a distinct clinical group and support the clinical utility of the 4T score.

  6. Anti-Platelet Factor 4/Heparin Antibody Plays a Significant Role in Progression of Arterial Stiffness among Hemodialysis Patients

    PubMed Central

    Kuo, Chieh; Tsai, Chiang-Chin; Chen, Chien-An; Tsai, Yueh-Feng; Chen, Yen-Hsun

    2017-01-01

    Background Arterial stiffness is a determinant of cardiovascular disease in end stage renal disease. Hemodialysis patients may develop anti-platelet factor 4/heparin antibody (PF4-H Ab) because of heparin treatment in dialysis. We tested whether PF4-H Ab was associated with progression of arterial stiffness in a 3-year follow-up. Methods We enrolled 74 hemodialysis patients and studied their clinical, biochemical and arterial stiffness measurement with brachial-ankle pulse wave velocity (baPWV) over 3 years. Baseline and changes in baPWV after 3 years (ΔbaPWV) were collected and compared with related clinical and biochemical parameters. PF4-H Ab was evaluated by the enzyme-linked immunosorbent assay and titer ≥ 0.4 was defined to have PF4-H Ab. Results We found a positive PF4-H Ab status in 25 of 74 patients. Mean baPWV was 16.1 ± 3.8 (m/s) at baseline and 17.6 ± 4.0 (m/s) after 3 years. Mean ΔbaPWV was 3.4 ± 2.2 (m/s) in the PF4-H Ab positive group, and 0.6 ± 1.2 (m/s) in the PF4-H Ab negative group. Baseline baPWV was only significantly associated with age (β = 0.49, p < 0.01). ΔbaPWV was significantly different between the PF4-H Ab positive and negative groups (p < 0.01). In multivariate regression analysis, only PF4-H Ab was positively associated with ΔbaPWV (β = 0.71, p < 0.01). Conclusions Our study concluded that PF4-H Ab was associated with progression of arterial stiffness in hemodialysis patients. PMID:28344423

  7. Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

    PubMed

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

    2016-11-01

    This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O-H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.

  8. GPIIIa-(49-66) is a major pathophysiologically relevant antigenic determinant for anti-platelet GPIIIa of HIV-1-related immunologic thrombocytopenia.

    PubMed

    Nardi, M A; Liu, L X; Karpatkin, S

    1997-07-08

    High-affinity (Kd = 1 x 10(-9) M) anti-platelet GPIIIa has been isolated from serum immune complexes of immunologic thrombocytopenic HIV-1-infected patients (HIV-1-ITP). Affinity-purified anti-platelet antibody reacted with a recombinant GPIIIa-(1-200) and -(1-66) fusion peptide and with an 18-mer GPIIIa-(49-66) peptide but not with seven other GPIIIa peptides spanning the length of GPIIIa. Most of the anti-platelet antibody ( approximately 85%) could be adsorbed to and eluted from a GPIIIa-(49-66) affinity column. Binding of antibody to platelets could be inhibited by GPIIIa-(49-66) or an equimolar peptide-albumin conjugate (IC50 = 2 microM). Sera from 7 control subjects and 10 classic autoimmune thrombocytopenic patients gave background reactivity with GPIIIa-(49-66). HIV-1-ITP sera from 16 patients reacted with a mean OD 6-fold greater than background (range, 4- to 9-fold). Serum anti-GPIIIa-(49-66) concentration correlated inversely with platelet count, R2 = 0.51, n = 31, P < 0. 0001. Because mouse platelet GPIIIa-(49-66) has 83% homology with human GPIIIa and mouse monocytes contain Fc receptors for the human IgG1-kappa/lambda antibody, we determined the in vivo effect of human anti-GPIIIa on mouse platelets. Affinity-purified antibody, 25-50 microg given i.p., resulted in a precipitous drop in platelet count to 30% of baseline, with nadir at 4 hr and return to normal in 36 hr. No effect was noted with control IgG. Acute thrombocytopenia could be prevented or reversed by the injection of the GPIIIa-(49-66) albumin conjugate at zero time or 2 hr after antibody, respectively, but not with a scrambled peptide-albumin conjugate. Thus HIV-1-ITP patients have high-affinity anti-platelet GPIIIa against a major antigenic determinant, GPIIIa-(49-66), which correlates inversely with platelet count and induces thrombocytopenia in mice.

  9. Anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan from Myristica fragrans.

    PubMed

    Kang, Jung Won; Min, Byung-Sun; Lee, Jeong-Hyung

    2013-11-01

    Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin- and platelet-activating factor (PAF)-induced platelet aggregation without affecting platelet damage in a concentration-dependent manner with IC50 values of 3.2 ± 0.4 and 3.4 ± 0.3 μM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin-induced serotonin and ATP release, and thromboxane B2 formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca(2+) mobilization in thrombin-activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti-platelet activity of EATN isolated from M. fragrans.

  10. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect.

    PubMed

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Kanunfre, Carla Cristine; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

    2016-07-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects.

  11. The crystal structure of the active domain of Anopheles anti-platelet protein, a powerful anti-coagulant, in complex with an antibody.

    PubMed

    Sugiyama, Kanako; Iyori, Mitsuhiro; Sawaguchi, Asuka; Akashi, Satoko; Tame, Jeremy R H; Park, Sam-Yong; Yoshida, Shigeto

    2014-06-06

    Blood clotting is a vitally important process that must be carefully regulated to prevent blood loss on one hand and thrombosis on the other. Severe injury and hemophilia may be treated with pro-coagulants, whereas risk of obstructive clotting or embolism may be reduced with anti-coagulants. Anti-coagulants are an extremely important class of drug, one of the most widely used types of medication, but there remains a pressing need for novel treatments, however, as present drugs such as warfarin have significant drawbacks. Nature provides a number of examples of anti-coagulant proteins produced by blood-sucking animals, which may provide templates for the development of new small molecules with similar physiological effects. We have, therefore, studied an Anopheles anti-platelet protein from a malaria vector mosquito and report its crystal structure in complex with an antibody. Overall the protein is extremely sensitive to proteolysis, but the crystal structure reveals a stable domain built from two helices and a turn, which corresponds to the functional region. The antibody raised against Anopheles anti-platelet protein prevents it from binding collagen. Our work, therefore, opens new avenues to the development of both novel small molecule anti-clotting agents and anti-malarials.

  12. [Enzyme therapy in treatment of mastopathy. A randomized double-blind clinical study].

    PubMed

    Rammer, E; Friedrich, F

    1996-01-01

    In this randomized double-blind clinical study the efficacy of an enzyme preparation (Wobenzym) was compared with hormone therapy (Lynestrenol) in 29 women with mastopathy. There was a significantly greater decrease in number of hardenings of the mammary gland after 2 months of enzyme therapy than Lynestrenol therapy: improvement in the former group was 100%, in the latter group 78.6%. No significant difference was observed regarding the numbers of lumps, or number and size of cysts, sensitivity to touch, feeling of tension, spontaneous pain, and pain on pressure. The efficacy of both medicines is valued as good. Wobenzym therapy was tolerated very well. No side effects appeared at all. Enzyme therapy is an alternative, low-risk therapy for the management of mastopathy, which does not interfere with the already upset hormonal balance of the patients.

  13. Statistical examination of laser therapy effects in controlled double-blind clinical trial

    NASA Astrophysics Data System (ADS)

    Boerner, Ewa; Podbielska, Halina

    2001-10-01

    For the evaluation of the therapy effects the double-blind clinical trial followed by statistical analysis was performed. After statistical calculations it was stated that laser therapy with IR radiation has a significant influence on the decrease of the level of pain in the examined group of patients suffering from various locomotive diseases. The level of pain of patients undergoing laser therapy was statistically lower than the level of pain of patients undergoing placebo therapy. It means that laser therapy had statistically significant influence on the decrease of the level of pain. The same tests were performed for evaluation of movement range. Although placebo therapy contributes to the increase of the range of movement, the statistically significant influence was stated in case of the therapeutic group treated by laser.

  14. Fluid Therapy: Double-Edged Sword during Critical Care?

    PubMed

    Benes, Jan; Kirov, Mikhail; Kuzkov, Vsevolod; Lainscak, Mitja; Molnar, Zsolt; Voga, Gorazd; Monnet, Xavier

    2015-01-01

    Fluid therapy is still the mainstay of acute care in patients with shock or cardiovascular compromise. However, our understanding of the critically ill pathophysiology has evolved significantly in recent years. The revelation of the glycocalyx layer and subsequent research has redefined the basics of fluids behavior in the circulation. Using less invasive hemodynamic monitoring tools enables us to assess the cardiovascular function in a dynamic perspective. This allows pinpointing even distinct changes induced by treatment, by postural changes, or by interorgan interactions in real time and enables individualized patient management. Regarding fluids as drugs of any other kind led to the need for precise indication, way of administration, and also assessment of side effects. We possess now the evidence that patient centered outcomes may be altered when incorrect time, dose, or type of fluids are administered. In this review, three major features of fluid therapy are discussed: the prediction of fluid responsiveness, potential harms induced by overzealous fluid administration, and finally the problem of protocol-led treatments and their timing.

  15. Fluid Therapy: Double-Edged Sword during Critical Care?

    PubMed Central

    Benes, Jan; Kirov, Mikhail; Kuzkov, Vsevolod; Lainscak, Mitja; Molnar, Zsolt; Voga, Gorazd; Monnet, Xavier

    2015-01-01

    Fluid therapy is still the mainstay of acute care in patients with shock or cardiovascular compromise. However, our understanding of the critically ill pathophysiology has evolved significantly in recent years. The revelation of the glycocalyx layer and subsequent research has redefined the basics of fluids behavior in the circulation. Using less invasive hemodynamic monitoring tools enables us to assess the cardiovascular function in a dynamic perspective. This allows pinpointing even distinct changes induced by treatment, by postural changes, or by interorgan interactions in real time and enables individualized patient management. Regarding fluids as drugs of any other kind led to the need for precise indication, way of administration, and also assessment of side effects. We possess now the evidence that patient centered outcomes may be altered when incorrect time, dose, or type of fluids are administered. In this review, three major features of fluid therapy are discussed: the prediction of fluid responsiveness, potential harms induced by overzealous fluid administration, and finally the problem of protocol-led treatments and their timing. PMID:26798642

  16. Double-bullet radioimmunotargeting therapy in 31 primary liver cancer patients

    PubMed Central

    Wu, Ying-De; Zhou, De-Nan; Gang, You-Quan; Hu, Xiao-Hua; Li, Zhi-Ge; Song, Xiang-Qun; He, Hai-Ping; Yang, Ke-Zheng; Huang, Bing-Yan

    1997-01-01

    AIM: To observe the effect of double bullet immunotargeting therapy with chemotherapy and internal radiotherapy on primary liver cancer. METHODS: The polyclonal horse antibody against human AFP (anti-AFPAb) and the monoclonal murine antibody against human AFP (anti-AFPMcAb) were used as carriers, and 131I and mitomycin C (MMC) were used as warheads to form double bullet, i.e. 131I anti-AFPMcAb-MMC (double bullet 1) and 131I anti-AFPAb-MMC (double bullet 2) prepared using the modified chloramine T method. Double bullet targeting therapy was administered by intravenous drip once a month in 31 patients (treatment group) with unresectable primary liver cancer. Among them, 4, 17 and 10 patients were administered 1, 2 and 3 times, and the median radiation dose (MBq/case) was 193.5 ± 37.74; 651.9 ± 232.4, and 992.0 ± 230.5 respectively. METHODS: Tumor shrinkage, decrease in AFP, and 1 and 2 -year survival rates were significantly higher than the control groups who received transarterial infusion (TAI) or transarterial chemoembolization (TACE) at the same time (50.0%, 15/30 vs 30.0%, 9/30, P < 0.05; 66.7%, 18/27 vs 28.0%, 7/25, P < 0.01 and 50.0%, 34.0% vs 33.0%, 3.3%, P < 0.01, respectively). Furthermore, the tumor progression rate (10%) in the treatment group was significantly lower than that of the control group (40.0%, P < 0.01). CONCLUSION: Double bullet target therapy is more effective than traditional therapies due to the synergistic effects of the antibody, radioisotope, and anticancer agents, which together, enhance tumor killing. PMID:27239136

  17. Opportunities for improvement in anti-thrombotic therapy and other strategies for the management of acute coronary syndromes: Insights from EPICOR, an international study of current practice patterns.

    PubMed

    Bueno, Héctor; Sinnaeve, Peter; Annemans, Lieven; Danchin, Nicolas; Licour, Muriel; Medina, Jesús; Pocock, Stuart; Sánchez-Covisa, Joaquín; Storey, Robert F; Jukema, J Wouter; Zeymer, Uwe; Van de Werf, Frans

    2016-02-01

    To describe international patterns and opportunities for improvement of pre- and in-hospital care of patients hospitalized for acute coronary syndromes (ACS), with special focus on anti-thrombotic therapy. EPICOR (long-tErm follow-uP of anti-thrombotic management patterns In acute CORonary syndrome patients), an international, cohort study, which enrolled 10,568 consecutive ACS survivors from 555 hospitals in 20 countries across Europe and Latin America (September 2010 to March 2011), prospectively registered detailed information on pre- and in-hospital management. Globally, 4738 (44.8%) were attended before hospitalization, 4241 (40.1%) had an ECG, 2119 (20%) received anti-platelet therapy and 101 STEMI patients (2%) fibrinolysis. In-hospital, 7944 patients (75.2%) received dual anti-platelet therapy, most often with clopidogrel (69.7%), and less with prasugrel (5.4%); 1705 (16.1%) had triple anti-platelet therapy, and 849 (8%) single anti-platelet therapy. STEMI patients more often received pre-hospital anti-thrombotics, and prasugrel, GP IIb/IIIa inhibitors and UFH in-hospital (all p < 0.001). More NSTE-ACS patients received clopidogrel, single anti-platelet therapy, and fondaparinux (all p < 0.001). As many as 33% of ACS patients were medically managed. A significant decreasing gradient was found between Northern, Southern and Eastern Europe and Latin America in use of more potent patterns of anti-platelet therapy, reperfusion therapy and invasive strategy. This large international study shows room for improvement in use of anti-thrombotic drugs and other strategies for optimal management of ACS, including pre-hospital ECG and anti-thrombotic therapy. Regional practice differences not based on evidence or conditioned by economic constraints should be reduced. © The European Society of Cardiology 2015.

  18. Effectiveness and safety of warfarin and anti-platelet drugs for the primary prevention of stroke in patients with non-valvular atrial fibrillation: a meta-analysis

    PubMed Central

    Shi, Xin-Xiu; Ren, Guang-Hao; Wang, Jie; Zhang, Ni; Yu, Ming-Zhu; Wang, Yan-Qiu; Shao, Yan-Kun

    2015-01-01

    Objective: To evaluate the effectiveness and safety of warfarin and anti-platelet drugs as the primary approach to the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: Three English databases (the Cochrane library, Embase, and Medline), and three Chinese databases (the Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Chinese Periodical Full-text Database of Science and Technology) were searched to select potentially eligible studies published before May, 2014. The studies were randomized controlled trials (RCTs) that investigated the effectiveness and safety of using warfarin and anti-platelet drugs in preventing stroke in NVAF patients; The statistical analysis was performed using the Review Manager 5.2 software provided by the Cochrane Collaboration. Results: nine articles were finally included. Compared with antiplatelet drugs, warfarin treatment significantly reduced the risk of stroke (OR = 0.62, 95% CI 0.50-05.77), systemic embolism events (OR = 0.49, 95% CI 0.31-0.77), ischemic stroke events (OR = 0.46, 95% CI 0.36-0.59), stroke-related disability or death events (OR = 0.66, 95% CI 0.52-0.84). Warfarin did not increase the incidence of All-cause death events (OR = 0.92, 95% CI 0.78-1.08), intracranial hemorrhage events (OR = 1.28, 95% CI 0.85-1.93), major hemorrhage events (OR = 1.01, 95% CI 0.79-1.29). Conclusions: This meta-analysis found that compared with antiplatelet drugs, warfarin treatment significantly reduced the risk of stroke, systemic embolism events, ischemic stroke events, stroke-related disability or death events. And warfarin did not increase the incidence of All-cause death events, intracranial hemorrhage events, major hemorrhage events. PMID:26309492

  19. Sequential therapy compared with standard triple therapy for Helicobacter pylori eradication in children: a double-blind, randomized, controlled trial.

    PubMed

    Albrecht, Piotr; Kotowska, Maria; Szajewska, Hania

    2011-07-01

    To determine the effectiveness of sequential therapy compared with standard triple therapy for Helicobacter pylori eradication in children. In 107 children with H pylori infection confirmed with 2 of 3 tests ((13)C-urea breath test, histopathology, rapid urease test), we conducted a double-blind, randomized, controlled trial comparing a sequential treatment (amoxicillin and omeprazole for 5 days followed by clarithromycin, tinidazole, and omeprazole for 5 days) to a 7-day standard triple eradication regimen (amoxicillin and clarithromycin plus omeprazole) followed by placebo for 3 days. In the experimental group (n=52) compared with the control group (n=51), there was a significant difference in the H pylori eradication rate at 6 to 8 weeks after the completion of treatment (primary outcome), as confirmed with negative results on (13)C-urea breath test (45/52 or 86.5% versus 35/51 or 68.6%; relative risk, 1.26; 95% CI, 1.02-1.60). Groups did not differ in any of the secondary outcomes (ie, adverse effects, the need for discontinuation of the H pylori therapy, compliance with therapy). In children with H pylori infection, sequential eradication therapy compared with standard triple therapy resulted in a higher eradication rate, although the difference was of borderline statistical significance. Copyright © 2011 Mosby, Inc. All rights reserved.

  20. Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy In Vitro.

    PubMed

    El-Azizi, Mohamed

    2016-01-01

    An in vitro microdilution method was developed to assess double and triple combinations of antibiotics. Five antibiotics including ciprofloxacin, amikacin, ceftazidime, piperacillin, and imipenem were tested against 10 clinical isolates of Pseudomonas aeruginosa. Each isolate was tested against ten double and nine triple combinations of the antibiotics. A 96-well plate was used to test three antibiotics, each one alone and in double and triple combinations against each isolate. The minimum bacteriostatic and bactericidal concentrations in combination were determined with respect to the most potent antibiotic. An Interaction Code (IC) was generated for each combination, where a numerical value was designated based on the 2-fold increase or decrease in the MICs with respect to the most potent antibiotic. The results of the combinations were verified by time-kill assay at constant concentrations of the antibiotics and in a chemostat. Only 13% of the double combinations were synergistic, whereas 5% showed antagonism. Forty-three percent of the triple combinations were synergistic with no antagonism observed, and 100% synergism was observed in combination of ciprofloxacin, amikacin, and ceftazidime. The presented protocol is simple and fast and can help the clinicians in the early selection of the effective antibiotic therapy for treatment of severe infections.

  1. In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy.

    PubMed

    Le Thomas, I; Couetdic, G; Clermont, O; Brahimi, N; Plésiat, P; Bingen, E

    2001-10-01

    We report the emergence after 4 days of ciprofloxacin monotherapy of a double mutant of Pseudomonas aeruginosa overexpressing the multidrug efflux system MexAB-OprM and harbouring a mutation in the gyrB gene. Compared with its initial susceptible counterpart, this mutant exhibited a significant increase in resistance to most of the beta-lactam antibiotics tested (16 x MIC of ticarcillin) and to ciprofloxacin (128 x MIC). Combined ceftazidime and amikacin therapy finally eradicated the resistant isolate and cured the patient of his infection. This case illustrates how strains of P. aeruginosa may develop high levels of fluoroquinolone resistance by combining efflux mechanisms and target alterations.

  2. Double-carbapenem combination as salvage therapy for untreatable infections by KPC-2-producing Klebsiella pneumoniae.

    PubMed

    Souli, M; Karaiskos, I; Masgala, A; Galani, L; Barmpouti, E; Giamarellou, H

    2017-02-16

    We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40.7%) had severe sepsis (five) or septic shock (six). The clinical and microbiological success was 77.8 and 74.1% respectively. Crude mortality was 29.6% with attributable mortality of 11.1%. Adverse events, none of them severe, were reported in four patients (14.8%). The double-carbapenem combination as an exclusive regimen represents a safe and valid salvage therapy for untreatable infections by extensively- or pandrug-resistant KPC-producing K.pneumoniae.

  3. Comparison of the chemical profiles and anti-platelet aggregation effects of two "Dragon's Blood" drugs used in traditional Chinese medicine.

    PubMed

    Yi, Tao; Chen, Hu-Biao; Zhao, Zhong-Zhen; Yu, Zhi-Ling; Jiang, Zhi-Hong

    2011-01-27

    "Dragon's Blood" has been used as a medicine since ancient times by many cultures. In traditional Chinese medicine, the resin obtained from Daemonorops draco (RDD) and the resin from Dracaena cochinchinensis (RDC) are equally prescribed as "Dragon's Blood" for facilitating blood circulation. To verify the traditional efficacy and elucidate the mechanism, the present study compared the chemical profiles and the pharmacological effects of two species of "Dragon's Blood" mainly used in China. A UPLC-MS fingerprinting method was developed to compare the chemical profiles of the two medicines. The anti-platelet aggregation effects of the two medicines induced by arachidonic acid (AA) were investigated. The chemical profiles of these two species of "Dragon's Blood" were significantly different. The characteristic constituents were found to be: flavanes in RDD and stilbenes in RDC. In the in vivo platelet inhibition test, performed with the dose of 200 mg/kg on rats, the peak inhibitory effects of RDD and RDC were 35.8% and 27.6%, respectively, compared with the control group. With the in vitro concentrations of 0.2, 0.4 and 0.8 mg/ml, RDD exerted significant inhibition of aggregation by 18.7%, 20.0%, and 61.6%, respectively, and RDC exerted significant inhibition of aggregation by 13.3%, 20.2%, and 31.6%, respectively. The fingerprinting method used here is suitable for distinguishing them. All pharmacological tests indicated that RDD was more potent than RDC against platelet aggregation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. cDNA cloning of a snake venom metalloproteinase from the eastern diamondback rattlesnake (Crotalus adamanteus), and the expression of its disintegrin domain with anti-platelet effects.

    PubMed

    Suntravat, Montamas; Jia, Ying; Lucena, Sara E; Sánchez, Elda E; Pérez, John C

    2013-03-15

    A 5' truncated snake venom metalloproteinase was identified from a cDNA library constructed from venom glands of an eastern diamondback rattlesnake (Crotalus adamanteus). The 5'-rapid amplification of cDNA ends (RACE) was used to obtain the 1865 bp full-length cDNA sequence of a snake venom metalloproteinase (CamVMPII). CamVMPII encodes an open reading frame of 488 amino acids, which includes a signal peptide, a pro-domain, a metalloproteinase domain, a spacer, and an RGD-disintegrin domain. The predicted amino acid sequence of CamVMPII showed a 91%, 90%, 83%, and 82% sequence homology to the P-II class enzymes of C. adamanteus metalloproteinase 2, Crotalus atrox CaVMP-II, Gloydius halys agkistin, and Protobothrops jerdonii jerdonitin, respectively. Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Therefore, the disintegrin domain (Cam-dis) of CamVMPII was amplified by PCR, cloned into a pET-43.1a vector, and expressed in Escherichia coli BL21. Affinity purified recombinantly modified Cam-dis (r-Cam-dis) with a yield of 8.5 mg/L culture medium was cleaved from the fusion tags by enterokinase cleavage. r-Cam-dis was further purified by two-step chromatography consisting of HiTrap™ Benzamidine FF column, followed by Talon Metal affinity column with a final yield of 1 mg/L culture. r-Cam-dis was able to inhibit all three processes of platelet thrombus formation including platelet adhesion with an estimated IC(50) of 1 nM, collagen- and ADP-induced platelet aggregation with the estimated IC(50)s of 18 and 6 nM, respectively, and platelet function on clot retraction. It is a potent anti-platelet inhibitor, which should be further investigated for drug discovery to treat stroke patients or patients with thrombotic disorders.

  5. Evaluation of I-123 and In-111 labeled anti-platelet monoclonal antibody for the scintigraphic localization of in vivo thrombi

    SciTech Connect

    Srivastava, S.C.; Meinken, G.E.; Oster, Z.H.; Som, P.; Coller, B.; Atkins, H.L.; Scudder, L.E.; Mausner, L.F.; Yamamoto, K.; Brill, A.B.

    1984-01-01

    Development of a method to selectively label platelets in whole blood in vitro or in vivo is a highly desirable goal. The authors have investigated the labeling with I-123, I-131, and In-111 of an IgG/sub 1/ monoclonal antibody, 7E3 (MAb) that specifically inhibits the interaction of dog platelets with fibrinogen-coated beads and blocks ADP-induced aggregation of dog platelets. The MAb, typically 100 ..mu..g, was radioiodinated using the chloramine T method. Following a G-25 or P-6 column purification, labeling yields of approx. =70% were achieved (2 I/MAb). The MAb-DTPA conjugate was labeled with In-111 in >80% yields with a specific activity of 10-30 ..mu..Ci/..mu..g (approx. =0.1 In/MAb). Retention of inhibiting activity in the fibrinogen-coated bead assay was excellent for both I-123 and In-111 labeled 7E3. In dogs, the blood pool activity persisted for up to 24 hr and some urinary excretion (In-111) and deiodination (I-123) were observed in vivo. When In-111-MAb was incubated with whole blood (0.13 ..mu..g/ml) and the mixture then clotted with thrombin (l..mu../ml), 68% of the radioactivity remained with the clot despite repeated washing. Preliminary in vivo data in dogs suggest that the label becomes localized at the site of vascular injury and/or thrombus formation. The authors conclude that radiolabeled monoclonal anti-platelet antibodies may show promise for imaging vascular lesions and thrombi.

  6. A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

    PubMed

    Boulaiz, Houria; Aránega, Antonia; Cáceres, Blanca; Blanca, Cáceres; Alvarez, Pablo; Pablo, Alvarez; Serrano-Rodríguez, Fernando; Fernando, Rodríguez-Serrano; Carrillo, Esmeralda; Esmeralda, Carrillo; Melguizo, Consolación; Consolación, Melguizo; Prados, Jose; Jose, Prados

    2014-02-01

    Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

  7. Managing tissue heating in laser therapy to enable double-blind clinical study

    NASA Astrophysics Data System (ADS)

    Catanzaro, Brian; de Taboada, Luis; Streeter, Jackson

    2006-02-01

    Laser devices in clinical applications must eventually be tested via clinical trials. An essential component in clinical trials is the double-blind study whereby the patient and the treating physician have no knowledge as to whether a given treatment is active or placebo. In pharmaceuticals, the problem is easily addressed. With laser therapy this can be very challenging. For some optical therapies, laser heating of tissue, by even as little as a few degrees can indicate to the patient and/or the physician that the device is active, un-blinding the study. This problem has been analyzed for a specific laser therapy using a combination of clinical data, analytical methods, finite element modeling, and laboratory testing. The methods used arrived at a solution, but not necessarily one that could have been predicted easily. This paper will present a model of tissue heating and the methods used to mask the effects from the laser in an effort to make active treatment and placebo indistinguishable.

  8. Reiki therapy for postoperative oral pain in pediatric patients: Pilot data from a double-blind, randomized clinical trial

    PubMed Central

    Kundu, Anjana; Lin, Yuting; Oron, Assaf P.; Doorenbos, Ardith Z.

    2014-01-01

    Purpose To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Methods This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Results Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Implications Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. PMID:24439640

  9. Reiki therapy for postoperative oral pain in pediatric patients: pilot data from a double-blind, randomized clinical trial.

    PubMed

    Kundu, Anjana; Lin, Yuting; Oron, Assaf P; Doorenbos, Ardith Z

    2014-02-01

    To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Extracorporeal shock wave therapy for lateral epicondylitis--a double blind randomised controlled trial.

    PubMed

    Speed, C A; Nichols, D; Richards, C; Humphreys, H; Wies, J T; Burnet, S; Hazleman, B L

    2002-09-01

    Extracorporeal shock wave therapy (ESWT) is an increasingly popular therapeutic approach to the treatment of a number of soft tissue complaints. Whilst benefit has been demonstrated in calcific tendinitis, evidence is lacking for benefit in the management of non-calcific rotator cuff disorders. To perform a double-blind placebo controlled trial of moderate dose ESWT in chronic lateral epicondylitis. Adults with lateral epicondylitis were randomised to receive either active treatment (1500 pulses ESWT at 0.12 mJ/ mm2) or sham therapy, monthly for three months. All were assessed before each treatment and one month after completion of therapy. Outcome measures consisted of visual analogue scores for pain in the day and at night. Seventy-five subjects participated and there were no significant differences between the two groups at baseline. The mean duration of symptoms was 15.9 and 12 months in the ESWT and sham groups, respectively. Both groups showed significant improvements from two months. No significant difference existed between the groups with respect to the degrees of change in pain scores over the study period. In the ESWT group the mean (SD, range) pain score was 73.4 (14.5, 38-99) at baseline and 47.9 (31.4, 3-100) at three months. In the sham group the mean (SD, range) pain score was 67.2 (21.7, 12-100) at baseline and 51.5 (32.5, 3-100) at three months. At three months, 50% improvement from baseline was noted in 35% of the ESWT group and 34% of the sham group with respect to pain. There appears to be a significant placebo effect of moderate dose ESWT in subjects with lateral epicondylitis but there is no evidence of added benefit of treatment when compared to sham therapy.

  11. Non-Carriers of Reduced-Function CYP2C19 Alleles are Most Susceptible to Impairment of the Anti-Platelet Effect of Clopidogrel by Proton-Pump Inhibitors: A Pilot Study

    PubMed Central

    Lee, Jen-Kuang; Wu, Cho-Kai; Juang, Jyh-Ming; Tsai, Chia-Ti; Hwang, Juey-Jen; Lin, Jiuun-Lee; Chiang, Fu-Tien

    2016-01-01

    Background The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet MappingTM (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Results Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome. PMID:27122952

  12. Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Roohi-Azizi, Mahtab; Arabzadeh, Somaye; Amidfar, Meysam; Salimi, Samrand; Zarindast, Mohammad Reza; Talaei, Ali; Akhondzadeh, Shahin

    Residual symptoms of major depressive disorder are a source of long-term morbidity. New therapeutic strategies are required to alleviate this morbidity and enhance patient quality of life. Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder. Here, we test citicoline effectiveness as an adjuvant therapy in major depression. A double-blind randomized trial was designed on 50 patients with major depressive disorder who were under treatment with citalopram. Patients were allocated to 2 groups and received citicoline (100 mg twice a day) or placebo as an adjuvant treatment for 6 weeks. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4, and 6. Significantly greater improvement was observed in the HDRS scores of the citicoline group compared with the placebo group from baseline to weeks 2, 4, and 6 (Ps = 0.030, 0.032, and 0.021, respectively). Repeated-measures general linear model demonstrated a significant effect for time × treatment interaction on the HDRS score (F2.10,101.22 = 3.12, P = 0.04). Remission rate was significantly higher in the citicoline group compared with the placebo group (P = 0.045). Citicoline was an effective adjuvant to citalopram in the therapy of major depressive disorder.

  13. Contribution to Neutron Fluence and Neutron Absorbed Dose from Double Scattering Proton Therapy System Components

    PubMed Central

    Pérez-Andújar, A.; Newhauser, W. D.; DeLuca, P. M.

    2010-01-01

    Proton therapy offers low integral dose and good tumor comformality in many deep-seated tumors. However, secondary particles generated during proton therapy, such as neutrons, are a concern, especially for passive scattering systems. In this type of system, the proton beam interacts with several components of the treatment nozzle that lie along the delivery path and can produce secondary neutrons. Neutron production along the beam's central axis in a double scattering passive system was examined using Monte Carlo simulations. Neutron fluence and energy distribution were determined downstream of the nozzle's major components at different radial distances from the central axis. In addition, the neutron absorbed dose per primary proton around the nozzle was investigated. Neutron fluence was highest immediately downstream of the range modulator wheel (RMW) but decreased as distance from the RMW increased. The nozzle's final collimator and snout also contributed to the production of high-energy neutrons. In fact, for the smallest treatment volume simulated, the neutron absorbed dose per proton at isocenter increased by a factor of 20 due to the snout presence when compared with a nozzle without a snout. The presented results can be used to design more effective local shielding components inside the treatment nozzle as well as to better understand the treatment room shielding requirements. PMID:20871789

  14. Chinese Herb and Formulas for Promoting Blood Circulation and Removing Blood Stasis and Antiplatelet Therapies

    PubMed Central

    Liu, Yue; Yin, Hui-Jun; Shi, Da-zhuo; Chen, Ke-ji

    2012-01-01

    Atherothrombosis, which directly threatens people's health and lives, is the main cause of morbidity and mortality all over the world. Platelets play a key role in the development of acute coronary syndromes (ACSs) and contribute to cardiovascular events. Oral antiplatelet drugs are a milestone in the therapy of cardiovascular atherothrombotic diseases. In recent years, many reports have shown the possibility that “resistance” to oral anti-platelet drugs and many adverse reactions, such as serious bleeding risk, which provides an impetus for developing new anti-platelet drugs possesses highly efficiency and fewer adverse effects. Study on the blood stasis syndrome and promoting blood circulation and removing blood stasis is the most active field of research of integration of traditional and western medicine in China. Blood-stasis syndrome and platelet activation have close relationship, many Chinese herb and formulas for promoting blood circulation and removing blood stasis possess definite anti-platelet effect. This paper covers the progress of anti-platelet mechanism of Chinese herb and formulas for promoting blood circulation and removing blood stasis and is to be deeply discussed in further research. PMID:22454656

  15. Combined chemotherapy and photodynamic therapy using a nanohybrid based on layered double hydroxides to conquer cisplatin resistance.

    PubMed

    Wang, Zhigang; Ma, Rong; Yan, Li; Chen, Xianfeng; Zhu, Guangyu

    2015-07-25

    A nanohybrid is assembled by ratiometrically co-loading Pt(IV) prodrugs and photosensitizers into layered double hydroxide nanoparticles. The nanohybrid shows synergistic cell-killing effects and is significantly active against the proliferation of cisplatin-resistant human cancer cells with nanomolar IC50 values. Profound mechanistic investigations confirm its action mode of combined chemo- and photodynamic therapy.

  16. Interferential and horizontal therapies in chronic low back pain: a randomized, double blind, clinical study.

    PubMed

    Zambito, A; Bianchini, D; Gatti, D; Viapiana, O; Rossini, M; Adami, S

    2006-01-01

    Chronic Low Back Pain (CLBP) is one of the most frequent medical problems. Electrical nerve stimulation is frequently used but its efficacy remains controversial. Twenty-six men and 94 women with CLBP associated with either degenerative disk disease or previous multiple vertebral osteoporotic fractures were randomly assigned to either interferential currents (IFT), horizontal therapy (HT) or sham HT administered for 10, 40 and 40 minutes, respectively, daily for 5 days per week for two weeks together with a standard flexion-extension stretching exercise program, Blind efficacy assessment were obtained at baseline and at week 2, 6 and 14 and included a functional questionnaire (Backill), the standard visual analog scale (VAS) and the mean analgesic consumption. At week 2 a significant and similar improvement in both the VAS and Backill score was observed in all three groups. The Backill score continued to improve only in the two active groups with changes significantly greater than those observed in control patients at week 14. The pain VAS score returned to baseline values at week 6 and 14 in the control group while in the IFT and HT groups it continued to improve (p< 0.01 vs controls). The use of analgesic medications significantly improved at week 14 versus pretreatment assessment and over control patients only in the HT group. This randomized double-blind controlled study provides the first evidence that IFT and HT therapy are significantly effective in alleviating both pain and disability in patients with CLBP. The placebo effect is remarkable at the beginning of the treatment but it tends to vanish within a couple of weeks.

  17. Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial.

    PubMed

    Sit, Dorothy K; McGowan, James; Wiltrout, Christopher; Diler, Rasim Somer; Dills, John Jesse; Luther, James; Yang, Amy; Ciolino, Jody D; Seltman, Howard; Wisniewski, Stephen R; Terman, Michael; Wisner, Katherine L

    2017-10-03

    Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality. The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less. At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4-6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted β=-5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them. The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

  18. Efficacy of Electroconvulsive Therapy in Treatment Resistant Schizophreinia : A double-blind study

    PubMed Central

    Goswami, Utpal; Kumar, Unnati; Singh, Baljit

    2003-01-01

    Background : ECT, though not favoured in the West for treating schizophrenia, is regularly practiced in India for this indication, particularly in poorly responding/treatment resistant cases.Therefore, its role in treatment-resistant schizophrenia is a subject of systematic investigation. Aim : To compare the effectiveness and safety of Electroconvulsive therapy (ECT) in a group of treatment-resistant schizophrenia patients with a control group. Method : Eligible and consenting patients were randomly allocated to the ECT or Sham ECT groups. Both received antipsychotic drugs.Twenty-five patients completed the study (ECT, n= IS; Sham ECT, n= 10).The study was conducted in a double-blind manner. Clinical change was assessed weekly with BPRS, CGI and adverse event measures.ANOVA for repeated measures and other post-hoc comparisons were used for data analysis. Results: ECT treated patients improved significantly over successive weeks (p< 0.002) after 6 ECTs, whereas the group receiving sham-ECT did not In both the groups, however, CGI scores did not change significantly, suggesting a dissociated response pattern. ECT was associated with greater relief among carers and lower rehospitalization. Conclusion : ECT augmentation may well have a significant impact on the clinical course of patients with treatment resistance schizophrenia. It is unclear, but possible, that these changes may be reinforced and maintained by maintenance ECTs. Replication of the present investigation and further studies on maintenance ECT would be rewarding. PMID:21206809

  19. Efficacy of Electroconvulsive Therapy in Treatment Resistant Schizophreinia : A double-blind study.

    PubMed

    Goswami, Utpal; Kumar, Unnati; Singh, Baljit

    2003-01-01

    ECT, though not favoured in the West for treating schizophrenia, is regularly practiced in India for this indication, particularly in poorly responding/treatment resistant cases.Therefore, its role in treatment-resistant schizophrenia is a subject of systematic investigation. To compare the effectiveness and safety of Electroconvulsive therapy (ECT) in a group of treatment-resistant schizophrenia patients with a control group. Eligible and consenting patients were randomly allocated to the ECT or Sham ECT groups. Both received antipsychotic drugs.Twenty-five patients completed the study (ECT, n= IS; Sham ECT, n= 10).The study was conducted in a double-blind manner. Clinical change was assessed weekly with BPRS, CGI and adverse event measures.ANOVA for repeated measures and other post-hoc comparisons were used for data analysis. ECT treated patients improved significantly over successive weeks (p< 0.002) after 6 ECTs, whereas the group receiving sham-ECT did not In both the groups, however, CGI scores did not change significantly, suggesting a dissociated response pattern. ECT was associated with greater relief among carers and lower rehospitalization. ECT augmentation may well have a significant impact on the clinical course of patients with treatment resistance schizophrenia. It is unclear, but possible, that these changes may be reinforced and maintained by maintenance ECTs. Replication of the present investigation and further studies on maintenance ECT would be rewarding.

  20. Double-blind randomized controlled trial of low-level laser therapy in carpal tunnel syndrome.

    PubMed

    Irvine, Jamie; Chong, Su L; Amirjani, Nasim; Chan, K Ming

    2004-08-01

    Several studies have suggested that low-level laser therapy (LLLT) is effective in patients with carpal tunnel syndrome (CTS). In a double-blind randomized controlled trial of LLLT, 15 CTS patients, 34 to 67 years of age, were randomly assigned to either the control group (n = 8) or treatment group (n =7). Both groups were treated three times per week for 5 weeks. Those in the treatment group received 860 nm galium/aluminum/arsenide laser at a dosage of 6 J/cm2 over the carpal tunnel, whereas those in the control group were treated with sham laser. The primary outcome measure was the Levine Carpal Tunnel Syndrome Questionnaire, and the secondary outcome measures were electrophysiological data and the Purdue pegboard test. All patients completed the study without adverse effects. There was a significant symptomatic improvement in both the control (P = 0.034) and treatment (P =0.043) groups. However, there was no significant difference in any of the outcome measures between the two groups. Thus, LLLT is no more effective in the reduction of symptoms of CTS than is sham treatment.

  1. Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model.

    PubMed

    Freytag, Svend O; Paielli, Dell; Wing, Mark; Rogulski, Ken; Brown, Steve; Kolozsvary, Andy; Seely, John; Barton, Ken; Dragovic, Alek; Kim, Jae Ho

    2002-11-01

    The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10(10) vp) of the replication-competent Ad5-CD/TKrep adenovirus. Two days later, mice were administered 4 weeks of 5-fluorocytosine + GCV prodrug therapy and 56 Gy EBRT to the pelvic region. The toxicity of trimodal therapy was assessed by histopathologic analysis of major organs and clinical chemistries. In both the i.m. DU145 and intraprostatic LNCaP C4-2 tumor models, trimodal therapy significantly improved primary tumor control beyond that of EBRT alone. In the DU145 model, trimodal therapy resulted in a tumor growth delay (70 days) that was more than twice that (32 days) of EBRT alone. Whereas EBRT failed to eradicate DU145 tumors, trimodal therapy resulted in 25% tumor cure. In the LNCaP C4-2 tumor model, EBRT slowed the growth of intraprostatic tumors, but resulted in no tumor cures, and 57% of the mice developed retroperitoneal lymph node metastases at 3 months. By contrast, trimodal therapy resulted in 44% tumor cure and reduced significantly the percentage (13%) of lymph node metastases relative to EBRT alone. Overall, trimodal therapy was associated

  2. Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy Trials for Major Depressive Disorder.

    PubMed

    Berger, Douglas

    2015-01-01

    While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive-behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, "partially-controlled clinical data" because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials.

  3. Electroacupuncture Therapy in Nicotine Dependence: A Double Blind, Sham-Controlled Study.

    PubMed

    Bilici, Mustafa; Güven, Sertaç; Köşker, Selcen; Şafak, Ayşe; Semiz, Ümit Başar

    2016-03-01

    The number of non-pharmacological controlled studies is insufficient in the treatment of nicotine dependence (ND). Nevertheless, non-pharmacological treatments, such as electroacupuncture (EA), are becoming increasingly popular in the treatment of ND. The aims of this study were to determine the efficacy and safety of "true EA therapy" (TEAT) compared to those of "sham EA therapy" (SEAT) in ND treatment. Eligible patients who met the DSM-IV criteria for ND (n=450) were included in the study. This study was a double-blinded, sham-controlled clinical trial with a 4-week treatment period and 4-week follow-up conducted between June and December 2009 at a psychiatry outpatient clinic. One hundred and sixty four adult (≥18 years; 44 men, 120 women) cigarette smokers out of 450 patients who met the inclusion and exclusion criteria were enrolled in the study in a ratio of 1:1 to receive TEAT (n=84) or SEAT (n=80). Routine biochemical and hematological tests, chest X-Ray, and ECG were carried out; end-expired carbon monoxide (CO) levels were measured too. Clinical characteristics were obtained through the Fagerström Nicotine Dependence Test (FNDT), Hamilton Rating Scale for Depression (HRSD), and Hamilton Anxiety Scale (HAS). EA was carried out by a trademark device, Antismoke 3000®. Efficacy analyses were performed on "intent-to-treat analysis." Primary outcome was the differences from baseline to endpoint in mean FNDT, number of cigarettes smoked per day, and CO levels at week 4. Secondary outcomes were the same variables at week 8. These variables were assessed via analysis of covariance (ANCOVA). Mean baseline FNDT, HRSD, HAS, and CO levels of the groups were statistically similar. TEAT and SEAT groups demonstrated no significant changes in the outcome variables and smoking cessation rates (35.7% and 30%, respectively). Of those remaining outside of the study, 8.3% were from the TEAT group and 8.7% were from the SEAT group; there was no statistical difference

  4. Fast Pencil Beam Dose Calculation for Proton Therapy Using a Double-Gaussian Beam Model

    PubMed Central

    da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

    2015-01-01

    The highly conformal dose distributions produced by scanned proton pencil beams (PBs) are more sensitive to motion and anatomical changes than those produced by conventional radiotherapy. The ability to calculate the dose in real-time as it is being delivered would enable, for example, online dose monitoring, and is therefore highly desirable. We have previously described an implementation of a PB algorithm running on graphics processing units (GPUs) intended specifically for online dose calculation. Here, we present an extension to the dose calculation engine employing a double-Gaussian beam model to better account for the low-dose halo. To the best of our knowledge, it is the first such PB algorithm for proton therapy running on a GPU. We employ two different parameterizations for the halo dose, one describing the distribution of secondary particles from nuclear interactions found in the literature and one relying on directly fitting the model to Monte Carlo simulations of PBs in water. Despite the large width of the halo contribution, we show how in either case the second Gaussian can be included while prolonging the calculation of the investigated plans by no more than 16%, or the calculation of the most time-consuming energy layers by about 25%. Furthermore, the calculation time is relatively unaffected by the parameterization used, which suggests that these results should hold also for different systems. Finally, since the implementation is based on an algorithm employed by a commercial treatment planning system, it is expected that with adequate tuning, it should be able to reproduce the halo dose from a general beam line with sufficient accuracy. PMID:26734567

  5. Magnetic resonance therapy for knee osteoarthritis: a randomized, double blind placebo controlled trial.

    PubMed

    Gökşen, Nurgül; Çaliş, Mustafa; Doğan, Serap; Çaliş, Havva T; Özgöçmen, Salih

    2016-08-01

    Therapeutic nuclear magnetic resonance therapy (MRT) works based on the electromagnetic fields. To investigate efficacy of MRT in knee osteoarthritis (OA). Prospective, randomized, double-blind, placebo controlled trial. Outpatient clinic, university hospital. Patients who had mild to moderate knee OA at a single knee joint and between 30-75-years-old were randomized by blinded chip cards (1:1). The treatment group received ten sessions of one hour daily MRT, controls received placebo MRT. All patients underwent clinical examination at baseline, after 2 weeks, and 12 weeks. Imaging included blindly assessed ultrasonography and magnetic resonance (MR) of the knee. Ninety-seven patients completed the study. Both groups improved significantly but the average change from baseline in outcome parameters was similar in MRT group (on VAS-pain,-2.6; WOMAC-pain, -2.09; WOMAC-stiffness, -1.81; WOMAC-physical, -1.96) compared to placebo after two weeks (VAS-pain,-1.6; WOMAC-pain, -1.91; WOMAC-stiffness, -1.27; WOMAC-physical, -1.54). Also changes were quite similar at the 12th week after the treatment. SF-36 components at 12th week improved but changes were not significant. Imaging arm also failed to show significant differences between groups in terms of cartilage thickness on US and MR scores. No adverse events were recorded. MRT is safe, but not superior to placebo in terms of improvement in clinical or imaging parameters after a 10-day course of treatment in mild to moderate knee OA. The present study does not promote use of a 10-day course of MRT in mild to moderate knee OA.

  6. Fast Pencil Beam Dose Calculation for Proton Therapy Using a Double-Gaussian Beam Model.

    PubMed

    da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

    2015-01-01

    The highly conformal dose distributions produced by scanned proton pencil beams (PBs) are more sensitive to motion and anatomical changes than those produced by conventional radiotherapy. The ability to calculate the dose in real-time as it is being delivered would enable, for example, online dose monitoring, and is therefore highly desirable. We have previously described an implementation of a PB algorithm running on graphics processing units (GPUs) intended specifically for online dose calculation. Here, we present an extension to the dose calculation engine employing a double-Gaussian beam model to better account for the low-dose halo. To the best of our knowledge, it is the first such PB algorithm for proton therapy running on a GPU. We employ two different parameterizations for the halo dose, one describing the distribution of secondary particles from nuclear interactions found in the literature and one relying on directly fitting the model to Monte Carlo simulations of PBs in water. Despite the large width of the halo contribution, we show how in either case the second Gaussian can be included while prolonging the calculation of the investigated plans by no more than 16%, or the calculation of the most time-consuming energy layers by about 25%. Furthermore, the calculation time is relatively unaffected by the parameterization used, which suggests that these results should hold also for different systems. Finally, since the implementation is based on an algorithm employed by a commercial treatment planning system, it is expected that with adequate tuning, it should be able to reproduce the halo dose from a general beam line with sufficient accuracy.

  7. [Analgesic efficacy of TENS therapy in patients with gonarthrosis. A prospective, randomised, placebo-controlled, double-blind study].

    PubMed

    Gschiel, B; Kager, H; Pipam, W; Weichart, K; Likar, R

    2010-09-01

    The goal of the study was to substantiate the influence of TENS on pain development and medication needs of patients with proven gonarthrosis and chronic pain. The study included a 3-week stimulation period and 2-week observation period after the end of stimulation. Patients (at least 20 per group) were assigned to either an active treatment group or placebo group in a randomised, double-blind, placebo-controlled trial. For the active treatment group the TENS therapy device with HAN stimulation (alternating phase of stimulation) was used (TENStem eco).Total length of time: 30 min at least two times a day. The length of therapy was 3 weeks (therapy), followed by an observation period of 2 weeks (follow-up). The total length of the study was 5 weeks, whereby at the beginning and at the end of weeks 1, 3 and 5 the SF-36, WOMAC score and Lysholm score were documented; the pain score was documented daily. There are no significant demographic differences between the groups. In the active treatment group there was clear relief in pain intensity in the morning, midday and evening over the 3-week period of therapy. The Lysholm score in the active treatment group was 53.4 at the beginning, 90 after 1 week, 94.5 after the third week and 91 by the fifth week (significant difference). There were no side effects. TENS therapy with HAN stimulation resulted in pain relief in patients with gonarthrosis during the therapy period with TENS, but the pain relief did not last beyond the end of the TENS therapy. There was an improvement in the Lysholm score and the WOMAC score during the therapy. This improvement remained over the following 2-week period of observation without further TENS therapy. TENS therapy is a simple and effective method to treat gonarthrosis with very few side effects.

  8. A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

    DTIC Science & Technology

    2007-11-01

    established vector systems, new viruses are also being developed for targeted gene therapy . One promising example is the measles virus , an enveloped...promising approach. However, the gene delivery efficiency of human serotype 5 recombinant adeno- viruses (Ad5) in cancer gene therapy clinical trials to...replicative viruses , is a highly attractive approach, and an alternate approach to standard cancer therapies , including gene therapies . Virotherapy exploits

  9. A new analytical formula for neutron capture gamma dose calculations in double-bend mazes in radiation therapy

    PubMed Central

    Ghiasi, Hosein; Mesbahi, Asghar

    2012-01-01

    Background Photoneutrons are produced in radiation therapy with high energy photons. Also, capture gamma rays are the byproduct of neutrons interactions with wall material of radiotherapy rooms. Aim In the current study an analytical formula was proposed for capture gamma dose calculations in double bend mazes in radiation therapy rooms. Materials and methods A total of 40 different layouts with double-bend mazes and a 18 MeV photon beam of Varian 2100 Clinac were simulated using MCNPX Monte Carlo (MC) code. Neutron capture gamma ray dose equivalent was calculated by the MC method along the maze and at the maze entrance door of all the simulated rooms. Then, all MC resulted data were fitted to an empirical formula for capture gamma dose calculations. Wu–McGinley analytical formula for capture gamma dose equivalent at the maze entrance door in single-bend mazes was also used for comparison purposes. Results For capture gamma dose equivalents at the maze entrance door, the difference of 2–11% was seen between MC and the derived equation, while the difference of 36–87% was found between MC and the Wu–McGinley methods. Conclusion Our results showed that the derived formula results were consistent with the MC results for all of 40 different geometries. However, as a new formula, further evaluations are required to validate its use in practical situations. Finally, its application is recommend for capture gamma dose calculations in double-bend mazes to improve shielding calculations. PMID:24377027

  10. Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro

    PubMed Central

    Sun, Ying; Duan, You Rong; Du, Lian Fang

    2016-01-01

    A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic. PMID:27835907

  11. Immediate pain relief effect of low level laser therapy for sports injuries: Randomized, double-blind placebo clinical trial.

    PubMed

    Takenori, A; Ikuhiro, M; Shogo, U; Hiroe, K; Junji, S; Yasutaka, T; Hiroya, K; Miki, N

    2016-12-01

    To determine the immediate pain relief effect of low-level laser therapy on sports injuries in athletes and degree of pain relief by the therapy. Double-blind, randomized, comparative clinical study. Participants were 32 college athletes with motion pain at a defined site. Participants were randomized into two groups in which the tested or placebo laser therapy was administered to determine pain intensity from painful action before and after laser irradiation, using the Modified Numerical Rating Scale. The post-therapeutic Modified Numerical Rating Scale score was subtracted from the pre-therapeutic Modified Numerical Rating Scale score to determine pain intensity difference, and the rate of pain intensity difference to pre-therapeutic Modified Numerical Rating Scale was calculated as pain relief rate. Low-level laser therapy was effective in 75% of the laser group, whereas it was not effective in the placebo group, indicating a significant difference in favor of the laser group (p<0.001). Pain relief rate was significantly higher in the laser group than in the placebo group (36.94% vs. 8.20%, respectively, p<0.001), with the difference in pain relief rate being 28.74%. Low-level laser therapy provided an immediate pain relief effect, reducing pain by 28.74%. It was effective for pain relief in 75% of participants. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  12. A prospective, randomized, double-blind evaluation of trigger-point injection therapy for low-back pain.

    PubMed

    Garvey, T A; Marks, M R; Wiesel, S W

    1989-09-01

    The efficacy of trigger-point injection therapy in treatment of low-back strain was evaluated in a prospective, randomized, double-blind study. The patient population consisted of 63 individuals with low-back strain. Patients with this diagnosis had nonradiating low-back pain, normal neurologic examination, absence of tension signs, and lumbosacral roentgenograms interpreted as being within normal limits. They were treated conservatively for 4 weeks before entering the study. Injection therapy was of four different types: lidocaine, lidocaine combined with a steroid, acupuncture, and vapocoolant spray with acupressure. Results indicated that therapy without injected medication (63% improvement rate) was at least as effective as therapy with drug injection (42% improvement rate), at a P value of 0.09. Trigger-point therapy seems to be a useful adjunct in treatment of low-back strain. The injected substance apparently is not the critical factor, since direct mechanical stimulus to the trigger-point seems to give symptomatic relief equal to that of treatment with various types of injected medication.

  13. ABC, GCB, and Double-Hit Diffuse Large B-Cell Lymphoma: Does Subtype Make a Difference in Therapy Selection?

    PubMed

    Nowakowski, Grzegorz S; Czuczman, Myron S

    2015-01-01

    Personalized therapy for the treatment of patients with cancer is rapidly approaching and is an achievable goal in the near future. A substantial number of novel targets have been developed into therapeutic agents. There is a substantial variability to antitumor activity by novel therapeutics because of the unique heterogeneity and biology that exists both between and within lymphoma subtypes. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Approximately 40% of patients have refractory disease or disease that will relapse after an initial response, and the majority of patients with relapsed DLBCL will succumb to the disease. There are two major biologically distinct molecular subtypes of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC). ABC DLBCL is associated with substantially worse outcomes when treated with standard chemoimmunotherapy. In addition to GCB and ABC subtypes, double-hit lymphomas (approximately 5% to 10% of patients) and double-expressor lymphomas, which overexpress MYC and BCL2 protein, are aggressive DLBCLs and are also associated with a poor prognosis. Double-hit lymphomas have concurrent chromosomal rearrangements of MYC plus BCL2 (or less likely, BCL6). Advances in molecular characterization techniques and the development of novel agents targeting specific subtypes of DLBCL have provided a foundation for personalized therapy of DLBCL based on molecular subtype. A number of early clinical trials evaluating combinations of novel targeted agents with standard chemotherapy (R-CHOP) have been completed and have demonstrated the feasibility of this approach with encouraging efficacy. As such, molecular classification of DLBCL is not only important for prognostication, but moves to center stage for personalization of therapy for DLBCL.

  14. Hemorrhagic thoracic schwannoma presenting with intradural hematoma and acute paraplegia after spinal manipulation therapy

    PubMed Central

    Goodwin, C. Rory; Sciubba, Daniel; Bydon, Ali; Wolinsky, Jean-Paul; Witham, Timothy; Gokaslan, Ziya L.

    2016-01-01

    Hemorrhagic conversion of spinal schwannomas represents a rare occurrence; also rare is the development of a spinal intradural hematoma after spinal manipulation therapy. We report a unique presentation of paraplegia in a patient who underwent spinal manipulation therapy and was found to have a hemorrhagic thoracic schwannoma at time of surgery in the setting of anti-platelet therapy use. In patients with spinal schwannomas, tumor hemorrhage is a rare occasion, which can be considered in the setting of additive effects of spinal manipulation therapy and antiplatelet therapy. PMID:28377856

  15. Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae.

    PubMed

    Cprek, Jessica B; Gallagher, Jason C

    2015-11-09

    We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

    PubMed Central

    Cprek, Jessica B.

    2015-01-01

    We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options. PMID:26552970

  17. Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial.

    PubMed

    Jarrett, R B; Schaffer, M; McIntire, D; Witt-Browder, A; Kraft, D; Risser, R C

    1999-05-01

    Patients with atypical depression are more likely to respond to monoamine oxidase inhibitors than to tricyclic antidepressants. They are frequently offered psychotherapy in the absence of controlled tests. There are no prospective, randomized, controlled trials, to our knowledge, of psychotherapy for atypical depression or of cognitive therapy compared with a monoamine oxidase inhibitor. Since there is only 1 placebo-controlled trial of cognitive therapy, this trial fills a gap in the literature on psychotherapy for depression. Outpatients with DSM-III-R major depressive disorder and atypical features (N = 108) were treated in a 10-week, double-blind, randomized, controlled trial comparing acute-phase cognitive therapy or clinical management plus either phenelzine sulfate or placebo. Atypical features were defined as reactive mood plus at least 2 additional symptoms: hypersomnia, hyperphagia, leaden paralysis, or lifetime sensitivity to rejection. With the use of an intention-to-treat strategy, the response rates (21-item Hamilton Rating Scale for Depression score, < or =9) were significantly greater after cognitive therapy (58%) and phenelzine (58%) than after pill placebo (28%). Phenelzine and cognitive therapy also reduced symptoms significantly more than placebo according to contrasts after a repeated-measures analysis of covariance and random regression with the use of the blind evaluator's final Hamilton Rating Scale for Depression score. The scores between cognitive therapy and phenelzine did not differ significantly. Supplemental analyses of other symptom severity measures confirm the finding. Cognitive therapy may offer an effective alternative to standard acute-phase treatment with a monoamine oxidase inhibitor for outpatients with major depressive disorder and atypical features.

  18. A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF ORAL MATRICARIA RECUTITA (CHAMOMILE) EXTRACT THERAPY OF GENERALIZED ANXIETY DISORDER

    PubMed Central

    Amsterdam, Jay D.; Li, Yimei; Soeller, Irene; Rockwell, Kenneth; Mao, Jun James; Shults, Justine

    2013-01-01

    Objective We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate Generalized Anxiety Disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile. Materials & Methods 61 outpatients with mild to moderate GAD were enrolled and 57 were randomized to either double blind chamomile extract (n=28) or placebo (n=29) therapy for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory score, Psychological Well Being score, Clinical Global Impression Severity score, and the proportion of patients with ≥50% reduction in baseline HAM-A score. Results We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (p=0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or ≥3 adverse events was not significantly different between groups (p=0.417). Conclusion This is the first, controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations. PMID:19593179

  19. Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral Lichen Planus Lesions Presenting Poor Response to Therapy

    PubMed Central

    Dillenburg, Caroline S.; Martins, Marco A.T.; Almeida, Luciana O.; Meurer, Luise; Squarize, Cristiane H.; Martins, Manoela D.; Castilho, Rogerio M.

    2015-01-01

    Abstract Epigenetics refers to changes in cell characteristics that occur independently of modifications to the deoxyribonucleic acid (DNA) sequence. Alterations mediated by epigenetic mechanisms are important factors in cancer progression. Although an exciting prospect, the identification of early epigenetic markers associated with clinical outcome in premalignant and malignant disorders remains elusive. We examined alterations in chromatin acetylation in oral lichen planus (OLP) with distinct clinical behavior and compared the alterations to the levels of DNA double-strand breaks (DSBs). We analyzed 42 OLP patients, who had different responses to therapy, for acetyl-histone H3 at lys9 (H3K9ac), which is associated with enhanced transcription and nuclear decondensation, and the presence of DSBs, as determined by accumulation of phosphorylated γH2AX foci. Patients with high levels of H3K9ac acetylation failed to respond to therapy or experienced disease recurrence shortly after therapy. Similar to H3K9ac, patients who responded poorly to therapy had increased accumulation of DNA DSB, indicating genomic instability. These findings suggest that histone modifications occur in OLP, and H3K9ac and γH2AX histones may serve as epigenetic markers for OLP recurrence. PMID:26222871

  20. BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study

    PubMed Central

    Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

    2015-01-01

    Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee. PMID:26078768

  1. BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study.

    PubMed

    Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

    2015-01-01

    Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee.

  2. Standard Triple Therapy versus Sequential Therapy in Helicobacter pylori Eradication: A Double-Blind, Randomized, and Controlled Trial.

    PubMed

    Eisig, Jaime Natan; Navarro-Rodriguez, Tomás; Teixeira, Ana Cristina Sá; Silva, Fernando Marcuz; Mattar, Rejane; Chinzon, Decio; Haro, Christiane; Diniz, Márcio Augusto; Moraes-Filho, Joaquim Prado; Fass, Ronnie; Barbuti, Ricardo Correa

    2015-01-01

    Aim. To compare 10-day standard triple therapy versus sequential therapy as first-line treatment in patients infected with H. pylori. Methods. One hundred H. pylori positive patients (diagnosed by rapid urease test and histology), with average age of 47.2, M/F = 28/72, were randomized to receive either standard triple treatment (TT) as follows: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 g, b.i.d. for ten days, or sequential treatment (ST) as follows: lansoprazole 30 mg, amoxicillin and placebo 1.0 g b.i.d for the first five days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and tinidazole 500 mg b.i.d, for the remaining five days. Eradication rates were determined 60 days after treatment by urease, histology, or (13)C-urea breath test. Results. In intention to treat (ITT) analysis, the rate of H. pylori eradication in the TT and ST groups was the same for both regimens as follows: 86% (43/50), 95% CI 93,3 to 73.4%. In Per protocol (PP) analysis, the rate of H. pylori eradication in the TT and ST groups was 87.8% (43/49), 95% CI 94,5 to 75.3% and 89.6% (43/48), 95% CI 95,8 to 77.3%, respectively. Conclusions. In Brazil, standard triple therapy is as equally effective as sequential therapy in eradicating Helicobacter pylori patients. This study was registered under Clinical Trials with number ISRCTN62400496.

  3. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties

    PubMed Central

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder

    2015-01-01

    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5 h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5 h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNFα whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M

  4. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties.

    PubMed

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder

    2015-12-01

    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNFα whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M cell

  5. Laser Assisted Non-surgical Periodontal Therapy: A Double Blind, Randomized Clinical Trial

    PubMed Central

    Everett, Joseph D.; Rossmann, Jeffrey A.; Kerns, David G.; Al-Hashimi, Ibtisam

    2017-01-01

    The objective of this study was to examine potential benefits of using laser therapy for secular decontamination in conjunction with scaling and root planing in the treatment of chronic periodontitis. The study was performed on 173 teeth in 14 patients in a split-mouth design, one side received scaling and root planing followed by laser therapy using a carbon dioxide (CO2) laser with an ablative handpiece (test group); the contralateral side received scaling and root planing without laser (control group). Clinical and laboratory parameters were evaluated prior to treatment and at 3 and 6 months following therapy; clinical measurements were performed by two blinded examiners. The clinical parameters included measurement of gingival recession (REC), bleeding on probing (BOP), clinical attachment level (CAL), pocket depth (PD), furcation involvement (FUR), and tooth mobility (MOB). Laboratory testing to determine the levels of periodontal pathogens was performed using PCR techniques. The results of the study revealed statistically significant differences in clinical and laboratory parameters at 3 and 6 months after therapy for both test and control groups, but no significant difference was observed between the two groups. However, sites receiving laser therapy tended to show a greater decrease in probing depths, gain in clinical attachment level, and reduced bacterial levels. In conclusion, the overall results of the study suggest a potential benefit of using laser therapy in conjunction with scaling and root planing for the treatment of chronic periodontitis. PMID:28357001

  6. Anti-platelet drugs in patients with femoral neck fractures undergoing cemented hip hemiarthroplasty surgery. A study of complications and mortality.

    PubMed

    Agudo Quiles, M; Sanz-Reig, J; Alcalá-Santaella Oria de Rueca, R

    2015-01-01

    To assess complications and factors predicting one-year mortality in patients on antiplatelet agents presenting with femoral neck fractures undergoing hip hemiarthroplasty surgery. A review was made on 50 patients on preoperative antiplatelet agents and 83 patients without preoperative antiplatelet agents. Patients in both groups were treated with cemented hip hemiarthroplasty. A statistical comparison was performed using epidemiological data, comorbidities, mental state, complications and mortality. There was no lost to follow-up. The one-year mortality was 20.3%. In patients without preoperative antiplatelet agents it was 14.4% and in patients with preoperative antiplatelet agents was 30%. Age, ASA grade, number of comorbidities and antiplatelet agent therapy were predictors of one-year mortality. The one-year mortality of patients on clopidogrel was 46.1%, versus 24.3% in patients on acetylsalicylic acid. Patients with preoperative antiplatelet therapy were older and had greater number of comorbidities, ASA grade, delayed surgery, and a longer length of stay than patients without antiplatelet therapy. The one-year mortality was higher in patients with preoperative antiplatelet therapy. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  7. Interferential and horizontal therapies in chronic low back pain due to multiple vertebral fractures: a randomized, double blind, clinical study.

    PubMed

    Zambito, A; Bianchini, D; Gatti, D; Rossini, M; Adami, S; Viapiana, O

    2007-11-01

    Chronic low back pain due to multiple vertebral fractures is of difficult management. Electrical nerve stimulation is frequently used, but its efficacy has never been properly evaluated. In a randomized placebo-controlled clinical trial, we have shown that both interferential currents and horizontal therapy are more effective than placebo for functional. Multiple vertebral fractures almost invariably ensue in chronic low back pain that remains of difficult management. Electrical nerve stimulation is frequently used but its efficacy has never been properly evaluated. One hundred and fifteen women with chronic back pain due to previous multiple vertebral osteoporotic fractures (CBPMF) were randomly assigned to either interferential currents (IFT), horizontal therapy (HT) or sham HT administered for 30 minutes daily for 5 days per week for two weeks together with a standard exercise program. Efficacy assessment was obtained at baseline and at week 2, 6 and 14 and included a functional questionnaire (Backill), the standard visual analog scale (VAS) and the mean analgesic consumption. At week 2 a significant and similar improvement in both the VAS and Backill score was observed in the three groups. The two scores continued to improve in the two active groups with changes significantly (p < 0.001) greater than those observed in control patients at week 6 and 14. The use of analgesic medications improved only in the HT group. This randomized double-blind controlled study provides the first evidence that IFT and HT therapy are significantly effective in alleviating both pain and disability in patients with CBPMF.

  8. Dutasteride in men receiving testosterone therapy: a randomised, double-blind study.

    PubMed

    Kacker, R; Harisaran, V; Given, L; Miner, M; Rittmaster, R; Morgentaler, A

    2015-03-01

    We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty-three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (-0.46 ± 0.81 ng ml(-1) ; P = 0.04) and in PV (-6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (-0.46 versus 0.21 ng ml(-1) ; P = 0.11), PV (-6.65% versus 3.4%; P = 0.08) and MSHQ scores (-10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy.

  9. A randomised double blind comparative study of low level laser therapy following surgical extraction of lower third molar teeth.

    PubMed

    Fernando, S; Hill, C M; Walker, R

    1993-06-01

    A randomised, double blind comparative study was undertaken to assess the efficacy of low level laser therapy in the reduction of postoperative pain and swelling in patients undergoing the extraction of bilaterally impacted mandibular third molar teeth. Healing of the sockets was also compared after 1 week. A group of 64 patients had one randomly-selected operation side treated with a semi-conductor laser and the other side with an apparently identical but non-operating model. Complete data were obtained from 52 of the 64 patients. The results showed that there was no evidence of a difference in pain and swelling on the third day after operation between laser and placebo sides. There was no difference between the two sides when they were assessed for healing 7 days after surgery.

  10. Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial

    PubMed Central

    Vogel, Thomas; Verreault, René; Gourdeau, Marie; Morin, Michèle; Grenier-Gosselin, Lise; Rochette, Louis

    2004-01-01

    Background The optimal duration of antibiotic therapy in older patients with uncomplicated urinary tract infection (UTI) is still a matter of debate. The aim of this randomized controlled double-blind noninferiority trial was to compare the efficacy and safety of 3-day and 7-day courses of oral ciprofloxacin for uncomplicated symptomatic UTI in older women. Methods A total of 183 women at least 65 years of age with acute uncomplicated UTI were recruited from ambulatory clinics and hospital acute care units. Patients with pyelonephritis, contraindications to fluoroquinolones, recent use of antibiotics, urinary tract abnormalities and diabetes mellitus were excluded. Women were randomly assigned to receive either ciprofloxacin 250 mg twice daily orally for 3 days followed by placebo for 4 days (the 3-day group, 93 patients) or ciprofloxacin 250 mg twice daily orally for 7 days (the 7-day group, 90 patients). Bacterial eradication, clinical improvement and occurrence of adverse events were determined 2 days after completion of treatment, and occurrence of reinfection or relapse were determined 6 weeks after completion of treatment. Bacterial eradication and relapse were determined by urine culture. Double-blind procedures were maintained throughout data collection. Results The proportion of patients with bacterial eradication at 2 days after treatment was 98% (91/93) in the 3-day group and 93% (83/89) in the 7-day group (p = 0.16). The frequency of adverse events, including drowsiness, headache, nausea or vomiting, and loss of appetite, was significantly lower in the 3-day group. Interpretation These results suggest that a 3-day course of antibiotic therapy is not inferior to a 7-day course for treatment of uncomplicated symptomatic UTI in older women, and that the shorter course is better tolerated. PMID:14970093

  11. Chronic lateral humeral epicondylitis--a double-blind controlled assessment of pulsed electromagnetic field therapy.

    PubMed

    Devereaux, M D; Hazleman, B L; Thomas, P P

    1985-01-01

    Pulsed electromagnetic fields (PEMF) have been shown to be beneficial in the treatment of rotator cuff tendinitis. As lateral humeral epicondylitis (tennis elbow) is a similar chronic tendon lesion, 30 patients with both clinical and thermographic evidence of tennis elbow were randomly allocated to receive either active or inactive PEMF therapy. Treatment was continued for a minimum period of eight weeks. At this time there was no statistical difference between the two groups.

  12. Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial

    PubMed Central

    MacDonald, Thomas M; Williams, Bryan; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Mackenzie, Isla S; Salsbury, Jackie; Morant, Steve; Ford, Ian; Brown, Morris J

    2015-01-01

    Introduction Previous studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension. Methods and analysis The study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg. Ethics and dissemination PATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the

  13. Aerobic training abolishes ambulatory blood pressure increase induced by estrogen therapy: a double blind randomized clinical trial.

    PubMed

    Cardoso, Crivaldo Gomes; Rosas, Fabrício Collares; Oneda, Bruna; Labes, Eliana; Tinucci, Taís; Abrahão, Sandra Balieiro; da Fonseca, Angela Maggio; Mion, Decio; Forjaz, Cláudia Lúcia de Moraes

    2011-06-01

    Emerging data reveal that oral estrogen therapy can increase clinic blood pressure (BP) in post-menopausal women; however, it is important to establish its effects on ambulatory BP, which is a better predictor for target-organ damage. Besides estrogen therapy, aerobic training is widely recommended for post-menopausal women, and it can decrease ambulatory BP levels. This study was designed to evaluate the effect of aerobic training and estrogen therapy on the ambulatory BP of post-menopausal women. Forty seven healthy hysterectomized women were randomly divided (in a double-blind manner) into 4 groups: placebo-control (PLA-CO=12), estrogen therapy-control (ET-CO=14), placebo-aerobic training (PLA-AT=12), and estrogen therapy-aerobic training (ET-AT=09). The ET groups received estradiol valerate (1 mg/day) and the AT groups performed cycle ergometer, 3×/week at moderate intensity. Hormonal status (blood analysis), maximal cardiopulmonary exercise test (VO(2) peak) and ambulatory BP (24-h, daytime and nighttime) was evaluated before and 6 months after interventions. A significant increase in VO(2) peak was observed only in women who participated in aerobic training groups (+4.6±1.0 ml kg(-1) min(-1), P=0.00). Follicle-stimulating hormone was a significant decreased in the ET groups (-18.65±5.19 pg/ml, P=0.00), and it was accompanied by an increase in circulating estrogen (56.1±6.6 pg/ml). A significant increase was observed in the ET groups for daytime (P=0.01) and nighttime systolic BP (P=0.01), as well as nighttime diastolic BP (P=0.02). However, daytime diastolic BP was increased only in the ET-CO group (+3.4±1.2 mmHg, P=0.04), and did not change in any other groups. No significant effect was found in ambulatory heart rate. In conclusion, aerobic training abolished the increase of daytime ambulatory BP induced by estrogen therapy in hysterectomized, healthy, normotensive and postmenopausal women. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Synergistic effect of anti-platelet and anti-inflammation of drug-coated Co-Cr substrates for prevention of initial in-stent restenosis.

    PubMed

    Lih, Eugene; Jung, Jee Won; Joung, Yoon Ki; Ahn, Dong June; Han, Dong Keun

    2016-04-01

    Antiplatelet and antithrombotic therapies are systematically considered to prevent restenosis following coronary stent implantation. Currently, patients receiving medicated stents are prescribed to orally take anticoagulants and antiplatelet drugs such as aspirin (ASP) and prasugrel (PRAS). Propolis (PROP) known as a natural organic compound was recently evaluated for its antiplatelet activity, antibiotics and immunomodulatory activities. In this study, antiplatelet drug-coated Co-Cr substrates were prepared with biodegradable poly(d,l-lactide) (PDLLA) containing ASP, PRA, or PROP using electrospray and the blood compatibility of the different substrates was investigated by measuring protein adsorption and platelet adhesion. In addition, the anti-inflammatory properties of the modified Co-Cr surfaces were assessed by measuring IL-8 and IL-6 expression levels in human endothelial cell cultures. Drug-coated surfaces were found to resist the adsorption of fibrinogen when compared to bare Co-Cr or PDLLA-coated Co-Cr. Interestingly, ASP- and PROP-containing substrates not only showed reduced adhesion of platelets and delayed coagulation time, but also drastically reduced the expression level of IL-8 and IL-6. Such results are supported that ASP- or PROP-coated Co-Cr can be potentially used as a stent material to mitigate early stage of restenosis. The developed coating materials might be an interesting alternative to systemic anticoagulant therapies prescribed after stent implantation. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy

    PubMed Central

    Galati, Giovanni; Rampa, Lorenzo; Vespasiani-Gentilucci, Umberto; Marino, Mirella; Pisani, Francesco; Cota, Carlo; Guidi, Alessandro; Picardi, Antonio

    2016-01-01

    B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in onco-haematological diseases. PMID:27803769

  16. Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy.

    PubMed

    Galati, Giovanni; Rampa, Lorenzo; Vespasiani-Gentilucci, Umberto; Marino, Mirella; Pisani, Francesco; Cota, Carlo; Guidi, Alessandro; Picardi, Antonio

    2016-10-18

    B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in onco-haematological diseases.

  17. A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

    DTIC Science & Technology

    2005-11-01

    Toxicol Methods 1997; 38: 59-69. toxicity. Clin Cancer Res 2004; 10: 8697-8703. 47 Chartier C et al. Efficient generation of recombinant adenovirus 32...described above) essentially as described (Krasnykh et al., 1998). pVK700 is derived from pTG3602 ( Chartier et al.. 1996), but contains an almost complete...tropism in ovarian cancer gene therapy. Hum Gene Ther 15(5), 509-18. Chartier , C., Degryse, E., Gantzer. M., Dieterle, A., Pavirani, A., and Mehtali, M

  18. Double-edged sword of radiotherapy: a cause of secondary angiosarcoma after breast conservation therapy.

    PubMed

    Iqbal, Fahad Mujtaba; Ahmed, Balen; Vidya, Raghavan

    2016-04-25

    Angiosarcomas are rare and aggressive malignant tumours of vascular or endothelial origin that can originate in the breast. They can be classified as primary or secondary, with the latter most commonly due to postoperative radiotherapy as part of breast conservation therapy (wide local excision and adjuvant radiotherapy) for breast cancer. We report a case of postirradiation secondary angiosarcoma in a 56-year-old woman, alongside a review of the current literature, to inform clinicians of its clinical presentation and characteristics as a high index of clinical suspicion is required for an accurate diagnosis. 2016 BMJ Publishing Group Ltd.

  19. Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

    PubMed Central

    Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

    2014-01-01

    Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

  20. Primary Double-Strike Therapy for Cancers to Overcome EGFR Kinase Inhibitor Resistance: Proposal from the Bench

    PubMed Central

    Suda, Kenichi; Bunn, Paul A.; Rivard, Christopher J.; Mitsudomi, Tetsuya; Hirsch, Fred R.

    2017-01-01

    Diverse molecular mechanisms that confer acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in lung cancers with sensitive EGFR mutations have been reported. However, it is not realistic to analyze for all these mechanisms at the time of resistance in clinical practice and establish adequate treatment targeting these numerous resistance mechanisms. Therefore, we believe that we should move our research focus from the exploration of “established” diverse resistance mechanisms to the elucidation of molecular mechanisms that enable cancer cells to remain alive at the early phase of the treatment. Here in this review, we summarize up-to-date molecular mechanisms that maintain residual tumor cells against EGFR TKI monotherapy in lung cancers with EGFR mutations. We classified these mechanisms into three categories. The first is a pre-existing minor subpopulation with a resistance mechanism such as a pretreatment T790M mutation that can be detected by highly sensitivity methods. The second is the reversible drug-tolerant state that is often observed in cell line models and accounts for the lack of complete response and continued survival of cells exposed to EGFR TKIs in patients. And the last is the role of the microenvironment, including survival signaling from fibroblasts or dying cancer cells and the role of poor vascularization. Primary double-strike cancer therapy, or even initial multiple-strike therapy, to cancer cells that cotarget EGFR and survival mechanism(s) simultaneously would be a promising strategy to improve the outcomes of patients with EGFR mutations. PMID:27642065

  1. Double-blind controlled randomised study of lactulose and lignin hydrolysed combination in complex therapy of atopic dermatitis

    PubMed Central

    Perlamutrov, Yuri N.; Olhovskaya, Kira B.; Zakirova, Svetlana A.

    2016-01-01

    Background Atopic dermatitis (AD) is an immune mediated disease with complex pathogenesis characterised by persistency, frequent exacerbations, and inefficacy of existing therapies. Damaged or weakened intestinal microbiocenosis is considered as an important aetiological factor of AD. The aim of this study was to evaluate the efficacy and safety of medical preparation Lactofiltrum (lactulose and sorbent (lignin hydrolysed)) in comparison with placebo in complex with standard therapy of AD. Methods Double-blind, placebo controlled, randomised comparative study of effectiveness and safety of 400 mg lactulose and 120 mg lignin hydrolysed combination as a part of standard combined AD treatment, conducted in parallel groups of patients aged 18–60. Results Comparison of clinical efficacy of Lactofiltrum in combination with the standard treatment has been demonstrated by measuring the following parameters: administration of Lactofiltrum results in 1) distinct clinical improvement in 56.75% of patients, 2) decrease of the mean values of scoring atopic dermatitis (SCORAD) index in 71.94% of patients, 3) elimination of itching in 50% of patients, and 4) life quality improvement for 76.41%. In the placebo group, 1) distinct clinical improvement was observed in 20% of patients, 2) decrease in SCORAD index values observed by 56.98%, 3) itching relief in 15.56%, and 4) life quality improvement by 36.38%. Conclusions Clinical improvement and persistent termination of clinical symptoms provide evidence of effectiveness in use of Lactofiltrum combined with the standard treatment of AD. PMID:27341938

  2. Mannose-conjugated layered double hydroxide nanocomposite for targeted siRNA delivery to enhance cancer therapy.

    PubMed

    Li, Li; Zhang, Run; Gu, Wenyi; Xu, Zhi Ping

    2017-06-22

    Sheet-like layered double hydroxide nanoparticles (LDH NPs) have showed great potentials in biomedical applications such as nanocarriers for drug and gene delivery, biosensors and imaging agents. However, target delivery of drugs and genes using LDH NPs to the desired tumor sites is a major challenge in cancer therapy. The aim of this study is to develop a functional LDH-based nanocomposite for target delivery of siRNA to cancer cells. Mannose as a targeting moiety was firstly conjugated onto SiO2-coated LDH nanocomposite. Cellular uptake data have demonstrated that siRNA is more efficiently delivered to osteosarcoma (U2OS) cells by mannose-conjugated SiO2 coated LDH nanocomposite (Man-SiO2@LDH) compared to unmodified LDH NP. A commercial cell death-siRNA (CD-siRNA) delivered by Man-SiO2@LDH can kill cancer cells more effectively. These results reveal that the Man-SiO2@LDH nanocomposite is capable of target-delivering siRNA or drugs to tumor cells for more effective cancer treatment, which provides great potentials in cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Double-flash, large-fraction radiation therapy as palliative treatment of malignant superior vena cava syndrome in the elderly.

    PubMed

    Lonardi, Federico; Gioga, Gloria; Agus, Graziella; Coeli, Manuela; Campostrini, Franco

    2002-03-01

    Rapid control of symptoms is mandatory in cancer-induced superior vena cava syndrome (SVCS), but older patients often do not tolerate aggressive approaches. In order to maximize symptom relief and minimize treatment-related discomfort of aged patients in poor health we adopted a short-course, large-fraction radiation therapy (RT) schedule. Twenty-three consecutive patients aged over 70 who were suffering from solid-malignancy-related SVCS were enrolled. A total dose of 12 Gy was given in two 6-Gy fractions, 1 week apart, mainly in an out-patient setting. Completion of therapy to give up to 37-40 Gy was planned in the best-responding patients. Symptom relief was experienced by 8 patients as early as 4-5 days after the first fraction. The overall response rate was 87%. Despite some mild systemic side effects (chest pain, fever) reported by 5 patients (22%), overall toxicity was negligible. Short-course, double-flash RT stands as an effective and safe tool in the palliative treatment of malignant SVCS in older patients. Fractions larger than 6 Gy can be avoided in order to minimize side and toxic effects.

  4. In vivo vitiligo induction and therapy model: double-blind, randomized clinical trial.

    PubMed

    van Geel, Nanja; Speeckaert, Reinhart; Mollet, Ilse; De Schepper, Sofie; De Wolf, Julie; Tjin, Esther P M; Luiten, Rosalie M; Lambert, Jo; Brochez, Lieve

    2012-01-01

    In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner's phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to three Koebner induction methods: cryotherapy, 755 nm laser therapy, and epidermal abrasion. In addition, four cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied. Koebnerization was efficiently induced by all three induction methods. In general, cryotherapy was the best method of Koebner induction, followed by 755 nm laser therapy and epidermal abrasion. Reproducible results were obtained, which showed enhanced depigmented surface areas and higher amounts of T lymphocytes in placebo-treated test zones compared to active treated areas. Tacrolimus and local steroids were better inhibitors of Koebner's process (P < 0.05) compared to pimecrolimus. Our in vivo vitiligo induction model is very informative to investigate vitiligo induction and to determine the efficacy of topical treatments in vitiligo. This proof of concept confirms the efficient comparison of head-to-head therapeutic strategies intra-individually in a standardized, specific and better timed way.

  5. Caffeine as an adjuvant therapy to opioids in cancer pain: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Suh, Sang-Yeon; Choi, Youn Seon; Oh, Sang Cheul; Kim, Young Sung; Cho, Kyunghee; Bae, Woo Kyung; Lee, Ju Hyun; Seo, Ah-Ram; Ahn, Hong-Yup

    2013-10-01

    Opioid therapy often shows insufficient efficacy and substantial adverse events in patients with advanced cancer. To assess the efficacy of caffeine infusion as an adjuvant analgesic to opioid therapy in patients with advanced cancer. A double-blind, randomized, placebo-controlled trial was conducted in the palliative care wards of two teaching hospitals in South Korea. A total of 20 of 41 participants were assigned to the caffeine group and 21 to the placebo group. The participants received caffeine (200mg) or normal saline intravenously once a day for two days. The primary outcome was pain, which was measured using a 10-point rating scale. Other outcomes included drowsiness, confusion, nausea, sleep disturbance, fatigue, and sadness. Three participants (two in the caffeine group and one in the placebo group) dropped out after the first intervention because of insomnia; thus, 38 participants completed the trial. Pain score was significantly lower in the caffeine group than in the placebo group after the second trial (P=0.038). The mean reduction in pain intensity in the caffeine group was 0.833 (95% confidence interval [CI] 0.601-1.066), whereas that in the placebo group was 0.350 (95% CI 0.168-0.532). Considering an improvement higher than 30% from baseline as the threshold value, drowsiness improved significantly in the caffeine group after the first trial (P=0.041). Adverse event rate did not differ between the two groups. Caffeine infusion significantly reduced pain and drowsiness, but the reduction did not reach clinical significance in patients with advanced cancer undergoing opioid therapy. Further investigations are warranted. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  6. Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

    PubMed Central

    Worth, Heinrich; Schacher, Christian; Dethlefsen, Uwe

    2009-01-01

    Background The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. Methods In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Results Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Conclusion Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane. Trial registration ISRCTN07600011 PMID:19624838

  7. Gold Nanorods, DNA Origami, and Porous Silicon Nanoparticle-functionalized Biocompatible Double Emulsion for Versatile Targeted Therapeutics and Antibody Combination Therapy.

    PubMed

    Kong, Feng; Zhang, Hongbo; Qu, Xiangmeng; Zhang, Xu; Chen, Dong; Ding, Ruihua; Mäkilä, Ermei; Salonen, Jarno; Santos, Hélder A; Hai, Mingtan

    2016-12-01

    Gold nanorods, DNA origami, and porous silicon nanoparticle-functionalized biocompatible double emulsion are developed for versatile molecular targeted therapeutics and antibody combination therapy. This advanced photothermal responsive all-in-one biocompatible platform can be easily formed with great therapeutics loading capacity for different cancer treatments with synergism and multidrug resistance inhibition, which has great potential in advancing biomedical applications.

  8. PSA doubling time kinetics during prostate cancer biochemical relapse after external beam radiation therapy

    SciTech Connect

    Bates, Andrew Tom . E-mail: andrew.bates@doctors.org.uk; Pickles, Tom; Paltiel, Chuck

    2005-05-01

    Purpose: To investigate whether prostate-specific antigen PSA doubling time (PSADT) is constant in men with biochemical prostate cancer relapse after external beam radiotherapy (EBRT). Methods and Materials: A total of 513 men treated radically with EBRT, with or without androgen ablation (AA), between 1993 and 2000, developed biochemical relapse. The slope of the ln (PSA) vs. time graph is calculated for the first two values after PSA nadir (first slope), the last two recorded PSAs (last slope), and all values excluding the first and final PSA (mid slope). Differences in these slopes were compared statistically with subgroup analysis for AA and secondary intervention. Results: For men treated with EBRT and AA first slope was faster than either mid slope (p = 0.031) or last slope (p < 0.001). Men treated with EBRT alone had no change in PSADT over time unless they subsequently received secondary intervention. This group had a more rapid last slope compared with mid slope (p < 0.001). Conclusions: PSA initially rises more rapidly after AA cessation, probably because of testosterone recovery. A subgroup of patients, who received secondary intervention after treatment with radiotherapy alone, showed a change in PSADT, to a faster velocity. This greater than constant exponential PSA growth is presumably the catalyst for secondary intervention. Otherwise, PSADT did not change during prostate cancer biochemical relapse.

  9. A double-regulated oncolytic adenovirus with improved safety for adenocarcinoma therapy

    SciTech Connect

    Wei, Na; Fan, Jun Kai; Gu, Jin Fa; He, Ling Feng; Tang, Wen Hao; Cao, Xin; Liu, Xin Yuan

    2009-10-16

    Safety and efficiency are equally important to be considered in developing oncolytic adenovirus. Previously, we have reported that ZD55, an oncolytic adenovirus with the deletion of E1B-55K gene, exhibited potent antitumor activity. In this study, to improve the safety of ZD55, we utilized MUC1 promoter to replace the native promoter of E1A on the basis of ZD55, and generated a double-regulated adenovirus, named MUD55. Our data demonstrated that the expression of early and late genes of MUD55 was both reduced in MUC1-negative cells, resulting in its stricter glandular-tumor selective progeny production. The cytopathic effect of MUD55 was about 10-fold lower than mono-regulated adenovirus ZD55 or Ad.MUC1 in normal cells and not obviously attenuated in glandular tumor cells. Moreover, MUD55 showed the least liver toxicity when administrated by intravenous injection in nude mice. These results indicate that MUD55 could be a promising candidate for the treatment of adenocarcinoma.

  10. Dental extraction in patients receiving dual antiplatelet therapy

    PubMed Central

    Sánchez-Palomino, Paulino; Sánchez-Cobo, Paulino; Rodriguez-Archilla, Alberto; González-Jaranay, Maximino; Moreu, Gerardo; Calvo-Guirado, José-Luis; Peñarrocha-Diago, Miguel

    2015-01-01

    Background Dual anti platelet therapy consists of administering antiplatelet (antiaggregant) drugs (clopidogrel and aspirin) to prevent thrombotic processes, as a preventative measure in patients with acute coronary disease, or in patients subjected to percutaneous coronary intervention. Objectives The purpose of this study was to evaluate the efficacy of a protocol for performing dental extraction in patients receiving dual anti platelet therapy. Material and Methods Thirty-two patients undergoing dental extractions were included in the study. The variables evaluated were: collagen-epinephrine fraction, collagen- adenosine diphosphate fraction, surgical surface, post-surgical measures, and adverse effects. Alveolar sutures and gauzes impregnated with an antifibrinolytic agent (tranexamic acid), which the patient pressed in place for 30 minutes, were applied to all patients as post-surgical measures. Descriptive statistics were calculated and analyzed with Student’s t-test to compare pairs of quantitative variables; simple regression analysis was performed using Pearson’s correlation coefficient. Statistical significance was set at p<0.05. Results Collagen/epinephrine fraction was 264.53±55.624 seconds with a range of 135 to 300 seconds, and collagen/ADP fraction was 119.41±44.216 seconds, both values being higher than normal. As a result of the post-surgical measures taken, no patients presented postoperative bleeding, hematoma or infection. Conclusions Dental extraction was safe for patients receiving dual anti-platelet therapy when using sutures and gauze impregnated with tranexamic acid, which the patient pressed in place for 30 minutes. Key words: Aspirin, clopidogrel, tranexamic acid, dental extraction, platelet function. PMID:26241454

  11. A double-blind randomized study comparing the effects of continuing or not continuing rosiglitazone + metformin therapy when starting insulin therapy in people with Type 2 diabetes1

    PubMed Central

    Home, P D; Bailey, C J; Donaldson, J; Chen, H; Stewart, M W

    2007-01-01

    Aims To compare the efficacy and safety of either continuing or discontinuing rosiglitazone + metformin fixed-dose combination when starting insulin therapy in people with Type 2 diabetes inadequately controlled on oral therapy. Methods In this 24-week double-blind study, 324 individuals with Type 2 diabetes inadequately controlled on maximum dose rosiglitazone + metformin therapy were randomly assigned to twice-daily premix insulin therapy (target pre-breakfast and pre-evening meal glucose ≤ 6.5 mmol/l) in addition to either rosiglitazone + metformin (8/2000 mg) or placebo. Results Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 ± 1.5 U/day, mean ± se) compared with placebo [59.0 ± 3.0 U/day; model-adjusted difference −26.6 (95% CI −37.7, −15,5) U/day, P < 0.001]. Despite this, there was greater improvement in glycaemic control [HbA1c rosiglitazone + metformin vs. placebo 6.8 ± 0.1 vs. 7.5 ± 0.1%; difference −0.7 (−0.8, −0.5)%, P < 0.001] and more individuals achieved glycaemic targets (HbA1c < 7.0% 70 vs. 34%, P < 0.001). The proportion of individuals reporting at least one hypoglycaemic event during the last 12 weeks of treatment was similar in the two groups (rosiglitazone + metformin vs. placebo 25 vs. 27%). People receiving rosiglitazone + metformin in addition to insulin reported greater treatment satisfaction than those receiving insulin alone. Both treatment regimens were well tolerated but more participants had oedema [12 (7%) vs. 4 (3%)] and there was more weight gain [3.7 vs. 2.6 kg; difference 1.1 (0.2, 2.1) kg, P = 0.02] with rosiglitazone + metformin. Conclusions Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated. PMID:17403121

  12. [A double gallbladder].

    PubMed

    Mink van der Molen, A B; Salu, M K

    1991-04-06

    A 59-year-old woman is described with symptomatic cholelithiasis. A double gallbladder was incidentally found during abdominal surgery. The literature on a double gallbladder is reviewed with respect to incidence, anatomy, diagnosis and therapy.

  13. Electroacupuncture Therapy in Nicotine Dependence: A Double Blind, Sham-Controlled Study

    PubMed Central

    BİLİCİ, Mustafa; GÜVEN, Sertaç; KÖŞKER, Selcen; ŞAFAK, Ayşe; SEMİZ, Ümit Başar

    2016-01-01

    Introduction The number of non-pharmacological controlled studies is insufficient in the treatment of nicotine dependence (ND). Nevertheless, non-pharmacological treatments, such as electroacupuncture (EA), are becoming increasingly popular in the treatment of ND. The aims of this study were to determine the efficacy and safety of “true EA therapy” (TEAT) compared to those of “sham EA therapy” (SEAT) in ND treatment. Methods Eligible patients who met the DSM-IV criteria for ND (n=450) were included in the study. This study was a double-blinded, sham-controlled clinical trial with a 4-week treatment period and 4-week follow-up conducted between June and December 2009 at a psychiatry outpatient clinic. One hundred and sixty four adult (≥18 years; 44 men, 120 women) cigarette smokers out of 450 patients who met the inclusion and exclusion criteria were enrolled in the study in a ratio of 1:1 to receive TEAT (n=84) or SEAT (n=80). Routine biochemical and hematological tests, chest X-Ray, and ECG were carried out; end-expired carbon monoxide (CO) levels were measured too. Clinical characteristics were obtained through the Fagerström Nicotine Dependence Test (FNDT), Hamilton Rating Scale for Depression (HRSD), and Hamilton Anxiety Scale (HAS). EA was carried out by a trademark device, Antismoke 3000®. Efficacy analyses were performed on “intent-to-treat analysis.” Primary outcome was the differences from baseline to endpoint in mean FNDT, number of cigarettes smoked per day, and CO levels at week 4. Secondary outcomes were the same variables at week 8. These variables were assessed via analysis of covariance (ANCOVA). Results Mean baseline FNDT, HRSD, HAS, and CO levels of the groups were statistically similar. TEAT and SEAT groups demonstrated no significant changes in the outcome variables and smoking cessation rates (35.7% and 30%, respectively). Of those remaining outside of the study, 8.3% were from the TEAT group and 8.7% were from the SEAT group

  14. Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

    PubMed Central

    2012-01-01

    Abstract Background Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015. Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda. Methods In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups. Results Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms. Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0). Among 127 HIV uninfected children receiving the placebo, case fatality was 7

  15. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome

    PubMed Central

    Huang, Jehn-Yu; Yeh, Po-Ting; Hou, Yu-Chih

    2016-01-01

    Purpose To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). Methods A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer’s test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. Results Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti-SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer’s test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. Conclusion Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable-based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES. PMID:27274185

  16. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    SciTech Connect

    Mumbrekar, Kamalesh Dattaram; Fernandes, Donald Jerard; Goutham, Hassan Venkatesh; Sharan, Krishna; Vadhiraja, Bejadi Manjunath; Satyamoorthy, Kapaettu; Bola Sadashiva, Satish Rao

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  17. Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2012-01-01

    Background Treatment of shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration Clinical

  18. Double antiplatelet therapy after drug-eluting stent implantation: risk associated with discontinuation within the first year.

    PubMed

    Ferreira-González, Ignacio; Marsal, Josep R; Ribera, Aida; Permanyer-Miralda, Gaietà; García-Del Blanco, Bruno; Martí, Gerard; Cascant, Purificación; Masotti-Centol, Mónica; Carrillo, Xavier; Mauri, Josepa; Batalla, Nuria; Larrousse, Eduard; Martín, Eva; Serra, Antonio; Rumoroso, José Ramón; Ruiz-Salmerón, Rafael; de la Torre, Jose M; Cequier, Angel; Gómez-Hospital, Jose A; Alfonso, Fernando; Martín-Yuste, Victoria; Sabatè, Manel; García-Dorado, David

    2012-10-09

    The goal of this study was to assess the risk associated with double antiplatelet therapy (DAT) discontinuation, and specifically, temporary discontinuation, during the first year after drug-eluting stent (DES) implantation. Doubts remain about the risk of temporary DAT discontinuation within 1 year after DES implantation. A total of 1,622 consecutive patients undergoing DES implantation at 29 hospitals were followed up at 3, 6, 9, and 12 months to record the 1-year antiplatelet therapy discontinuation (ATD) rate, the number of days without DAT, and the rate of 1-year major cardiac events. Cox regression was used to analyze the association between ATD considered as a time-dependent covariate and 1-year cardiac events. One hundred seventy-two (10.6%) patients interrupted at least 1 antiplatelet drug during the first year after DES implantation, although only 1 during the first month. Most (n=111, 64.5%) interrupted DAT temporarily (median: 7 days; range: 5 to 8.5): 79 clopidogrel (31 temporarily), 38 aspirin (27 temporarily), and 55 both drugs (53 temporarily). Discontinuation was followed by acute coronary syndrome in 7 (4.1%; 95% confidence interval [CI]: 1.7 to 8.2), a similar rate of major cardiac events to that in patients without ATD (n=80; 5.5%; 95% CI: 4.4 to 6.8; p=0.23). ATD was not independently associated with 1-year major cardiac events (hazard ratio: 1.32 [95% CI: 0.56 to 3.12]). ATD within the first year and beyond the first month after DES is not exceptional, is usually temporary, and does not appear to have a large impact on risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome.

    PubMed

    Huang, Jehn-Yu; Yeh, Po-Ting; Hou, Yu-Chih

    2016-01-01

    To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer's test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti-SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer's test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable-based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES.

  20. A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis

    PubMed Central

    Huang, Jeannie; Meixner, Linda; Fernandez, Susan; McCutchan, J. Allen

    2012-01-01

    Objective To evaluate the efficacy of a single dose of intravenous zoledronate for the treatment of HIV-associated osteopenia and osteoporosis. Design A double-blinded, randomized, placebo-controlled, 12 month trial of 5 mg intravenous zoledronate dose to treat 30 HIV-infected men and women with osteopenia and osteoporosis. Methods Following zoledronate or placebo infusions, participants were followed for 12 months on daily calcium and vitamin D supplements. Lumbar spine and hip bone density was assessed at baseline, 6 and 12 months. Biomarkers of bone metabolism were measured at baseline, 2 weeks, 3, 6, 9, and 12 months. Student’s t-test and repeated measure analyses were used to evaluate bone density and bone marker changes over time. Results In the 30 HIV-infected men (27) and women (3) in the trial, median T-scores at entry were -1.7 for the lumbar spine and -1.4 for the hip. Median CD4 count was 461 cells/μL, 93% had HIV-RNA viral loads <400 copies/mL, and 97% were taking antiretroviral medications. Bone density measured either absolutely or as sex-adjusted T-scores significantly improved in zoledronate recipients as compared to minimal changes in those receiving placebo. Bone resorption markers significantly decreased over the study period in the zoledronate recipients as compared to placebo controls. No acute infusion reactions were detected, but one patient developed uveitis, a recognized complication of zoledronate, which responded to therapy. Conclusions In this small study, annual zoledronate appears to be a safe and effective therapy for HIV-associated bone loss. PMID:19050386

  1. Efficacy of low level laser therapy in reducing postoperative pain after endodontic surgery-- a randomized double blind clinical study.

    PubMed

    Kreisler, M B; Haj, H Al; Noroozi, N; Willershausen, B d'Hoedt

    2004-01-01

    The aim of the study was to evaluate the effect of low level laser application on postoperative pain after endodontic surgery in a double blind, randomized clinical study. Fifty-two healthy adults undergoing endodontic surgery were included into the study. Subsequently to suturing, 26 patients had the operation site treated with an 809 nm-GaAlAs-laser (oralaser voxx, Oralia GmbH, Konstanz, Germany) at a power output of 50 mW and an irradiation time of 150 s. Laser treatment was simulated in further 26 patients. Patients were instructed to evaluate their postoperative pain on 7 days after surgery by means of a visual analogue scale (VAS). The results revealed that the pain level in the laser group was lower than in the placebo group throughout the 7 day follow-up period. The differences, however, were significant only on the first postoperative day (Mann-Whitney U-test, p<0.05). Low level laser therapy can be beneficial for the reduction of postoperative pain. Its clinical efficiency and applicability with regard to endodontic surgery, however require further investigation. This is in particular true for the optimal energy dosage and the number of laser treatments needed after surgery.

  2. The Effects of Hormonal Therapy and Exercise on Bone Turnover in Postmenopausal Women: A Randomised Double-Blind Pilot Study.

    PubMed

    Honisett, Suzy Y; Tangalakis, Kathy; Wark, John; Apostolopoulos, Vasso; Stojanovska, Lily

    2016-11-01

    Hormone replacement therapy (HRT) and walking were investigated independently and in combination, to determine which treatment provided most effect on bone turnover in postmenopausal women. Using a randomised double-blind pilot study, 10 subjects received HRT (transdermal estradiol, 50 μg/day and oral MPA 5 mg/day) and 12 received placebo for 20 weeks. Following a baseline period of treatment, both groups undertook a graduated walking regimen, which increased in intensity, duration and frequency parameters from weeks 8-20. Measurements of aerobic capacity, female sex hormones, bone formation markers [osteocalcin (OC) and bone alkaline phosphatase (BAP)] and bone resorption markers [deoxypyridinoline (DPD) and pyridinoline (PYR)] were measured at baseline (T1), week 8 (T2) and week 20 (T3). Age, time of postmenopause, weight or body mass index were no different between each groups. The HRT group had significantly higher estradiol levels compared with the placebo group at T2 and T3. FSH and LH levels were significantly reduced following HRT. DPD and PYR were significantly reduced from baseline levels at T2 and T3 with HRT. No significant changes occurred in OC or BAP levels with either HRT or walking. Walking did not change bone turnover markers in either the HRT or placebo group. HRT reduces bone resorption, however, walking alone at the intensity and duration prescribed, or the combination of HRT and walking, provided no additional benefit after menopause. Therefore, HRT, but not walking is an effective treatment in reducing bone turnover in postmenopause women.

  3. Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults.

    PubMed

    Beaulieu, Karen; Beland, Patricia; Pinard, Marilee; Handfield, Guilène; Handfield, Nicole; Goffaux, Philippe; Corriveau, Hélène; Léonard, Guillaume

    2016-01-01

    Previous studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm(2) Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0-100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

  4. TU-CD-303-02: Beyond Radiation Induced Double Strand Breaks - a New Horizon for Radiation Therapy Research

    SciTech Connect

    Chang, S.

    2015-06-15

    Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of

  5. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial.

    PubMed

    Vestbo, Jørgen; Papi, Alberto; Corradi, Massimo; Blazhko, Viktor; Montagna, Isabella; Francisco, Catherine; Cohuet, Géraldine; Vezzoli, Stefano; Scuri, Mario; Singh, Dave

    2017-05-13

    Limited data are available for the efficacy of triple therapy with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We compared treatment with extrafine beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; fixed triple) with tiotropium, and BDP/FF plus tiotropium (open triple). For this double-blind, parallel-group, randomised, controlled trial, eligible patients had COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) of less than 50%, at least one moderate-to-severe COPD exacerbation in the previous 12 months, and a COPD Assessment Test total score of at least 10. After a 2-week run-in period receiving one inhalation per day via single-dose dry-powder inhaler of open-label 18 μg tiotropium, patients were randomised (2:2:1) using a interactive response technology system to 52 weeks treatment with tiotropium, fixed triple, or open triple. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was moderate-to-severe COPD exacerbation rate. The key secondary endpoint was change from baseline in pre-dose FEV1 at week 52. The trial is registered with ClinicalTrials.gov, number NCT01911364. Between Jan 21, 2014, and March 18, 2016, 2691 patients received fixed triple (n=1078), tiotropium (n=1075), or open triple (n=538). Moderate-to-severe exacerbation rates were 0·46 (95% CI 0·41-0·51) for fixed triple, 0·57 (0·52-0·63) for tiotropium, and 0·45 (0·39-0·52) for open triple; fixed triple was superior to tiotropium (rate ratio 0·80 [95% CI 0·69-0·92]; p=0·0025). For week 52 pre-dose FEV1, fixed triple was superior to tiotropium (mean difference 0·061 L [0·037 to 0·086]; p<0·0001) and non-inferior to open triple (-0·003L [-0·033 to 0·027]; p=0·85). Adverse events were reported by 594 (55%) patients with fixed triple, 622 (58%) with tiotropium, and 309 (58%) with open triple. In our TRINITY study

  6. Video-assisted thoracoscopic lobectomy for non-small cell lung cancer: a morbidity limiting approach in a patient on chronic hemodialysis and double agent antiplatelet therapy.

    PubMed

    Caroli, Guido; Dolci, Giampiero; Dell'Amore, Andrea; Asadi, Nizar; Greco, Domenico; Chadi, Ammari; Bini, Alessandro; Stella, Franco

    2015-03-01

    Patients with end-stage renal disease on hemodialysis undergoing surgery for lung cancer represent a high-risk group because of electrolyte imbalance, anemia, hemodynamic instability, bleeding tendency, and immunocompromised state. We describe a patient on hemodialysis with three lung adenocarcinoma of the right lower lobe as an incidental finding during the clinical course of a myocardial infarction treated with drug-eluting stent implantation and double-agent antiplatelet therapy. Considering patient comorbidities, we decided to perform a right lower lobectomy and complete lymph node dissection by a minimally invasive technique. In our experience, the thoracoscopic approach allowed us to perform lobectomy with complete lymph nodes dissection without morbidity. The use of ultrasound scalpel permits a complete lymph node dissection minimizing bleeding even in a double antiplatelet therapy patient.

  7. Metabolic Effects of Liothyronine Therapy in Hypothyroidism: A Randomized, Double-Blind, Crossover Trial of Liothyronine Versus Levothyroxine

    PubMed Central

    Zemskova, Marina; Linderman, Joyce D.; Smith, Sheila; Drinkard, Bart; Sachdev, Vandana; Skarulis, Monica C.; Kozlosky, Merel; Csako, Gyorgy; Costello, Rene; Pucino, Frank

    2011-01-01

    Context: Levothyroxine (l-T4) therapy is based on the assumption that the conversion of T4 into T3 provides adequate amounts of active hormone at target tissues. However, in rodents, l-T4 alone does not restore a euthyroid state in all tissues. Previous combination l-T4/liothyronine (l-T3) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action. Objective: Our objective was to evaluate the efficacy of thyroid hormone replacement with l-T4 or l-T3 at doses producing equivalent normalization of TSH. Participants, Design, and Setting: Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center. Interventions: l-T3 or l-T4 were administered thrice daily to achieve a target TSH from 0.5–1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH. Main Outcome Measures: Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated. Results: No difference was observed in TSH between l-T3 and l-T4 treatments. l-T3 resulted in significant weight loss [l-T4, 70.6 ± 12.5, vs. l-T3, 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity. Conclusions: The substitution of l-T3 for l-T4 at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity. PMID:21865366

  8. Efficacy of urea therapy in children with ichthyosis. A multicenter randomized, placebo-controlled, double-blind, semilateral study.

    PubMed

    Küster, W; Bohnsack, K; Rippke, F; Upmeyer, H J; Groll, S; Traupe, H

    1998-01-01

    Ichthyoses are genetic disorders of keratinization which are uncomfortable due to their conspicuous scaling, itching and cosmetic problems. Especially in childhood, ichthyoses can lead to social discrimination and psychological problems. Efficient therapies are necessary which are safe and well tolerated. The aim of the study was to investigate the keratolytic and moisturizing properties as well as the tolerance of a new urea lotion when applied to hyperkeratotic and ichthyotic skin in childhood. The study was conducted as a multicenter, randomized, placebo-controlled, double-blind, semilateral investigation. Sixty children between 1 and 16 years treated one side of the most affected extremity with Laceran 10% urea lotion for 8 weeks. On the other side the urea-free Laceran lotion base was given. On each side of the body a control area was left untreated. The investigators evaluated the global severity of ichthyotic symptoms with the help of a visual analogue scale. The analysis of the global estimation of severity of ichthyosis showed improvements being stronger in the body areas treated with Laceran 10% urea lotion (from 4.8 to 2.0 points) than in the areas treated with the urea-free Laceran lotion base (from 4.8 to 2.5 points). The response rates were 65% after 4 weeks and 78% after 8 weeks for Laceran 10% urea lotion, 50% after 4 weeks and 72% after 8 weeks for the urea-free Laceran lotion base. It can be ascertained that Laceran 10% urea lotion has a strong positive effect on generalized ichthyotic keratinization disorders.

  9. Maintenance nifedipine therapy for preterm symptomatic placenta previa: A randomized, multicenter, double-blind, placebo-controlled trial.

    PubMed

    Verspyck, Eric; de Vienne, Claire; Muszynski, Charles; Bubenheim, Michael; Chanavaz-Lacheray, Isabella; Dreyfus, Michel; Deruelle, Philippe; Benichou, Jacques

    2017-01-01

    To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding. PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis. Women were randomly allocated to receive either 20 mg of slow-release nifedipine three times daily (n = 54) or placebo (n = 55) until 36 + 6 weeks of gestation. The primary outcome for the trial was length of pregnancy measured in days after enrolment. Main secondary outcomes were rates of recurrent bleeding, cesarean delivery due to hemorrhage, blood transfusion, maternal side effects, gestational age at delivery and adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage > grade 2, perventricular leukomalacia > grade 1, or necrotizing enterocolitis). Analysis was by intention to treat. Mean (SD) prolongation of pregnancy was not different between the nifedipine (n = 54) and the placebo (n = 55) group; 42.5 days ± 23.8 versus 44.2 days ± 24.5, p = 0.70. Cesarean due to hemorrhage performed before 37 weeks occurred more frequently in the nifedipine group in comparison with the placebo group (RR, 1.66; 95% confidence interval, 1.05-2.72). Adverse perinatal outcomes were comparable between groups; 3.8% for nifedipine versus 5.5% for placebo (relative risk, 0.52; 95% confidence interval 0.10-2.61). No maternal mortality or perinatal death occurred. Maintenance oral nifedipine neither prolongs duration of pregnancy nor improves maternal or perinatal outcomes. ClinicalTrials.gov NCT00620724.

  10. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study.

    PubMed

    Ladson, Gwinnett; Dodson, William C; Sweet, Stephanie D; Archibong, Anthony E; Kunselman, Allen R; Demers, Laurence M; Williams, Nancy I; Coney, Ponjola; Legro, Richard S

    2011-03-01

    To determine if the combination of lifestyle (caloric restriction and exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in improving the polycystic ovary syndrome (PCOS) phenotype. Double-blind randomized 6-month trial of MET versus PBO. Two academic medical centers. One hundred fourteen subjects with PCOS were randomized to MET (N = 55) or PBO (N = 59). Subjects collected urine daily for ovulation monitoring, had monthly monitoring of hormones and weight and determination of body composition by dual-energy x-ray absorptiometry, glucose tolerance, and were evaluated for quality of life at baseline and completion. Ovulation rates and testosterone levels. Dropout rates were high. There was no significant difference in ovulation rates. Testosterone levels were significantly lower compared with baseline in the MET group at 3 mos but not at 6 mos. There were no differences in weight loss between groups, but MET showed a significant decline at 6 months compared with baseline (-3.4 kg, 95% confidence interval -5.3 to -1.5 kg). We noted divergent effects of MET versus PBO on oral glucose tolerance test indices of insulin sensitivity (increased) and secretion (worsened). Total bone mineral density increased significantly in MET. There were no differences in quality of life measures between the groups. The MET group had increased diarrhea and headache, but fewer bladder infections and musculoskeletal complaints. The addition of metformin to lifestyle therapy produced little reproductive or glycemic benefit in women with PCOS, although our study had limited power owing to a high dropout rate. It is not possible at baseline to identify women likely to drop out. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Effect of radial shock wave therapy for carpal tunnel syndrome: A prospective randomized, double-blind, placebo-controlled trial.

    PubMed

    Wu, Yung-Tsan; Ke, Ming-Jen; Chou, Yu-Ching; Chang, Chih-Ya; Lin, Ching-Yueh; Li, Tsung-Ying; Shih, Feng-Mei; Chen, Liang-Cheng

    2016-06-01

    Three recent studies demonstrated the positive effect of extracorporeal shock wave therapy (ESWT) for treating carpal tunnel syndrome (CTS). However, none have entirely proved the effects of ESWT on CTS because all studies had a small sample size and lacked a placebo-controlled design. Moreover, radial ESWT (rESWT) has not been used to treat CTS. We conducted a prospective randomized, controlled, double-blinded study to assess the effect of rESWT for treating CTS. Thirty-four enrolled patients (40 wrists) were randomized into intervention and control groups (20 wrists in each). Participants in the intervention group underwent three sessions of rESWT with nightly splinting, whereas those in the control group underwent sham rESWT with nightly splinting. The primary outcome was visual analog scale (VAS), whereas the secondary outcomes included the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), cross-sectional area (CSA) of the median nerve, sensory nerve conduction velocity of the median nerve, and finger pinch strength. Evaluations were performed before treatment and at 1, 4, 8, and 12 weeks after the third rESWT session. A significantly greater improvement in the VAS, BCTQ scores, and CSA of the median nerve was noted in the intervention group throughout the study as compared to the control group (except for BCTQ severity at week 12 and CSA at weeks 1 and 4) (p < 0.05). This is the first study to assess rESWT in a randomized placebo-controlled trial and demonstrate that rESWT is a safe and effective method for relieving pain and disability in patients with CTS. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:977-984, 2016.

  12. Maintenance nifedipine therapy for preterm symptomatic placenta previa: A randomized, multicenter, double-blind, placebo-controlled trial

    PubMed Central

    Verspyck, Eric; de Vienne, Claire; Muszynski, Charles; Bubenheim, Michael; Chanavaz-Lacheray, Isabella; Dreyfus, Michel; Deruelle, Philippe; Benichou, Jacques

    2017-01-01

    Objective To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding. Methods PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis. Women were randomly allocated to receive either 20 mg of slow-release nifedipine three times daily (n = 54) or placebo (n = 55) until 36 + 6 weeks of gestation. The primary outcome for the trial was length of pregnancy measured in days after enrolment. Main secondary outcomes were rates of recurrent bleeding, cesarean delivery due to hemorrhage, blood transfusion, maternal side effects, gestational age at delivery and adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage > grade 2, perventricular leukomalacia > grade 1, or necrotizing enterocolitis). Analysis was by intention to treat. Results Mean (SD) prolongation of pregnancy was not different between the nifedipine (n = 54) and the placebo (n = 55) group; 42.5 days ± 23.8 versus 44.2 days ± 24.5, p = 0.70. Cesarean due to hemorrhage performed before 37 weeks occurred more frequently in the nifedipine group in comparison with the placebo group (RR, 1.66; 95% confidence interval, 1.05–2.72). Adverse perinatal outcomes were comparable between groups; 3.8% for nifedipine versus 5.5% for placebo (relative risk, 0.52; 95% confidence interval 0.10–2.61). No maternal mortality or perinatal death occurred. Conclusion Maintenance oral nifedipine neither prolongs duration of pregnancy nor improves maternal or perinatal outcomes. Trial registration ClinicalTrials.gov NCT00620724 PMID:28333939

  13. Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy

    SciTech Connect

    Lee, Andrew K. . E-mail: aklee@mdanderson.org; Levy, Larry B.; Cheung, Rex; Kuban, Deborah

    2005-10-01

    Purpose: To determine whether prostate-specific antigen (PSA) doubling time predicts clinical outcomes in patients with prostate cancer that has been treated with combined radiation and hormone therapy. Methods and Materials: We reviewed the medical records of 621 men with nonmetastatic prostate cancer treated with radiation therapy and hormone therapy between 1989 and 2003. 'Any' clinical failure was defined as any distant, nodal, or local failure, or the use of salvage therapy. 'True' clinical failure was defined as any distant, nodal, or local failure. PSA doubling time was calculated by using the log PSA values from patients with a PSA failure as defined by the American Society of Therapeutic Radiology Oncology consensus statement. One hundred thirty-seven men were at intermediate risk for PSA failure (as determined by T2b, Gleason score of 7, or PSA 10.1-0 ng/mL) and 484 men were at high risk for failure (T2c-4; Gleason 8-10; or PSA >20 ng/mL). Pretreatment PSA value, Gleason score, tumor stage, timing and duration of hormone therapy, radiation therapy dose, and PSA doubling time were analyzed for any associations with time to clinical failure by using Cox regression analysis. Estimates of survival were calculated by using the Kaplan-Meier method. Pairwise comparisons were made by using the log-rank test. Results: Sixty-two men experienced any clinical failure, and 22 men experienced true clinical failure. Multivariate analysis revealed that pretreatment PSA (p = 0.013), Gleason score (p = 0.0019), and a PSA doubling time (PSADT) {<=}8 months (p < 0.001) were independently associated with time to any clinical failure. Tumor stage, hormone therapy timing, hormone therapy duration, and radiation therapy dose were not statistically significant on multivariate or univariate analysis. Only hormone therapy duration (p 0.008) and PSADT {<=}8 months (<0.001) were significantly associated with time to true clinical failure. The estimated 5-year rate of any clinical

  14. Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

    PubMed

    Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

    2017-01-01

    We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

  15. Light therapy for better mood and insulin sensitivity in patients with major depression and type 2 diabetes: a randomised, double-blind, parallel-arm trial.

    PubMed

    Brouwer, Annelies; van Raalte, Daniël H; Diamant, Michaela; Rutters, Femke; van Someren, Eus J W; Snoek, Frank J; Beekman, Aartjan T F; Bremmer, Marijke A

    2015-07-24

    Major depression and type 2 diabetes often co-occur. Novel treatment strategies for depression in type 2 diabetes patients are warranted, as depression in type 2 diabetes patients is associated with poor prognosis and treatment results. Major depression and concurrent sleep disorders have been related to disturbances of the biological clock. The biological clock is also involved in regulation of glucose metabolism by modulating peripheral insulin sensitivity. Light therapy has been shown to be an effective antidepressant that 'resets' the biological clock. We here describe the protocol of a study that evaluates the hypothesis that light therapy improves mood as well as insulin sensitivity in patients with a major depressive episode and type 2 diabetes. This study is a randomised, double-blind, parallel-arm trial in 98 participants with type 2 diabetes and a major depressive episode, according to DSM-IV criteria. We will assess whether light therapy improves depressive symptoms and insulin sensitivity, our primary outcome measures, and additionally investigate whether these effects are mediated by restoration of the circadian rhythmicity, as measured by sleep and hypothalamic-pituitary-adrenal axis activity. Participants will be randomly allocated to a bright white-yellowish light condition or dim green light condition. Participants will undergo light therapy for half an hour every morning for 4 weeks at home. At several time points, namely before the start of light therapy, during light therapy, after completion of 4 weeks of light therapy and after 4 weeks follow-up, several psychometrical, psychophysiological and glucometabolic measures will be performed. If light therapy effectively improves mood and insulin sensitivity in type 2 diabetes patients with a major depressive episode, light therapy may be a valuable patient friendly addition to the currently available treatment strategies. Additionally, if our data support the role of restoration of circadian

  16. [Double responses].

    PubMed

    Motté, G; Dinanian, S; Sebag, C; Drieu, L; Slama, M

    1995-12-01

    Double response is a rare electrocardiographic phenomenon requiring two atrioventricular conduction pathways with very different electrophysiological properties. Double ventricular responses are the usual manifestation: an atrial depolarisation (spontaneous or provoked, anticipated or not) is followed by a first ventricular response dependent on an accessory pathway or a rapid nodal pathway and then a second response resulting from sufficiently delayed transmission through a nodal pathway for the ventricles to have recovered their excitability when the second wave of activation reaches them. A simple curiosity when isolated and occurring under unusual conditions, particularly during electrophysiological investigation of the Wolff-Parkinson-White syndrome, the double response may initiate symptomatic non-reentrant junctional tachycardia when associated with nodal duality and repeating from atria in sinus rhythm. The functional incapacity and resistance to antiarrhythmic therapy may require referral for ablation of the slow pathway.

  17. Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study.

    PubMed

    Mercadante, Sebastiano; Arcuri, Edoardo; Tirelli, Walter; Villari, Patrizia; Casuccio, Alessandra

    2002-01-01

    Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of

  18. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial.

    PubMed

    Tremoulet, Adriana H; Jain, Sonia; Jaggi, Preeti; Jimenez-Fernandez, Susan; Pancheri, Joan M; Sun, Xiaoying; Kanegaye, John T; Kovalchin, John P; Printz, Beth F; Ramilo, Octavio; Burns, Jane C

    2014-05-17

    Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance. We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks-17 years who had a fever (temperature ≥38·0°C) for 3-10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435. 196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1

  19. The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF).

    PubMed

    Mesa, Ruben; Vannucchi, Alessandro M; Yacoub, Abdulraheem; Zachee, Pierre; Garg, Mamta; Lyons, Roger; Koschmieder, Steffen; Rinaldi, Ciro; Byrne, Jennifer; Hasan, Yasmin; Passamonti, Francesco; Verstovsek, Srdan; Hunter, Deborah; Jones, Mark M; Zhen, Huiling; Habr, Dany; Martino, Bruno

    2017-01-01

    The randomized, double-blind, double-dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)-related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV-related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm -symptom assessment form total symptom score cytokine symptom cluster (TSS-C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib- and hydroxycarbamide-treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82-4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13-16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening-to-baseline TSS-C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV-related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement. © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  20. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.

    PubMed

    Mercadante, S; Arcuri, E; Tirelli, W; Casuccio, A

    2000-10-01

    Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation ("empty head") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.

  1. Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy.

    PubMed

    Wei, Pei-Ru; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Lee, Chia-Hung

    2015-09-01

    We designed a study for photodynamic therapy (PDT) using chitosan coated Mg-Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH-NH₂-ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH-NH₂-ICG and single layer chitosan-coated LDH-NH₂-ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy.

  2. Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy

    PubMed Central

    Wei, Pei-Ru; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Lee, Chia-Hung

    2015-01-01

    We designed a study for photodynamic therapy (PDT) using chitosan coated Mg–Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH–NH2–ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH–NH2–ICG and single layer chitosan-coated LDH–NH2–ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy. PMID:26340627

  3. Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study.

    PubMed

    Maschmeyer, G; Heinz, W J; Hertenstein, B; Horst, H-A; Requadt, C; Wagner, T; Cornely, O A; Löffler, J; Ruhnke, M

    2013-05-01

    Empirical antifungal therapy is widely used in high-risk neutropenic hematology patients with fever persisting for more than 4 days. This clinical trial assessed whether immediate empirical therapy with voriconazole could lower the rates of invasive fungal infections (IFIs) compared with this approach. In a double-blind, placebo-controlled, multicenter study, patients with acute leukemia undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients were randomized to broad-spectrum antibacterial therapy plus voriconazole (immediate) or placebo (deferred) after the onset of neutropenic fever. If fever persisted for 96 h, patients were switched to open-label intravenous voriconazole; oral treatment was permitted after 96 h. The primary endpoint was the rate of proven/probable IFIs between Days 2 and 28 after fever onset in the modified intent-to-treat (mITT) complete-case population. One hundred and forty-seven patients were randomized to immediate (n = 81) or deferred (n = 66) voriconazole. In the mITT population, six patients in the immediate group and nine in the deferred group developed proven/probable IFI between Days 2 and 28 (p = 0.258). The safety profiles were similar in both groups. While immediate empirical therapy with voriconazole appears to be safe in febrile neutropenic high-risk patients, it was not associated with a significant reduction in IFIs compared with therapy deferred for 96 h after fever onset.

  4. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng.

    PubMed

    Fung, Foon Yin; Wong, Wan Hui; Ang, Seng Kok; Koh, Hwee Ling; Kun, Mei Ching; Lee, Lai Heng; Li, Xiaomei; Ng, Heng Joo; Tan, Chuen Wen; Zhao, Yan; Linn, Yeh Ching

    2017-08-15

    Herbs with "blood-activating" properties by traditional medicine theory often raise concerns for their possible anti-platelet or anticoagulation effects based on reports from in vitro studies. Such herbs have been implicated for bleeding manifestations based on only anecdotal reports. In particular, the combination of such herbs with anti-platelet agents is often empirically advised against despite lack of good clinical evidence. Here we studied 3 commonly used herbal preparations Curcuma longa, Angelica sinensis and Panax ginseng on their respective anti-platelet and anticoagulation effect, alone and in combination with aspirin. This is a randomized, double-blind, placebo-controlled trial involving 25 healthy volunteers for each herbal preparation. Each subject underwent 3 phases comprising of herbal product alone, aspirin alone and aspirin with herbal product, where each phase lasted for 3 weeks with 2 weeks of washout between phases. PT/APTT, platelet function by light transmission aggregometry and thrombin generation assay by calibrated automated thrombogram were measured at baseline and after each phase. Information on adverse reaction including bleeding manifestations was collected after each phase. On the whole there was no clinically relevant impact on platelet and coagulation function. With the exception of 5 of 24 subjects in the Curcuma longa group, 2 of 24 subjects in the Angelica sinensis group and 1 of 23 subjects in the Panax ginseng group who had an inhibition in arachidonic-acid induced platelet aggregation, there was no effect of these 3 herbals products on platelet aggregation by other agonists. Combination of these herbal products with aspirin respectively did not further aggravate platelet inhibition caused by aspirin. None of the herbs impaired PT/APTT or thrombin generation. There was no significant bleeding manifestation. This study on healthy volunteers provides good evidence on the lack of bleeding risks of Curcuma longa, Angelica sinensis

  5. SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

    SciTech Connect

    Silva, D; Salmon, H; Pavan, G; Nardi, S; Anderson, E; Fairbanks, L; Junior, J; Cursino, F; Colodette, K

    2014-06-01

    Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plans were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.

  6. A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.

    PubMed

    Del Favero, A; Menichetti, F; Martino, P; Bucaneve, G; Micozzi, A; Gentile, G; Furno, P; Russo, D; D'Antonio, D; Ricci, P; Martino, B; Mandelli, F

    2001-10-15

    In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.

  7. Effects of whole body cryo-chamber therapy on pain in patients with chronic low back pain: a prospective double blind randomised controlled trial.

    PubMed

    Nugraha, B; Günther, J T; Rawert, H; Siegert, R; Gutenbrunner, C

    2015-04-01

    It is believed that treatment with low temperature can reduce pain perception in chronic pain patients, including chronic low back pain patients. To evaluate the effects of a two-week repeated intervention of -67 °C cryo-chamber in patients with chronic low back pain. A prospective randomized double blind study design. Hospital-based outpatients department Outpatients with chronic low back pain. Comparing intervention group (-67 °C) with higher temperature (-5 °C) which was supposed as a control group in a cryo-chamber. Similar effectiveness in pain reduction in both intervention and control groups Cryochamber therapy with -67 °C is not superior to (sham cryo chamber) with -5 °C. Cryo chambers therapy show positive effect by improving pain. For the treatment, -5 °C seems to be sufficient for these patients.

  8. The Effectiveness of Group Cognitive Behavioral Therapy in Treating Obsessive-Compulsive Disorder in Women with Multiple Sclerosis (MS): A randomized double-blind controlled trial.

    PubMed

    Sayyah, Mehdi; Bagheri, Parisa; Karimi, Negar; Ghasemzadeh, Azizreza

    2016-04-01

    Obsessive-compulsive disorder (OCD) is one of the most prevalent psychiatric disorders and can cause problems for individuals in all aspects of life, including social and personal dimensions. To study the effect of group cognitive-behavioral therapy on the reduction of OCD symptoms in female participants with multiple sclerosis (MS). This double-blind randomized control trial was conducted from May 2012 to December 2014. The participants included 75 patients with MS who suffered from OCD and were referred to the Loghman Hakim and Imam Khomeini hospitals in Tehran, Iran. Thirty participants had been diagnosed through Yale-Brown Obsessive-Compulsive Symptoms (Y-BOCS). The participants were randomly divided into an experimental group (n=15) and a control group (n=15). Eleven sessions of cognitive-behavioral therapy were provided for the experimental group. Patients in the control group continued with their normal living. Hypotheses were tested using an analysis of covariance (ANCOVA). A significant reduction was found in the experimental group's obsessive-compulsive symptoms after cognitive-behavioral therapy (p<0.001). In addition, mean scores for participants in the experimental group were significantly lower than for those in the control group (p=0.000). It can be inferred that cognitive-behavioral therapy could considerably reduce OCD symptoms in women with MS. The application of this method by therapists, especially Iranian clinicians, is recommended.

  9. The Effectiveness of Group Cognitive Behavioral Therapy in Treating Obsessive-Compulsive Disorder in Women with Multiple Sclerosis (MS): A randomized double-blind controlled trial

    PubMed Central

    Sayyah, Mehdi; Bagheri, Parisa; Karimi, Negar; Ghasemzadeh, Azizreza

    2016-01-01

    Background Obsessive-compulsive disorder (OCD) is one of the most prevalent psychiatric disorders and can cause problems for individuals in all aspects of life, including social and personal dimensions. Objective To study the effect of group cognitive-behavioral therapy on the reduction of OCD symptoms in female participants with multiple sclerosis (MS). Methods This double-blind randomized control trial was conducted from May 2012 to December 2014. The participants included 75 patients with MS who suffered from OCD and were referred to the Loghman Hakim and Imam Khomeini hospitals in Tehran, Iran. Thirty participants had been diagnosed through Yale-Brown Obsessive-Compulsive Symptoms (Y-BOCS). The participants were randomly divided into an experimental group (n=15) and a control group (n=15). Eleven sessions of cognitive-behavioral therapy were provided for the experimental group. Patients in the control group continued with their normal living. Hypotheses were tested using an analysis of covariance (ANCOVA). Results A significant reduction was found in the experimental group’s obsessive-compulsive symptoms after cognitive-behavioral therapy (p<0.001). In addition, mean scores for participants in the experimental group were significantly lower than for those in the control group (p=0.000). Conclusion It can be inferred that cognitive-behavioral therapy could considerably reduce OCD symptoms in women with MS. The application of this method by therapists, especially Iranian clinicians, is recommended. PMID:27279999

  10. Efficacy of Topical Compound Danxiong Granules for Treatment of Dermatologic Toxicities Induced by Targeted Anticancer Therapy: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Tian, Aiping; Zhou, Aiping; Bi, Xinyu; Hu, Shangying; Jiang, Zhichao; Zhang, Wen; Huang, Zhen; Shi, Hongzhe; Yang, Boyan; Chen, Wei

    2017-01-01

    Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosa Andr., Cortex Phellodendri, Geranium sibiricum L., and Flos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P < 0.0001). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction.

  11. Efficacy of Topical Compound Danxiong Granules for Treatment of Dermatologic Toxicities Induced by Targeted Anticancer Therapy: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Bi, Xinyu; Zhang, Wen

    2017-01-01

    Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosa Andr., Cortex Phellodendri, Geranium sibiricum L., and Flos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P < 0.0001). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction. PMID:28845183

  12. Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage: a double-blind randomized controlled trial.

    PubMed

    Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

    2016-01-01

    To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). A double-blind randomized controlled trial with one-week follow-up. Patients received five consecutive days of occupational therapy at home, combined with either anodal (n = 8) or sham (n = 7) tDCS. The primary outcome was ADL performance, which was assessed with the Jebsen-Taylor test (JTT). Both groups improved JTT over time (p < 0.01). The anodal group improved grip strength compared with the sham group from baseline to post-assessment (p = 0.025). However, this difference was attenuated at one-week follow-up. There was a non-significant tendency for greater improvement in JTT in the anodal group compared with the sham group, from baseline to post-assessment (p = 0.158). Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is a promising add-on intervention regarding training of upper limb motor impairment. It is well tolerated by patients and can easily be applied for home-based training. Larger studies with long-term follow-up are needed to further explore possible effects of tDCS in patients with ICH. Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is well tolerated by patients and can easily be applied for home-based rehabilitation.

  13. A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

    PubMed

    Naito, Yuji; Yamaguchi, Shinnichi; Mori, Yasuhiro; Nakajima, Kouji; Hashimoto, Sanshiro; Tomaru, Masakazu; Satoh, Yoshihiko; Hitomi, Yuji; Karita, Masakazu; Hiwatashi, Tomoaki; Kawahito, Yutaka; Yoshikawa, Toshikazu

    2013-07-01

    Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA.

  14. A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis

    PubMed Central

    Naito, Yuji; Yamaguchi, Shinnichi; Mori, Yasuhiro; Nakajima, Kouji; Hashimoto, Sanshiro; Tomaru, Masakazu; Satoh, Yoshihiko; Hitomi, Yuji; Karita, Masakazu; Hiwatashi, Tomoaki; Kawahito, Yutaka; Yoshikawa, Toshikazu

    2013-01-01

    Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA. PMID:23874073

  15. Double-differential fragmentation cross-section measurements of 95 MeV/nucleon 12C beams on thin targets for hadron therapy

    NASA Astrophysics Data System (ADS)

    Dudouet, J.; Juliani, D.; Labalme, M.; Cussol, D.; Angélique, J. C.; Braunn, B.; Colin, J.; Finck, Ch.; Fontbonne, J. M.; Guérin, H.; Henriquet, P.; Krimmer, J.; Rousseau, M.; Saint-Laurent, M. G.; Salvador, S.

    2013-08-01

    During therapeutic treatment with heavy ions like carbon, the beam undergoes nuclear fragmentation and secondary light charged particles, in particular protons and α particles, are produced. To estimate the dose deposited into the tumors and the surrounding healthy tissues, an accurate prediction on the fluences of these secondary fragments is necessary. Nowadays, a very limited set of double differential carbon fragmentation cross sections are being measured in the energy range used in hadron therapy (40 to 400 MeV/nucleon). Therefore, new measurements are performed to determine the double differential cross section of carbon on different thin targets. This work describes the experimental results of an experiment performed on May 2011 at GANIL. The double differential cross sections and the angular distributions of secondary fragments produced in the 12C fragmentation at 95 MeV/nucleon on thin targets (C, CH2, Al, Al2O3, Ti, and PMMA) have been measured. The experimental setup will be precisely described, the systematic error study will be explained and all the experimental data will be presented.

  16. Influence of beam efficiency through the patient-specific collimator on secondary neutron dose equivalent in double scattering and uniform scanning modes of proton therapy.

    PubMed

    Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K

    2010-06-01

    Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a

  17. Can Low-Cost Strategies Improve Attendance Rates in Brief Psychological Therapy? Double-Blind Randomized Controlled Trial.

    PubMed

    Delgadillo, Jaime; Moreea, Omar; Murphy, Elizabeth; Ali, Shehzad; Swift, Joshua K

    2015-12-01

    To assess if telephone text message appointment reminders and orientation leaflets can increase the proportion of patients who attend brief interventions after being assessed as suitable for guided self-help following cognitive behavioral therapy principles. Attendance was operationally defined as having accessed at least 1 therapy appointment. A secondary outcome was the proportion of attenders who completed or dropped out of therapy. After initial assessment, 254 patients with depression and anxiety disorders were randomly assigned to 1 of 3 groups: (a) usual waitlist control, (b) leaflet, (c) leaflet plus text message. Differences in the proportions of patients who started and completed therapy across groups were assessed using chi-square and logistic regression analyses. Overall, 63% of patients in this sample attended therapy. Between-group differences were not significant for attendance, x(2) (2) = 3.94, p = .14, or completion rates, x(2) (2) = 2.98, p = .23. These results were not confounded by demographic or clinical characteristics. Low-cost strategies appear to make no significant difference to therapy attendance and completion rates. © 2015 Wiley Periodicals, Inc.

  18. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study.

    PubMed

    Tsimikas, Sotirios; Viney, Nicholas J; Hughes, Steven G; Singleton, Walter; Graham, Mark J; Baker, Brenda F; Burkey, Jennifer L; Yang, Qingqing; Marcovina, Santica M; Geary, Richard S; Crooke, Rosanne M; Witztum, Joseph L

    2015-10-10

    Lipoprotein(a) (Lp[a]) is a risk factor for cardiovascular disease and calcific aortic valve stenosis. No effective therapies to lower plasma Lp(a) concentrations exist. We have assessed the safety, pharmacokinetics, and pharmacodynamics of ISIS-APO(a)Rx, a second-generation antisense drug designed to reduce the synthesis of apolipoprotein(a) (apo[a]) in the liver. In this randomised, double-blind, placebo-controlled, phase 1 study at the PAREXEL Clinical Pharmacology Research Unit (Harrow, Middlesex, UK), we screened for healthy adults aged 18-65 years, with a body-mass index less than 32·0 kg/m(2), and Lp(a) concentration of 25 nmol/L (100 mg/L) or more. Via a randomisation technique, we randomly assigned participants to receive a single subcutaneous injection of ISIS-APO(a)Rx (50 mg, 100 mg, 200 mg, or 400 mg) or placebo (3:1) in the single-dose part of the study or to receive six subcutaneous injections of ISIS-APO(a)Rx (100 mg, 200 mg, or 300 mg, for a total dose exposure of 600 mg, 1200 mg, or 1800 mg) or placebo (4:1) during a 4 week period in the multi-dose part of the study. Participants, investigators, and study staff were masked to the treatment assignment, except for the pharmacist who prepared the ISIS-APO(a)Rx or placebo. The primary efficacy endpoint was the percentage change from baseline in Lp(a) concentration at 30 days in the single-dose cohorts and at 36 days for the multi-dose cohorts. Safety and tolerability was assessed 1 week after last dose and included determination of the incidence, severity, and dose relation of adverse events and changes in laboratory variables, including lipid panel, routine haematology, blood chemistry, urinalysis, coagulation, and complement variables. Other assessments included vital signs, a physical examination, and 12-lead electrocardiograph. This trial is registered with European Clinical Trials Database, number 2012-004909-27. Between Feb 27, 2013, and July 15, 2013, 47 (23%) of 206 screened volunteers were

  19. Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

    PubMed

    Godino, Cosmo; Mendolicchio, Loredana; Figini, Filippo; Latib, Azeem; Sharp, Andrew Sp; Cosgrave, John; Calori, Giliola; Cera, Michela; Chieffo, Alaide; Castelli, Alfredo; Maseri, Attilio; Ruggeri, Zaverio M; Colombo, Antonio

    2009-05-06

    Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition. We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E1; 2) VerifyNow-P2Y12 test, in which results are reported as absolute P2Y12-Reaction-Units (PRU) or % of inhibition (% inhibition). Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E1 was 25.4% (IQR: 21.4-33.1%) and 3.5% (1.7-9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1st quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84-0.98, p < 0.0001) for % inhibition and 0.85 (0.72-0.93, p < 0.005) for PRU. Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC. In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

  20. Photobiomodulation Therapy Improves Performance and Accelerates Recovery of High-Level Rugby Players in Field Test: A Randomized, Crossover, Double-Blind, Placebo-Controlled Clinical Study.

    PubMed

    Pinto, Henrique D; Vanin, Adriane A; Miranda, Eduardo F; Tomazoni, Shaiane S; Johnson, Douglas S; Albuquerque-Pontes, Gianna M; Aleixo, Ivo de O; Grandinetti, Vanessa Dos S; Casalechi, Heliodora L; de Carvalho, Paulo de Tarso C; Leal, Ernesto Cesar P

    2016-12-01

    Pinto, HD, Vanin, AA, Miranda, EF, Tomazoni, SS, Johnson, DS, Albuquerque-Pontes, GM, de Oliveira Aleixo Junior, I, Grandinetti, VdS, Casalechi, HL, de Tarso Camillo de Carvalho, P, and Pinto Leal Junior. Photobiomodulation therapy improves performance and accelerates recovery of high-level rugby players in field test: A randomized, crossover, double-blind, placebo-controlled clinical study. J Strength Cond Res 30(12): 3329-3338, 2016-Although growing evidence supports the use of photobiomodulation therapy (PBMT) for performance and recovery enhancement, there have only been laboratory-controlled studies. Therefore, the aim of this study was to analyze the effects of PBMT in performance and recovery of high-level rugby players during an anaerobic field test. Twelve male high-level rugby athletes were recruited in this randomized, crossover, double-blinded, placebo-controlled trial. No interventions were performed before the Bangsbo sprint test (BST) at familiarization phase (week 1); at weeks 2 and 3, pre-exercise PBMT or placebo were randomly applied to each athlete. Photobiomodulation therapy irradiation was performed at 17 sites of each lower limb, employing a cluster with 12 diodes (4 laser diodes of 905 nm, 4 light emitting diodes [LEDs] of 875 nm, and 4 LEDs of 640 nm, 30 J per site, manufactured by Multi Radiance Medical). Average time of sprints, best time of sprints, and fatigue index were obtained from BST. Blood lactate levels were assessed at baseline, and at 3, 10, 30, and 60 minutes after BST. Athletes' perceived fatigue was also assessed through a questionnaire. Photobiomodulation therapy significantly (p ≤ 0.05) improved the average time of sprints and fatigue index in BST. Photobiomodulation therapy significantly decreased percentage of change in blood lactate levels (p ≤ 0.05) and perceived fatigue (p ≤ 0.05). Pre-exercise PBMT with the combination of super-pulsed laser (low-level laser), red LEDs, and infrared LEDs can enhance performance

  1. Additive effects of low-level laser therapy with exercise on subacromial syndrome: a randomised, double-blind, controlled trial.

    PubMed

    Abrisham, Seyyed Mohammad Jalil; Kermani-Alghoraishi, Mohammad; Ghahramani, Rahil; Jabbari, Latife; Jomeh, Hossein; Zare, Maryam

    2011-10-01

    The subacromial syndrome is the most common source of shoulder pain. The mainstays of conservative treatment are non-steroidal anti-inflammatory drugs and exercise therapy. Recently, low-level laser therapy (LLLT) has been popularized in the treatment of various musculoskeletal disorders. The aim of this study is to evaluate the additive effects of LLLT with exercise in comparison with exercise therapy alone in treatment of the subacromial syndrome. We conducted a randomised clinical study of 80 patients who presented to clinic with subacromial syndrome (rotator cuff and biceps tendinitis). Patients were randomly allocated into two groups. In group I (n = 40), patients were given laser treatment (pulsed infrared laser) and exercise therapy for ten sessions during a period of 2 weeks. In group II (n = 40), placebo laser and the same exercise therapy were given for the same period. Patients were evaluated for the pain with visual analogue scale (VAS) and shoulder range of motion (ROM) in an active and passive movement of flexion, abduction and external rotation before and after treatment. In both groups, significant post-treatment improvements were achieved in all parameters (P = 0.00). In comparison between the two groups, a significant improvement was noted in all movements in group I (P = 0.00). Also, there was a substantial difference between the groups in VAS scores (P = 0.00) which showed significant pain reduction in group I. This study indicates that LLLT combined exercise is more effective than exercise therapy alone in relieving pain and in improving the shoulder ROM in patients with subacromial syndrome.

  2. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial.

    PubMed

    Miyasaka, Nobuyuki; Hara, Masako; Koike, Takao; Saito, Eizo; Yamada, Masahito; Tanaka, Yoshiya

    2012-06-01

    High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo-controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy.

  3. Treatment of tension-type headache with articulatory and suboccipital soft tissue therapy: A double-blind, randomized, placebo-controlled clinical trial.

    PubMed

    Espí-López, Gemma V; Gómez-Conesa, Antonia; Gómez, Anna Arnal; Martínez, Josep Benítez; Pascual-Vaca, Angel Oliva; Blanco, Cleofás Rodríguez

    2014-10-01

    This study researches the effectiveness of two manual therapy treatments focused on the suboccipital region for tension-type headache. A randomized double-blind clinical trial was conducted over a period of four weeks with a follow-up at one month. Eighty-four patients with a mean age of 39.7 years (SD 11.4) with tension-type headache were assigned to 4 groups which included the following manual therapy treatment: suboccipital soft tissue inhibition; occiput-atlas-axis global manipulation; combination of both techniques; and a control group. The primary assessment consisted of collecting socio-demographic data and headache characteristics in a one-month base period, data such as age, gender, severity of pain, intensity and frequency of headache, among other. Outcome secondary assessment were: impact of headache, disability, ranges of motion of the craniocervical junction, frequency and intensity of headache, and pericranial tenderness. In the month prior to the study, average pain intensity, was rated at 6.49 (SD 1.69), and 66.7% subjects suffered headaches of moderate intensity. After 8 weeks, statistically significant improvements were noted. OAA manipulative treatment and combined therapy treatments proved to be more effective than suboccipital soft tissue inhibition for tension-type headache. The treatment with suboccipital soft tissue inhibition, despite producing less significant results, also has positive effects on different aspects of headache. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Incidence of middle ear barotrauma in staged versus linear chamber compression during hyperbaric oxygen therapy: a double blinded, randomized controlled trial.

    PubMed

    Ng, Andrew W A; Muller, Reinhold; Orton, John

    2017-01-01

    Middle ear barotrauma (MEB) is common during chamber compression in hyperbaric oxygen therapy. However, little evidence exists on an optimal compression protocol to minimize the incidence and severity of MEB. To compare the incidence of MEB during hyperbaric oxygen therapy using two different chamber compression protocols. Double-blinded, randomized controlled trial. Hyperbaric Medicine Unit, The Townsville Hospital, Queensland, Australia, September 2012 to December 2014. 100 participants undergoing their first hyperbaric oxygen therapy session. Random assignment to a staged (n=50) or a linear (n=50) compression protocols. Photographs of tympanic membranes were taken pre- and post-treatment and then graded. Middle ear barotrauma was defined as an increase of at least one grade on a modified TEED scale. The observed MEB incidence under the staged protocol was 48% compared to 62% using the linear protocol (P=0.12, exact one-sided binomial test), and thus the staged protocol did not show a significant improvement in MEB. However, the staged protocol resulted in significantly less severe deteriorations in MEB grades when compared to the linear protocol (P=0.028, exact one-sided Mann-Whitney type test). The use of the assessed staged compression protocol for the first hyperbaric oxygen treatment showed no significant effect on the overall incidence of MEB when compared to the gold standard linear protocol but resulted in a significant improvement in the severity of the experienced MEBs. Further studies are needed to elucidate an optimal compression protocol to minimize middle ear barotrauma.

  5. Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).

    PubMed

    Malerba, Mario; Ponticiello, Antonio; Radaeli, Alessandro; Bensi, Giuliano; Grassi, Vittorio

    2004-01-01

    The objective of this prospective, randomized, double-blind, placebo-controlled, multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria with value of FEV1 between > or =60 and 80% of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo. The percentage of patients free from exacerbation at 6 months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56% with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with more severe baseline symptoms, ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo: 63 vs. 38% (p=0.038). In conclusion, we did not find a significant difference between long-term ambroxol therapy and placebo, in preventing exacerbations in patients with COPD. In patients with more severe respiratory symptoms at baseline, however, we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo, suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD.

  6. Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model

    PubMed Central

    Jun, Hong Young; Ryu, Jong-Hyun; Byun, Seung Jae; Jeong, Chang Won; Kim, Tae-Hoon; Lee, Young Hwan

    2015-01-01

    Objective To evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model. Materials and Methods Renal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test. Results The contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 ± 9.9% vs. 77.4 ± 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 ± 0.7 mm for the RFA only group and 8.5 ± 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 ± 3.9% in no-therapy group, 10.3 ± 4.5% in the RFA only group, and 2.1 ± 0.7% in the RFA with DAAP group (ANOVA, p < 0.001). Conclusion Our results suggest the potential value of combining RFA with anti-angiogenic therapy. PMID:26175576

  7. Boron Neutron Capture Therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval.

    PubMed

    Monti Hughes, Andrea; Pozzi, Emiliano C C; Heber, Elisa M; Thorp, Silvia; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Molinari, Ana J; Garabalino, Marcela A; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

    2011-11-01

    Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10+BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10+BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10+BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Recurrent Proliferative Glomerulonephritis With Monoclonal IgG Deposits After a Renal Transplant Which Was Insensitive to Pulse Therapy Remitted by Double Filtration Plasmapheresis.

    PubMed

    Wu, Di; Chen, Jin-Song; Cheng, Dong-Rui; Chen, Hao; Li, Xue; Ji, Shu-Ming; Xie, Ke-Nan; Ni, Xue-Feng; Liu, Zhi-Hong; Wen, Ji-Qiu

    2015-10-01

    Proliferative glomerulonephritis with monoclonal IgG deposits manifesting as a nephrotic syndrome recently has been described as a renal disease with the pathological features of mesangial and subendothelial deposits of monoclonal IgG. Eight cases of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after a renal transplant have been reported. Almost all of these patients had a certain remission of proteinuria by steroids alone or with cyclophosphamide, and had further remission through other special treatments (ie, rituximab and plasmapheresis). We present a case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits of the IgG3? subtype after a renal transplant, which was insensitive to pulse intravenous methyl-prednisolone and cyclophosphamide remitted by double filtration plasmapheresis. This case report reveals that recurrent proliferative glomerulo-nephritis with monoclonal IgG deposits may be insensitive to intravenous pulse therapy of methylprednisolone and cyclophosphamide. We advocate double filtration plasmapheresis as an effective treatment of proliferative glomerulo-nephritis with monoclonal IgG deposits on remission of proteinuria.

  9. Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation. Intracoronary Stenting and Antithrombotic Regimen: CAUTION in Discontinuing Clopidogrel Therapy--ISAR-CAUTION.

    PubMed

    Fiedler, K Anette; Mehilli, Julinda; Kufner, Sebastian; Schlichting, Anna; Ibrahim, Tareq; Sibbing, Dirk; Ott, Ilka; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Schulz, Stefanie

    2014-06-01

    There is little evidence on the optimal mode of clopidogrel discontinuation. Epidemiological studies observed clustering of thrombotic events after cessation of chronic clopidogrel therapy. The underlying mechanism has been ascribed to transient platelet hyper-reactivity. Gradual tapering of clopidogrel may have the potential to attenuate this phenomenon. The objective of the present study was to assess whether in patients with drug-eluting stents (DES) gradual discontinuation of clopidogrel maintenance therapy is superior to conventional, abrupt discontinuation. Patients with planned discontinuation of chronic clopidogrel therapy after DES implantation were randomised in a double-blinded fashion to either gradual discontinuation (according to a tapering schema over four weeks) or abrupt discontinuation (after continued clopidogrel therapy for additional four weeks). The primary endpoint was the composite of cardiac death, myocardial infarction, stroke, stent thrombosis, major bleeding or rehospitalisation due to an acute coronary syndrome at 90 days. Enrollment of 3,000 patients was planned. The study was stopped prematurely due to slow recruitment after enrollment of 782 patients. At 90 days, nine of 392 patients (2.3%) with tapered cessation reached the primary endpoint compared to five of 390 patients (1.3%) with abrupt cessation (p=0.284). The composite of death or myocardial infarction occurred in three patients with tapered and three patients with abrupt discontinuation (p=0.764). In conclusion, tapered discontinuation of chronic clopidogrel therapy is not superior to abrupt discontinuation regarding the primary endpoint in this study. However, the results must be interpreted in view of the premature termination of the trial and low event rates.

  10. Effects of six-week clarithromycin therapy in corticosteroid-dependent asthma: A randomized, double-blind, placebo-controlled pilot study

    PubMed Central

    Gotfried, Mark H; Jung, Rose; Messick, Chad R; Rubinstein, Israel; Garey, Kevin W; Rodvold, Keith A; Danziger, Larry H

    2004-01-01

    Background: Although corticosteroids such as prednisone are efficacious for the treatment of severe asthma, chronic administration of oral corticosteroid therapy is associated with significant adverse effects. Previous studies have shown that clarithromycin is effective in reducing bronchial hyperresponsiveness and allergen-induced bronchoconstriction. However, the effect of long-term clarithromycin therapy in patients with prednisone-dependent asthma is uncertain. Objective: This study was conducted to determine the effects of oral clarithromycin on prednisone daily dosage, pulmonary function, quality of life (QOL), and asthmatic symptoms in patients with corticosteroid-dependent asthma. Methods: This 14-week, prospective, randomized, double-blind, placebo-controlled pilot study was conducted at Pulmonary Associates (Phoenix, Arizona) and the University of Illinois at Chicago Medical Center (Chicago, Illinois). Patients aged 18 to 75 years with an established diagnosis of asthma and who had been receiving ≥5 mg/d of prednisone for the preceding 6 months were enrolled. After a 4-week data-collection period, patients received clarithromycin 500 mg BID for 6 weeks, followed by a 4-week follow-up period. The effects of clarithromycin therapy on prednisone dosage requirements, pulmonary function (as assessed using spirometry), QOL, and asthmatic symptoms (nocturnal asthma, shortness of breath, chest discomfort, wheezing, and cough) were assessed. Results: Fourteen patients (9 men, 5 women; mean [SD] age, 62 [13] years) completed the study and were included in the final analysis. One patient withdrew from the study due to clarithromycin-related nausea. After 6 weeks of clarithromycin therapy, patients were able to tolerate a significant reduction in mean (SD) prednisone dosage from baseline (30% [18%]; P- 0.020). Pulmonary function, QOL, and asthmatic symptoms did not significantly worsen despite reduction in prednisone dose. All patients who completed the study

  11. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study.

    PubMed

    Cavo, Michele; Tacchetti, Paola; Patriarca, Francesca; Petrucci, Maria Teresa; Pantani, Lucia; Galli, Monica; Di Raimondo, Francesco; Crippa, Claudia; Zamagni, Elena; Palumbo, Antonio; Offidani, Massimo; Corradini, Paolo; Narni, Franco; Spadano, Antonio; Pescosta, Norbert; Deliliers, Giorgio Lambertenghi; Ledda, Antonio; Cellini, Claudia; Caravita, Tommaso; Tosi, Patrizia; Baccarani, Michele

    2010-12-18

    Thalidomide plus dexamethasone (TD) is a standard induction therapy for myeloma. We aimed to assess the efficacy and safety of addition of bortezomib to TD (VTD) versus TD alone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma. Patients (aged 18-65 years) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May, 2006, and April, 2008, and data collection continued until June 30, 2010. Patients were randomly allocated (1:1 ratio) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily for the first 14 days and 200 mg daily thereafter) plus dexamethasone (40 mg daily on 8 of the first 12 days, but not consecutively; total of 320 mg per cycle), either alone or with bortezomib (1·3 mg/m(2) on days 1, 4, 8, and 11). The randomisation sequence was computer generated by the study coordinating team and was stratified by disease stage. After double autologous stem-cell transplantation, patients received two 35-day cycles of their assigned drug regimen, VTD or TD, as consolidation therapy. The primary endpoint was the rate of complete or near complete response to induction therapy. Analysis was by intention to treat. Patients and treating physicians were not masked to treatment allocation. This study is still underway but is not recruiting participants, and is registered with ClinicalTrials.gov, number NCT01134484, and with EudraCT, number 2005-003723-39. 480 patients were enrolled and randomly assigned to receive VTD (n=241 patients) or TD (n=239). Six patients withdrew consent before start of treatment, and 236 on VTD and 238 on TD were included in the intention-to-treat analysis. After induction therapy, complete or near complete response was achieved in 73 patients (31%, 95% CI 25·0-36·8) receiving VTD, and 27 (11%, 7·3-15·4) on TD (p<0·0001). Grade 3 or 4 adverse events were recorded in a significantly higher

  12. The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

    PubMed Central

    2014-01-01

    Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

  13. How Should Disaster Base Hospitals Prepare for Dialysis Therapy after Earthquakes? Introduction of Double Water Piping Circuits Provided by Well Water System.

    PubMed

    Ikegaya, Naoki; Seki, George; Ohta, Nobutaka

    2016-01-01

    After earthquakes, continuing dialysis for patients with ESRD and patients suffering from crush syndrome is the serious problem. In this paper, we analyzed the failure of the provision of dialysis services observed in recent disasters and discussed how to prepare for disasters to continue dialysis therapy. Japan has frequently experienced devastating earthquakes. A lot of dialysis centers could not continue dialysis treatment owing to damage caused by these earthquakes. The survey by Japanese Society for Dialysis Treatment (JSDT) after the Great East Japan Earthquake in 2011 showed that failure of lifelines such as electric power and water supply was the leading cause of the malfunction of dialysis treatment. Our hospital is located in Shizuoka Prefecture, where one of the biggest earthquakes is predicted to occur in the near future. In addition to reconstructing earthquake-resistant buildings and facilities, we therefore have adopted double electric and water lifelines by introducing emergency generators and well water supply systems. It is very important to inform politicians, bureaucrats, and local water departments that dialysis treatment, a life sustaining therapy for patients with end stage renal diseases, requires a large amount of water. We cannot prevent an earthquake but can curb the extent of a disaster by preparing for earthquakes.

  14. How Should Disaster Base Hospitals Prepare for Dialysis Therapy after Earthquakes? Introduction of Double Water Piping Circuits Provided by Well Water System

    PubMed Central

    Ohta, Nobutaka

    2016-01-01

    After earthquakes, continuing dialysis for patients with ESRD and patients suffering from crush syndrome is the serious problem. In this paper, we analyzed the failure of the provision of dialysis services observed in recent disasters and discussed how to prepare for disasters to continue dialysis therapy. Japan has frequently experienced devastating earthquakes. A lot of dialysis centers could not continue dialysis treatment owing to damage caused by these earthquakes. The survey by Japanese Society for Dialysis Treatment (JSDT) after the Great East Japan Earthquake in 2011 showed that failure of lifelines such as electric power and water supply was the leading cause of the malfunction of dialysis treatment. Our hospital is located in Shizuoka Prefecture, where one of the biggest earthquakes is predicted to occur in the near future. In addition to reconstructing earthquake-resistant buildings and facilities, we therefore have adopted double electric and water lifelines by introducing emergency generators and well water supply systems. It is very important to inform politicians, bureaucrats, and local water departments that dialysis treatment, a life sustaining therapy for patients with end stage renal diseases, requires a large amount of water. We cannot prevent an earthquake but can curb the extent of a disaster by preparing for earthquakes. PMID:27999820

  15. Does anodyne light therapy improve peripheral neuropathy in diabetes? A double-blind, sham-controlled, randomized trial to evaluate monochromatic infrared photoenergy.

    PubMed

    Lavery, Lawrence A; Murdoch, Douglas P; Williams, Jayme; Lavery, David C

    2008-02-01

    The purpose of this study was to determine the efficacy of anodyne monochromatic infrared photo energy (MIRE) in-home treatments over a 90-day period to improve peripheral sensation and self-reported quality of life in individuals with diabetes. This was a double-blind, randomized, sham-controlled clinical trail. We randomly assigned 69 individuals with diabetes and a vibration perception threshold (VPT) between 20 and 45 V to two treatment groups: active or sham treatment. Sixty patients (120 limbs) completed the study. Anodyne units were used at home every day for 40 min for 90 days. We evaluated nerve conduction velocities, VPT, Semmes-Weinstein monofilaments (SWM) (4-, 10-, 26-, and 60-g monofilaments), the Michigan Neuropathy Screening Instrument (MNSI), a 10-cm visual analog pain scale, and a neuropathy-specific quality of life instrument. We used a nested repeated-measures multiple ANOVA design. Two sites (great toe and fifth metatarsal) were tested on both the left and right feet of each patient, so two feet were nested within each patient and two sites were nested within each foot. To analyze the ordinal SWM scores, we used a nonparametric factorial analysis for longitudinal data. There were no significant differences in measures for quality of life, MNSI, VPT, SWM, or nerve conduction velocities in active or sham treatment groups (P > 0.05). Anodyne MIRE therapy was no more effective than sham therapy in the treatment of sensory neuropathy in individuals with diabetes.

  16. A prospective, multicenter, randomized, double-blind study comparing ertapenem and ceftriaxone followed by appropriate oral therapy for complicated urinary tract infections in adults.

    PubMed

    Jimenez-Cruz, Fernando; Jasovich, Abel; Cajigas, Jaime; Jiang, Qi; Imbeault, Danielle; Woods, Gail L; Gesser, Richard M

    2002-07-01

    To compare the efficacy and safety of ertapenem, a new once-daily parenteral beta-lactam, with that of ceftriaxone for the initial empiric treatment of adults with complicated urinary tract infections (cUTIs). In a multicenter, prospective, double-blind study, patients with cUTIs were stratified as to whether they had acute pyelonephritis or other cUTIs (without pyelonephritis) and randomized to receive ertapenem, 1 g once a day, or ceftriaxone, 1 g once a day. After 3 days, patients with a satisfactory clinical response could be switched to an oral antimicrobial agent. Of 258 randomized patients, 97 (55.4%) in the ertapenem group and 53 (63.9%) in the ceftriaxone group were evaluated microbiologically. Almost all patients in each treatment group were switched to oral therapy. The mean duration of therapy was similar in both treatment groups: parenteral, approximately 4 days; total, approximately 13 days. The most common pathogen was Escherichia coli. At the primary efficacy endpoint, 5 to 9 days after treatment, 85.6% of patients who received ertapenem and 84.9% who received ceftriaxone had a favorable microbiologic response, indicating that the two treatment groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study, ertapenem was as effective as ceftriaxone for the initial treatment of cUTI in adults, was generally well tolerated, and had a similar safety profile.

  17. Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

    PubMed Central

    Park, Dae Won; Peck, Kyong Ran; Chung, Moon Hyun; Lee, Jin Seo; Park, Yoon Soo; Kim, Hyo Youl; Lee, Mi Suk; Kim, Jung Yeon; Yeom, Joon Sup

    2012-01-01

    The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs. PMID:22563210

  18. Comparison of ertapenem and ceftriaxone therapy for acute pyelonephritis and other complicated urinary tract infections in Korean adults: a randomized, double-blind, multicenter trial.

    PubMed

    Park, Dae Won; Peck, Kyong Ran; Chung, Moon Hyun; Lee, Jin Seo; Park, Yoon Soo; Kim, Hyo Youl; Lee, Mi Suk; Kim, Jung Yeon; Yeom, Joon Sup; Kim, Min Ja

    2012-05-01

    The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs.

  19. Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells.

    PubMed

    Okumura, Kakuji; Kinashi, Yuko; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

    2013-01-01

    Understanding the biological effects of neutron mixed-beam irradiation used for boron neutron capture therapy (BNCT) is important in order to improve the efficacy of the therapy and to reduce side effects. In the present study, cell viability and DNA double-strand breaks (DNA-DSBs) were examined in Chinese hamster ovary cells (CHO-K1) and their radiosensitive mutant cells (xrs5, Ku80-deficient), following neutron mixed-beam irradiation for BNCT. Cell viability was significantly impaired in the neutron irradiation groups compared to the reference gamma-ray irradiation group. The relative biological effectiveness for 10% cell survival was 3.3 and 1.2 for CHO-K1 and xrs5 cells, respectively. There were a similar number of 53BP1 foci, indicators of DNA-DSBs, in the neutron mixed-beam and the gamma-ray groups. In addition, the size of the foci did not differ between groups. However, neutron mixed-beam irradiation resulted in foci with different spatial distributions. The foci were more proximal to each other in the neutron mixed-beam groups than the gamma-ray irradiation groups. These findings suggest that neutron beams may induce another type of DNA damage, such as clustered DNA-DSBs, as has been indicated for other high-LET irradiation.

  20. Efficacy of Levofloxacin and Rifaximin based Quadruple Therapy in Helicobacter pylori Associated Gastroduodenal Disease: A Double-Blind, Randomized Controlled Trial

    PubMed Central

    Choi, Kang Hyun; Lee, Kang-Moon; Paik, Chang Nyol; Kim, Eun Jung; Kang, Bong Koo; Oak, Ju Hyun; Jung, Sung Hoon

    2011-01-01

    The aim of this study was to evaluate the efficacy of levofloxacin and rifaximin based quadruple regimen as first-line treatment for Helicobacter pylori infection. A prospectively randomized, double-blinded, parallel group, comparative study was performed. Three hundred consecutive H. pylori positive patients were randomized to receive: omeprazole, amoxicillin, clarithromycin (OAC); omeprazole, amoxicillin, levofloxacin (OAL); and omeprazole, amoxicillin, levofloxacin, rifaximin (OAL-R). The eradication rates in the intention to treat (ITT) and per protocol (PP) analyses were: OAC, 77.8% and 85.6%; OAL, 65.3% and 73.6%; and OAL-R, 74.5% and 80.2%. The eradication rate achieved with OAC was higher than with OAL on the ITT (P = 0.05) and PP analysis (P = 0.04). OAL-R regimen was not inferior to OAC. The frequency of moderate to severe adverse effects was significantly higher in OAC treatment group. Especially, diarrhea was most common complaint, and there was a significantly low rate of moderate to severe diarrhea with the rifaximin containing regimen. In conclusion, the levofloxacin and rifaximin based regimen comes up to the standard triple therapy, but has a limited efficacy in a Korean cohort. The rifaximin containing regimen has a very high safety profile for H. pylori eradication therapy. PMID:21655065

  1. Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells

    PubMed Central

    Okumura, Kakuji; Kinashi, Yuko; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

    2013-01-01

    Understanding the biological effects of neutron mixed-beam irradiation used for boron neutron capture therapy (BNCT) is important in order to improve the efficacy of the therapy and to reduce side effects. In the present study, cell viability and DNA double-strand breaks (DNA-DSBs) were examined in Chinese hamster ovary cells (CHO-K1) and their radiosensitive mutant cells (xrs5, Ku80-deficient), following neutron mixed-beam irradiation for BNCT. Cell viability was significantly impaired in the neutron irradiation groups compared to the reference gamma-ray irradiation group. The relative biological effectiveness for 10% cell survival was 3.3 and 1.2 for CHO-K1 and xrs5 cells, respectively. There were a similar number of 53BP1 foci, indicators of DNA-DSBs, in the neutron mixed-beam and the gamma-ray groups. In addition, the size of the foci did not differ between groups. However, neutron mixed-beam irradiation resulted in foci with different spatial distributions. The foci were more proximal to each other in the neutron mixed-beam groups than the gamma-ray irradiation groups. These findings suggest that neutron beams may induce another type of DNA damage, such as clustered DNA-DSBs, as has been indicated for other high-LET irradiation. PMID:22966174

  2. Evaluating the Role of Corticosteroid Pulse Therapy in Patients With Secondary Progressive Multiple Sclerosis Receiving Mitoxantrone: A Double Blind Randomized Controlled Clinical Trial

    PubMed Central

    Rahimdel, Abolghasem; Zeinali, Ahmad; Mellat, Ali

    2015-01-01

    Background: Multiple sclerosis (MS) is a central nervous system disorder with periods of recurrence and recovery. Mitoxantrone has been approved for secondary progressive MS (SPMS) treatment but data lacks the role of corticosteroid pulse therapy in SPMS. Objectives: To evaluate the role of corticosteroid pulse therapy in patients with SPMS receiving mitoxantrone. Patients and Methods: A double blind randomized controlled clinical trial was performed on 71 patients with SPMS referred to Shahid Sadoughi Hospital (Yazd, Iran) for receiving mitoxantrone in two groups. The first group (35 patients) received 20 mg mitoxantrone plus 500 mg methylprednisolone monthly for six months. The second group (36 patients) received the same dosage of mitoxantrone plus 100 CC of 5% dextrose water monthly for six months. Expanded disability status scale (EDSS), MRI plaques in both groups before and after the treatment completion and six months after the end of trial were compared together. Results: 28 men and 43 women enrolled in the study. MRI plaques number reduced in groups significantly (2.29 vs. 2.17) without significant difference between the groups (P = 0.782). Six months after trial completion, plaques number increased in groups without significantly difference (0.72 vs. 0.77, P = 0.611). The mean value of EDSS showed significant reduction at the end of treatment in groups (0.79 and 0.53) without significant difference between the groups (P = 0.953). Six months after trial completion, EDSS increased in groups without significant difference (0.35 vs. 0.43, P = 0.624). Conclusions: Corticosteroid pulse therapy in SPMS was effective in inflammatory process, but could not postpone or decline the neurodegenerative process and besides the imposing side effects could not result in significant improvement in EDSS and MRI plaques number in long term. PMID:26566454

  3. The effect of gallium arsenide aluminum laser therapy in the management of cervical myofascial pain syndrome: a double blind, placebo-controlled study.

    PubMed

    Dundar, U; Evcik, D; Samli, F; Pusak, H; Kavuncu, V

    2007-06-01

    The efficacy of low-level laser therapy (LLLT) in myofascial pain syndrome (MPS) seems controversial. A prospective, double-blind, randomized controlled trial was conducted in patients with chronic MPS in the neck to evaluate the effects of low-level 830-nm gallium arsenide aluminum (Ga-As-Al) laser therapy. The study group consisted of 64 MPS patients. The patients were randomly assigned into two groups. In group 1 (n = 32), Ga-As-Al laser treatment was applied over three trigger points bilaterally for 2 min over each point once a day for 15 days during a period of 3 weeks. In group 2 (n = 32), the same treatment protocol was given, but the laser instrument was switched off during applications. All patients in both groups performed daily isometric exercise and stretching exercises for cervical region. Parameters were measured at baseline and after 4 weeks. All patients were evaluated with respect to pain (at rest, movement, and night) and assessed by visual analog scale, measurement of active range of motion using an inclinometer and a goniometer, and the neck disability index. In both groups, statistically significant improvements were detected in all outcome measures compared with baseline (p < 0.05). However, no significant differences were obtained between the two groups (p > 0.05). In conclusion, although the laser therapy has no superiority over placebo groups in this study, we cannot exclude the possibility of effectivity with another treatment regimen including different laser wavelengths and dosages (different intensity and density and/or treatment interval).

  4. Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study.

    PubMed

    Straub, Rainer H; Härle, Peter; Yamana, Seizo; Matsuda, Takemasa; Takasugi, Kiyoshi; Kishimoto, Tadamitsu; Nishimoto, Norihiro

    2006-06-01

    Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly evident in the increase in adrenal androgen levels during anti-TNF therapy. This study investigated the influence on steroidogenesis of an interleukin-6 (IL-6)-neutralizing strategy using IL-6 receptor monoclonal antibodies (referred to as MRA). In a placebo-controlled, double-blind, randomized study over 12 weeks in 29 patients with RA being treated with prednisolone, 13 of whom received placebo and 16 of whom received 8 mg MRA/kg body weight, the effects of MRA on serum levels of adrenocorticotropic hormone (ACTH), cortisol, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (ASD), estrone, and 17beta-estradiol, as well as their respective molar ratios, were determined. MRA therapy markedly improved clinical signs of inflammation (the erythrocyte sedimentation rate, swollen joint score, and Disease Activity Score in 28 joints). Serum levels of ACTH and cortisol and the molar ratio of cortisol to ACTH did not change. Although serum levels of DHEA and DHEAS remained stable during therapy, the DHEAS:DHEA molar ratio significantly decreased in treated patients (P = 0.048). Serum levels of ASD as well as the ASD:cortisol and ASD:17OHP molar ratios increased in MRA-treated patients (minimum P < 0.004). Serum levels of estrone and 17beta-estradiol did not change. but the estrone:ASD molar ratio (an indicator of aromatization) decreased during 12 weeks of MRA treatment (P = 0.001). Neutralization of IL-6 increases secretion of biologically active adrenal androgens in relation to that of precursor hormones and estrogens. This is another important indication that proinflammatory cytokines interfere with adrenal androgen steroidogenesis in patients with RA.

  5. Combined cimetidine-alginate antacid therapy versus single agent treatment for reflux oesophagitis: results of prospective double-blind randomised clinical trial.

    PubMed

    Eriksen, C A; Cheadle, W G; Cranford, C A; Cuschieri, A

    1988-01-01

    This randomised double-blind study compared the effects of cimetidine 400 mg four times daily (q.d.s.), Gastrocote (alginic acid, aluminium hydroxide gel, magnesium trisilicate, sodium bicarbonate) two tablets q.d.s. and a combination of both on ambulatory 24-hour oesophageal pH, endoscopic findings and symptoms in patients with reflux oesophagitis. Patients were treated for ten weeks with assessments at entry, after four weeks and at the end of the study. Before treatment, oesophageal pH was less than 5.0 for 25% overall of the 24 hours monitoring in all three treatment groups. After ten weeks, the percentage of time with an oesophageal pH less than 5.0 was 26% on Gastrocote, 26% on cimetidine and 14% on the combination (P less than 0.05, combined therapy versus cimetidine alone). The severity of the heartburn was reduced on all three treatments. The average number of days with heartburn per week was 5.0, 3.6 and 3.4 in the Gastrocote, cimetidine and combined groups respectively. The difference between Gastrocote and the combination was statistically significant (P less than 0.05). There was a clear trend towards improvement of endoscopic oesophagitis at ten weeks in the combined therapy group when compared to single agent treatment with cimetidine or Gastrocote although the difference was not significant due to inadequate numbers. This study indicates that combined cimetidine and Gastrocote is a more effective treatment for reflux oesophagitis than single agent therapy with either drug.

  6. Assessment of the effectiveness of low-level laser therapy on the hands of patients with rheumatoid arthritis: a randomized double-blind controlled trial.

    PubMed

    Meireles, Sandra Mara; Jones, Anamaria; Jennings, Fabio; Suda, Alina Lica; Parizotto, Nivaldo Antônio; Natour, Jamil

    2010-05-01

    Assess the effectiveness of low-level laser therapy on pain reduction and improvement in function in the hands of patients with rheumatoid arthritis. A randomized double-blind controlled trial was carried out on 82 patients with rheumatoid arthritis. The experimental group was submitted to the application of laser therapy, whereas the control group received a placebo laser. Aluminum gallium arsenide laser was used, at a wavelength of 785 nm, dose of 3 J/cm(2) and mean power of 70 mW. The groups were homogenous at the beginning of the study with regard to the main variables (p > 0.05). There were no statistically significant differences between groups in most of the measurements taken at the end of the intervention including the primary variables; the following variables were the exceptions: favoring the experimental group-inflammation of the interphalangeal joint of the right thumb (p = 0.012) and perimetry of the interphalangeal joint of the left thumb (p = 0.013); and favoring the control group-flexion of the proximal interphalangeal joint of the right fifth finger (p = 0.021), perimetry of the third proximal interphalangeal joint of the right hand (p = 0.044), grip strength in the left hand (p = 0.010), and the work domain of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (p = 0.010). We conclude that low-level aluminum gallium arsenide laser therapy is not effective at the wavelength, dosage, and power studied for the treatment of hands among patients with rheumatoid arthritis.

  7. Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study.

    PubMed

    Oki, Eiji; Emi, Yasunori; Kojima, Hiroshi; Higashijima, Jun; Kato, Takeshi; Miyake, Yasuhiro; Kon, Masanori; Ogata, Yutaka; Takahashi, Kenichi; Ishida, Hideyuki; Saeki, Hiroshi; Sakaguchi, Yoshihisa; Yamanaka, Takeharu; Kono, Toru; Tomita, Naohiro; Baba, Hideo; Shirabe, Ken; Kakeji, Yoshihiro; Maehara, Yoshihiko

    2015-08-01

    Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG's potential for reducing peripheral neuropathy in patients with colorectal cancer. Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.

  8. Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

    PubMed Central

    Davison, Beth A.; Filippatos, Gerasimos S.; Radovanovic, Slavica; Beleslin, Branko; Merkely, Bela; Musialek, Piotr; Wojakowski, Wojciech; Andreka, Peter; Horvath, Ivan G.; Katz, Amos; Dolatabadi, Dariouch; El Nakadi, Badih; Arandjelovic, Aleksandra; Edes, Istvan; Seferovic, Petar M.; Obradovic, Slobodan; Vanderheyden, Marc; Jagic, Nikola; Petrov, Ivo; Atar, Shaul; Halabi, Majdi; Gelev, Valeri L.; Shochat, Michael K.; Kasprzak, Jaroslaw D.; Sanz-Ruiz, Ricardo; Heyndrickx, Guy R.; Nyolczas, Noémi; Legrand, Victor; Guédès, Antoine; Heyse, Alex; Moccetti, Tiziano; Fernandez-Aviles, Francisco; Jimenez-Quevedo, Pilar; Bayes-Genis, Antoni; Hernandez-Garcia, Jose Maria; Ribichini, Flavio; Gruchala, Marcin; Waldman, Scott A.; Teerlink, John R.; Gersh, Bernard J.; Povsic, Thomas J.; Henry, Timothy D.; Metra, Marco; Hajjar, Roger J.; Tendera, Michal; Behfar, Atta; Alexandre, Bertrand; Seron, Aymeric; Stough, Wendy Gattis; Sherman, Warren; Cotter, Gad; Wijns, William

    2017-01-01

    Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted. PMID:28025189

  9. Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study.

    PubMed

    Dias, Rodrigo S; Kerr-Corrêa, Florence; Moreno, Ricardo A; Trinca, Luzia A; Pontes, Anagloria; Halbe, Hans W; Gianfaldoni, Arlete; Dalben, Ivete S

    2006-01-01

    This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). Seventy-two menopausal women (mean age: 53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study.

  10. Photobiomodulation therapy (PBMT) and/or cryotherapy in skeletal muscle restitution, what is better? A randomized, double-blinded, placebo-controlled clinical trial.

    PubMed

    de Paiva, Paulo Roberto Vicente; Tomazoni, Shaiane Silva; Johnson, Douglas Scott; Vanin, Adriane Aver; Albuquerque-Pontes, Gianna Móes; Machado, Caroline Dos Santos Monteiro; Casalechi, Heliodora Leão; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

    2016-12-01

    Cryotherapy for post-exercise recovery remains widely used despite the lack of quality evidence. Photobiomodulation therapy (PBMT) studies (with both low-level laser therapy and light-emitting diode therapy) have demonstrated positive scientific evidence to suggest its use. The study aims to evaluate PBMT and cryotherapy as a single or combined treatment on skeletal muscle recovery after eccentric contractions of knee extensors. Fifty healthy male volunteers were recruited and randomized into five groups (PBMT, cryotherapy, cryotherapy + PBMT, PMBT + cryotherapy, or placebo) for a randomized, double-blinded, placebo-controlled trial that evaluated exercise performance (maximum voluntary contraction (MVC)), delayed onset muscle soreness (DOMS), and muscle damage (creatine kinase (CK)). Assessments were performed at baseline; immediately after; and at 1, 24, 48, 72, and 96 h. Comparator treatments was performed 3 min after exercise and repeated at 24, 48, and 72 h. PBMT was applied employing a cordless, portable GameDay(™) device (combination of 905 nm super-pulsed laser and 875- and 640-nm light-emitting diodes (LEDs); manufactured by Multi Radiance Medical(™), Solon - OH, USA), and cryotherapy by flexible rubber ice packs. PBMT alone was optimal for post-exercise recovery with improved MVC, decreased DOMS, and CK activity (p < 0.05) from 24 to 96 h compared to placebo, cryotherapy, and cryotherapy + PBMT. In the PBMT + cryotherapy group, the effect of PBMT was decreased (p > 0.05) but demonstrated significant improvement in MVC, decreased DOMS, and CK activity (p < 0.05). Cryotherapy as single treatment and cryotherapy + PBMT were similar to placebo (p > 0.05). We conclude that PBMT used as single treatment is the best modality for enhancement of post-exercise restitution, leading to complete recovery to baseline levels from 24 h after high-intensity eccentric contractions.

  11. Safety and effectiveness of autoinoculation therapy in cutaneous warts: a double--blind, randomized, placebo--controlled study.

    PubMed

    Lal, Niharika Ranjan; Sil, Amrita; Gayen, Tirthankar; Bandyopadhyay, Debabrata; Das, Nilay Kanti

    2014-01-01

    In spite of the availability of multiple treatment options, viral warts are known for their persistence and recurrence, causing frustration to patients and treating physicians. To study the effectiveness and safety of autoinoculation as a treatment modality in cutaneous warts. A double-blind, placebo-controlled study was carried out. In the treatment group, full-thickness warty tissue was excised, minced and implanted in a small dermal pocket. In the control group, warty tissue was only excised and not implanted, though a dermal pocket was made. Patients were evaluated every four weeks with lesion counts. The procedure was repeated at 4 and 8 weeks. Response was assessed at each visit and at 12 weeks. Forty-eight patients with cutaneous warts (male: female=32:16) were randomized into autoinoculation and control groups. The number of warts at baseline was comparable in both groups (P=0.293). Reduction in the number of warts was significantly more in the autoinoculation group (8.50±13.88) than in the control group (10.04±5.80) from 8 weeks onwards (P=0.010). Complete resolution occurred only in the autoinoculation group, in 62.5% of cases. Adverse effects were seen in 11 patients, including infection of the donor site (5 cases), keloid formation (3) and hypopigmentation (3). Autoinoculation may be an effective therapeutic modality for cutaneous warts and two sessions may be required for optimum results.

  12. Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system.

    PubMed

    Pérez-Andújar, Angélica; Newhauser, Wayne D; Deluca, Paul M

    2009-02-21

    In this work the neutron production in a passive beam delivery system was investigated. Secondary particles including neutrons are created as the proton beam interacts with beam shaping devices in the treatment head. Stray neutron exposure to the whole body may increase the risk that the patient develops a radiogenic cancer years or decades after radiotherapy. We simulated a passive proton beam delivery system with double scattering technology to determine the neutron production and energy distribution at 200 MeV proton energy. Specifically, we studied the neutron absorbed dose per therapeutic absorbed dose, the neutron absorbed dose per source particle and the neutron energy spectrum at various locations around the nozzle. We also investigated the neutron production along the nozzle's central axis. The absorbed doses and neutron spectra were simulated with the MCNPX Monte Carlo code. The simulations revealed that the range modulation wheel (RMW) is the most intense neutron source of any of the beam spreading devices within the nozzle. This finding suggests that it may be helpful to refine the design of the RMW assembly, e.g., by adding local shielding, to suppress neutron-induced damage to components in the nozzle and to reduce the shielding thickness of the treatment vault. The simulations also revealed that the neutron dose to the patient is predominated by neutrons produced in the field defining collimator assembly, located just upstream of the patient.

  13. DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy.

    PubMed

    Kinashi, Yuko; Yokomizo, Natsuya; Takahashi, Sentaro

    2017-04-01

    To use the 53BP1 foci assay to detect DNA double-strand breaks induced by fractionated neutron beam irradiation of normal cells. The Kyoto University Research Reactor heavy-water facility and gamma-ray irradiation system were used as experimental radiation sources. After fixation of Chinese Hamster Ovary cells with 3.6% formalin, immunofluorescence staining was performed. Number and size of foci were analyzed using ImageJ software. Fractionated neutron irradiation induced 25% fewer 53BP1 foci than single irradiation at the same dose. By contrast, gamma irradiation induced 30% fewer 53BP1 foci than single irradiation at the same dose. Fractionated neutron irradiation induced larger foci than gamma irradiation, raising the possibility that persistent unrepaired DNA damage was amplified due to the high linear energy transfer component in the neutron beam. Unrepaired cluster DNA damage was more prevalent after fractionated neutron irradiation than after gamma irradiation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system

    PubMed Central

    Pérez-Andújar, Angélica; Newhauser, Wayne D; DeLuca, Paul M

    2014-01-01

    In this work the neutron production in a passive beam delivery system was investigated. Secondary particles including neutrons are created as the proton beam interacts with beam shaping devices in the treatment head. Stray neutron exposure to the whole body may increase the risk that the patient develops a radiogenic cancer years or decades after radiotherapy. We simulated a passive proton beam delivery system with double scattering technology to determine the neutron production and energy distribution at 200 MeV proton energy. Specifically, we studied the neutron absorbed dose per therapeutic absorbed dose, the neutron absorbed dose per source particle and the neutron energy spectrum at various locations around the nozzle. We also investigated the neutron production along the nozzle's central axis. The absorbed doses and neutron spectra were simulated with the MCNPX Monte Carlo code. The simulations revealed that the range modulation wheel (RMW) is the most intense neutron source of any of the beam spreading devices within the nozzle. This finding suggests that it may be helpful to refine the design of the RMW assembly, e.g., by adding local shielding, to suppress neutron-induced damage to components in the nozzle and to reduce the shielding thickness of the treatment vault. The simulations also revealed that the neutron dose to the patient is predominated by neutrons produced in the field defining collimator assembly, located just upstream of the patient. PMID:19147903

  15. Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy

    PubMed Central

    Dungl, Daniela A.; Maginn, Elaina N.; Stronach, Euan A.

    2015-01-01

    Platinum-based chemotherapy is the cornerstone of ovarian cancer treatment, and its efficacy is dependent on the generation of DNA damage, with subsequent induction of apoptosis. Inappropriate or aberrant activation of the DNA damage response network is associated with resistance to platinum, and defects in DNA repair pathways play critical roles in determining patient response to chemotherapy. In ovarian cancer, tumor cell defects in homologous recombination – a repair pathway activated in response to double-strand DNA breaks (DSB) – are most commonly associated with platinum-sensitive disease. However, despite initial sensitivity, the emergence of resistance is frequent. Here, we review strategies for directly interfering with DNA repair pathways, with particular focus on direct inhibition of non-homologous end joining (NHEJ), another DSB repair pathway. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a core component of NHEJ and it has shown considerable promise as a chemosensitization target in numerous cancer types, including ovarian cancer where it functions to promote platinum-induced survival signaling, via AKT activation. The development of pharmacological inhibitors of DNA-PKcs is on-going, and clinic-ready agents offer real hope to patients with chemoresistant disease. PMID:26579492

  16. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    SciTech Connect

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-04-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with

  17. Oxymatrine therapy for chronic hepatitis B: A randomized double-blind and placebo-controlled multi-center trial

    PubMed Central

    Lu, Lun-Gen; Zeng, Min-De; Mao, Yi-Min; Li, Ji-Qiang; Wan, Mo-Bin; Li, Cheng-Zhong; Chen, Cheng-Wei; Fu, Qing-Chun; Wang, Ji-Yao; She, Wei-Min; Cai, Xiong; Ye, Jun; Zhou, Xia-Qiu; Wang, Hui; Wu, Shan-Ming; Tang, Mei-Fang; Zhu, Jin-Shui; Chen, Wei-Xiong; Zhang, Hui-Quan

    2003-01-01

    AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 wk, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B. PMID:14606080

  18. Antibody-directed double suicide gene therapy targeting of MUC1- positive leukemia cells in vitro and in vivo.

    PubMed

    Dong, Xiao-Ya; Wang, Wen-Qian; Zhao, Yu; Li, Xu-Dong; Fang, Zhi-Gang; Lin, Dong-Jun; Xiao, Ruo-Zhi; Huang, Ren-Wei; Pan, Guang-Jin; Liu, Jia-Jun

    2013-10-01

    Our aim was to specifically transfer the cytosine deaminase (CD) and thymidine kinase (TK) genes into mucin 1 (MUC1)-positive leukemia cells by anti-MUC1 antibody directed infection of replication-defective lentivirus and to evaluate the targeted cytotoxicity of double suicide genes to leukemia. The target gene vector (containing CD and TK) and envelope (containing GFP and anti-MUC1) and packaging plasmids were cotransfected into 293T cells to produce the recombinant lentivirus. Suicide genes in virus-infected leukemia cells (U937, Jurkat, and K562) were detected by western blot. The cytotoxicity and bystander effect in vitro and the therapeutic effect in vivo were detected after treatment with the prodrugs. The results revealed that combined treatment with prodrug 5-fluorocytosine (5-FC) and ganciclovir (GCV) inhibited leukemia cell growth and caused significant bystander effect than treatment with either prodrug alone. TK/GCV treatment alone induced degeneration and cell death while the effect of CD/5-FC alone mainly caused vacuolar degeneration and necrosis. The addictive effects of combinatorial use of GCV and 5-FC mainly induced swelling of the mitochondria followed by necrosis of the leukemia cells. In vivo experiments revealed that both single and combinatorial prodrug treatments could prolong the survival time of leukemic mice. In summary, anti-MUC1 antibody directed lentiviral vector successfully transduced dual suicide genes and exerted targeted cytotoxicity against MUC1 positive leukemia cells. This targeted lentiviral dual suicide gene delivering system provides a promising approach for clinical treatment of leukemia in future.

  19. Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial.

    PubMed

    Donnino, Michael W; Andersen, Lars W; Berg, Katherine M; Chase, Maureen; Sherwin, Robert; Smithline, Howard; Carney, Erin; Ngo, Long; Patel, Parth V; Liu, Xiaowen; Cutlip, Donald; Zimetbaum, Peter; Cocchi, Michael N

    2016-04-03

    The purpose of this study was to determine whether the provision of corticosteroids improves time to shock reversal and outcomes in patients with post-cardiac arrest shock. We conducted a randomized, double-blind trial of post-cardiac arrest patients in shock, defined as vasopressor support for a minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal. Fifty patients were included with 25 in each group. There was no difference in time to shock reversal between groups (hazard ratio: 0.83 [95% CI: 0.40-1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52% vs. 60%, p = 0.57), good neurological outcome (24% vs. 32%, p = 0.53) or survival to discharge (28% vs. 36%, p = 0.54) between the hydrocortisone and placebo groups. Of the patients with a baseline cortisol < 15 ug/dL, 100% (6/6) in the hydrocortisone group achieved shock reversal compared to 33% (1/3) in the placebo group (p = 0.08). All patients in the placebo group died (100%; 3/3) whereas 50% (3/6) died in the hydrocortisone group (p = 0.43). In a population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal, rate of shock reversal, or clinical outcomes when compared to placebo. Clinicaltrials.gov: NCT00676585, registration date: May 9, 2008.

  20. The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema.

    PubMed

    Wood, Douglas E; Nader, Daniel A; Springmeyer, Steven C; Elstad, Mark R; Coxson, Harvey O; Chan, Andrew; Rai, Navdeep S; Mularski, Richard A; Cooper, Christopher B; Wise, Robert A; Jones, Paul W; Mehta, Atul C; Gonzalez, Xavier; Sterman, Daniel H

    2014-10-01

    Lung volume reduction surgery improves quality of life, exercise capacity, and survival in selected patients but is accompanied by significant morbidity. Bronchoscopic approaches may provide similar benefits with less morbidity. In a randomized, sham procedure controlled, double-blind trial, 277 subjects were enrolled at 36 centers. Patients had emphysema, airflow obstruction, hyperinflation, and severe dyspnea. The primary effectiveness measure was a significant improvement in disease-related quality of life (St. George's Respiratory Questionnaire) and changes in lobar lung volumes. The primary safety measure was a comparison of serious adverse events. There were 6/121 (5.0%) responders in the treatment group at 6 months, significantly >1/134 (0.7%) in the control group [Bayesian credible intervals (BCI), 0.05%, 9.21%]. Lobar volume changes were significantly different with an average decrease in the treated lobes of -224 mL compared with -17 mL for the control group (BCI, -272, -143). The proportion of responders in St. George's Respiratory Questionnaire was not greater in the treatment group. There were significantly more subjects with a serious adverse event in the treatment group (n=20 or 14.1%) compared with the control group (n=5 or 3.7%) (BCI, 4.0, 17.1), but most were neither procedure nor device related. This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results. Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies. Further studies need to focus on improved patient selection and a different treatment algorithm. ClinicalTrials.gov NCT00475007.

  1. Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial.

    PubMed

    Hadley, Sallie J; Mandel, Francine S; Schweizer, Edward

    2012-04-01

    To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients (N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with a benzodiazepine for 8-52 weeks were stabilized for 2-4 weeks on alprazolam in the range of 1-4 mg/day. Patients were then randomized to 12 weeks of double-blind treatment with either pregabalin 300-600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment. Outcome measures included ability to remain benzodiazepine-free (primary) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist (PWC). At endpoint, a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo (51.4% vs 37.0%). Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo (-2.5 vs +1.3; p < 0.001), and lower endpoint mean PWC scores (6.5 vs 10.3; p = 0.012). Thirty patients (53%) in the pregabalin group and 19 patients (37%) in the placebo group completed the study, reducing the power to detect a significant difference on the primary outcome. The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy.

  2. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial

    PubMed Central

    Yatham, L N; Beaulieu, S; Schaffer, A; Kauer-Sant'Anna, M; Kapczinski, F; Lafer, B; Sharma, V; Parikh, S V; Daigneault, A; Qian, H; Bond, D J; Silverstone, P H; Walji, N; Milev, R; Baruch, P; da Cunha, A; Quevedo, J; Dias, R; Kunz, M; Young, L T; Lam, R W; Wong, H

    2016-01-01

    Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry (‘0-weeks' group) or (ii) at 24 weeks after entry (‘24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study (‘52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains

  3. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword

    PubMed Central

    Chen, Jun; Lariviere, William R.

    2010-01-01

    Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. PMID:20558236

  4. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial.

    PubMed

    Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

    2014-08-01

    Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse

  5. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial

    PubMed Central

    Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

    2014-01-01

    Summary Background Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. Methods In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Findings Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10–2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87–2·38, p=0·151

  6. Smoking cessation or reduction with nicotine replacement therapy: a placebo-controlled double blind trial with nicotine gum and inhaler

    PubMed Central

    2009-01-01

    Background Even with effective smoking cessation medications, many smokers are unable to abruptly stop using tobacco. This finding has increased interest in smoking reduction as an interim step towards complete cessation. Methods This multi-center, double-blind placebo-controlled study evaluated the efficacy and safety of nicotine 4 mg gum or nicotine 10 mg inhaler in helping smokers (N = 314) to reduce or quit smoking. It included smokers willing to control their smoking, and participants could set individual goals, to reduce or quit. The study was placebo-controlled, randomized in a ratio of 2:1 (Active:Placebo), and subjects could choose inhaler or gum after randomization. Outcome was short-term (from Week 6 to Month 4) and long-term (from Month 6 to Month 12) abstinence or reduction. Abstinence was defined as not a single cigarette smoked and expired CO readings of <10 ppm. Smoking reduction was defined as a reduction in number of cigarettes per day by 50% or more versus baseline, verified by a lower-than-baseline CO reading at each visit during the same periods. Results Significantly more smokers managed to quit in the Active group than in the Placebo group. Sustained abstinence rates at 4 months were 42/209 (20.1%) subjects in the Active group and 9/105 (8.6%) subjects in the Placebo group (p = 0.009). Sustained abstinence rates at 12 months were 39/209 (18.7%) and 9/105 (8.6%), respectively (p = 0.019). Smoking reduction did not differ between the groups, either at short-term or long-term. Twelve-month reduction results were 17.2% vs. 18.1%, respectively. No serious adverse events were reported. Conclusion In conclusion, treatment with 10 mg nicotine inhaler or 4 mg nicotine chewing gum resulted in a significantly higher abstinence rate than placebo. In addition a large number of smokers managed to reduce their cigarette consumption by more than 50% compared to baseline. PMID:19943947

  7. Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial.

    PubMed

    Diener, Hans-Christoph; Agosti, Reto; Allais, Gianni; Bergmans, Paul; Bussone, Gennaro; Davies, Brendan; Ertas, Mustafa; Lanteri-Minet, Michel; Reuter, Uwe; Sánchez Del Río, Margarita; Schoenen, Jean; Schwalen, Susanne; van Oene, Joop

    2007-12-01

    Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. 559 patients (68.3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; p<0.0001) than in the topiramate group (0.10, -0.36 to 0.56; p=0.5756; mean difference between groups -1.09, -1.75 to -0.43; p=0.0011) [corrected] Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups -0.95, -1.49 to -0.41; p=0.0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. Sustained benefit was reported after discontinuation of topiramate, although number

  8. Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction? A prospective, randomized, double-blind, placebo-controlled study.

    PubMed

    Olsen, Anne B; Persiani, Marie; Boie, Sidsel; Hanna, Milad; Lund, Lars

    2015-01-01

    The aim of this study was to investigate whether low-intensity extracorporeal shockwave therapy (LI-ESWT) can be used as a treatment for men with erectile dysfunction of organic origin. This prospective, randomized, blinded, placebo-controlled study included 112 men unable to have intercourse either with or without medication. Erectile dysfunction was assessed at screening and 5, 12 and 24 weeks after treatment. Assessment was performed by interview and using the Erection Hardness Scale (EHS) and the International Index of Erectile Function (IIEF-15) questionnaire. The men were randomly assigned either to LI-ESWT (n = 51, active group) or placebo (n = 54, placebo group). They received five treatments over 5 weeks. Both the participants and the doctors were blinded to the treatment. After 10 weeks, the placebo group received active treatment (active placebo group). Twenty-nine men (57%, active group) were able to obtain an erection after treatment and to have sexual intercourse without the use of medication. In the placebo group, only five men (9%) showed similar results (p = 0.0001). The EHS after 5 weeks showed that men in the active group experienced a significant improvement in their erectile dysfunction, but no significant result was found with the use of the IIEF - Erectile Function domain. This placebo-controlled study over 5 weeks shows that 57% of the men who suffered from erectile dysfunction had an effect from LI-ESWT. After 24 weeks, seven (19%, active group) and nine (23%, active placebo group) men were still able to have intercourse without medication. This study shows a possible cure in some patients, but more research, longer follow-up in the placebo group and an international multicentre randomized study are needed.

  9. Outcome of Four Pretreatment Regimes on Hemodynamics during Electroconvulsive Therapy: A Double-blind Randomized Controlled Crossover Trial

    PubMed Central

    Parikh, Devangi Ashutosh; Garg, Sanchita Nitin; Dalvi, Naina Parag; Surana, Priyanka Pradip; Sannakki, Deepa; Tendolkar, Bharati Anil

    2017-01-01

    Context: Electroconvulsive therapy (ECT) is associated with tachycardia and hypertension. Aims: The aim of this study was to compare two doses of dexmedetomidine, esmolol, and lignocaine with respect to hemodynamics, seizure duration, emergence agitation (EA), and recovery profile. Methodology: Thirty patients undergoing ECT were assigned to each of the following pretreatment regimes over the course of five ECT sessions in a randomized crossover design: Group D1 (dexmedetomidine 1 μg/kg), Group D0.5 (dexmedetomidine0.5 μg/kg), Group E (esmolol 1 mg/kg), Group L (lignocaine 1 mg/kg), and Group C (saline as placebo) before induction. Heart rate (HR), mean arterial pressure (MAP), seizure duration, EA, and time to discharge were evaluated. Results: Groups D1, D0.5, and esmolol had significantly reduced response of HR, MAP compared to lignocaine and control groups at 1, 3, 5 min after ECT (P < 0.05). Motor seizure duration was comparable in all groups except Group L (P = 0.000). Peak HR was significantly decreased in all groups compared to control. Total propofol requirement was reduced in D1 (P = 0.000) and D0.5 (P = 0.001) when compared to control. Time to spontaneous breathing was comparable in all the groups (P > 0.05). Time to eye opening and time to discharge were comparable in all groups (P > 0.05) except Group D1 (P = 0.001). EA score was least in Group D1 (P = 0.000). Conclusion: Dexmedetomidine 1 μg/kg, 0.5 μg/kg, and esmolol produced significant amelioration of cardiovascular response to ECT without affecting seizure duration, results being best with dexmedetomidine 1 μg/kg. However, the latter has the shortcoming of delayed recovery. PMID:28074804

  10. Ultrasonographic evaluation of plantar fasciitis after low-level laser therapy: results of a double-blind, randomized, placebo-controlled trial.

    PubMed

    Kiritsi, Olga; Tsitas, Konstantinos; Malliaropoulos, Nikolaos; Mikroulis, Grogorios

    2010-03-01

    The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on plantar fasciitis documented by the ultrasonographic appearance of the aponeurosis and by patients' pain scores. Thirty individuals with diagnosis of unilateral plantar fasciitis were enrolled in a randomized, double-blind, placebo-controlled trial, but 25 participants completed the therapeutic protocol. The contralateral asymptomatic fascia was used as control. After enrolment, symptomatic individuals were randomly assigned to receive LLLT, or identical placebo, for 6 weeks. Ultrasonography was performed at baseline and after completion of therapy. The subjective subcalcaneal pain was recorded at baseline and after treatment on a visual analogue scale (VAS). After LLLT, plantar fascia thickness in both groups showed significant change over the experimental period and there was a difference (before treatment and after treatment) in plantar fascia thickness between the two groups. However, plantar fascia thickness was insignificant (mean 3.627 +/- 0.977 mm) when compared with that in the placebo group (mean 4.380 +/- 1.0042 mm). Pain estimation on the visual analogue scale had improved significantly in all test situations (after night rest, daily activities) after LLLT when compared with that of the placebo group. (P=0.006 and P=0.01, respectively). Additionally, when the difference in pain scores was compared between the two groups, the change was statistically significant (after night rest P=0.000; daily activities P=0.001). In summary, while ultrasound imaging is able to depict the morphologic changes related to plantar fasciitis, 904 nm gallium-arsenide (GaAs) infrared laser may contribute to healing and pain reduction in plantar fasciitis.

  11. The Addition of Inhaled Budesonide to Standard Therapy Shortens the Length of Stay in Hospital for Asthmatic Preschool Children: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Razi, Cem Hasan; Akelma, Ahmet Zulfikar; Harmanci, Koray; Kocak, Mesut; Kuras Can, Yasemin

    2015-01-01

    Asthma exacerbations lead to frequent emergency visits and hospitalizations, and are associated with high morbidity and occasionally mortality. New therapeutic strategies are needed. We sought to investigate whether the addition of high-dose inhaled budesonide to standard therapy would shorten the length of stay (LOS) in hospital of children admitted for asthma exacerbations. The study was designed as a single-center, double-blind, placebo-controlled and parallel-group trial. Children aged 7-72 months and admitted with an asthma exacerbation clinical asthma score (CAS) of between 3 and 9 were allocated to either the budesonide (n = 50) or the placebo (n = 50) group. Hospital LOS was compared between children who received 2 mg/day of budesonide versus placebo in addition to standard management of asthma exacerbation involving oxygen inhalation and β2-agonist, anticholinergic and oral corticosteroid therapy. All patients were assessed every 4 h. Children with a CAS <3, a peripheral oxygen saturation >95% and normal pulmonary function, and those with a symptom-free period of at least 4 h after salbutamol treatment were discharged. Total hospital LOS was significantly shorter in the budesonide group than in the placebo group (median: 44 vs. 80 h, respectively; p = 0.01). When compared with placebo, the number of inpatients was significantly less in the budesonide group at all the assessed end points (Kaplan-Meier; p = 0.022). Additionally, nebulized budesonide was found to reduce the overall cost of treatment. We demonstrated that, for children hospitalized for asthma exacerbations, an additional 2 mg/day of nebulized budesonide significantly reduced hospital LOS as well as the overall cost of treatment.

  12. Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial.

    PubMed

    Akhondzadeh, Shahin; Ghayyoumi, Raofeh; Rezaei, Farzin; Salehi, Bahman; Modabbernia, Amir-Hossein; Maroufi, Azad; Esfandiari, Gholam-Reza; Naderi, Mehrangiz; Ghebleh, Fariba; Tabrizi, Mina; Rezazadeh, Shams-Ali

    2011-02-01

    It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia. This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial. Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45 years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6 mg/day) plus sildenafil (75 mg/day) and 20 to risperidone (6 mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS). Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F = 4.77, df = 1; P = 0.03; F = 5.91, df = 1, P = 0.02 respectively). Therapy with 75 mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).

  13. Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression: a randomized, double-blind controlled study.

    PubMed

    Straasø, Birgit; Lauritzen, Lise; Lunde, Marianne; Vinberg, Maj; Lindberg, Lone; Larsen, Erik Roj; Dissing, Steen; Bech, Per

    2014-10-01

    To evaluate to what extent a twice daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was superior to once daily in patients with treatment-resistant depression as to obtaining symptom remission after 8 weeks of augmentation therapy. A self-treatment set-up of the T-PEMF device was used allowing self-administration by patients in own homes. All patients were treated for 30 min per T-PEMF session. The antidepressant medication the patients were receiving at baseline remained unchanged during the trial. The patients were randomised to either one T-PEMF dose (active dose in the morning and sham in the afternoon) or two T-PEMF doses (active dose both morning and afternoon) in a double-blind procedure. A score of 7 or less on the Hamilton Depression Scale (HAM-D17) was the criterion of remission. In total 34 patients received active T-PEMF once a day and 31 patients twice daily. After 5 weeks of therapy remission was obtained in 26.5% and 32.3% on one dose and two doses of T-PEMF, respectively. After 8 weeks the rate of remission was 73.5% and 67.7%, respectively. The side effects as measured by the Udvalget for Kliniske Undersøgelser scale showed a better toleration of the antidepresssive medication in both treatment groups, which was reflected by the WHO-5 well-being scale with increased scores in both groups of patients. The high remission rate obtained by the T-PEMF augmentation was not a dose effect (one versus two daily T-PEMF sessions) but was explained by the extension of the treatment period from 5 to 8 weeks.

  14. The Efficacy of Shugan Jianpi Zhixie Therapy for Diarrhea-Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

    PubMed Central

    Sun, Xiaomin; Tang, Yang; Cheng, Jingru; Wang, Tian; Li, Fei; Kuang, Yuxiang; Luo, Ren; Zhao, Xiaoshan

    2015-01-01

    Background Shugan Jianpi Zhixie therapy (SJZT) has been widely used to treat diarrhea-predominant irritable bowel syndrome (IBS-D), but the results are still controversial. A meta-analysis of randomized, double-blind, placebo-controlled trials was performed to assess the efficacy and tolerability of SJZT for IBS-D. Methods The MEDLINE, EMBASE, Cochrane Library, the China National Knowledge Infrastructure database, the Chinese Biomedical Literature database and the Wanfang database were searched up to June 2014 with no language restrictions. Summary estimates, including 95% confidence intervals (CI), were calculated for global symptom improvement, abdominal pain improvement, and Symptom Severity Scale (BSS) score. Results Seven trials (N=954) were included. The overall risk of bias assessment was low. SJZT showed significant improvement for global symptom compared to placebo (RR 1.61; 95% CI 1.24, 2.10; P =0.0004; therapeutic gain = 33.0%; number needed to treat (NNT) = 3.0). SJZT was significantly more likely to reduce overall BSS score (SMD –0.67; 95% CI –0.94, –0.40; P < 0.00001) and improve abdominal pain (RR 4.34; 95% CI 2.64, 7.14; P < 0.00001) than placebo. The adverse events of SJZT were no different from those of placebo. Conclusions This meta-analysis suggests that SJZT is an effective and safe therapy option for patients with IBS-D. However, due to the high clinical heterogeneity and small sample size of the included trials, further standardized preparation, large-scale and rigorously designed trials are needed. PMID:25853241

  15. GLP-1-Based Therapies Have No Microvascular Effects in Type 2 Diabetes Mellitus: An Acute and 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Diamant, Michaela; Serné, Erik H; van Raalte, Daniël H

    2016-10-01

    To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus. We studied 57 patients with type 2 diabetes mellitus (mean±SD age: 62.8±6.9 years; body mass index: 31.8±4.1 kg/m(2); HbA1c [glycated hemoglobin] 7.3±0.6%) in an acute and 12-week randomized, placebo-controlled, double-blind trial conducted at the Diabetes Center of the VU University Medical Center. In the acute study, the GLP-1 receptor agonist exenatide (therapeutic concentrations) or placebo (saline 0.9%) was administered intravenously. During the 12-week study, patients received the GLP-1 receptor agonist liraglutide (1.8 mg daily), the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg daily), or matching placebos. Capillary perfusion was assessed by nailfold skin capillary videomicroscopy and vasomotion by laser Doppler fluxmetry, in the fasting state and after a high-fat mixed meal. In neither study, treatment affected fasting or postprandial capillary perfusion compared with placebo (P>0.05). In the fasting state, acute exenatide infusion increased neurogenic vasomotion domain power, while reducing myogenic domain power (both P<0.05). After the meal, exenatide increased endothelial domain power (P<0.05). In the 12-week study, no effects on vasomotion were observed. Despite modest changes in vasomotion, suggestive of sympathetic nervous system activation and improved endothelial function, acute exenatide infusion does not affect skin capillary perfusion in type 2 diabetes mellitus. Twelve-week treatment with liraglutide or sitagliptin has no effect on capillary perfusion or vasomotion in these patients. Our data suggest that the effects of GLP-1-based therapies on glucose are not mediated through microvascular responses. © 2016 American Heart Association, Inc.

  16. Rufinamide as an adjunctive therapy for Lennox-Gastaut syndrome: a randomized double-blind placebo-controlled trial in Japan.

    PubMed

    Ohtsuka, Yoko; Yoshinaga, Harumi; Shirasaka, Yukiyoshi; Takayama, Rumiko; Takano, Hiroki; Iyoda, Kuniaki

    2014-11-01

    To evaluate the efficacy, safety, and pharmacokinetics of rufinamide as an adjunctive therapy for patients with Lennox-Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial. We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to rufinamide or placebo. The primary efficacy variable was the percent change in the tonic-atonic seizure frequency per 28 days. Of the 59 patients, 29 were randomized to the rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the rufinamide group than in the placebo group; the median percent change in frequency of tonic-atonic seizures was -24.2% and -3.3%, respectively, (p=0.003) and that of total seizures was -32.9% and -3.1%, respectively (p<0.001). Subgroup analyses indicated that the efficacy of rufinamide was consistent independent of clinical background characteristics. The common treatment-related adverse events in the rufinamide group were decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%). Transient seizure aggravations were observed in 13 (22.0%) of the 59 patients, though a causal relationship with rufinamide was suspected in only one patient. All adverse events were mild to moderate in severity. The mean plasma concentration of rufinamide between 1 and 9 within 12h after administration was 17.2 μg/mL. The present results showed a favorable risk-benefit profile for rufinamide as an adjunctive therapy for patients with LGS. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  17. A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?

    PubMed

    Rekart, Michael L; Ndifon, Wilfred; Brunham, Robert C; Dushoff, Jonathan; Park, Sang Woo; Rawat, Sanjana; Cameron, Caroline E

    2017-08-01

    Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum. This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with

  18. ECAMulticapa: Effectiveness of double-layered compression therapy for healing venous ulcers in primary care: a Study Protocol.

    PubMed

    Folguera-Álvarez, Carmen; Garrido-Elustondo, Sofia; Verdú-Soriano, José; García-García-Alcalá, Diana; Sánchez-Hernández, Mónica; Torres-de Castro, Oscar German; Barceló-Fidalgo, Maria Luisa; Martínez-González, Olga; Ardiaca-Burgués, Lidia; Solano-Villarrubia, Carmen; Lebracón-Cortés, Pilar Raquel; Molins-Santos, Carmen; Fresno-Flores, Mar; Cánovas-Lago, Maria Carmen; Benito-Herranz, Luisa Fernanda; García-Sánchez, Maria Teresa; Castillo-Pla, Olga; Morcillo-San Juan, María Sol; Ayuso-de la Torre, Maria Begoña; Burgos-Quintana, Pilar; López-Torres-Escudero, Ana; Ballesteros-García, Gema; García-Cabeza, Piedad; de Francisco-Casado, Maria Ángeles; Rico-Blázquez, Milagros

    2016-01-01

    Chronic venous insufficiency, in its final stage can cause venous ulcers. Venous ulcers have a prevalence of 0.5 % to 0.8 % in the general population, and increases starting at 60 years of age. This condition often causes increased dependency in affected individuals, as well as a perceived reduced quality of life and family overload. Local Treating chronic venous ulcers has 2 components: topically healing the ulcer and controlling the venous insufficiency. There is evidence that compressive therapy favours the healing process of venous ulcers. The studies we have found suggest that the use of multilayer bandage systems is more effective than the use of bandages with a single component, these are mostly using in Spain. Multilayer compression bandages with 2 layers are equally effective in the healing process of chronic venous ulcers as 4-layer bandages and are better tolerated and preferenced by patients. More studies are needed to specifically compare the 2-layer bandages systems in the settings where these patients are usually treated. Randomised, controlled, parallel, multicentre clinical trial, with 12 weeks of follow-up and blind evaluation of the response variable. The objective is to assess the efficacy of multilayer compression bandages (2 layers) compared with crepe bandages, based on the incidence of healed venous ulcers in individuals treated in primary care nursing consultations, at 12 weeks of follow-up. The study will include 216 individuals (108 per branch) with venous ulcers treated in primary care nursing consultations. The primary endpoint is complete healing at 12 weeks of follow-up. The secondary endpoints are the degree of healing (Resvech.2), quality of life (CCVUQ-e), adverse reactions related to the healing process. Prognosis and demographic variables are also recorder. Effectiveness analysis using Kaplan-Meier curves, a log-rank test and a Cox regression analysis. The analysis was performed by intention to treat. The study results can

  19. Antihelminthic Therapy and Antimony in Cutaneous Leishmaniasis: A Randomized, Double-Blind, Placebo-Controlled Trial in Patients Co-Infected with Helminths and Leishmania braziliensis

    PubMed Central

    Newlove, Tracey; Guimarães, Luiz H.; Morgan, Daniel J.; Alcântara, Leda; Glesby, Marshall J.; Carvalho, Edgar M.; Machado, Paulo R.

    2011-01-01

    Helminth infections influence the clinical response to certain diseases and are associated with delayed healing time of patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. We conducted a randomized, double-blind, placebo-controlled clinical trial to examine the role of early versus deferred treatment of intestinal helminth infection on the clinical course of patients with CL treated with pentavalent antimony. (Clinicaltrials.gov number NCT00469495). A total of 90 patients were enrolled, 51.1% (N = 23) of control patients had persistent lesions at Day 90, compared with 62.2% (N = 28) in the treatment group (difference 11.1%, 95% confidence interval = −9.1–30.0%). There was no statistically significant difference in overall time to cure between groups, although there was a tendency for shorter cure times in the control group. This study shows that early introduction of antihelminthic therapy does not improve clinical outcome in patients co-infected with helminths and L. braziliensis. PMID:21460008

  20. Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety.

    PubMed

    Asih, Prita R; Wahjoepramono, Eka J; Aniwiyanti, Vilia; Wijaya, Linda K; de Ruyck, Karl; Taddei, Kevin; Fuller, Stephanie J; Sohrabi, Hamid; Dhaliwal, Satvinder S; Verdile, Giuseppe; Carruthers, Malcolm; Martins, Ralph N

    2015-01-01

    Testosterone replacement therapy (TRT) has been investigated in older men as a preventative treatment against Alzheimer's disease and dementia. However, previous studies have been contradictory. We assessed TRT physiological effects in 44 older men (aged 61 ± 7.7 years) with subjective memory complaints using a double blind, randomized, crossover, placebo-controlled study. Participants were randomized into 2 groups, one group received transdermal testosterone (50 mg) daily for 24 weeks, followed by a 4 week wash-out period, then 24 weeks of placebo; the other group received the reverse treatment. Blood evaluation revealed significant increases in total testosterone, free (calculated) testosterone, dihydrotestosterone, and a decrease in luteinizing hormone levels (p<0.001) following TRT. Although there were significant increases in red blood cell counts, hemoglobin and prostate specific antigen levels following TRT, they remained within normal ranges. No significant differences in plasma amyloid beta, estradiol, sex hormone binding globulin, insulin levels, body fat percentage, or body mass index were detected. This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men on blood biomarkers linked to dementia risk. Our study suggests TRT is safe and well-tolerated in this Indonesian cohort, yet longitudinal studies with larger cohorts are needed to assess TRT further, and to establish whether TRT reduces dementia risk.

  1. Assessment of cetirizine, an antihistamine, to prevent cutaneous reactions to nevirapine therapy: results of the viramune-zyrtec double-blind, placebo-controlled trial.

    PubMed

    Launay, O; Roudière, L; Boukli, N; Dupont, B; Prévoteau du Clary, F; Patey, O; David, F; Lortholary, O; Devidas, A; Piketty, C; Rey, E; Urbinelli, R; Allaert, F A; Tréluyer, J M; Caumes, E

    2004-04-15

    We conducted a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of cetirizine to assess the ability of antihistamines to prevent nevirapine-associated rash in patients infected with human immunodeficiency virus type 1. Patients initiating treatment with nevirapine were randomized to receive either cetirizine, 10 mg q.d. (104 patients), or placebo (96 patients) during the first 6 weeks of therapy. Rash occurred in 22 (11%) of 200 patients; 10 (9.6%) were in the cetirizine group and 12 (12.5%) were in the placebo group (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.31-1.81; P=.5). Five of 22 rashes were cases of hypersensitivity syndrome. The rate of nevirapine discontinuation due to rash was similar in the 2 groups (7.7% and 6.25% in the cetirizine and placebo groups, respectively; P=.4). Multivariate analysis showed no treatment-group effect but indicated that age >40 years (OR, 3.83; 95% CI, 1.4-10.46; P=.008) was associated with an increased risk of rash. Cetirizine has no preventive effect on nevirapine-associated rash.

  2. Effects of Korean red ginseng as an adjuvant to bile acids in medical dissolution therapy for gallstones: a prospective, randomized, controlled, double-blind pilot trial.

    PubMed

    Lee, Jun Kyu; Kang, Hyoun Woo; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho

    2013-01-01

    Although ginseng, the root of Panax quinquefolium and P. ginseng, was reported to have anti-cholelithogenic effects in animal experiments, there have, to date, been no human studies. We conducted this prospective, controlled, double-blind pilot trial to evaluate the safety and efficiency of Korean red ginseng (KRG), the steamed root of P. ginseng C.A. Meyer. Twenty eight consecutive patients were randomized to receive either KRG (7.5 g divided into three daily doses) or a placebo as an adjuvant to the standard regimen of bile acids for gallstones (500 mg of chenodeoxycholic acid and 500 mg of ursodeoxycholic acid divided into three daily doses) for 24 weeks. No case of serious adverse reaction occurred in both groups. Although the decrease in stone burden was larger in the KRG group (3.4 ± 0.6 ml3) than in the placebo group (2.3 ± 1.1 ml(3)), it did not reach statistical significance (p = 0.09). Also there were no differences in the rate of complete dissolution, subjective improvement in symptoms, and the rate of cholecystectomy due to worsening pain or the development of complications and changes in laboratory tests before and after treatment. In conclusion, the addition of KRG as an adjuvant was safe for patients undergoing bile acid dissolution therapy for gallstones although it did not affect the results. Large-scaled trials to optimize regimens are expectantly needed.

  3. Effect of estrogen replacement therapy on symptoms of depression and anxiety in non-depressive menopausal women: a randomized double-blind, controlled study.

    PubMed

    Demetrio, Frederico Navas; Rennó, Joel; Gianfaldoni, Arlete; Gonçalves, Marcelo; Halbe, Hans Wolfgang; Filho, Antônio Hélio Guerra V; Gorenstein, Clarice

    2011-12-01

    The efficacy of estrogen replacement therapy (ERT) for mood disturbances associated with menopause has yet to be firmly established. The objective of this study was to investigate the efficacy of ERT for improving mood and anxiety of non-depressive postmenopausal women. This double-blind, randomized, placebo-controlled study involved two treatment groups: one receiving conjugated equine estrogens (CEEs; 0.625 mg/day) and the other placebo, for six cycles of 28 days each. Subjects were hysterectomized, healthy, non-depressive (according to Schedule for Affective Disorders and Schizophrenia, Life Time Version [SADS-L]) women. Depressive and anxiety symptoms were assessed with the Beck Depression Inventory (BDI), and the Hamilton Anxiety Scale (HAMA), respectively. The Profile of Mood States (POMS) and other scales were used to characterize symptoms. In both groups, BDI scores were significantly lower at cycles 1, 2, 3, and 6, compared with baseline assessments (p<0.01). Anxiety scores for both groups significantly improved from cycle 3 to study endpoint. The only significant difference favoring the active group occurred at cycle 1. POMS scores were significantly improved at the end of cycles 1, 2, 3 and 6 among treated subjects and at the end of cycles 2, 3, and 6 among placebo subjects. ERT is not associated with improvements in mood or anxiety symptoms in non-depressive, hysterectomized, postmenopausal women.

  4. Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

    PubMed Central

    Mortazavi, Mehran; Farzin, Davood; Zarhghami, Mehran; Hosseini, Seyed Hamzeh; Mansoori, Parisa; Nateghi, Gholamreza

    2015-01-01

    Background: Zinc can modulate fast-excitatory transmission, facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors. There are also emerging evidences discussing the implication of these neurotransmitters in pathophysiology of schizophrenia. Objectives: The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week, double-blind and placebo-controlled trial. Patients and Methods: Eligible participants were 30 inpatients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Patients were randomly allocated into two equal groups; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate (each containing 50 mg elemental Zn) three times a day and another group received risperidone 6 mg/day plus placebo. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the psychotic symptoms and aggression risk at baseline, week 2, 4, and 6 of the study. Results: The results of this study showed that both protocols significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study. However, this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group. No major clinical side-effects were detected. Conclusions: It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia. PMID:26576178

  5. Effects of vibration therapy on hormone response and stress in severely disabled patients: a double-blind randomized placebo-controlled clinical trial.

    PubMed

    Seco, J; Rodríguez-Pérez, V; López-Rodríguez, A F; Torres-Unda, J; Echevarria, E; Díez-Alegre, M I; Ortega, A; Morán, P; Mendoza-Laíz, N; Abecia Inchaurregui, L C

    2015-01-01

    To assess the effects of vibration therapy (VT) on quality of life and hormone response in severely disabled patients compared with placebo. A longitudinal prospective, double-blind, randomized placebo-controlled trial, with pre and postintervention assessments. A total of 20 severely disabled individuals were recruited from a National Reference Centre in Spain: 13 (65%) men and 7 (35%) women, 45.5 ± 9.32 years of age (range 41: 22-63). We evaluated their physical stress and state anxiety. No statistically significant changes were found in the socio-psychological variables studied, while in the experimental group state anxiety decreased significantly with p < 0.01 (Z = 2.38; one-tailed p = .009) and, among the biological variables, the level of cortisol fell (p = 0.03). Short periods of exposure to low-frequency and low-amplitude local vibration are a safe and effective mechanical stimulus that can have a positive effect in terms of hormone response. VT can be considered to have an anti-stress effect. © 2013 Association of Rehabilitation Nurses.

  6. Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study.

    PubMed

    Pariser, David; Loss, Robert; Jarratt, Michael; Abramovits, William; Spencer, James; Geronemus, Roy; Bailin, Philip; Bruce, Suzanne

    2008-10-01

    The use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK). We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light. We conducted a multicenter, double-blind, randomized study. A total of 49 patients with 363 AK lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients with 360 AK lesions had vehicle cream similarly applied. The lesions were then illuminated (630 nm, light dose 37 J/cm2) with repeated treatment 1 week later. Complete lesion and patient (all lesions showing complete response) response rates were evaluated 3 months after last treatment. MAL PDT was superior (P<.0001) to vehicle PDT with respect to lesion complete response (86.2% vs 52.2%, odds ratio 6.9 [95% confidence interval 4.7-10.3]) and patient complete response (59.2% vs 14.9%, odds ratio 13.2 [95% confidence interval 4.1-43.1]). The study population may not be representative of all patients with AK. MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.

  7. Placebo controlled, prospectively randomized, double-blinded study for the investigation of the effectiveness and safety of the acoustic wave therapy (AWT(®)) for cellulite treatment.

    PubMed

    Russe-Wilflingseder, Katharina; Russe-Wilfingsleder, Katharina; Russe, Elisabeth; Vester, Johannes C; Haller, Gerd; Novak, Pavel; Krotz, Alexander

    2013-06-01

    Placebo controlled double-blinded, prospectively randomized clinical trial with 17 patients (11 verum, 5 placebo) for evaluation of cellulite treatment with Acoustic Wave Therapy, (AWT(®)) was performed. The patients were treated once a week for 7 weeks, a total of 8 treatments with the D-ACTOR(®) 200 by Storz Medical AG. Data were collected at baseline, before 8th treatment, at 1 month (follow-up 1) and at 3 months (follow-up 2) after the last treatment with a patients' questionnaire, weight control, measurement of circumference and standardized photography. Treatment progress was further documented using a specially designed 3D imaging system (SkinSCAN(3D), 3D-Shape GmbH) providing an objective measure of cellulite (primary efficacy criteria). Patient's questionnaire in the verum group revealed an improvement in number and depth of dimples, skin firmness and texture, in shape and in reduction of circumference. The overall result (of skin waviness, Sq and Sz, surface and volume of depressions and elevations, Vvv and Vmp) at two follow-up visits indicates a more than medium sized superiority (MW = 0.6706) and is statistically significant (pWei-Lachin = 0.0106). The placebo group revealed no statistical significance. No side effects were seen. This indicates the efficacy and safety of AWT(®) for patients with cellulite.

  8. [A Case of Double Cancer of Initially Unresectable Sigmoid Colon Cancer and Advanced Gastric Cancer Treated with Curative Resection after mFOLFOX6 Therapy].

    PubMed

    Yoshikawa, Toru; Aoki, Kazunori; Mitsuhashi, Yuto; Tomiura, Satoko; Suto, Akiko; Miura, Takuya; Ikenaga, Shojirokazunori; Shibasaki, Itaru; Endo, Masaaki

    2016-03-01

    A 61-year-old man was admitted to our hospital because of a complaint of blood in stool. He was diagnosed with advanced colon and gastric cancers. Computed tomography (CT) revealed a sigmoid tumor with invasion to the bladder, a metastatic tumor in the lateral segmental branch of the left hepatic lobe, and ascites. He was diagnosed with initially unresectable double cancer. Ileostomy was performed immediately, and he was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). After 6 courses of the mFOLFOX6 regimen, CT revealed that the primary lesion of the sigmoid colon and liver metastasis had reduced in size, and the ascites had disappeared. Gastroscopy revealed that the gastric cancer had disappeared. Biopsy results were negative. Accordingly, his gastric cancer was diagnosed as treatment effect Grade 3. After 8 courses of mFOLFOX6 therapy, sigmoidectomy, partial resection of the bladder, and partial resection of the liver were performed. Gastric cancer was not resected in accordance with his will. Although 40 months has passed after the radical resection, neither the sigmoid colon cancer nor the gastric cancer recurred.

  9. SHORT-TERM EFFICACY OF LOW-LEVEL LASER THERAPY IN PATIENTS WITH KNEE OSTEOARTHRITIS: A RANDOMIZED PLACEBO-CONTROLLED, DOUBLE-BLIND CLINICAL TRIAL

    PubMed Central

    Fukuda, Vanessa Ovanessian; Fukuda, Thiago Yukio; Guimarães, Márcio; Shiwa, Silvia; de Lima, Bianca Del Cor; Martins, Rodrigo Álvaro Brandão Lopes; Casarotto, Raquel Aparecida; Alfredo, Patrícia Pereira; Bjordal, Jan Magnus; Fucs, Patrícia Maria Moraes Barros

    2015-01-01

    Objective: This study was designed to evaluate the short-term efficacy of low-level laser therapy (LLLT) for improving pain and function in patients with knee osteoarthritis. Methods: Forty-seven patients with knee osteoarthritis (79 knees), of both genders, participated in this randomized controlled double-blind clinical trial. They were randomly allocated to two groups: laser group with 25 patients (41 knees) and placebo group with 22 patients (38 knees). LLLT was performed three times a week, totaling nine sessions, using a AsGa 904 nm laser with mean power of 60 mW and beam area of 0.5 cm2. Nine points were irradiated on the knee, with energy of 3.0 J/point. The placebo group was treated with the same laser device, but with a sealed probe. Evaluations using Lequesne, visual numerical scale (VNS), Timed Up and Go (TUG), goniometry and dynamometry were conducted before the treatment started and after the nine sessions of LLLT. Results: A significant improvement in pain and function was found in all the assessments applied to the laser group. On comparing the laser group with the placebo group, significant differences were found in the VNS-resting and Lequesne evaluations. Conclusion: Treatment with LLLT improves pain and function over the short term in patients with knee osteoarthritis. PMID:27027049

  10. The effect of oscillating-energy manual therapy on lateral epicondylitis: a randomized, placebo-control, double-blinded study.

    PubMed

    Nourbakhsh, Mohammad Reza; Fearon, Frank J

    2008-01-01

    Symptoms of lateral epicondylitis (LE) are attributed to degenerative changes and inflammatory reactions in the common extensor tendon induced by microscopic tears in the tissue after repetitive or overload functions of the wrist and hand extensor muscles. Conventional treatments, provided on the premise of inflammatory basis of LE, have shown 39-80% failure rate. An alternative approach suggests that symptoms of LE could be due to active tender points developed in the origin of hand and wrist extensor muscles after overuse or repetitive movements. Oscillating-energy Manual Therapy (OEMT), also known as V-spread, is a craniosacral manual technique that has been clinically used for treating tender points over the suture lines in the skull. Considering symptoms of LE may result from active tender points, the purpose of this study was to investigate the effect of OEMT on pain, grip strength, and functional abilities of subjects with chronic LE. Twenty-three subjects with chronic LE (>3mo) between ages of 24 and 72 years participated in this study. Before their participation, all subjects were screened to rule out cervical and other pathologies that could possibly contribute to their lateral elbow pain. Subjects who met the inclusion criteria were randomized into treatment and placebo treatment groups by a second (treating) therapist. Subjects were blinded to their group assignment. Subjects in the treatment group received OEMT for six sessions. During each treatment session, first a tender point was located through palpation. After proper hand placement, the therapist focused the direction of the oscillating energy on the localized tender point. Subjects in the placebo group underwent the same procedure, but the direction of the oscillating energy was directed to an area above or below the tender points, not covering the affected area. Jamar Dynamometer, Patient Specific Functional Scale (PSFS), and Numeric Rating Scale (NRS) were used to measure grip strength

  11. Effect of low-level laser therapy on the post-surgical inflammatory process after third molar removal: study protocol for a double-blind randomized controlled trial

    PubMed Central

    2013-01-01

    determination of the actual effect of laser therapy on this model. The present study aims to provide a randomized, controlled, double-blind trial to compare four different LLLT parameters in relation to the outcomes of pain, swelling and muscle spasm following surgery for the extraction of impacted third molars and evaluate the effects os surgery on patients' quality os life (QOL). Trial registration Brazilian Registry of Clinical Trials - Rebec (RBR-6XSB5H). PMID:24195796

  12. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

    PubMed Central

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-01-01

    Summary Background Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of

  13. Shock wave therapy associated with eccentric strengthening versus isolated eccentric strengthening for Achilles insertional tendinopathy treatment: a double-blinded randomised clinical trial protocol.

    PubMed

    Mansur, Nacime Salomão Barbachan; Faloppa, Flávio; Belloti, João Carlos; Ingham, Sheila J McNeill; Matsunaga, Fabio Teruo; Santos, Paulo Roberto Dias Dos; Santos, Bruno Schiefer Dos; Carrazzone, Oreste Lemos; Peixoto, Gabriel; Aoyama, Bruno Takeshi; Tamaoki, Marcel Jun Sugawara

    2017-01-27

    There is no consensus regarding the treatment of Achilles insertional tendinopathies. Eccentric training remains the main choice in the conservative treatment of this illness; however, the good results in the management of non-insertional Achilles tendinopathy were not replicated in the insertional condition. Low energy shock wave therapy has been described as an alternative to these patients, but has yet to be empirically tested. Shock wave therapy, adjunctive to the eccentric strengthening protocol, will improve measures of pain and function. Double blind, placebo-controlled, parallel groups, randomised clinical trial. 93 patients with a diagnosis of chronic insertional tendinopathy, referred from primary or secondary healthcare services, will be assessed and enrolled in this study. They will be divided into two groups (randomised by sequentially numbered identical envelopes, which will be administered serially to participants), one containing the combination of low energy shock wave and eccentric exercises, as treatment and the other comprehending the exercises and the placebo treatment (an apparatus placed in the therapeutic head). The assessments will occur in 2, 4, 6, 12 and 24 weeks. Patients will be evaluated primarily by the Victorian Institute of Sport Assessment-Achilles questionnaire and secondarily by the visual analogue scale, Algometry, the American Orthopedic Foot and Ankle Society scale, the Foot and Ankle Outcome Score and the 12-item Short Form Health Survey. We will use comparison of two proportions via relative frequency analysis, the Pearson Correlation the χ(2) test and the analysis of variance for statistical analyses. This study intends to demonstrate if the association of the eccentric exercise programme with the shock wave therapy can produce good results regarding the treatment of the Achilles insertional tendinopathy. In an attempt to prevent the high costs and complications associated with the surgical intervention, we will try to

  14. Shock wave therapy associated with eccentric strengthening versus isolated eccentric strengthening for Achilles insertional tendinopathy treatment: a double-blinded randomised clinical trial protocol

    PubMed Central

    Mansur, Nacime Salomão Barbachan; Faloppa, Flávio; Belloti, João Carlos; Ingham, Sheila J McNeill; Matsunaga, Fabio Teruo; dos Santos, Paulo Roberto Dias; dos Santos, Bruno Schiefer; Carrazzone, Oreste Lemos; Peixoto, Gabriel; Aoyama, Bruno Takeshi; Tamaoki, Marcel Jun Sugawara

    2017-01-01

    Background There is no consensus regarding the treatment of Achilles insertional tendinopathies. Eccentric training remains the main choice in the conservative treatment of this illness; however, the good results in the management of non-insertional Achilles tendinopathy were not replicated in the insertional condition. Low energy shock wave therapy has been described as an alternative to these patients, but has yet to be empirically tested. Hypothesis Shock wave therapy, adjunctive to the eccentric strengthening protocol, will improve measures of pain and function. Design Double blind, placebo-controlled, parallel groups, randomised clinical trial. Materials and methods 93 patients with a diagnosis of chronic insertional tendinopathy, referred from primary or secondary healthcare services, will be assessed and enrolled in this study. They will be divided into two groups (randomised by sequentially numbered identical envelopes, which will be administered serially to participants), one containing the combination of low energy shock wave and eccentric exercises, as treatment and the other comprehending the exercises and the placebo treatment (an apparatus placed in the therapeutic head). The assessments will occur in 2, 4, 6, 12 and 24 weeks. Patients will be evaluated primarily by the Victorian Institute of Sport Assessment-Achilles questionnaire and secondarily by the visual analogue scale, Algometry, the American Orthopedic Foot and Ankle Society scale, the Foot and Ankle Outcome Score and the 12-item Short Form Health Survey. We will use comparison of two proportions via relative frequency analysis, the Pearson Correlation the χ2 test and the analysis of variance for statistical analyses. Discussion This study intends to demonstrate if the association of the eccentric exercise programme with the shock wave therapy can produce good results regarding the treatment of the Achilles insertional tendinopathy. In an attempt to prevent the high costs and complications

  15. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

    PubMed

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-09-01

    Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in

  16. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

    PubMed Central

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-01-01

    Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127. PMID:26935876

  17. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    SciTech Connect

    Choo, Richard; Lukka, Himu; Cheung, Patrick; Corbett, Tom; Briones-Urbina, Rosario; Vieth, Reinhold; Ehrlich, Lisa; Kiss, Alex; Danjoux, Cyril

    2013-04-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

  18. Leg edema with (S)-amlodipine vs conventional amlodipine given in triple therapy for hypertension: a randomized double blind controlled clinical trial.

    PubMed

    Galappatthy, Priyadarshani; Waniganayake, Yasindu C; Sabeer, Mohomad I M; Wijethunga, Thusitha J; Galappatthy, Gamini K S; Ekanayaka, Ruvan Ai

    2016-09-01

    Leg edema is a common adverse effect of dihydropyridine Calcium Channel Blockers (CCB) that may need dose reduction or drug withdrawal, adversely affecting the antihypertensive efficacy. Leg edema is reported to occur less often with (S)-amlodipine compared to conventional racemic amlodipine. We aimed to find the incidence of leg edema as a primary outcome and antihypertensive efficacy with (S)-amlodipine compared to conventional amlodipine. This prospective, double-blind, controlled clinical trial randomized 172 hypertensive patients, not controlled on beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), to either conventional amlodipine (5-10 mg; n = 86) or (S)-amlodipine (2.5-5 mg; n = 86), while continuing their previous anti-hypertensive medications. Sample was sufficient to find a difference in edema between the interventions with 80 % power at 5 % significance level. Intension to treat analysis (ITT) for safety data and per protocol analysis for efficacy data was performed. Fischer's exact test was applied to observe difference between responder rates and proportions of subjects having peripheral edema in the two groups. Pitting edema test scores were compared using Mann-Whitney test. Altogether 146 patients (amlodipine, n = 76 and (S)-amlodipine, n = 70) completed 120 days treatment. Demographic variables and treatment adherence were comparable in the two groups. Incidence of new edema after randomization was 31.40 % in test group and 46.51 % in control group [p = 0.03; absolute risk reduction (ARR) = 15.1 %; Number Needed to Treat (NNT) = 7, ITT analysis]. Pitting edema score and patient rated edema score increased significantly in the control compared to test group (p = 0.038 and 0.036 respectively) after treatment period. Edema scores increased significantly in the control group from baseline (p < 0.0001). Responders in blood pressure were 98.57 % in test

  19. Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China.

    PubMed

    Zhou, Lei; Liu, Weibin; Li, Wei; Li, Haifeng; Zhang, Xu; Shang, Huifang; Zhang, Xu; Bu, Bitao; Deng, Hui; Fang, Qi; Li, Jimei; Zhang, Hua; Song, Zhi; Ou, Changyi; Yan, Chuanzhu; Liu, Tao; Zhou, Hongyu; Bao, Jianhong; Lu, Jiahong; Shi, Huawei; Zhao, Chongbo

    2017-09-01

    To determine the efficacy of low-dose, immediate-release tacrolimus in patients with myasthenia gravis (MG) with inadequate response to glucocorticoid therapy in a randomized, double-blind, placebo-controlled study. Eligible patients had inadequate response to glucocorticoids (GCs) after ⩾6 weeks of treatment with prednisone ⩾0.75 mg/kg/day or 60-100 mg/day. Patients were randomized to receive 3 mg tacrolimus or placebo daily (orally) for 24 weeks. Concomitant glucocorticoids and pyridostigmine were allowed. Patients continued GC therapy from weeks 1-4; from week 5, the dose was decreased at the discretion of the investigator. The primary efficacy outcome measure was a reduction, relative to baseline, in quantitative myasthenia gravis (QMG) score assessed using a generalized linear model; supportive analyses used alternative models. Of 138 patients screened, 83 [tacrolimus (n = 45); placebo (n = 38)] were enrolled and treated. The change in adjusted mean QMG score from baseline to week 24 was -4.9 for tacrolimus and -3.3 for placebo (least squares mean difference: -1.7, 95% confidence interval: -3.5, -0.1; p = 0.067). A post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group (68.2%) versus the placebo group (44.7%; p = 0.044). Adverse event profiles were similar between treatment groups. Tacrolimus 3 mg treatment for patients with MG and inadequate response to GCs did not demonstrate a statistically significant improvement in the primary endpoint versus placebo over 24 weeks; however, a post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group versus the placebo group. This study was limited by the low number of patients, the absence of testing for acetylcholine receptor antibody and the absence of stratification by disease duration (which led to a disparity between the two groups). ClinicalTrials.gov identifier

  20. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study.

    PubMed

    Jabbour, Serge A; Hardy, Elise; Sugg, Jennifer; Parikh, Shamik

    2014-01-01

    To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin. In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day). Baseline HbA1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA1c levels (-0.5% [-4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (-2.1 and -0.3 kg) and reduced HbA1c levels in patients with baseline values ≥8.0% (-0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (-24.1 mg/dL [-1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%). These results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides

  1. [Antithrombotic therapy in atrial arrhythmia].

    PubMed

    Cohen, Ariel

    2004-02-15

    The principal complication of the atrial arrythmias is the thrombo-embolic accident, notably the cerebro-vascular accident. The efficacity of the oral anticoagulants in reducing cerebro-vascular accidents has been demonstrated in numerous studies. This is significantly superior to that obtained with the anti-platelet drugs. However, the anti-vitamin K drugs (warfarin) carry a risk of serious haemorrhage of around 5% per year. This restricts the proposal of this treatment to patients with an elevated risk of vascular accidents: age, diabetes, previous cerebro-vascular accidents, and cardiac failure are the risk factors. Nevertheless, the risk of haemorrhage is responsible for an under prescription of the anticoagulants in the elderly. This explains the interest aroused by alternative therapeutics: the results of trials on ximelagatran, a direct anti-thrombin, are promising. In patients with an arrythmia, cardioversion carries a thrombo-embolic risk of around 1%. This risk is reduced by prior anticoagulant treatment. The procedure for this treatment is orientated by a trans-oesophageal echocardiogram. The incertitude of the duration of anticoagulant therapy without cardioversion calls for respect of the arrythmia. The treatment of this is limited to control of the cardiac rhythm and anticoagulant treatment.

  2. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

    PubMed Central

    Emery, Paul; Vencovský, Jiří; Sylwestrzak, Anna; Leszczyński, Piotr; Porawska, Wieslawa; Baranauskaite, Asta; Tseluyko, Vira; Zhdan, Vyacheslav M; Stasiuk, Barbara; Milasiene, Roma; Barrera Rodriguez, Aaron Alejandro; Cheong, Soo Yeon; Ghil, Jeehoon

    2017-01-01

    Objectives To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. Results 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was −9.41% to 4.98%, which is completely contained within the predefined equivalence margin of −15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). Conclusions SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN. Trial registration numbers NCT01895309, EudraCT 2012-005026-30. PMID:26150601

  3. Radial Extracorporeal Shock Wave Therapy Is Not More Effective Than Placebo in the Management of Lateral Epicondylitis: A Double-Blind, Randomized, Placebo-Controlled Trial.

    PubMed

    Capan, Nalan; Esmaeilzadeh, Sina; Oral, Aydan; Basoglu, Ceyhun; Karan, Ayse; Sindel, Dilsad

    2016-07-01

    The aim of this study was to investigate the effects of radial extracorporeal shock wave therapy (rESWT) on pain, function, and grip strength in the treatment of patients with lateral epicondylitis unresponsive to previous treatments. A double-blind, randomized, placebo-controlled trial was conducted in outpatient clinics in a medical faculty hospital. Fifty-six patients with lateral epicondylitis were randomized to rESWT (n = 28) or sham rESWT (n = 28) groups. Both the patients and the outcome assessing investigator were blinded to group assignment. The rESWT was administered to the painful epicondyle at the elbow with a total of 2000 pulses of 10 Hz frequency at a 1.8 bar of air pressure at each session at three once weekly sessions. Sham rESWT was applied without the contact of the applicator at the same area. Study patients were assessed at baseline and at 1 and 3 mos after treatment using a visual analog scale for pain and Roles and Maudsley scale and Patient-Rated Tennis Elbow Evaluation for pain and function. Grip strength of the affected extremity was also measured using a hand dynamometer. Both rESWT and sham rESWT groups showed a significant improvement in all outcome measures at posttreatment follow-up points. Favorable absolute and percentage changes in assessments at 1- and 3-mo posttreatment did not show any significant difference between groups. The rESWT does not seem to be more effective either in reducing pain or improving function or grip strength in patients with lateral epicondylitis at least at 3 mos after treatment when compared with sham rESWT.

  4. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy.

    PubMed

    Emery, Paul; Vencovský, Jiří; Sylwestrzak, Anna; Leszczyński, Piotr; Porawska, Wieslawa; Baranauskaite, Asta; Tseluyko, Vira; Zhdan, Vyacheslav M; Stasiuk, Barbara; Milasiene, Roma; Barrera Rodriguez, Aaron Alejandro; Cheong, Soo Yeon; Ghil, Jeehoon

    2017-01-01

    To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN. NCT01895309, EudraCT 2012-005026-30. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Synbiotic therapy decreases microbial translocation and inflammation and improves immunological status in HIV-infected patients: a double-blind randomized controlled pilot trial

    PubMed Central

    2012-01-01

    Background HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production. Methods A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks. Results We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma (p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces (p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly (p = 0.016). Conclusions Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources. PMID:23101545

  6. A double-blind randomized controlled trial to assess the efficacy of daylight photodynamic therapy with methyl-aminolevulinate vs. Placebo and daylight in patients with facial photodamage.

    PubMed

    Sanclemente, G; Mancilla, G A; Hernandez, G

    2016-04-01

    Daylight PDT (dPDT) is easy to use and does not require light equipment. Such therapy has been exhaustively proved to be successful in the treatment of actinic keratosis, but its use in skin photodamage remains unclear. To evaluate dPDT's efficacy in skin facial photodamage. This was a parallel-group double-blind, randomized placebo-controlled trial. Sixty participants with symmetric facial photodamage were allocated to topical methyl aminolevulinate (MAL) and daylight vs. matching placebo and daylight. Primary outcome was global photodamage improvement/failure 1 month after the third session. Secondary outcomes included: pain evaluation; specific photodamage severity scores; sun irradiance quantification and Skindex-29 scores. Adverse events were also investigated. Primary analysis included all randomized patients. All patients sun-exposed for 120min in 3 sessions. The risk of failure was lower in the MAL-dPDT group than in the placebo plus daylight group (RR: 0.18; 95% CI: 0.08-0.41). Mean solar irradiance (W/m(2)) during the first, second and third sessions was 480.82, 430.07 and 435.84, respectively. Items 5 and 14 of Skindex-29 in the MAL-dPDT group showed statistical significant differences. Two patients in the MAL-dPDT group had serious and non-serious events not directly related to the product. dPDT with MAL was un-painful, effective and safe for the treatment of facial photodamage. Herpes simplex prophylaxis should be considered before sessions. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

  7. Effects of low-level laser therapy on performance, inflammatory markers, and muscle damage in young water polo athletes: a double-blind, randomized, placebo-controlled study.

    PubMed

    Zagatto, Alessandro Moura; de Paula Ramos, Solange; Nakamura, Fábio Yuzo; de Lira, Fábio Santos; Lopes-Martins, Rodrigo Álvaro Brandão; de Paiva Carvalho, Rodrigo Leal

    2016-04-01

    This study aimed to evaluate the effects of 5 days of 810-nm low-level laser therapy (LLLT) intervention on inflammatory and muscle damage markers and performance in young water polo players. Twenty young male water polo players participated in the study, which was designed as a randomized, double-blinded, placebo-controlled trial. Active LLLT or an identical placebo LLLT were delivered to eight points on the adductor muscle region immediately after each training day. Performance was measured by a 200-m maximal swimming (P200) and a 30-s crossbar jump test (30CJ) which was performed every day before training, and blood samples were drawn pre and post the final LLLT intervention to measure interleukins (IL) and muscle damage markers. There was no significant change in the P200 exercise in the LLLT group compared with the placebo group but there was a moderate improvement in the 30CJ (8.7 ± 2.6 %). IL-1β and tumor necrosis factor-alpha presented increased (P < 0.016) concentration within group 48 h after the last LLLT intervention compared to pre, 0, and 24 h, but did not differ between groups. IL-10 increased over time in the placebo group and reached a moderate effect compared to the LLLT group. The creatine kinase decreased significantly (P = 0.049) over the time within the LLLT treatment group, but there was no significant change in lactate dehydrogenase (P = 0.150). In conclusion, LLLT resulted in a non-significant, but small to moderate effect on inflammatory and muscle damage markers and a moderate effect on performance in water polo players. In addition, the lack of positive results could be due to the small area covered by irradiation and this should be considered in future studies.

  8. Low level laser therapy associated with a strength training program on muscle performance in elderly women: a randomized double blind control study.

    PubMed

    Toma, Renata Luri; Vassão, Patrícia Gabrielli; Assis, Livia; Antunes, Hanna Karen Moreira; Renno, Ana Claudia Muniz

    2016-08-01

    The aging process leads to a gradual loss of muscle mass and muscle performance, leading to a higher functional dependence. Within this context, many studies have demonstrated the benefits of a combination of physical exercise and low level laser therapy (LLLT) as an intervention that enhances muscle performance in young people and athletes. The aim of this study was to evaluate the effects of combination of LLLT and strength training on muscle performance in elderly women. For this, a hundred elderly women were screened, and 48 met all inclusion criteria to participate in this double-blind placebo-controlled trial. Volunteers were divided in three groups: control (CG = 15), strength training associated with placebo LLLT (TG = 17), and strength training associated with active LLLT (808 nm, 100 mW, 7 J) (TLG = 16). The strength training consisted of knee flexion-extension performed with 80 % of 1-repetition maximum (1-RM) during 8 weeks. Several outcomes related to muscle performance were analyzed through the 6-min walk test (6-MWT), isokinetic dynamometry, surface electromyography (SEMG), lactate concentration, and 1-RM. The results revealed that a higher work (p = 0.0162), peak torque (p = 0.0309), and power (p = 0.0223) were observed in TLG compared to CG. Furthermore, both trained groups increased the 1-RM load (TG vs CG: p = 0.0067 and TLG vs CG: p < 0.0001) and decreased the lactate concentration in the third minute after isokinetic protocol (CG vs TLG: p = 0.0289 and CG vs TG: p = 0.0085). No difference in 6-MWT and in fatigue levels were observed among the groups. The present findings suggested that LLLT in combination with strength training was able to improve muscle performance in elderly people.

  9. Golden plaster for pain therapy in patients with knee osteoarthritis: study protocol for a multicenter randomized, double-blind, placebo-controlled trial.

    PubMed

    Liu, Jin-Tao; Tang, De-Zhi; Li, Xiao-Feng; Zhang, Zhi-Gang; Ji, Wan-Bo; Tao, Shuai; Wang, Yong-Jun; Jiang, Hong

    2013-11-13

    Osteoarthritis is a relatively common musculoskeletal disorder that increases in prevalence with age. Worldwide, knee osteoarthritis is one of the leading causes of disability, particularly in the elderly. In numerous trials of agents for long-term pain therapy, no well-established and replicable results have been achieved. Complementary and alternative medical approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the golden plaster is the preferred and most commonlyused method in China to reduce pain in patients with knee osteoarthritis, as it causes few adverse effects. The purpose of this study will be to evaluate the efficacy and safety of golden plaster on pain in patients with knee osteoarthritis. This study will be a multicenter randomized, double-blind, placebo-controlled trial. A total of 320 participants aged 45 to 79 years with knee osteoarthritis, whose scores on a visual analog scale (VAS) are more than 20 mm,will be randomly allocated into a treatment group and a control group. A golden plaster will be administered externally to participants in the treatment group for 2 weeks, while the control group will receive a placebo plaster externally for 2 weeks. Follow-up will be at regular intervals during a 4-week period with a VAS score for pain, quality of life, and complications. This study will be a methodologically sound randomized controlled trial to assess pain relief after the intervention of golden plaster, compared to a placebo intervention in patients with knee osteoarthritis. ClinicalTrials.gov identifier: ChiCTR-TRC-13003418.

  10. The Efficacy of Augment of D-Cycloserine and Cognitive-behavioral Therapy on Adolescent with one Type of Anxiety Disorders: A Double-blind Randomized Controlled Trial

    PubMed Central

    Arman, Soroor; Soheilimehr, Ali; Maracy, Mohammad Reza

    2017-01-01

    Background: This study was designed to investigating the effect of combining D-cycloserine (DCS) and cognitive-behavioral therapy (CBT) on adolescent with at least one type of anxiety disorders. Materials and Methods: The present study was conducted as a double-blind randomized controlled trial on 36 adolescent with anxiety disorders. Patients were assessed in two groups. In addition to 4 sessions of weekly CBT in both groups; case group, received a 50-mg DCS capsules, control group, received Placebo daily for a month. Patients received DCS capsules or placebo 1 h before sessions of CBT. Age, sex, kind of anxiety disorders “screen for child anxiety related disorders (SCARED)” and “cognitive abilities test (CATS)” scores were evaluated and compared between groups. Results: The mean age of the studied patients (29 females (80.6%) and 7 males (19.4%)) was 14.1 ± 1.8 years. The most frequent anxiety disorder among the study population was generalized social disorder (GAD) (77.7%). Age, sex and the frequency of anxiety disorders were not statistically significant between the study groups (P > 0.05). The mean score of “SCARED” and “CATS” at before starting the treatment, after treatment and three month after the treatment were not statistically significant between groups (P > 0.05). Also, decrease in values of “SCARED” and “CATS” during the evaluation time periods was not statistically significant between groups (P > 0.05). Conclusions: Findings of this study showed that there has been no difference in symptoms improvement in adolescent with anxiety disorder who received treatment protocol including 4 sessions of CBT, weekly, together with 50 mgs of DCS compared to the patients of the control group. PMID:28299303

  11. A randomized, double-blind, placebo-controlled, parallel-group study of rufinamide as adjunctive therapy for refractory partial-onset seizures.

    PubMed

    Biton, Victor; Krauss, Gregory; Vasquez-Santana, Blanca; Bibbiani, Francesco; Mann, Allison; Perdomo, Carlos; Narurkar, Milind

    2011-02-01

    Efficacy and safety of adjunctive rufinamide (3,200 mg/day) was assessed in adolescents and adults with inadequately controlled partial-onset seizures receiving maintenance therapy with up to three antiepileptic drugs (AEDs). This randomized, double-blind, placebo-controlled, parallel-group, multicenter study comprised a 56-day baseline phase (BP), 12-day titration phase, and 84-day maintenance phase (MP). The primary efficacy variable was percentage change in total partial seizure frequency per 28 days (MP vs. BP). Secondary efficacy outcome measures included ≥50% responder rate and reduction in mean total partial seizure frequency during the MP. Safety and tolerability evaluation included adverse events (AEs), physical and neurologic examinations, and laboratory values. Pharmacokinetic and pharmacodynamic assessments were conducted. Three hundred fifty-seven patients were randomized: 176 to rufinamide and 181 to placebo. Patients had a median of 13.3 seizures per 28 days during BP; 86% were receiving ≥2 AEDs. For the intent-to-treat population, the median percentage reduction in total partial seizure frequency per 28 days was 23.25 for rufinamide versus 9.80 for placebo (p = 0.007). Rufinamide-treated patients were more than twice as likely to have had a ≥50% reduction in partial seizure frequency (32.5% vs. 14.3%; p < 0.001) and had a greater reduction in median total partial seizure rate per 28 days during the MP (13.2 vs. 5.2; p < 0.001). Treatment-emergent AEs occurring at ≥5% higher incidence in the rufinamide group compared with placebo were dizziness, fatigue, nausea, somnolence, and diplopia. Adjunctive treatment with rufinamide reduced total partial seizures in refractory patients. AEs reported were consistent with the known tolerability profile of rufinamide. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  12. Pregabalin add-on therapy using a flexible, optimized dose schedule in refractory partial epilepsies: a double-blind, randomized, placebo-controlled, multicenter trial.

    PubMed

    Lee, Byung In; Yi, Sangdoe; Hong, Seung Bong; Kim, Myeong-Kyu; Lee, Sang Ahm; Lee, Sang Kun; Shin, Dong-Jin; Kim, Jae Moon; Song, Hong Ki; Heo, Kyoung; Lowe, Wing; Leon, Teresa

    2009-03-01

    To evaluate the efficacy and safety of pregabalin (PGB) as adjunctive therapy, using a flexible-dosing schedule in Korean patients with refractory partial-onset seizures. This randomized, double-blind (DB), placebo-controlled trial consists of a 6-week baseline, a 12-week DB treatment, and a 1-week taper phase. Patients having recurrent partial seizures (>or=4 seizures during baseline phase) under adequate pharmacotherapy were recruited to be randomized to PGB or placebo (PLC) in a 2 to 1 ratio. Starting dose was 150 mg/day, increased every 2 weeks by 150-mg/day increments up to maximum dose of 600 mg/day. The primary efficacy parameter was response ratio (RRatio) for all partial seizures. A total of 178 patients (119 in PGB, 59 in PLC) were assigned to the study. Median daily doses of PGB and PLC were 367 and 420 mg/day, respectively. RRatio least squares (LS) mean was -35.8 in the PGB group and -23.2 in the PLC group, with estimated difference in RRatios being -12.6 [95% confidence interval (CI): -22.7 to -2.5, p = 0.015] in the intent-to-treat (ITT) population. Analysis of secondary efficacy measures showed a general trend favoring PGB over PLC. Seventy-seven patients (64.7%) in the PGB group and 18 patients (30.5%) in the PLC group developed adverse events (AEs) related to the study drug. Seven patients (5.9%) in the PGB group discontinued the study prematurely because of AEs. In the post hoc analysis, a significant weight gain (>or=7% of baseline body weight) was found in 24.8% of patients taking PGB, which was more frequent in patients with a lower body mass index (BMI

  13. Efficacy of low-level laser therapy applied at acupuncture points in knee osteoarthritis: a randomised double-blind comparative trial.

    PubMed

    Al Rashoud, A S; Abboud, R J; Wang, W; Wigderowitz, C

    2014-09-01

    To evaluate the efficacy of low-level laser therapy (LLLT) applied to acupuncture points on the knee joint in combination with exercise and advice in patients with knee osteoarthritis. Randomised, double-blind, comparative clinical trial. Forty-nine patients with knee osteoarthritis were assigned at random into two groups: active laser group (n=26) and placebo laser group (n=23). Using a gallium aluminium arsenide laser device, patients received either active or placebo LLLT at five acupuncture points on the affected knee during nine sessions. Patients were assessed using a visual analogue scale (VAS) and the Saudi Knee Function Scale (SKFS) at baseline, the fifth treatment session, the last treatment session, 6 weeks post intervention and 6 months post intervention. VAS scores showed a significant improvement in the active laser group compared with the placebo laser group at 6 weeks post intervention [mean difference -1.3, 95% confidence interval (CI) of the difference -2.4 to -0.3; P=0.014] and 6 months post intervention (mean difference -1.8, 95% CI of the difference -3.0 to -0.7; P=0.003) using the independent samples test. SKFS scores also showed a significant improvement in the active laser group compared with the placebo laser group at the last treatment session (median difference -15, 95% CI of the difference -27 to -2; P=0.035) and 6 months post intervention (median difference -21, 95% CI of the difference -34 to -7; P=0.006) using the Mann-Whitney U test. The results demonstrate that short-term application of LLLT to specific acupuncture points in association with exercise and advice is effective in reducing pain and improving quality of life in patients with knee osteoarthritis. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  14. Effect of low-level laser therapy (808 nm) on markers of muscle damage: a randomized double-blind placebo-controlled trial.

    PubMed

    Felismino, Amanda Soares; Costa, Eduardo Caldas; Aoki, Marcelo Saldanha; Ferraresi, Cleber; de Araújo Moura Lemos, Telma Maria; de Brito Vieira, Wouber Hérickson

    2014-05-01

    The aim of this randomized double-blind placebo-controlled study was to investigate the effect of low-level laser therapy (LLLT) on markers of muscle damage (creatine kinase (CK) and strength performance) in the biceps brachii. Twenty-two physically active men were randomized into two groups: placebo and laser. All volunteers were submitted to an exercise-induced muscle damage protocol for biceps brachii (biceps curl, 10 sets of 10 repetitions with load of 50% of one-repetition maximum test (1RM)). Active LLLT (808 nm; 100 mW; 35.7 W/cm(2), 357.14 J/cm(2) per point, energy of 1 J per point applied for 10 s on four points of the biceps brachii belly of each arm) or placebo was applied between the sets of the biceps curl exercise. CK activity and maximum strength performance (1RM) were measured before, immediately after, 24, 48, and 72 h after the exercise-induced muscle damage protocol. There was an increase in CK activity after the muscle damage protocol in both groups; however, this increase was attenuated in the laser group compared to the placebo group at 72 h (placebo = 841 vs. laser = 357%; p < 0.05). Maximum strength performance was decreased immediately after the muscle damage protocol in both groups (p < 0.05), but at 24, 48, and 72 h, and it returned to the baseline level in both groups. In conclusion, the LLLT attenuated CK activity 72 h after the muscle damage protocol but did not have a positive effect on the recovery of strength performance.

  15. Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment of complicated urinary tract infections in adults: results of a prospective, randomized, double-blind multicenter study.

    PubMed

    Tomera, Kevin M; Burdmann, Emmanuel A; Reyna, Oscar G Pamo; Jiang, Qi; Wimmer, Wendy M; Woods, Gail L; Gesser, Richard M

    2002-09-01

    The efficacy and safety of intravenous (i.v.) ertapenem (1 g once a day) with the option to switch to an oral agent for treatment of adults with complicated urinary tract infections (UTIs) were compared with that of i.v. ceftriaxone (1 g daily) with the same oral switch option in a multicenter, double-blind, prospective, randomized study. At entry, 592 patients were assigned to one of two strata: acute pyelonephritis or other complicated UTI without acute pyelonephritis. After a minimum of 3 days, patients could be switched to an oral antimicrobial agent. A total of 159 patients in the ertapenem group and 171 patients in the ceftriaxone group were microbiologically evaluable. Approximately 95% of patients in each treatment group were switched to oral therapy. The most common pathogens were Escherichia coli and Klebsiella pneumoniae. At the primary efficacy endpoint 5 to 9 days after treatment, 91.8% of patients who received ertapenem and 93.0% of those who received ceftriaxone had a favorable microbiological response (95% confidence interval for the difference, adjusting for strata, -7.6 to 5.1%), indicating that outcomes in the two treatment groups were equivalent. Microbiological success rates for the two treatment groups were similar when compared by stratum and also by severity of infection. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study, ertapenem was as effective as ceftriaxone for the initial treatment of complicated UTIs in adults, was generally well tolerated, and had a similar overall safety profile.

  16. Ertapenem versus Ceftriaxone Followed by Appropriate Oral Therapy for Treatment of Complicated Urinary Tract Infections in Adults: Results of a Prospective, Randomized, Double-Blind Multicenter Study

    PubMed Central

    Tomera, Kevin M.; Burdmann, Emmanuel A.; Pamo Reyna, Oscar G.; Jiang, Qi; Wimmer, Wendy M.; Woods, Gail L.; Gesser, Richard M.

    2002-01-01

    The efficacy and safety of intravenous (i.v.) ertapenem (1 g once a day) with the option to switch to an oral agent for treatment of adults with complicated urinary tract infections (UTIs) were compared with that of i.v. ceftriaxone (1 g daily) with the same oral switch option in a multicenter, double-blind, prospective, randomized study. At entry, 592 patients were assigned to one of two strata: acute pyelonephritis or other complicated UTI without acute pyelonephritis. After a minimum of 3 days, patients could be switched to an oral antimicrobial agent. A total of 159 patients in the ertapenem group and 171 patients in the ceftriaxone group were microbiologically evaluable. Approximately 95% of patients in each treatment group were switched to oral therapy. The most common pathogens were Escherichia coli and Klebsiella pneumoniae. At the primary efficacy endpoint 5 to 9 days after treatment, 91.8% of patients who received ertapenem and 93.0% of those who received ceftriaxone had a favorable microbiological response (95% confidence interval for the difference, adjusting for strata, −7.6 to 5.1%), indicating that outcomes in the two treatment groups were equivalent. Microbiological success rates for the two treatment groups were similar when compared by stratum and also by severity of infection. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study, ertapenem was as effective as ceftriaxone for the initial treatment of complicated UTIs in adults, was generally well tolerated, and had a similar overall safety profile. PMID:12183244

  17. Golden plaster for pain therapy in patients with knee osteoarthritis: study protocol for a multicenter randomized, double-blind, placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Osteoarthritis is a relatively common musculoskeletal disorder that increases in prevalence with age. Worldwide, knee osteoarthritis is one of the leading causes of disability, particularly in the elderly. In numerous trials of agents for long-term pain therapy, no well-established and replicable results have been achieved. Complementary and alternative medical approaches have been employed for thousands of years to relieve knee osteoarthritis pain. Among herbal medicines, the golden plaster is the preferred and most commonlyused method in China to reduce pain in patients with knee osteoarthritis, as it causes few adverse effects. The purpose of this study will be to evaluate the efficacy and safety of golden plaster on pain in patients with knee osteoarthritis. Methods/Design This study will be a multicenter randomized, double-blind, placebo-controlled trial. A total of 320 participants aged 45 to 79 years with knee osteoarthritis, whose scores on a visual analog scale (VAS) are more than 20 mm,will be randomly allocated into a treatment group and a control group. A golden plaster will be administered externally to participants in the treatment group for 2 weeks, while the control group will receive a placebo plaster externally for 2 weeks. Follow-up will be at regular intervals during a 4-week period with a VAS score for pain, quality of life, and complications. Discussion This study will be a methodologically sound randomized controlled trial to assess pain relief after the intervention of golden plaster, compared to a placebo intervention in patients with knee osteoarthritis. Trial registration ClinicalTrials.gov identifier: ChiCTR-TRC-13003418 PMID:24220504

  18. Comparison of the therapeutic efficacy of double-modality therapy, phonophoresis and cryotherapy in the management of musculoskeletal injuries in adult Nigerian subjects.

    PubMed

    Onuwe, H A; Amadi, K; Odeh, S O

    2013-12-20

    This study was designed to compare the efficacy of double-modality therapy, phonophoresis and cryotherapy in the management of pain among subjects who suffered from musculoskeletal injuries (MSIs).Sixty (60) subjects were assigned randomly to one of three groups: DMT group (n=20) received cryotherapy and 15% methyl salicylate phonophoresis, PHONO group (n=20) received 15% methyl salicylate phonophoresis and CRYO group (n=20) received cryotherapy and "sham‟ phonophoresis. Ultrasound at an intensity of 1.5 W/cm² and frequency of 1MHz was used to apply methyl salicylate while intermittent cryotherapy was the mode of application. Subjects‟ pre- and post-treatment pain perception scores (PPS) using visual analogue scale (VAS) were assessed and the sessions of treatment in all groups were recorded. Treatment was administered on alternate days and discharges were made in all groups when subjects were pain free. A total of 275 treatment sessions was recorded - 72 (26.2%) in DMT, 105 (38.2%) in PHONO and 98 (35.6%) in CRYO group respectively which indicated no significant difference (P>0.05). Nineteen (19), thirteen (13) and twelve (12) subjects were pain free in DMT, CRYO or PHONO groups respectively after 1 to 5 treatments. The difference in the severity of pain was significant (P<0.05) in each group post-treatment which suggests that DMT, phonophoresis and cryotherapy were equally effective. The study has demonstrated therapeutic efficacy of DMT, but it was not superior to the single treatment protocol of phonophoresis or cryotherapy. However, it might take fewer sessions in the DMT group to treat and make more than 90% of the subjects pain free and fit to return to active performance.

  19. Effects of low-level laser therapy applied before or after plyometric exercise on muscle damage markers: randomized, double-blind, placebo-controlled trial.

    PubMed

    Fritsch, Carolina Gassen; Dornelles, Maurício Pinto; Severo-Silveira, Lucas; Marques, Vanessa Bernardes; Rosso, Isabele de Albuquerque; Baroni, Bruno Manfredini

    2016-12-01

    Promising effects of phototherapy on markers of exercise-induced muscle damage has been already demonstrated in constant load or isokinetic protocols. However, its effects on more functional situations, such as plyometric exercises, and when is the best moment to apply this treatment (pre- or post-exercise) remain unclear. Therefore, the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) before or after plyometric exercise on quadriceps muscle damage markers. A randomized, double-blinded, placebo-controlled trial was conducted with 24 healthy men, 12 at pre-exercise treatment group and 12 at post-exercise treatment group. Placebo and LLLT (810 nm, 200 mW per diode, 6 J per diode, 240 J per leg) were randomly applied on right/left knee extensor muscles of each volunteer before/after a plyometric exercise protocol. Muscular echo intensity (ultrasonography images), soreness (visual analogue scale - VAS), and strength impairment (maximal voluntary contraction - MVC) were assessed at baseline, 24, 48, and 72 h post-exercise. Legs treated with LLLT before or after exercise presented significantly smaller increments of echo intensity (values up to 1 %) compared to placebo treatments (increased up to ∼7 %). No significant treatment effect was found for VAS and MVC, although a trend toward better results on LLLT legs have been found for VAS (mean values up to 30 % lesser than placebo leg). In conclusion, LLLT applied before or after plyometric exercise reduces the muscle echo intensity response and possibly attenuates the muscle soreness. However, these positive results were not observed on strength impairment.

  20. Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol.

    PubMed

    Pinto, Camila Bonin; Saleh Velez, Faddi Ghassan; Bolognini, Nadia; Crandell, David; Merabet, Lotfi B; Fregni, Felipe

    2016-07-06

    Despite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP. The objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees. A prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the

  1. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial.

    PubMed

    Greenberg, Barry; Butler, Javed; Felker, G Michael; Ponikowski, Piotr; Voors, Adriaan A; Desai, Akshay S; Barnard, Denise; Bouchard, Alain; Jaski, Brian; Lyon, Alexander R; Pogoda, Janice M; Rudy, Jeffrey J; Zsebo, Krisztina M

    2016-03-19

    Sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity is deficient in the failing heart. Correction of this abnormality by gene transfer might improve cardiac function. We aimed to investigate the clinical benefits and safety of gene therapy through infusion of adeno-associated virus 1 (AAV1)/SERCA2a in patients with heart failure and reduced ejection fraction. We did this randomised, multinational, double-blind, placebo-controlled, phase 2b trial at 67 clinical centres and hospitals in the USA, Europe, and Israel. High-risk ambulatory patients with New York Heart Association class II-IV symptoms of heart failure and a left ventricular ejection fraction of 0·35 or less due to an ischaemic or non-ischaemic cause were randomly assigned (1:1), via an interactive voice and web-response system, to receive a single intracoronary infusion of 1 × 10(13) DNase-resistant particles of AAV1/SERCA2a or placebo. Randomisation was stratified by country and by 6 min walk test distance. All patients, physicians, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was time to recurrent events, defined as hospital admission because of heart failure or ambulatory treatment for worsening heart failure. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01643330. Between July 9, 2012, and Feb 5, 2014, we randomly assigned 250 patients to receive either AAV1/SERCA2a (n=123) or placebo (n=127); 243 (97%) patients comprised the modified intention-to-treat population. Patients were followed up for at least 12 months; median follow-up was 17·5 months (range 1·8-29·4 months). AAV1/SERCA2a did not improve time to recurrent events compared with placebo (104 vs 128 events; hazard ratio 0·93, 95% CI 0·53-1·65; p=0·81). No safety signals were noted. 20 (16%) patients died in the placebo group and 25 (21%) patients died in the AAV1

  2. Efficacy and safety of extract of Ginkgo biloba as an adjunct therapy in chronic schizophrenia: A systematic review of randomized, double-blind, placebo-controlled studies with meta-analysis.

    PubMed

    Chen, Xichuang; Hong, Yuan; Zheng, Panpan

    2015-07-30

    Our study was to review and evaluate the efficacy and safety of extract of Gb (EGb) as an adjuvant therapy to antipsychotics in chronic schizophrenia treatment. We searched Pubmed/Medline, Embase, PsycINFO, the Cochrane library, and especially the Chinese periodical databases. Finally, eight randomized, double-blind, placebo-controlled trials (RCTs) of 1033 patients were enrolled, with 571 cases in EGb group and 462 in placebo. The result showed that EGb had a significant difference in ameliorating total and negative symptoms of chronic schizophrenia as an adjuvant therapy to antipsychotics. Thus, the EGb therapy plus antipsychotics might be more efficacious. Although the studies describing adverse reactions showed no distinguishable difference between EGb and placebo group in mean total scores of Treatment Emergent Symptom Scale (TESS) or a Rating Scale for Extrapyramidal Side Effects (RSESE), the results of subscores varied in different studies. In addition, the severity of side effects of EGb might be related to its daily dosage. Therefore, the safety of EGb therapy in chronic schizophrenia treatment might need more evidence. And all of these eight trials were carried out in China; thus, the results might be restricted to the race and we need more high-quality studies of multi-center and randomized double-blind clinical trials to compare, analyze, and confirm the findings further.

  3. Combination therapy with olmesartan medoxomil and hydrochlorothiazide: secondary analysis of the proportion of patients achieving recommended blood pressure goals from a randomized, double-blind, factorial study.

    PubMed

    Chrysant, Steven G; Chavanu, Kathleen J; Xu, Jianbo

    2009-01-01

    The combination of olmesartan medoxomil and hydrochlorothiazide (HCTZ) [olmesartan medoxomil/HCTZ] has previously been shown to produce significantly greater SBP/DBP reductions than monotherapy with either agent alone in a randomized, double-blind, factorial study in patients with stage 2 hypertension. Compared with the evaluation of a single mean BP reduction in a patient population, determining the efficacy of an antihypertensive agent in achieving multiple BP targets provides additional information about the range of BP reductions attainable within this study population. To conduct a secondary analysis of this study to evaluate the proportion of patients achieving combined SBP/DBP targets recommended in current hypertension treatment guidelines as well as individual SBP and DBP targets. A total of 502 patients with DBP >or=100 and therapy remained intact. All combined SBP/DBP goals were achieved by a

  4. Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial.

    PubMed

    Fekadu, Abebaw; Mesfin, Miraf; Medhin, Girmay; Alem, Atalay; Teferra, Solomon; Gebre-Eyesus, Tsehaysina; Seboxa, Teshale; Assefa, Abraham; Hussein, Jemal; Lemma, Martha T; Borba, Christina; Henderson, David C; Hanlon, Charlotte; Shibre, Teshome

    2013-11-27

    Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms.In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications. The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years' duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level of functioning. Whether

  5. Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

    2015-12-03

    This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p < 0.05) compared with placebo; AV relapse was delayed by up to 76 % (p < 0.05). Probiotic use also reduced and maintained low vaginal pH and Nugent score, and increased

  6. Short-term androgen deprivation and PSA doubling time: their association and relationship to disease progression after radiation therapy for prostate cancer.

    PubMed

    Hanlon, Alexandra L; Horwitz, Eric M; Hanks, Gerald E; Pollack, Alan

    2004-01-01

    The goal of this study was to investigate the relationship between PSA doubling time (PSADT) and initial management of prostate cancer with short-term androgen deprivation (STAD) and the impact of these factors on disease progression after radiation therapy. Between May 1989 and October 1998, 284 patients treated with 3D-CRT experienced biochemical failure (BF) as defined under the ASTRO consensus statement. All patients had sufficient follow-up data for PSADT calculations. Linear regression was used to assess predictors of PSADT among STAD, time to biochemical failure (TTBF), Gleason Score, tumor stage, dose, posttreatment PSA nadir, pretreatment PSA, and age. A composite covariate was created from the various combinations of factors found to be predictive of PSADT. The composite covariate was then included, along with PSADT and the factors previously mentioned, in proportional hazards modeling of freedom from distant metastasis (FDM), cause-specific survival (CSS), and overall survival (OS). Fifty-four (19%) patients developed distant metastasis, 20 (7%) died of prostate cancer, and 53 (19%) died of any cause. The median PSADT was 12 months. Predictors of a longer PSADT were TTBF >12 months, Gleason Score 2-6, and STAD. An ordinal composite covariate was created with eight levels on the basis of the magnitude of observed mean PSADT within the eight possible combinations of the three dichotomized predictors. The most significant predictor of higher FDM rates in Cox modeling was the composite covariate, followed by longer PSADT, STAD, lower PSA nadir, higher RT dose, and Gleason Score 2-6. Predictors of higher CSS rates were lower nadir, longer PSADT, T1/T2ab tumors, the composite covariate, and STAD. The most significant predictor of a higher OS rate was STAD, followed by longer PSADT, younger age at diagnosis, the composite covariate, lower nadir, and T1/T2ab tumors. Longer TTBF, Gleason Score 2-6 tumors, and STAD were predictive of longer PSADT. Even after

  7. Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy.

    PubMed

    Richard, Patrick O; Fleshner, Neil E; Bhatt, Jaimin R; Hersey, Karen M; Chahin, Rehab; Alibhai, Shabbir M H

    2015-11-01

    To investigate whether methylphenidate can alleviate fatigue, as measured by the Functional Assessment of Cancer Therapy: Fatigue subscale, in men with prostate cancer (PCa) treated with a luteinizing hormone-releasing hormone (LHRH) for a minimum of 6 months, and to assess changes in global fatigue and quality of life (QoL) as measured by the Bruera Global Fatigue Severity Scale (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), respectively. We performed a single-centre, randomised, double-blind, placebo-controlled trial with the aim of recruiting 128 participants. Men treated with a LHRH agonist for PCa were screened between February 2008 and June 2012 for fatigue at our outpatient clinics using the BFS. Participants were randomised to receive either 10 mg daily of methylphenidate or placebo. Change in fatigue levels and in SF-36 scores between both groups were compared using linear regression, adjusted for baseline scores. The study was closed prematurely because of poor accrual. Of the 790 subjects screened, 24 men were randomised to methylphenidate or placebo (12 per group). After 10 weeks, the improvement in mean [sd] fatigue score was greater in the methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022). The within-group analysis showed a significant improvement in fatigue scores in the methylphenidate arm (P = 0.008) but not in the placebo arm (P = 0.82). The use of methylphenidate also resulted in a significantly greater improvement in QoL as measured by the physical and mental component summary scores than did the use of placebo (P = 0.04 for both component scores). Our findings support the beneficial effect of methylphenidate on fatigue and QoL among men with LHRH-induced fatigue. Clinicians should be aware of these benefits and should consider discussing these findings with patients who have high levels of fatigue. © 2014 The Authors BJU International © 2014 BJU International Published by John

  8. A double-blind randomized controlled trial to assess the effect of bright light therapy on depression in patients with Parkinson's disease.

    PubMed

    Rutten, Sonja; Vriend, Chris; Smit, Jan H; Berendse, Henk W; Hoogendoorn, Adriaan W; van den Heuvel, Odile A; van der Werf, Ysbrand D

    2016-10-21

    A disturbed circadian rhythm seems to be a causal factor in the occurrence of depressive disorders in patients with Parkinson's disease (PD). The circadian rhythm can be restored with light. Therefore, Bright Light Therapy (BLT) might be a new treatment option for depression in PD patients. In this double-blind controlled trial, 84 subjects with idiopathic PD are randomized to either BLT or a control light condition. The BLT condition emits white light with an intensity of 10,000 Lux, while the control device emits dim white light of 200 Lux, which is presumed to be too low to influence the circadian rhythm. Subjects receive 30 min of home treatment twice daily for three months. Timing of treatment is based on the individual chronotype. After finishing treatment, subjects enter a follow-up period of six months. The primary outcome of the study is the severity of depressive symptoms, as measured with the Hamilton Depression Rating Scale. Secondary outcomes are alternative depression measures, objective and subjective sleep measures, and salivary melatonin and cortisol concentrations. For exploratory purposes, we also assess the effects on motor symptoms, global cognitive function, comorbid psychiatric disorders, quality of life and caregiver burden. Data will be analyzed using a linear mixed models analysis. Performing a placebo-controlled trial on the effects of BLT in PD patients is challenging, as the appearance of the light may provide clues on the treatment condition. Moreover, fixed treatment times lead to an improved sleep-wake rhythm, which also influences the circadian system. With our study design, we do not compare BLT to placebo treatment, i.e. an ineffective control treatment. Rather, we compare structuring of the sleep-wake cycle in both conditions with additional BLT in the experimental condition, and additional dim light in the control condition. Participants are not informed about the exact details of the two light devices and the expected

  9. A double-blind, placebo-controlled randomized trial evaluating the ability of low-level laser therapy to improve the appearance of cellulite.

    PubMed

    Jackson, Robert F; Roche, Gregory C; Shanks, Steven C

    2013-03-01

    Cellulite is present in 90% of post-adolescent women. Several technologies have been developed for treating cellulite; however, they all involve some degree of massage or mechanical manipulation. The purpose of this study was to assess the effectiveness of a low-level laser light device employing green 532 nm diodes as a stand-alone procedure without massage or mechanical manipulation for improving the appearance of cellulite in the thighs and buttocks. This double-blind study randomized subjects to undergo treatment with the LLLT device (N = 34) or sham treatment (N = 34). During a 2-week treatment phase, each subject received three weekly treatment sessions 2-3 days apart. During each session, the front and back of the hips, thighs, and waist were exposed for 15 minutes (30 minutes total). Nineteen subjects in the LLLT group achieved a decrease of one or more stages on the Nurnberger-Muller grading scale (55.88%) versus three subjects (8.82%) in the sham-treated group (P < 0.0001). Two LLLT-treated subjects achieved 2-stage improvements on the Nurnberger-Muller Scale at the 2-week study endpoint and four did at the 6-week follow-up evaluation versus none of the sham-treated subjects at either time point. Subjects treated with LLLT achieved a significant decrease in combined baseline thigh circumference at the 2-week study endpoint and 6-week follow-up evaluation (for each, p < 0.0001 vs. baseline) versus no change for sham-treated subjects. LLLT-treated subjects also showed significant decreases in mean baseline body weight (P < 0.0005), BMI (P < 0.001), and percent BSA affected by cellulite (P < 0.0005) versus no change for any parameter among sham-treated subjects. Most LLLT-treated subjects (62.1%) were Very Satisfied or Somewhat Satisfied with the improvement in cellulite they received versus 25.8% of sham-treated subjects. There were no reports of adverse events. Low-level laser therapy using green 532 nm diodes is safe

  10. Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent chest pain or dyspnea despite optimal medical and revascularization therapy: randomized, double-blind crossover pilot study

    PubMed Central

    Shammas, Nicolas W; Shammas, Gail A; Keyes, Kathleen; Duske, Shawna; Kelly, Ryan; Jerin, Michael

    2015-01-01

    Background Patients with ischemic cardiomyopathy (ICM) may continue to experience persistent chest pain and/or dyspnea despite pharmacologic therapy and revascularization. We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients. Methods In this randomized, double-blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less or equal 40%) were included after providing informed consent. A total of 24 patients completed both placebo and ranolazine treatments and were analyzed. All patients were on treatment with a beta blocker, an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker), and at least one additional antianginal drug. After randomization, patients received up to 1,000 mg ranolazine orally twice a day, as tolerated, versus placebo. The primary end point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ), or in dyspnea as assessed by the Rose Dyspnea Scale (RDS). Change in the RDS and SAQ score from baseline was compared, for ranolazine and placebo, using the Wilcoxon signed rank test or paired t-test. Results Patients had the following demographic and clinical variables: mean age of 71.5 years; male (82.1%); prior coronary bypass surgery (67.9%); prior coronary percutaneous intervention (85.7%); prior myocardial infarction (82.1%); diabetes (67.9%); and mean ejection fraction of 33.1%. No statistical difference was seen between baseline RDS score and that after placebo or ranolazine (n=20) (P≥0.05). There was however, an improvement in anginal frequency (8/10 patients) (P=0.058), quality of life (8/10 patients) (P=0.048), and mean score of all components of the SAQ questionnaire (n=10) (P=0.047) with ranolazine compared with placebo. Conclusion In optimally treated ICM patients with continued chest pain or dyspnea, ranolazine possibly had a positive impact on quality of life, a reduction in anginal frequency, and an overall improvement in the

  11. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study.

    PubMed

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-09-01

    The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. NCT01505127. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: a double-blind, placebo-controlled, randomized trial.

    PubMed

    Ghaleiha, Ali; Mohammadi, Effat; Mohammadi, Mohammad-Reza; Farokhnia, Mehdi; Modabbernia, Amirhossein; Yekehtaz, Habibeh; Ashrafi, Mandana; Hassanzadeh, Elmira; Akhondzadeh, Shahin

    2013-12-01

    A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders. The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications. This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial. The study enrolled male and female outpatients aged 5-12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy. Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks. Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups. Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech

  13. Efficacy and safety of rosuvastatin and fenofibric acid combination therapy versus simvastatin monotherapy in patients with hypercholesterolemia and hypertriglyceridemia: a randomized, double-blind study.

    PubMed

    Roth, Eli M; McKenney, James M; Kelly, Maureen T; Setze, Carolyn M; Carlson, Dawn M; Gold, Alex; Stolzenbach, James C; Williams, Laura A; Jones, Peter H

    2010-01-01

    To evaluate the efficacy and safety of fixed-dose combinations of rosuvastatin and fenofibric acid (rosuvastatin/fenofibric acid) compared with simvastatin in patients with high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Combination therapy with a statin and a fibrate is one of the treatment options to manage multiple lipid abnormalities in patients with hypercholesterolemia and elevated TGs. In this randomized, double-blind study, patients (n = 474) with LDL-C > or =160 mg/dL and < or =240 mg/dL and TG > or =150 mg/dL and <400 mg/dL were treated for 8 weeks with simvastatin 40 mg, rosuvastatin/fenofibric acid 5 mg/135 mg, rosuvastatin/fenofibric acid 10 mg/135 mg, or rosuvastatin/fenofibric acid 20 mg/135 mg. Primary and secondary variables were mean percent changes in LDL-C comparing rosuvastatin/fenofibric acid 20 mg/135 mg with simvastatin 40 mg and rosuvastatin/fenofibric acid 10 mg/135 mg and rosuvastatin/fenofibric acid 5 mg/135 mg with simvastatin 40 mg, respectively. Additional efficacy variables included non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein (Apo) B, HDL-C, TG, and high-sensitivity C-reactive protein (hsCRP). Safety was evaluated based on data collected for adverse events (AEs), physical and electrocardiographic examinations, vital sign measurements, and clinical laboratory tests. Significantly greater reductions in LDL-C levels from baseline values were observed with the combination of rosuvastatin/fenofibric acid 20 mg/135 mg (-47.2%, p < 0.001), rosuvastatin/fenofibric acid 10 mg/135 mg (-46.0%, p < 0.001), and rosuvastatin/fenofibric acid 5 mg/135 mg (-38.9%, p = 0.007) than with simvastatin 40 mg (-32.8%). Significant (p < or = 0.04 for all comparisons) improvements in non-HDL-C, ApoB, HDL-C, TG, and hsCRP levels were also observed with each of the rosuvastatin/fenofibric acid doses as compared with simvastatin 40 mg. Treatment-related AEs and discontinuations due to AEs were similar

  14. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial.

    PubMed

    Singh, Dave; Papi, Alberto; Corradi, Massimo; Pavlišová, Ilona; Montagna, Isabella; Francisco, Catherine; Cohuet, Géraldine; Vezzoli, Stefano; Scuri, Mario; Vestbo, Jørgen

    2016-09-03

    Few data are available for the efficacy of "triple therapy" with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We designed this study to assess efficacy of single-inhaler combination of an extra fine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) in COPD compared with beclometasone dipropionate and formoterol fumarate (BDP/FF) treatment. TRILOGY was a randomised, parallel group, double-blind, active-controlled study done in 159 sites across 14 countries. The sites were a mixture of primary, secondary, and tertiary care providers, and specialist investigation units. Eligible patients with COPD had post-bronchodilator forced expiratory volume in 1 s (FEV1) of lower than 50%, one or more moderate-to-severe COPD exacerbation in the previous 12 months, COPD Assessment Test total score of 10 or more, and a Baseline Dyspnea Index focal score of 10 or less. Patients who met the inclusion and exclusion criteria at screening entered a 2-week open-label run-in period where they received beclometasone dipropionate (100 μg) and formoterol fumarate (6 μg) in two actuations twice daily. Patients were then randomly assigned (1:1) with an interactive response technology system to either continue BDP (100 μg) and FF (6 μg) or step-up to BDP (100 μg), FF (6 μg), and GB (12·5 μg) in two actuations twice daily for 52 weeks via pressurised metered-dose inhaler. The three co-primary endpoints were pre-dose FEV1, 2-h post-dose FEV1, and Transition Dyspnea Index (TDI) focal score, all measured at week 26 in the intention-to-treat population (all patients who were randomly assigned and received at least one dose of study drug and had at least one post-baseline efficacy assessment). Safety outcomes were measured in the safety population (all patients who were randomly assigned and received at least one dose of study drug). Secondary endpoints included moderate

  15. Potent anti-platelet constituents from Centaurea iberica.

    PubMed

    Khan, Amna Nisar; Fatima, Itrat; Khaliq, Urooj Abdul; Malik, Abdul; Miana, Ghulam Abbas; Qureshi, Zia-Ur-Rehman; Rasheed, Huma

    2011-02-28

    New naturally occurring nitrogenous compounds 1 and 2, along with a new dimeric lignan glucoside 3, have been isolated from the ethyl acetate soluble fraction of Centaurea iberica. Their structures have been elucidated through spectroscopic techniques. All the isolated compounds showed significant platelet aggregation inhibition.

  16. A randomised, double-blind, placebo-controlled phase IIB clinical trial of repeated application of gene therapy in patients with cystic fibrosis.

    PubMed

    Alton, Eric W F W; Boyd, A Christopher; Cheng, Seng H; Cunningham, Steve; Davies, Jane C; Gill, Deborah R; Griesenbach, Uta; Higgins, Tracy; Hyde, Stephen C; Innes, J Alastair; Murray, Gordon D; Porteous, David J

    2013-11-01

    The UK Cystic Fibrosis Gene Therapy Consortium has been working towards clinical gene therapy for patients with cystic fibrosis for several years. We have recently embarked on a large, multi-dose clinical trial of a non-viral, liposome-based formulation powered for the first time to detect clinical benefit. The article describes the details of the protocol.

  17. Phase III, Double-Blind Study of Depot Octreotide Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy: Results of North Central Cancer Treatment Group N00CA

    PubMed Central

    Martenson, James A.; Halyard, Michele Y.; Sloan, Jeff A.; Proulx, Gary M.; Miller, Robert C.; Deming, Richard L.; Dick, Stephen J.; Johnson, Harold A.; Tai, T.H. Patricia; Zhu, Angela W.; Keit, Joan; Stien, Kathy J.; Atherton, Pamela J.

    2008-01-01

    Purpose To assess the effectiveness of depot octreotide for the prevention of diarrhea during pelvic radiation therapy. Patients and Methods Patients receiving pelvic radiation therapy (planned minimum dose, 45 Gy; 1.7 to 2.1 Gy daily) were eligible for the study. From May 10, 2002, through October 14, 2005, 125 patients were randomly allocated in a double-blind fashion to receive octreotide (100 μg, administered subcutaneously on day 1, followed by depot octreotide, 20 mg, administered intramuscularly on days 2 and 29; n = 62) or to receive a placebo (n = 63). Results Grade 0, 1, 2, and 3 diarrhea were observed in 18%, 31%, 31%, and 21% of patients in the octreotide arm, respectively, and in 25%, 32%, 22%, and 21% of patients in the placebo arm, respectively (P = .64). Grade 0, 1, 2, and 3 abdominal cramps were observed in 32%, 45%, 21%, and 2% of patients receiving octreotide, respectively, and in 51%, 24%, 21%, and 5% of patients receiving the placebo, respectively (P = .053). Some patient-reported symptoms were worse in the octreotide group, including nocturnal bowel movements (70% v 45%; P = .004), clustering of bowel movements (90% v 69%; P = .004), and bleeding with bowel movements (57% v 35%; P = .01). Conclusion As administered in this study, octreotide did not decrease diarrhea during pelvic radiation therapy. Some gastrointestinal symptoms were worse in patients treated with octreotide. Octreotide is not indicated for prevention of diarrhea during pelvic radiation therapy. PMID:18768432

  18. D-cycloserine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial.

    PubMed

    Siegmund, Anja; Golfels, Fabian; Finck, Claudia; Halisch, Anna; Räth, Daniela; Plag, Jens; Ströhle, Andreas

    2011-08-01

    D-cycloserine (DCS)-augmented exposure therapy has proven efficacy in the treatment of acrophobia, social phobia, panic disorder and OCD. Here we studied whether DCS can also improve the effect of cognitive behavioral therapy (CBT) in patients with agoraphobia and panic disorder. To this end, 39 patients with the diagnoses of agoraphobia and panic disorder were treated with 11 sessions of CBT including three individual in-vivo exposure sessions (flooding), augmented with either 50mg of DCS (N=20) or placebo (N=19) in a randomized double blind design. Primary outcome was the total score of the panic and agoraphobia scale. Both groups profited considerably from therapy and DCS did not significantly improve this outcome (p=0.475; η(2)p = 0.01). However, there was a statistical trend (p=0.075; η(2)p = 0.17) in the more severely ill patients that DCS accelerated symptom reduction in the primary outcome at post-therapy. No serious adverse effects occurred during the trial. We conclude that in patients with agoraphobia and panic disorder, DCS seems to lack an additional benefit to efficient cbt, probably due to a floor effect. Nonetheless, the acceleration of symptom reduction in severely ill patients might represent a valuable treatment option deserving further investigation.

  19. A double blind, placebo-controlled, crossover therapy study with natural human IL-2 (nhuIL-2) in combination with regular intravenous gammaglobulin (IVIG) infusions in 10 patients with common variable immunodeficiency (CVID)

    PubMed Central

    RUMP, J A; JAHREIS, A; SCHLESIER, M; STECHER, S; PETER, H H

    1997-01-01

    Ten CVID patients with defective IL-2 synthesis in vitro were treated with nhuIL-2 in a placebo-controlled, double blind, crossover therapy study during a period of 12 months. No severe side-effects of nhuIL-2 were recorded. Marginal serum nhuIL-2 levels were measurable in individual patients only during the therapy phase. Serum levels of soluble IL-2 receptors were unaffected by the therapy. nhuIL-2 and placebo groups did not differ significantly with respect to requirement of IVIG substitutions which were performed whenever serum IgG levels dropped below 5 g/l: a total of 53 IVIG infusions (corresponding to 17.6 g IgG/month per patient) was necessary during the placebo phase, and 48 infusions (16-4 g IgG/month per patient) during the nhuIL-2 treatment phase. Thus, nhuIL-2 therapy was ineffective in improving spontaneous IgG synthesis in vivo. Nevertheless, the group of patients receiving nhuIL-2 during the first 6 months of the study exhibited a significant reduction of severe infections (n = 25) during the following 6 months of placebo treatment (n = 7) (P < 0–045). The infection score dropped in this group from 181 to 23 (P < 0015). Patients of the second group receiving first placebo and then nhuIL-2 did not experience a significant difference in number and score of infectious episodes: 25 infections were recorded during the first 6 months and 24 during the following 6 months. We suppose that nhuIL-2 therapy of CVID patients reduces susceptibility to severe infections, possibly via the induction of a specific antibody response, which is effective at the earliest 6 months after initiating nhuIL-2 therapy. PMID:9367398

  20. Y2O3:Yb,Er@mSiO2-Cu(x)S double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging.

    PubMed

    Yang, Dan; Yang, Guixin; Wang, Xingmei; Lv, Ruichan; Gai, Shili; He, Fei; Gulzar, Arif; Yang, Piaoping

    2015-07-28

    Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large specific surface area and uniform shape is composed of an inner shell of luminescent Y2O3:Yb,Er and an outer mesoporous silica shell. Ultra small Cu(x)S nanoparticles (about 2.5 nm) served as photothermal agents, and a chemotherapeutic agent (doxorubicin, DOX) was then attached onto the surface of mesoporous silica, forming a DOX-DSHS-Cu(x)S composite. The composite exhibits high anti-cancer efficacy due to the synergistic photothermal therapy (PTT) induced by the attached Cu(x)S nanoparticles and the enhanced chemotherapy promoted by the heat from the Cu(x)S-based PTT when irradiated by 980 nm near-infrared (NIR) light. Moreover, the composite shows excellent in vitro and in vivo X-ray computed tomography (CT) and up-conversion fluorescence (UCL) imaging properties owing to the doped rare earth ions, thus making it possible to achieve the target of imaging-guided synergistic therapy.

  1. Double blinding requirement for validity claims in cognitive-behavioral therapy intervention trials for major depressive disorder. Analysis of Hollon S,  et al., Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial.

    PubMed

    Berger, Douglas

    2015-01-01

    This paper will focus on problems in the inability to double-blind cognitive-behavioral therapy (CBT) studies for major depressive disorder (MDD), and provides an analysis of a recently published study to show how this problem can lead to faulty conclusions. A study by Hollon et al. published in JAMA Psychiatry that compared an antidepressant medication-only arm with a combined CBT/antidepressant arm concluded that the cognitive therapy/antidepressant combination enhanced the recovery rates compared with antidepressant alone, and that the magnitude of this increment nearly doubled for patients with more severe depression. We propose that for subjects with greater severity, there could have been both antidepressant efficacy as well as more hope and expectation in the group who knew they had received combined cognitive therapy/medication, leading to an erroneous conclusion of greater efficacy for the combined group. The large subject number in this study could easily lead to an erroneous finding on statistical testing as a small amount of bias in the subjects adds-up. We opine that the conclusions of unblind CBT outcome research in conditions with subjective endpoints such as MDD need to be given with great caution. The validity of CBT (and its derivatives such as dialectical behavioral therapy) for indications other than MDD is also part of a larger problem in  the inability to blind outcome studies for these interventions.

  2. Double helicenes

    NASA Astrophysics Data System (ADS)

    Bachrach, Steven M.

    2016-12-01

    The even double helicenes with 4-12 phenyl groups in each helix were examined at B3LYP-D3/6-311G(d). The double helicenes with 4-10 phenyl rings are less than twice as strained as their component helicenes; the strain results from twisting about the shared naphthyl moiety, with accompanying loss of aromaticity. These compounds should be reasonable synthetic targets, and computed NMR shifts are provided to aid in their characterization.

  3. Predicting and verifying outcome of Tripterygium wilfordii Hook F. based therapy in rheumatoid arthritis: from open to double-blinded randomized trial

    PubMed Central

    Jiang, Miao; Zha, Qinglin; Zhang, Chi; Lu, Cheng; Yan, Xiaoping; Zhu, Wanhua; Liu, Wei; Tu, Shenghao; Hou, Liping; Wang, Chengwu; Zhang, Wandong; Liang, Qinghua; Fan, Bing; Yu, Jiangping; Zhang, Weidong; Liu, Xinru; Yang, Jing; He, Xiaojuan; Li, Li; Niu, Xuyan; Liu, Yan; Guo, Hongtao; He, Bing; Zhang, Ge; Bian, Zhaoxiang; Lu, Aiping

    2015-01-01

    Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P−) group, and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M&S) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P− group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P− group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations. PMID:26814847

  4. [Dental treatment and anti-thrombotic therapy. Part II: the era of new anti-thrombotic drugs].

    PubMed

    Chackartchi, T; Sachar Helft, S; Findler, M

    2014-01-01

    Surgical intra-oral treatment for patients under antithrombotic therapy presents a challenge for the dental team. Within the last few years evidence based systematic reviews established new clinical guidelines for wide groups of patients which need to use antithrombotic treatment. The expected increase in use of antithrombotic treatment forced the pharmaceutical industry to provide new treatments. The former anticoagulant and anti-platelets aggregation groups of drugs were limited to small variety of medication. The search for the new treatments with ideal properties led to newly invented groups of drugs. In this article we will describe the new advancements in anti-thrombotic treatments. The article will summarize the limited knowledge of surgical management of patients under the new anti-thrombotic medications and the recommended approach for oral surgical procedures.

  5. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.

    PubMed

    Coleman, Robert L; Oza, Amit M; Lorusso, Domenica; Aghajanian, Carol; Oaknin, Ana; Dean, Andrew; Colombo, Nicoletta; Weberpals, Johanne I; Clamp, Andrew; Scambia, Giovanni; Leary, Alexandra; Holloway, Robert W; Gancedo, Margarita Amenedo; Fong, Peter C; Goh, Jeffrey C; O'Malley, David M; Armstrong, Deborah K; Garcia-Donas, Jesus; Swisher, Elizabeth M; Floquet, Anne; Konecny, Gottfried E; McNeish, Iain A; Scott, Clare L; Cameron, Terri; Maloney, Lara; Isaacson, Jeff; Goble, Sandra; Grace, Caroline; Harding, Thomas C; Raponi, Mitch; Sun, James; Lin, Kevin K; Giordano, Heidi; Ledermann, Jonathan A

    2017-09-12

    Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0-1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous

  6. [Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes].

    PubMed

    Vetter, G; Brüggemann, G; Lettko, M; Schwieger, G; Asbach, H; Biermann, W; Bläsius, K; Brinkmann, R; Bruns, H; Dorn, E

    1988-01-01

    The use of nonsteroidal anti-inflammatory drugs (NSAID) such as diclofenac for treatment of degenerative rheumatic disorders of the lumbar spine is of great significance in orthopedic practice. Clinical studies have shown that concomitant treatment with vitamins B1, B6, B12 and diclofenac provides more efficient pain relief than treatment using diclofenac alone. This study was undertaken in order to determine whether the duration of treatment with diclofenac for lower back pain can be shortened by adding B-vitamins to the therapeutic regimen. From September through December of 1986, 256 patients participated in a multicenter, controlled, randomized double-blind trial which compared the clinical efficacy of diclofenac (50 mg) with a combined therapy of diclofenac (50 mg) and vitamins B1, B6, and B12 (thiamine nitrate, pyridoxine hydrochloride, and cyanocobalamine, resp.; in dosages of 50 mg, 50 mg, and 0.25 mg, resp.). Patients were treated with 3 X 1 capsule daily for a maximum of two weeks, having the option to terminate participation in the trial after 1 week in the event of total pain relief. The data of 238 patients were able to be included in the evaluation. 29 patients opted to discontinue therapy due to remission on symptoms. Nineteen (65.6%) of these patients belonged to the combined therapy group, the other 10 (34.4%) having taken diclofenac alone; this difference is statistically significant (p less than 0.05). An important aspect in the evaluation of therapy was the patient response regarding the improvement of painful symptoms which, in addition to their subjective feedback, was reflected in the test results of the "Hoppe Pain Questionnaire (HPQ)." All parameters used as a measure of pain relief indicated superior results with the B-vitamin supplemented therapy when compared with results obtained with diclofenac alone. Moreover, after 3 days of therapy the "sensory" pain factor "sharpness" improved significantly. Undesirable side-effects were documented

  7. Effects of a systemic enzyme therapy in healthy active adults after exhaustive eccentric exercise: a randomised, two-stage, double-blinded, placebo-controlled trial.

    PubMed

    Marzin, Tobias; Lorkowski, Gerhard; Reule, Claudia; Rau, Stefanie; Pabst, Elisabeth; Vester, Johannes C; Pabst, Helmut

    2016-01-01

    Systemic enzyme therapy may improve symptoms of exhaustive eccentric exercise due to anti-inflammatory properties. In a randomised, placebo-controlled, two-stage clinical trial, systemic enzyme therapy (Wobenzym) was administered for 72 hours before and 72 hours following a day on which subjects performed an exhaustive eccentric exercise (isokinetic loading of the quadriceps). Efficacy criteria (maximal strength and pain) and time points were selected to account for the multidimensional nature of exercise-induced muscle damage symptoms. Subjects were randomised in a crossover (stage I, n=28) and parallel group design (stage II, n=44). Analysis of stage I data demonstrated a significant superiority (Mann-Whitney=0.6153; p=0.0332; one sided) for systemic enzyme therapy compared with placebo. Stage II was designed as a randomised controlled parallel group comparison. Heterogeneity (I(2)>0.5) between stages led to separate analyses of stage I (endurance-trained subjects) and stage II (strength-trained subjects). Combined analysis resulted in no evidence for corresponding treatment effects. Analysis of pooled biomarker data, however, demonstrated significant favourable effects for systemic enzyme therapy in both stages. Systemic enzyme therapy before and after exhaustive eccentric exercise resulted in higher maximal concentric strength in the less strength-trained subjects (stage I) and in significant favourable effects on biomarkers (inflammatory, metabolic and immune) in all subjects. The application of these findings needs further evaluation.

  8. Effects of a systemic enzyme therapy in healthy active adults after exhaustive eccentric exercise: a randomised, two-stage, double-blinded, placebo-controlled trial

    PubMed Central

    Marzin, Tobias; Lorkowski, Gerhard; Reule, Claudia; Rau, Stefanie; Pabst, Elisabeth; Vester, Johannes C; Pabst, Helmut

    2016-01-01

    Background Systemic enzyme therapy may improve symptoms of exhaustive eccentric exercise due to anti-inflammatory properties. Methods In a randomised, placebo-controlled, two-stage clinical trial, systemic enzyme therapy (Wobenzym) was administered for 72 hours before and 72 hours following a day on which subjects performed an exhaustive eccentric exercise (isokinetic loading of the quadriceps). Efficacy criteria (maximal strength and pain) and time points were selected to account for the multidimensional nature of exercise-induced muscle damage symptoms. Subjects were randomised in a crossover (stage I, n=28) and parallel group design (stage II, n=44). Results Analysis of stage I data demonstrated a significant superiority (Mann-Whitney=0.6153; p=0.0332; one sided) for systemic enzyme therapy compared with placebo. Stage II was designed as a randomised controlled parallel group comparison. Heterogeneity (I2>0.5) between stages led to separate analyses of stage I (endurance-trained subjects) and stage II (strength-trained subjects). Combined analysis resulted in no evidence for corresponding treatment effects. Analysis of pooled biomarker data, however, demonstrated significant favourable effects for systemic enzyme therapy in both stages. Conclusion Systemic enzyme therapy before and after exhaustive eccentric exercise resulted in higher maximal concentric strength in the less strength-trained subjects (stage I) and in significant favourable effects on biomarkers (inflammatory, metabolic and immune) in all subjects. The application of these findings needs further evaluation. PMID:28879033

  9. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).

    PubMed

    Ostadal, Petr; Alan, David; Vejvoda, Jiri; Kukacka, Jiri; Macek, Milan; Hajek, Petr; Mates, Martin; Kvapil, Milan; Kettner, Jiri; Wiendl, Martin; Aschermann, Ondrej; Slaby, Josef; Holm, Frantisek; Telekes, Peter; Horak, David; Blasko, Peter; Zemanek, David; Veselka, Josef; Cepova, Jana

    2010-05-25

    Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS. The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy. We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037). This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS. NCT00171275.

  10. Efficacy of high and low level laser therapy in the treatment of Bell's palsy: a randomized double blind placebo-controlled trial.

    PubMed

    Alayat, Mohamed Salaheldien Mohamed; Elsodany, Ahmed Mohamed; El Fiky, Amir Abdel Raouf

    2014-01-01

    The aim of the present study was to investigate and compare the effects of high intensity laser therapy (HILT) and low level laser therapy (LLLT) on the treatment of patients with Bell's palsy. Forty-eight patients participated in and completed this study. The mean age was 43 ± 9.8 years. They were randomly assigned into three groups: HILT group, LLLT group, and exercise group. All patients were treated with facial massage and exercises, but the HILT and LLLT groups received the respective laser therapy. The grade of facial recovery was assessed by the facial disability scale (FDI) and the House-Brackmann scale (HBS). Evaluation was carried out 3 and 6 weeks after treatment for all patients. Laser treatments included eight points on the affected side of the face three times a week for 6 successive weeks. FDI and HBS were used to assess the grade of recovery. The scores of both FDI and HBS were taken before as well as 3 and 6 weeks after treatment. The Friedman test and Wilcoxon signed ranks test were used to compare the FDI and HBS scores within each group. The result showed that both HILT and LLLT significantly improved the recovery of patients with Bell's palsy. Moreover, HILT was the most effective treatment modality compared to LLLT and massage with exercises. Thus, both HILT and LLLT are effective physical therapy modalities for the recovery of patients with Bell's palsy, with HILT showing a slightly greater improvement than LLLT.

  11. The effects of two different low level laser therapies in the treatment of patients with chronic low back pain: A double-blinded randomized clinical trial.

    PubMed

    Koldaş Doğan, Şebnem; Ay, Saime; Evcik, Deniz

    2017-01-01

    The purpose of this study was to compare the effectiveness of two different laser therapy regimens on pain, lumbar range of motions (ROM) and functional capacity in patients with chronic low back pain (CLBP). Forty nine patients with CLBP were randomly assigned into two groups. Group 1 (n= 20) received hot-pack + laser therapy 1 (wavelength of 850 nm Gallium-Aluminum-Arsenide (Ga-Al-As) laser); group 2 (n= 29) received hot-pack + laser therapy 2 (wavelength of 650 nm Helyum-Neon (He-Ne), 785 ve 980 nm Gal-Al-As combined plaque laser) for 15 sessions. Pain severity, patient's and physician's global assessments were evaluated with visual analogue scale (VAS). Modified Schober test, right and left lateral flexion measurements were done. Modified Oswestry Disability Questionnaire (MODQ) was used for evaluation of functional disability. Measurements were done before and after the treatment. After treatment there were statistically significant improvements in pain severity, patient's and physician's global assessment, ROM and MODQ scores in both groups (P< 0.05). After the treatment there were statistically significant differences between the groups in lateral flexion measurements and MODQ scores (P< 0.05) except in pain severity, Modified Schober test, patient's and physician's global assessments (P> 0.05) in favor of those patients who received combined plaque laser therapy (group 2). Laser therapy applied with combined He-Ne and Ga-Al-As provides more improvements in lateral flexion measurements and disability of the patients, however no superiority of the two different laser devices to one another were detected on pain severity.

  12. Double Crater

    NASA Image and Video Library

    2012-03-23

    A double crater, called a crater doublet, is seen in the bottom right part of this image from NASA Dawn spacecraft of asteroid Vesta. This crater doublet was likely formed by the simultaneous impact of two fragments of a split projectile.

  13. The role of tumor protein 53 mutations in common human cancers and targeting the murine double minute 2-p53 interaction for cancer therapy.

    PubMed

    Hamzehloie, Tayebeh; Mojarrad, Majid; Hasanzadeh Nazarabadi, Mohammad; Shekouhi, Sahar

    2012-03-01

    The gene TP53 (also known as protein 53 or tumor protein 53), encoding transcription factor P53, is mutated or deleted in half of human cancers, demonstrating the crucial role of P53 in tumor suppression. There are reports of nearly 250 independent germ line TP53 mutations in over 100 publications. The P53 protein has the structure of a transcription factor and, is made up of several domains. The main function of P53 is to organize cell defense against cancerous transformation. P53 is a potent transcription factor that is activated in response to diverse stresses, leading to the induction of cell cycle arrest, apoptosis or senescence. The P53 tumor suppressor is negatively regulated in cells by the murine double minute 2 (MDM2) protein. Murine double minute 2 favors its nuclear export, and stimulates its degradation. Inhibitors of the P53-MDM2 interaction might be attractive new anticancer agents that could be used to activate wild-type P53 in tumors. Down regulation of MDM2 using an small interfering RNA (siRNA) approach has recently provided evidence for a new role of MDM2 in the P53 response, by modulating the inhibition of the cyclindependent kinase 2 (cdk2) by P21/WAF1 (also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1).

  14. Drug induced hypersensitivity syndrome by triple therapy of peginterferon alpha2b, ribavirin and telaprevir in patient with double positive for HBV and HCV.

    PubMed

    Takagi, Hitoshi; Hoshino, Takashi; Naganuma, Atsushi; Koitabashi, Eri; Uehara, Sanae; Sakamoto, Naomi; Kudo, Tomohiro; Ryusaki, Keiichirou; Kakizaki, Satoru; Okamoto, Hiroaki

    2013-10-01

    Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

  15. A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia.

    PubMed

    Maertens, Johan A; Madero, Luis; Reilly, Anne F; Lehrnbecher, Thomas; Groll, Andreas H; Jafri, Hasan S; Green, Michael; Nania, Joseph J; Bourque, Michael R; Wise, Beth Ann; Strohmaier, Kim M; Taylor, Arlene F; Kartsonis, Nicholas A; Chow, Joseph W; Arndt, Carola A S; DePauw, Ben E; Walsh, Thomas J

    2010-05-01

    Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or L-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. Eighty-two patients received study therapy (caspofungin 56, L-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; L-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and L-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of L-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for L-AmB. Caspofungin and L-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.

  16. Upper Digestive Bleeding in Atrial Fibrillation: Evaluation of Gastroscopy Prior to Oral Anticoagulant Therapy (GOAT), Prospective, Randomized, Double Blind Study on a Community Population

    PubMed Central

    Lagi, Alfonso; Spini, Simona; Meucci, Elisa; Cartei, Alessandro; Cencetti, Simone

    2011-01-01

    Background The aim of this study was to investigate the incidence of digestive hemorrhages in patients with non-valvular atrial fibrillation (NVAF), scheduled for oral anticoagulant therapy. Methods We conducted, over 24 months, a prospective, randomized, population-based observational study on consecutive patients with recurrent paroxysmal, persistent, or permanent NVAF, scheduled for oral anticoagulant therapy. The study initially included 268 patients with NVAF (162 males and 106 females) with a mean age of 74 years (range 42-86 years). Patients were split into two groups: those undergoing preventive Esophago-Gastro-Duodenoscopy (EGD) (Group A) and those who did not (Group B). All patients positive by EGD underwent medical treatment and subsequent 30-day endoscopic controls showed complete healing. The primary outcome of the study was to determine if previous EGD in patients with NVAF resulted in a low risk of bleeding during oral anticoagulant therapy. The two groups were comparable for most variables. Results Significant differences were found between groups for the incidence of antiarrhythmic drugs and for early hemorrhage (P <0.001). The incidences of early hemorrhages were significantly different between the two groups with 12 in group B (12%) and 2 in group A (1.7%). Conclusions Preventive EGD can identify hidden digestive diseases, which may increase the incidence of early hemorrhages.

  17. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    PubMed

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. © 2016 Blackwell Verlag GmbH.

  18. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease.

    PubMed

    Snow, Barry J; Rolfe, Fiona L; Lockhart, Michelle M; Frampton, Christopher M; O'Sullivan, John D; Fung, Victor; Smith, Robin A J; Murphy, Michael P; Taylor, Kenneth M

    2010-08-15

    Multiple lines of evidence point to mitochondrial oxidative stress as a potential pathogenic cause for Parkinson's disease (PD). MitoQ is a powerful mitochondrial antioxidant. It is absorbed orally and concentrates within mitochondria where it has been shown to protect against oxidative damage. We enrolled 128 newly diagnosed untreated patients with PD in a double-blind study of two doses of MitoQ compared with placebo to explore the hypothesis that, over 12 months, MitoQ would slow the progression of PD as measured by clinical scores, particularly the Unified Parkinson Disease Rating Scale. We showed no difference between MitoQ and placebo on any measure of PD progression. MitoQ does not slow the progression of PD, and this finding should be taken into account when considering the oxidative stress hypothesis for the pathogenesis of PD.

  19. Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy.

    PubMed

    Ronald, Sharon; Awate, Sanket; Rath, Abhijit; Carroll, Jennifer; Galiano, Floyd; Dwyer, Donard; Kleiner-Hancock, Heather; Mathis, J Michael; Vigod, Simone; De Benedetti, Arrigo

    2013-01-01

    The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 and Rad9, regulating double-strand break (DSB) repair and the DNA damage response (DDR). TLKs maintain genomic stability and are important therapeutic intervention targets. We identified specific inhibitors of TLKs from several compound libraries, some of which belong to the family of phenothiazine antipsychotics. The inhibitors prevented the TLK-mediated phosphorylation of Rad9(S328) and impaired checkpoint recovery and DSB repair. The inhibitor thioridazine (THD) potentiated tumor killing with chemotherapy and also had activity alone. Staining for γ-H2AX revealed few positive cells in untreated tumors, but large numbers in mice treated with low doxorubicin or THD alone, possibly the result of the accumulation of DSBs that are not promptly repaired as they may occur in the harsh tumor growth environment.

  20. [Kidney function in therapy with non-steroidal antiphlogistic drugs. A double-blind cross-over study with diclofenac, indomethacin and piroxicam].

    PubMed

    Lang, B; Hauk, P; Meske, S; Keller, E; Peter, H H

    1991-01-01

    The effect of piroxicam (1 x 20 mg daily), diclofenac (2 x 50 mg daily) and indomethacin (3 x 25 mg daily) on renal function was compared in a double-blind cross-over study of 33 patients with various rheumatologic diseases. Individuals with preexisting renal impairment were excluded. In 16 patients piroxicam was compared with diclofenac. In another group of 17 patients piroxicam was compared with indomethacin. Each drug was given for 28 days. The mean inhibition of renal prostaglandin E2 by the three drugs was comparable. There was no significant alteration of the renal function parameters in any of the drugs. These results confirm that nonsteroidal antiinflammatory drugs with short (diclofenac, indomethacin) but also with long half life (piroxicam) do not decrease renal function in individuals without renal impairment.

  1. Double Layers in Astrophysics

    NASA Technical Reports Server (NTRS)

    Williams, Alton C. (Editor); Moorehead, Tauna W. (Editor)

    1987-01-01

    Topics addressed include: laboratory double layers; ion-acoustic double layers; pumping potential wells; ion phase-space vortices; weak double layers; electric fields and double layers in plasmas; auroral double layers; double layer formation in a plasma; beamed emission from gamma-ray burst source; double layers and extragalactic jets; and electric potential between plasma sheet clouds.

  2. Double screening

    SciTech Connect

    Gratia, Pierre; Hu, Wayne; Joyce, Austin; Ribeiro, Raquel H.

    2016-06-15

    Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in a broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.

  3. Effectiveness of ultrasound treatment applied with exercise therapy on patients with ankylosing spondylitis: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Şilte Karamanlioğlu, Duygu; Aktas, Ilknur; Ozkan, Feyza Unlu; Kaysin, Meryem; Girgin, Nuray

    2016-05-01

    The aim of our study was to evaluate effectiveness of ultrasound treatment applied with exercise therapy in patients with ankylosing spondylitis. Fifty-two patients, who were diagnosed according to modified New York criteria, were aged 25-60, and have spine pain, were randomly assigned to two groups. Ultrasound (US) and exercise therapy were applied to treatment group (27); placebo US treatment and exercise therapy were applied to control group (25). Patients were evaluated before treatment, at the end of treatment, and 4 weeks after the treatment. Daily and night pain, morning stiffness, patient global assessment (PGA), doctor global assessment (DGA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR), and ASDAS C-reactive protein (CRP) were used as clinical parameters. In US group, all parameters showed significant improvements at 2 and 6 weeks, in comparison with the baseline. In placebo US group, significant improvement was obtained for all parameters (except tragus-to-wall distance and modified Schober test at 2 weeks and lumbar side flexion and modified Schober test at 6 weeks). Comparison of the groups showed significantly superior results of US group for parameters of BASMI (p < 0.05), tragus-wall distance (p < 0.05), PGA (p < 0.01), and DGA (p < 0.05) at 2 weeks as well as for the parameters of daily pain (p < 0.01), PGA (p < 0.05), DGA (p < 0.01), BASDAI (p < 0.05), ASDAS-CRP (p < 0.05), ASDAS-ESR (p < 0.01), lumbar side flexion (p < 0.01), the modified Schober test (p < 0.01), and ASQoL (p < 0.05) at 6 weeks. Our study showed that ultrasound treatment increases the effect of exercise in patients with ankylosing spondylitis.

  4. Effects of estrogen therapy and aerobic training on sympathetic activity and hemodynamics in healthy postmenopausal women: a double-blind randomized trial.

    PubMed

    Oneda, Bruna; Cardoso, Crivaldo G; Forjaz, Cláudia L M; Araújo, Tatiana G; Bernardo, Fernanda R; de Gusmão, Josiane Lima; Pinto, Luiz Gustavo; Labes, Eliana; Abrahão, Sandra B; Mion, Décio; Fonseca, Angela M; Tinucci, Taís

    2014-04-01

    The aim of this study was to evaluate the isolated and associated effects of aerobic training and estrogen therapy on sympathetic nerve activity and hemodynamics in healthy postmenopausal women. Forty-five postmenopausal women (mean [SD] age, 51 [3] y) were randomly divided into four groups: sedentary-placebo (SED-PLA; n = 11), sedentary-estrogen therapy (SED-ET; n = 14), aerobic training-placebo (AT-PLA; n = 12), and aerobic training-estrogen therapy (AT-ET; n = 8). The ET groups received oral estradiol valerate (1 mg/d), whereas the PLA groups received placebo. The AT groups performed aerobic exercise three times a week on a cycle ergometer for 50 minutes, whereas the SED groups remained sedentary. All participants were evaluated before and after 6 months. Muscle sympathetic nerve activity (MSNA; microneurography), forearm blood flow (plethysmography), blood pressure (oscillometry), and heart rate (HR) were measured at rest for 10 minutes. Data were analyzed by three-way analysis of variance. Estrogen administration itself did not change any of the studied parameters. AT improved forearm blood flow (AT-PLA, 2.02 [0.85] vs 2.92 [1.65] mL min(-1) 100 mL(-1), P = 0.03; AT-ET, 1.68 [1.11] vs 2.27 [0.76] mL min(-1) 100 mL(-1), P = 0.03), reduced MSNA in the AT-PLA group (39 [6] vs 34 [5] bursts/min(-1), P = 0.01), and decreased HR in the AT-ET group (65 [8] vs 62 [7] beats/min, P = 0.01). AT reduces sympathetic nerve activity and improves muscle blood flow in healthy hysterectomized postmenopausal women. Moreover, AT decreases HR when combined with ET. However, ET abolishes the reducing effect of AT on MSNA.

  5. A Phase III, Double-Blind, Placebo-Controlled Prospective Randomized Clinical Trial of d-Threo-Methylphenidate HCl in Brain Tumor Patients Receiving Radiation Therapy

    SciTech Connect

    Butler, Jerome M. Case, L. Douglas; Atkins, James; Frizzell, Bart; Sanders, George; Griffin, Patricia; Lesser, Glenn; McMullen, Kevin; McQuellon, Richard; Naughton, Michelle; Rapp, Stephen; Stieber, Volker; Shaw, Edward G.

    2007-12-01

    Purpose: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. Methods and Materials: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. Results: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. Conclusions: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL.

  6. Bright light therapy in pregnant women with major depressive disorder: study protocol for a randomized, double-blind, controlled clinical trial.

    PubMed

    Bais, Babette; Kamperman, Astrid M; van der Zwaag, Marjolein D; Dieleman, Gwen C; Harmsen van der Vliet-Torij, Hanneke W; Bijma, Hilmar H; Lieverse, Ritsaert; Hoogendijk, Witte J G; Lambregtse-van den Berg, Mijke P

    2016-11-08

    Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress

  7. A Local CC2 and TDA-DFT Double Hybrid Study on BODIPY/aza-BODIPY Dimers as Heavy Atom Free Triplet Photosensitizers for Photodynamic Therapy Applications.

    PubMed

    Momeni, Mohammad R; Brown, Alex

    2016-04-28

    A series of 11 different boron-dipyrromethene (BODIPY) dimers is carefully examined by means of ab initio and Tamm-Dancoff approximated density functional theory methods. Vertical and 0-0 excitation energies along with the tetraradical character of these dimers are determined. Possible application of a series of linked dimers for photodynamic therapy (PDT) was investigated through computing their excitation energies, spin-orbit coupling matrix elements, and singlet-triplet energy gaps. Finally through a systematic investigation of a series of 36 different BODIPY and aza-BODIPY dimers, a new class of near-IR heavy atom free photosensitizers for PDT action is introduced.

  8. Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components

    PubMed Central

    Dougados, M.; Combe, B.; Cantagrel, A.; Goupille, P.; Olive, P.; Schattenkirchner, M.; Meusser, S; Paimela, L; Rau, R.; Zeidler, H.; Leirisalo-Repo, M.; Peldan, K.

    1999-01-01

    OBJECTIVES—To investigate the potential clinical benefit of a combination therapy.
METHODS—205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (⩽1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).
RESULTS—The mean changes in the DAS during the one year follow up of the study was −1.15, −0.87, −1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).
CONCLUSION—This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

 Keywords: rheumatoid arthritis; combination therapy; sulphasalazine; methotrexate PMID:10364900

  9. Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Münzel, Thomas; Meinertz, Thomas; Tebbe, Ulrich; Schneider, Heinrich Theodor; Stalleicken, Dirk; Wargenau, Manfred; Gori, Tommaso; Klingmann, Ingrid

    2014-01-01

    Background The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study (‘CLEOPATRA’ study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. Methods and results A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. Conclusion Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity. PMID:24071762

  10. A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination: CYCLIN.

    PubMed

    Patti, F; Amato, M P; Filippi, M; Gallo, P; Trojano, M; Comi, G C

    2004-08-15

    The authors present and discuss a new protocol for active multiple sclerosis (MS) patients. A double blind randomized controlled multicenter study was planned to study the effects of a combination regimen therapy: cyclophosphamide plus beta interferon versus beta interferon alone on both relapsing-remitting and secondary MS patients with active disease. The primary endpoint of this study is the number of new gadolinium enhancing lesions at MRI evaluation. Secondary endpoints are new T2 lesions, new T1 lesions, T2 lesion load, T1 lesion load, cerebral atrophy, number of patients who were relapse-free, number of patients who improved, yearly relapses, quality of life, disability and cognitive impairment, frequency of neutralizing antibodies, safety of the combination therapy (cyclophosphamide + beta interferon). The study will enroll 225 patients in 25 Italian MS centers. Eligible for the study are patients with either relapsing-remitting or secondary MS according McDonald criteria on 6-24 months beta interferon treatment with active disease (new gadolinium enhancing lesion or who experienced a new relapse on beta interferon treatment). Clinical evaluation will be performed every 4 months, MRI yearly. Vital signs and eventual adverse events will be collected monthly. The study will last 36 months, 12 for the enrollment phase and 24 for the treatment phase. The study will start on April 2004.

  11. Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial.

    PubMed

    Münzel, Thomas; Meinertz, Thomas; Tebbe, Ulrich; Schneider, Heinrich Theodor; Stalleicken, Dirk; Wargenau, Manfred; Gori, Tommaso; Klingmann, Ingrid

    2014-04-01

    The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study ('CLEOPATRA' study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity.

  12. Iron Oxide Decorated MoS2 Nanosheets with Double PEGylation for Chelator-Free Radiolabeling and Multimodal Imaging Guided Photothermal Therapy

    PubMed Central

    Liu, Teng; Shi, Sixiang; Liang, Chao; Shen, Sida; Cheng, Liang; Wang, Chao; Song, Xuejiao; Goel, Shreya; Barnhart, Todd E.; Cai, Weibo; Liu, Zhuang

    2015-01-01

    Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur chemistry, forming MoS2-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, 64Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy. PMID:25562533

  13. A retrospective study showing the extent of compliance with perioperative guidelines in patients with coronary stents with regard to double antiplatelet therapy.

    PubMed

    Woolard, Austin A; Ehrenfeld, Jesse M; Eagle, Susan S; Wanderer, Jonathan P

    2016-09-01

    To evaluate perioperative dual antiplatelet therapy management in patients with previously placed coronary stents. Retrospective medical record review. Academic medical center. A total of 1891 surgical cases performed at Vanderbilt University Medical Center in 2012 were evaluated using a perioperative database. Of these, 161 had complete data records that were evaluated using 2 evidence-based and expert opinion-supported protocols. N/A. This study is meant to evaluate perioperative antiplatelet management decisions in patients with coronary stents. Management decisions were consistent with guidelines regarding antiplatelet therapy in 13% (21/161) of patients. Of the 87% (140/161) of cases where decisions were not consistent, 88% (123/140) were due to discontinuing aspirin preoperatively when there was not a high risk of surgical bleeding. This study revealed suboptimal adherence to current perioperative antiplatelet management guidelines in patients with coronary stents. The lack of adherence to current guidelines is concerning and could be used to support the notion of an anesthesiologist-led Perioperative Surgical Home. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials.

    PubMed Central

    Hays, J T; Croghan, I T; Schroeder, D R; Offord, K P; Hurt, R D; Wolter, T D; Nides, M A; Davidson, M

    1999-01-01

    OBJECTIVES: The purpose of this study was to determine the efficacy and safety of the nicotine patch for smoking cessation in an over-the-counter environment. The years of study were 1994 to 1995. METHODS: Parallel 6-week trials were conducted: a placebo-controlled trial of no-cost 22-mg, 24-hour nicotine patch therapy and an open label trial of the same therapy with patches purchased by subjects. Participants (n = 958) were 18 years or older, had smoked at least 15 cigarettes daily for at least 6 months, and were enrolled at 3 study sites. The main outcome measure was self-reported smoking abstinence confirmed by expired carbon monoxide measurements. RESULTS: Smoking cessation rates in the placebo-controlled trial were 16.8% and 9.6% at week 6 and 8.7% and 4.3% at week 24 for the active patch and placebo groups, respectively. Smoking cessation rates in the open label-pay trial were 19.0% and 10.8% at weeks 6 and 24, respectively. A slight increase in adverse cardiovascular events was noted only in the open label-pay group in comparison with the placebo group. CONCLUSIONS: In an over-the-counter environment, the 22-mg, 24-hour nicotine patch is effective and safe for smoking cessation treatment. PMID:10553392

  15. The Effect of Probiotic Plus Prebiotic Supplementation on the Tolerance and Efficacy of Helicobacter Pylori Eradication Quadruple Therapy: a Randomized Prospective Double Blind Controlled Trial

    PubMed Central

    Shafaghi, Afshin; Pourkazemi, Aydin; Khosravani, Mohsen; Fakhrie Asl, Saba; Amir Maafi, Alireza; Atrkar Roshan, Zahra; Abaspour Rahimabad, Jafar

    2016-01-01

    BACKGROUND Standard anti-Helicobacter pylori (H. pylori) treatment fails in the eradication of the organism in almost 10-35% of the patients and has different side effects. Recent studies have proposed that probiotic supplementations with or without prebiotic may improve the eradication rate and diminish the side effects, although it is still a controversial issue. We aimed to investigate the effect of probiotic with prebiotic supplementation on the eradication rate and side effects of anti H. pylori quadruple therapy. METHODS 76 patients with a positive biopsy specimen for H. pylori were enrolled. They were randomized to receive quadruple therapy of bismuth, clarithromycin, amoxicillin, and omeprazole for 14 days and also the synbiotic or the placebo. We asked them to answer study questionnaires at the beginning and during the treatment. Finally, urea breath test was done 8 weeks after the treatment. RESULTS The eradication rate was significantly better in the synbiotic group by intention-to-treat analysis (p<0.05). Treatment side effects such as diarrhea, nausea, vomiting, epigastric pain, flatulence, constipation, and taste abnormality were similar in both groups but anorexia was significantly better in the synbiotic group (p <0.05). CONCLUSION The eradication rate was significantly better in the synbiotic group by intention-to-treat analysis (p<0.05). Treatment side effects such as diarrhea, nausea, vomiting, epigastric pain, flatulence, but could improve the eradication by augmenting the treatment tolerance and compliance. PMID:27698967

  16. Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

    PubMed Central

    Thase, Michael E.

    2010-01-01

    Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

  17. Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

    PubMed

    Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

    2016-03-01

    There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

  18. Effectiveness of tenoxicam and ibuprofen for pain prevention following endodontic therapy in comparison to placebo: a randomized double-blind clinical trial.

    PubMed

    Arslan, Hakan; Topcuoglu, Huseyin S; Aladag, Halit

    2011-06-01

    Tenoxicam is an effective analgesic and anti-inflammatory agent for symptomatic treatment of various conditions. The purpose of this study was to evaluate clinically the effectiveness of prophylactic tenoxicam and prophylactic ibuprofen in reducing post-endodontic pain compared with placebo. A total of 48 patients consented to a double-blind, single dose, prophylactic oral administration of 20 mg of tenoxicam, 200 mg of ibuprofen, or a placebo before root canal treatment. The root canal treatment was performed in one visit. The patients registered their degree of discomfort on a 100-mm visual analog scale, immediately postoperative, and 6, 12, 24, 48 and 72 h after initiation of root canal treatment. The two-way ANOVA test and Tukey HSD post hoc test showed that in the 6-h period, both 20 mg of tenoxicam and 200 mg of ibuprofen provided significantly better pain relief than the placebo. Prophylactic administration of a single dose of 20 mg tenoxicam or 200 mg ibuprofen before RCT provides an effective reduction at 6 h (P < 0.05). Because of the advantages of tenoxicam, it may be useful as a prophylactic analgesic when post-endodontic pain is anticipated.

  19. Acute bronchitis therapy with ivy leaves extracts in a two-arm study. A double-blind, randomised study vs. an other ivy leaves extract.

    PubMed

    Cwientzek, Ute; Ottillinger, Bertram; Arenberger, Petr

    2011-10-15

    Ivy leaves extracts are authorised in medicinal products for the treatment of acute bronchitis. Different studies and the long experience on the market show safety and efficacy of this drug. A double-blind, randomised study was conducted to assess the efficacy and tolerability of ivy leaves soft extract with an other ivy leaves extract. 590 patients with acute bronchitis participated in this study. They were treated with test or comparator for 7 days (±1). The Bronchitis Severity Score (BSS) decreased gradually and to a similar extent from Day 1 to Day 7 in both treatment groups. Starting from values of 6.2-6.3±1.2, the BSS decreased by approximately 4.7-4.9 points until Day 7, so that patients left the study with a mean BSS of 1.4-1.6. The BSS subscales cough, sputum, rhales/rhonchi, chest pain during coughing, and dyspnoea improved to a similar extent in both treatment groups. Overall, 2.7% of patients (per group and overall) experienced an adverse event, all of which were non-serious. Fewer patients younger than ten years had adverse events than would have been expected from their share of the study population (p=0.015; Fisher's exact test). As a conclusion, the test product with ivy leaves soft extract proved to be non-inferior to the comparator ivy leaves extract in improving symptoms of acute bronchitis.

  20. Analgesic Effects of Intra-Articular Bupivacaine/Intravenous Parecoxib Combination Therapy versus Intravenous Parecoxib Monotherapy in Patients Receiving Total Knee Arthroplasty: A Randomized, Double-Blind Trial

    PubMed Central

    Shen, Shih-Jyun; Peng, Pei-Yu; Chen, Hsiu-Pin; Lin, Jr-Rung; Lee, Mel S.; Yu, Huang-Ping

    2015-01-01

    Objectives. The purpose of this double-blind, randomized study was to investigate whether the addition of intra-articular bupivacaine to intravenous parecoxib could improve pain relief in patients undergoing total knee arthroplasty. Methods. A total of 36 patients undergoing total knee arthroplasty were enrolled into our study. These patients were randomly allocated either to a placebo-controlled group or study group. Postoperative pain scores and analgesic consumption were evaluated. Results. Numeric rating scale (NRS) data of bupivacaine group in postoperative room were significantly lower than that of control group (control group versus bupivacaine group, 7.9 (6.7–9.1) (mean and 95% confidence interval) versus 4.5 (3.2–5.8) (mean and 95% confidence interval), p = 0.001). NRS data of bupivacaine group in ward were also significantly lower than that of control group. A significantly lower dose of meperidine was used in the study group postoperatively during the first 24 hours (control group versus bupivacaine group, 3.08 ± 0.80 mg/Kg versus 2.34 ± 0.42 mg/Kg, p = 0.001). Conclusion. Intra-articular bupivacaine in combination with intravenous parecoxib may improve pain relief and reduce the demand for rescue analgesics in patients undergoing total knee arthroplasty. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12615000463572). PMID:26171392

  1. Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial.

    PubMed

    Sabetnejad, Zahra; Assarian, Fatemeh; Omidi, Abdollah; Najarzadegan, Mohammad Reza

    2016-11-01

    Obsessive compulsive disorder (OCD) is a mental health concern due to its various negative consequences, especially in sexual function. Therefore, the treatment of sexual dysfunction in women with OCD is important in order to improve the patient's marital function and mental health. To compare the sexual behavior and sexual and marital satisfaction in women with obsessive-compulsive disorder (OCD) before and after treatment with fluoxetine and cognitive behavior therapy. This randomized clinical trial was conducted at psychiatric and psychological counseling centers in Kashan (Iran) from January 2, 2014, to December 29, 2014. Fifty-eight women with OCD were included in the study. In order to compare the effectiveness of pharmacological treatment (fluoxetine) and psychological treatment, cognitive behavior therapy (CBT), 58 female patients with OCD (diagnosed based on DSM-IV-T criteria) were randomized equally to either fluoxetine (at a dose of 60-80 mg daily for 3 months) or CBT (10 45-minute sessions). OCD and sexual behavior status of the patients before and after the intervention was assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Female Sexual Function Index (FSFI) questionnaire, respectively. The data were analyzed using SPSS version 22. To compare changes between the two groups, an independent T-test was used. Finally, the effects of all potential factors on treatment outcome were analyzed using factorial ANCOVA. The mean score for OCD in the fluoxetine group was 25.6 ± 4.8 at the beginning of the experiment and 18.79 ± 4.26 at the end of the study, while in the CBT group it was 25.6 ± 4.8 and 18.79 ± 4.26, respectively. No significant differences were found between two groups regarding obsession score changes. These scores in fluoxetine group were 58.1 and 52.8, respectively (p=0.046). There was a significant difference between the two groups in terms of sexual performance (p=0.003). In this study, our findings demonstrate a

  2. Effectiveness of cognitive behavioral therapy and fluoxetine on sexual function of women with obsessive compulsive disorder: A double-blind randomized controlled trial

    PubMed Central

    Sabetnejad, Zahra; Assarian, Fatemeh; Omidi, Abdollah; Najarzadegan, Mohammad Reza

    2016-01-01

    Background Obsessive compulsive disorder (OCD) is a mental health concern due to its various negative consequences, especially in sexual function. Therefore, the treatment of sexual dysfunction in women with OCD is important in order to improve the patient’s marital function and mental health. Objectives To compare the sexual behavior and sexual and marital satisfaction in women with obsessive-compulsive disorder (OCD) before and after treatment with fluoxetine and cognitive behavior therapy Methods This randomized clinical trial was conducted at psychiatric and psychological counseling centers in Kashan (Iran) from January 2, 2014, to December 29, 2014. Fifty-eight women with OCD were included in the study. In order to compare the effectiveness of pharmacological treatment (fluoxetine) and psychological treatment, cognitive behavior therapy (CBT), 58 female patients with OCD (diagnosed based on DSM-IV-T criteria) were randomized equally to either fluoxetine (at a dose of 60–80 mg daily for 3 months) or CBT (10 45-minute sessions). OCD and sexual behavior status of the patients before and after the intervention was assessed with the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) and Female Sexual Function Index (FSFI) questionnaire, respectively. The data were analyzed using SPSS version 22. To compare changes between the two groups, an independent T-test was used. Finally, the effects of all potential factors on treatment outcome were analyzed using factorial ANCOVA. Results The mean score for OCD in the fluoxetine group was 25.6 ± 4.8 at the beginning of the experiment and 18.79 ± 4.26 at the end of the study, while in the CBT group it was 25.6 ± 4.8 and 18.79 ± 4.26, respectively. No significant differences were found between two groups regarding obsession score changes. These scores in fluoxetine group were 58.1 and 52.8, respectively (p=0.046). There was a significant difference between the two groups in terms of sexual performance (p=0

  3. Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial.

    PubMed

    Mohammadpour, Nakisa; Jazayeri, Shima; Tehrani-Doost, Mehdi; Djalali, Mahmoud; Hosseini, Mostafa; Effatpanah, Mohammad; Davari-Ashtiani, Rozita; Karami, Elham

    2016-12-07

    Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD. Sixty-two children aged 5-12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed. Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P < 0.05). Evening symptoms and total score of WPREMB scale were significantly different at weeks 4 and 8 between the two groups (P = 0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales. Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism. The trial was registered in www.irct.ir is (IRCT201404222394N10).

  4. Perioperative Bromelain Therapy after Wisdom Teeth Extraction - A Randomized, Placebo-Controlled, Double-Blinded, Three-Armed, Cross-Over Dose-Finding Study.

    PubMed

    Bormann, Kai-Hendrik; Weber, Kristina; Kloppenburg, Heike; Koch, Armin; Meiser, Peter; Gellrich, Nils-Claudius

    2016-12-01

    Reduction in postoperative edema and inflammatory reactions is the key to the posttraumatic regeneration process. Use of bromelain is well established in this indication, but there is some controversy with regard to the optimal dosing of this drug. The aim of our study was therefore to investigate the efficacy of dosage-dependent therapy with bromelain in patients after wisdom teeth extraction by comparing the registered dosage 1000 FIP (Fédération Internationale Pharmaceutique) against higher dosages of 3000 FIP and 4500 FIP. A total of 75 patients were randomized to one of the three dosage arms, and 68 of these patients were finally analyzed in the modified intention-to-treat population. Patients involved underwent two surgery sessions: one study period being conducted under treatment with bromelain and the other with placebo. Postoperative swelling determined by a 3D face scanning system was defined as the primary endpoint; further efficacy parameters were maximum swelling, pain, difficulty in swallowing, and use of analgesics. A superiority of treatment with 3000 FIP and 4500 FIP versus 1000 FIP could not be demonstrated. The analysis of pooled bromelain treatments versus placebo did, however, show a clear trend in favor of bromelain for all assessments. Adverse events did not occur more frequently under bromelain therapy compared with placebo. This study thus clearly supports the clinical relevance of treatment of postoperative conditions with bromelain, and the recommended daily dose was sufficiently effective in this trial and indication. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Long-term effect of pulsed high-intensity laser therapy in the treatment of post-mastectomy pain syndrome: a double blind, placebo-control, randomized study.

    PubMed

    Ebid, Anwar Abdelgayed; El-Sodany, Ahmed Mohamed

    2015-08-01

    We assess the long-term effect of pulsed high-intensity laser therapy (HILT) in the treatment of the post-mastectomy pain syndrome (PMPS). A total of 61 women participated in this study (30 in the laser group and 31 in the placebo laser group), with a mean age of 53.56 ± 1.11 years. Patients who were randomly assigned to the laser group received HILT three times per week for 4 weeks, plus a routine physical therapy program (RPTP). The placebo laser group received placebo HILT plus RPTP. The outcomes measured were pain level by visual analog scale (VAS), shoulder range of motion (ROM), and quality of life (QOL). Statistical analysis was performed by ANOVA with repeated measures to compare the differences between baseline and post-treatment measurements and after 12 weeks of follow-up for both groups. The level of statistical significance was set at P < 0.05. Shoulder ROM significantly increased in the laser group after 4 weeks of treatment and after 12 weeks of follow-up compared with the placebo group. VAS results showed a significant decrease post-treatment in the laser group relative to the placebo group, and QOL results showed a significant improvement in the laser group compared with the placebo group and still improved after 12 weeks of follow-up. HILT combined with an RPTP appears to be more effective in patients with PMPS than a placebo laser procedure with RPTP.

  6. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial.

    PubMed

    Kim, Sae Woong; Park, Nam Cheol; Lee, Seung Wook; Yang, Dae Yul; Park, Jong Kwan; Moon, Du Geon; Yang, Sang-Kuk; Lee, Sung Won; Moon, Ki Hak; Ahn, Tai Young; Kim, Soo Woong; Park, Kwangsung; Min, Kweon Sik; Ryu, Ji-Kan; Son, Hankil; Jung, Jina; Hyun, Jae Seog

    2017-08-01

    Phosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). To assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED. A randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg. The primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24. The mean changes in total IPSS and IIEF-EF scores were -9.46 and 9.17 for FDC 0.4/5 mg and -8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period. The FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED. The study clearly demonstrated the advantage of FDC 0.4/5 mg. The main

  7. A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans.

    PubMed

    Rothbaum, Barbara Olasov; Price, Matthew; Jovanovic, Tanja; Norrholm, Seth D; Gerardi, Maryrose; Dunlop, Boadie; Davis, Michael; Bradley, Bekh; Duncan, Erica J; Rizzo, Albert; Ressler, Kerry J

    2014-06-01

    The authors examined the effectiveness of virtual reality exposure augmented with D-cycloserine or alprazolam, compared with placebo, in reducing posttraumatic stress disorder (PTSD) due to military trauma. After an introductory session, five sessions of virtual reality exposure were augmented with D-cycloserine (50 mg) or alprazolam (0.25 mg) in a double-blind, placebo-controlled randomized clinical trial for 156 Iraq and Afghanistan war veterans with PTSD. PTSD symptoms significantly improved from pre- to posttreatment across all conditions and were maintained at 3, 6, and 12 months. There were no overall differences in symptoms between D-cycloserine and placebo at any time. Alprazolam and placebo differed significantly on the Clinician-Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months posttreatment; the alprazolam group showed a higher rate of PTSD (82.8%) than the placebo group (47.8%). Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only. At posttreatment, the D-cycloserine group had the lowest cortisol reactivity and smallest startle response during virtual reality scenes. A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans, although there was no control condition for the virtual reality exposure. There was no advantage of D-cycloserine for PTSD symptoms in primary analyses. In secondary analyses, alprazolam impaired recovery and D-cycloserine enhanced virtual reality outcome in patients who demonstrated within-session learning. D-cycloserine augmentation reduced cortisol and startle reactivity more than did alprazolam or placebo, findings that are consistent with those in the animal literature.

  8. Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

    PubMed

    Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

    2016-03-01

    To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

  9. Extended Release Quetiapine Fumarate (Quetiapine XR) as Adjunct Therapy in Patients with Generalized Anxiety Disorder and a History of Inadequate Treatment Response: A Randomized, Double-Blind Study.

    PubMed

    Khan, Arifulla; Atkinson, Sarah; Mezhebovsky, Irina; She, Fahua; Leathers, Todd; Pathak, Sanjeev

    2011-05-15

    To evaluate the efficacy and tolerability of adjunct extended release quetiapine fumarate (quetiapine XR) in patients with generalized anxiety disorder (GAD) and inadequate response to selective serotonin reuptake inhibitors/ serotonin norepinephrine reuptake inhibitors (SSRI/SNRIs). 11-week (1-week single-blind placebo run-in; 8-week randomized treatment; 2-week post-treatment period), double-blind, placebo-controlled study. Patients were randomized to quetiapine XR or placebo adjunct to SSRI/SNRI. 50 mg initial dose; 150 mg/day, Day 3; 300 mg/day, Weeks × and 4 if indicated (Clinical Global Impressions-Severity of Illness [CGI-S] ≥ 4; 150 mg/day tolerated). Primary endpoint: change from randomization to Week 8 in HAM-A total score. Secondary variables: Hamilton Rating Scale for Anxiety (HAM-A) psychic/somatic clusters, response and remission; and CGI-S. 409 patients were randomized to quetiapine XR (n = 209) or placebo (n = 200); 41% and 55% of patients, respectively, had dose increases (300 mg/day). Week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (-10.74; p = 0.079) versus placebo (-9.61). Secondary variables were generally consistent with the primary analysis, except a significant reduction in HAM-A total score at Week 1 (-6.45, quetiapine XR versus -4.47, placebo; p < 0.001); significant improvements in HAM-A psychic cluster (p < 0.05) and CGI-S total (p < 0.05) scores at Week 8. Adverse events (.10% either group) were dry mouth, somnolence, sedation, headache, and dizziness. In patients with GAD and inadequate response to SSRI/SNRI, adjunct quetiapine XR did not show a statistically significant effect for the primary endpoint at Week 8, although some secondary endpoints were statistically significant versus placebo. Quetiapine XR was generally well tolerated.

  10. Extended Release Quetiapine Fumarate (Quetiapine XR) as Adjunct Therapy in Patients with Generalized Anxiety Disorder and a History of Inadequate Treatment Response: A Randomized, Double-Blind Study

    PubMed Central

    Khan, Arifulla; Atkinson, Sarah; Mezhebovsky, Irina; She, Fahua; Leathers, Todd; Pathak, Sanjeev

    2011-01-01

    Objective To evaluate the efficacy and tolerability of adjunct extended release quetiapine fumarate (quetiapine XR) in patients with generalized anxiety disorder (GAD) and inadequate response to selective serotonin reuptake inhibitors/ serotonin norepinephrine reuptake inhibitors (SSRI/SNRIs). Methods 11-week (1-week single-blind placebo run-in; 8-week randomized treatment; 2-week post-treatment period), double-blind, placebo-controlled study. Patients were randomized to quetiapine XR or placebo adjunct to SSRI/SNRI. 50 mg initial dose; 150 mg/day, Day 3; 300 mg/day, Weeks × and 4 if indicated (Clinical Global Impressions-Severity of Illness [CGI-S] ≥ 4; 150 mg/day tolerated). Primary endpoint: change from randomization to Week 8 in HAM-A total score. Secondary variables: Hamilton Rating Scale for Anxiety (HAM-A) psychic/somatic clusters, response and remission; and CGI-S. Results 409 patients were randomized to quetiapine XR (n = 209) or placebo (n = 200); 41% and 55% of patients, respectively, had dose increases (300 mg/day). Week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; p = 0.079) versus placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except a significant reduction in HAM-A total score at Week 1 (–6.45, quetiapine XR versus –4.47, placebo; p < 0.001); significant improvements in HAM-A psychic cluster (p < 0.05) and CGI-S total (p < 0.05) scores at Week 8. Adverse events (.10% either group) were dry mouth, somnolence, sedation, headache, and dizziness. Conclusions In patients with GAD and inadequate response to SSRI/SNRI, adjunct quetiapine XR did not show a statistically significant effect for the primary endpoint at Week 8, although some secondary endpoints were statistically significant versus placebo. Quetiapine XR was generally well tolerated. PMID:27738353

  11. Design Guidelines for a Double Scattering Compton Camera for Prompt-γ Imaging During Ion Beam Therapy: A Monte Carlo Simulation Study

    NASA Astrophysics Data System (ADS)

    Richard, M.-H.; Chevallier, M.; Dauvergne, D.; Freud, N.; Henriquet, P.; Le Foulher, F.; Letang, J. M.; Montarou, G.; Ray, C.; Roellinghoff, F.; Testa, E.; Testa, M.; Walenta, A. H.

    2011-02-01

    In hadrontherapy in order to fully take advantage of the assets of the ion irradiation, the position of the Bragg peak has to be monitored accurately. Here, we investigate a monitoring method relying on the detection in real time of the prompt γ emitted quasi instantaneously during the nuclear fragmentation processes. Our detection system combines a beam hodoscope and a double scattering Compton camera. The prompt-γ emission points are reconstructed by intersecting the ion trajectories given by the hodoscope and the Compton cones reconstructed with the camera. We propose here to study in terms of point spread function and efficiency the theoretical feasibility of the emission points reconstruction with our set-up in the case of a photon point source in air. First we analyze the nature of all the interactions which are likely to produce an energy deposit in the three detectors of the camera. It is underlined that upper energy thresholds in both scatter detectors are required in order to select mainly Compton events (one Compton interaction in each scatter detector and one interaction in the absorber detector). Then, we study the influence of various parameters such as the photon energy and the inter-detector distances on the Compton camera response. These studies are carried out by means of Geant4 simulations. We use a source with a spectrum corresponding to the prompt-γ spectrum emitted during the carbon ion irradiation of a water phantom. In the current configuration, the spatial resolution of the Compton camera is about 6 mm (Full Width at Half Maximum) and the detection efficiency 10-5. Finally, provided the detection efficiency is increased, the clinical applicability of our system is considered.

  12. Acid-suppressive therapy with esomeprazole for relief of unexplained chest pain in primary care: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Flook, Nigel W; Moayyedi, Paul; Dent, John; Talley, Nicholas J; Persson, Tore; Karlson, Björn W; Ruth, Magnus

    2013-01-01

    High-quality data regarding the efficacy of acid-suppressive treatment for unexplained chest pain are lacking. The aim of this study was to evaluate the efficacy of esomeprazole in primary-care treatment of patients with unexplained chest pain stratified for frequency of reflux/regurgitation symptoms. Patients with a ≥ 2-week history of unexplained chest pain (unrelated to gastroesophageal reflux) who had at least moderate pain on ≥ 2 of the last 7 days were stratified by heartburn/regurgitation frequency (≤ 1 day/week (stratum 1) vs. ≥ 2 days/week (stratum 2)) and randomized to 4 weeks of double-blind treatment with twice-daily esomeprazole 40 mg or placebo. Chest pain relief during the last 7 days of treatment (≤ 1 day with minimal symptoms assessed daily using a 7-point scale) was analyzed by stratum in keeping with the predetermined analysis plan. Overall, 599 patients (esomeprazole: 297, placebo: 302) were randomized. In stratum 1, more esomeprazole than placebo recipients achieved chest pain relief (38.7% vs. 25.5%; P=0.018); no between-treatment difference was observed in stratum 2 (27.2% vs. 24.2%; P=0.54). However, esomeprazole was superior to placebo in a post-hoc analysis of the whole study population (combined strata; 33.1% vs. 24.9%; P=0.035). A 4-week course of high-dose esomeprazole provided statistically significant relief of unexplained chest pain in primary-care patients who experienced infrequent or no heartburn/regurgitation, but there was no such significant reduction in patients with more frequent reflux symptoms.

  13. Short-term effects of 2% atorvastatin dentifrice as an adjunct to periodontal therapy: a randomized double-masked clinical trial.

    PubMed

    Rosenberg, David R; Andrade, Catherine X; Chaparro, Alejandra P; Inostroza, Carolina M; Ramirez, Valeria; Violant, Déborah; Nart, José

    2015-05-01

    The pleiotropic effects of statins, such as immunomodulation and anti-inflammatory effects, may also improve periodontal conditions. The aim of the present study is to assess the effectiveness of a dentifrice medicated with 2% atorvastatin in improving clinical periodontal parameters as a complement to non-surgical periodontal treatment (NSPT). A randomized, double-masked clinical trial was performed with two parallel groups: 1) atorvastatin group (NSPT plus medicated 2% atorvastatin dentifrice) and 2) placebo group (NSPT plus placebo dentifrice). The effectiveness of these treatments was assessed using periodontal measurements obtained at baseline and 1 month later. The measurements were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), and periodontal inflamed surface area (PISA). Multiple linear regression models were used to compare outcome variables after adjusting for sex, diabetes, and tobacco use. A total of 36 individuals participated in this study (atorvastatin group, n = 18; placebo group, n = 18). Both groups showed improvements in periodontal parameters. The atorvastatin group showed a decrease of 297.63 mm(2) in PISA (95% confidence interval = 76.04 to 519.23; P = 0.01), which was significantly greater than the reduction observed in the placebo group. There was also a significantly greater reduction in mean PD, percentage of sites with PD ≥5 mm, mean CAL, percentage of sites with CAL ≥5 mm, BOP, and GI in the atorvastatin group compared with the placebo group. NSPT plus 2% atorvastatin medicated dentifrice was more effective in improving clinical periodontal parameters than NSPT plus a placebo dentifrice.

  14. Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

    PubMed

    Eldabe, Sam; Duarte, Rui V; Madzinga, Grace; Batterham, Alan M; Brookes, Morag E; Gulve, Ashish P; Perruchoud, Christophe; Raphael, Jon H; Lorenzana, David; Buchser, Eric

    2017-05-01

    Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P  = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P  = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration.

  15. Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study.

    PubMed

    Dréno, B; Kaufmann, R; Talarico, S; Torres Lozada, V; Rodríguez-Castellanos, M A; Gómez-Flores, M; De Maubeuge, J; Berg, M; Foley, P; Sysa-Jedrzejowska, A; Kerrouche, N; Paliargues, F; Bettoli, V

    2011-08-01

    Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first-line option in the treatment of moderate to severe acne vulgaris. To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%-BPO 2·5% (A/BPO) fixed-dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. A total of 378 subjects were randomized in a double-blind, controlled trial to receive once-daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects 'clear' or 'almost clear'), skin tolerability, adverse events and patients' satisfaction. The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (-74·1%) than in the lymecycline with vehicle group (-56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were 'very satisfied' was significantly greater (P = 0·031). These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  16. Spontaneous Resolution of Non Traumatic Chronic Subdural Haematoma Despite Continued Antiplatelet Therapy: A Case Report.

    PubMed

    Tiwari, Ajeet Ramamani; Maheshwari, Shradha; Balasubramaniam, Srikant; Devendra, Tyagi; Savant, Hemantkumar

    2015-06-01

    Spontaneous resolution of traumatic chronic subdural haematoma (CSDH) has been reported in literature. However, those with non traumatic CSDH are exceedingly rare and none reported with continued antiplatelet therapy where it itself is an aetiological agent for development of non traumatic CSDH. A 50-year-old male presented to us with a non haemorrhagic cerebellar infarct with a concomitant CSDH without history of any trauma. Patient's PT/INR, Bleeding time and Clotting time were normal. Patient was started on antiplatelet therapy (Tablet Aspirin 150 mg OD) for the acute infarct. MR Brain at 1 month showed an increased size of CSDH. However patient denied surgical evacuation hence we continued conservative line of management, however we continued anti-platelet therapy with close neurological and coagulation profile monitoring that remained within normal range throughout the period of observation. CT at 5(th) month showed complete resolution of CSDH. Patient was on antiplatelet drugs throughout the period of observation. Our case argues about the role of antiplatelet therapy in patients with CSDH with contrary lesions requiring anticoagulation.

  17. Spontaneous Resolution of Non Traumatic Chronic Subdural Haematoma Despite Continued Antiplatelet Therapy: A Case Report

    PubMed Central

    Maheshwari, Shradha; Balasubramaniam, Srikant; Devendra, Tyagi; Savant, Hemantkumar

    2015-01-01

    Spontaneous resolution of traumatic chronic subdural haematoma (CSDH) has been reported in literature. However, those with non traumatic CSDH are exceedingly rare and none reported with continued antiplatelet therapy where it itself is an aetiological agent for development of non traumatic CSDH. A 50-year-old male presented to us with a non haemorrhagic cerebellar infarct with a concomitant CSDH without history of any trauma. Patient’s PT/INR, Bleeding time and Clotting time were normal. Patient was started on antiplatelet therapy (Tablet Aspirin 150 mg OD) for the acute infarct. MR Brain at 1 month showed an increased size of CSDH. However patient denied surgical evacuation hence we continued conservative line of management, however we continued anti-platelet therapy with close neurological and coagulation profile monitoring that remained within normal range throughout the period of observation. CT at 5th month showed complete resolution of CSDH. Patient was on antiplatelet drugs throughout the period of observation. Our case argues about the role of antiplatelet therapy in patients with CSDH with contrary lesions requiring anticoagulation. PMID:26266165

  18. Effect of low-level laser therapy on pain, quality of life and sleep in patients with fibromyalgia: study protocol for a double-blinded randomized controlled trial

    PubMed Central

    2012-01-01

    Background Low-level laser therapy (LLLT) has been widely used as adjuvant strategy for treatment of musculoskeletal disorders. The light-tissue interaction (photobiostimulation) promotes analgesic and anti-inflammatory effects and improves tissue healing, which could justify the recommendation of this therapy for patients with fibromyalgia, leading to an improvement in pain and possibly minimizing social impact related to this disease. The present study proposes to evaluate the effect of LLLT on tender points in patients with fibromyalgia, correlating this outcome with quality of life and sleep. Methods/design One hundred and twenty patients with fibromyalgia will be treated at the Integrated Health Center and the Sleep Laboratory of the Post Graduate Program in Rehabilitation Sciences of the Nove de Julho University located in the city of Sao Paulo, Brazil. After fulfilling the eligibility criteria, a clinical evaluation and assessments of pain and sleep quality will be carried out and self-administered quality of life questionnaires will be applied. The 120 volunteers will be randomly allocated to an intervention group (LLLT, n = 60) or control group (CLLLT, n = 60). Patients from both groups will be treated three times per week for four weeks, totaling twelve sessions. However, only the LLLT group will receive an energy dose of 6 J per tender point. A standardized 50-minute exercise program will be performed after the laser application. The patients will be evaluated regarding the primary outcome (pain) using the following instruments: visual analog scale, McGill Pain Questionnaire and pressure algometry. The secondary outcome (quality of life and sleep) will be assessed with the following instruments: Medical Outcomes Study 36-item Short-Form Health Survey, Fibromyalgia Impact Questionnaire, Berlin Questionnaire, Epworth Sleepiness Scale and polysomnography. ANOVA test with repeated measurements for the time factor will be performed to test between

  19. Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-Blind, randomized, placebo-controlled study

    PubMed Central

    2014-01-01

    Background Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. Methods In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). Results A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. Conclusions In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. Trial registration Current Controlled Trials ClinicalTrials.gov ID NCT01928342. PMID:24382338

  20. Finite Volume Scheme for Double Convection-Diffusion Exchange of Solutes in Bicarbonate High-Flux Hollow-Fiber Dialyzer Therapy

    PubMed Central

    Annan, Kodwo

    2012-01-01

    The efficiency of a high-flux dialyzer in terms of buffering and toxic solute removal largely depends on the ability to use convection-diffusion mechanism inside the membrane. A two-dimensional transient convection-diffusion model coupled with acid-base correction term was developed. A finite volume technique was used to discretize the model and to numerically simulate it using MATLAB software tool. We observed that small solute concentration gradients peaked and were large enough to activate solute diffusion process in the membrane. While CO2 concentration gradients diminished from their maxima and shifted toward the end of the membrane, HCO3 − concentration gradients peaked at the same position. Also, CO2 concentration decreased rapidly within the first 47 minutes while optimal HCO3 − concentration was achieved within 30 minutes of the therapy. Abnormally high diffusion fluxes were observed near the blood-membrane interface that increased diffusion driving force and enhanced the overall diffusive process. While convective flux dominated total flux during the dialysis session, there was a continuous interference between convection and diffusion fluxes that call for the need to seek minimal interference between these two mechanisms. This is critical for the effective design and operation of high-flux dialyzers. PMID:23197994

  1. Efficacy of focused low-intensity pulsed ultrasound therapy for the management of knee osteoarthritis: a randomized, double blind, placebo-controlled trial

    PubMed Central

    Jia, Lang; Wang, Yan; Chen, Jinyun; Chen, Wenzhi

    2016-01-01

    The aim of this study was to investigate the effects of focused low-intensity pulsed ultrasound (FLIPUS) therapy on the functional and health status of patients with knee osteoarthritis (KOA). A total of 106 subjects with bilateral KOA were randomized sequentially into two groups. Group I received FLIPUS + diclofenac sodium, and group II received sham FLIPUS + diclofenac sodium. The therapeutic effects of the interventions were evaluated by measuring changes in VAS pain, the WOMAC scores, and the LI scores after 10 days of treatment as well as changes in LI and VAS at follow-up, 4 and 12 weeks later. In addition, changes in the range of motion, ambulation speed, and the SF-36 in each group were recorded after 10 days of treatment. Compared with those in group II, patients in group Ishowed significant improvements in VAS, WOMAC, LI, ambulation speed, and most items in the SF-36 after 10 days of treatment. In addition, patients in group I showed significant improvements in LI and VAS at follow-up. There were no FLIPUS-related adverse events during and after the interventions. In conclusion, FLIPUS is a safe and effective treatment modality for relieving pain and improving the functions and quality of life of patients with KOA. PMID:27748432

  2. Finite volume scheme for double convection-diffusion exchange of solutes in bicarbonate high-flux hollow-fiber dialyzer therapy.

    PubMed

    Annan, Kodwo

    2012-01-01

    The efficiency of a high-flux dialyzer in terms of buffering and toxic solute removal largely depends on the ability to use convection-diffusion mechanism inside the membrane. A two-dimensional transient convection-diffusion model coupled with acid-base correction term was developed. A finite volume technique was used to discretize the model and to numerically simulate it using MATLAB software tool. We observed that small solute concentration gradients peaked and were large enough to activate solute diffusion process in the membrane. While CO(2) concentration gradients diminished from their maxima and shifted toward the end of the membrane, HCO(3)(-) concentration gradients peaked at the same position. Also, CO(2) concentration decreased rapidly within the first 47 minutes while optimal HCO(3)(-) concentration was achieved within 30 minutes of the therapy. Abnormally high diffusion fluxes were observed near the blood-membrane interface that increased diffusion driving force and enhanced the overall diffusive process. While convective flux dominated total flux during the dialysis session, there was a continuous interference between convection and diffusion fluxes that call for the need to seek minimal interference between these two mechanisms. This is critical for the effective design and operation of high-flux dialyzers.

  3. Treatment Effect of Antipsychotics in Combination with Horticultural Therapy on Patients with Schizophrenia: A Randomized, Double-blind, Placebo-controlled Study

    PubMed Central

    ZHU, Shunhong; WAN, Hengjing; LU, Zhide; WU, Huiping; ZHANG, Qun; QIAN, Xiaoqiong; YE, Chenyu

    2016-01-01

    Background As a newly developed treatment method for schizophrenia, horticultural therapy is gaining more attention. However, there is as of now little research investigating this topic as well as a general lack of studies adopting into standard treatment plans. Aims Investigate treatment effect of horticultural therapy on patients with schizophrenia and its possibility of standardized application in psychiatric hospitals. Methods 110 patients with schizophrenia who met the inclusion criteria and provided informed consent were selected from the rehabilitation ward of the Minhang District Mental Health Center from September 2015 to December 2015. We used random-number methods to classify patients into either the intervention group or the control group. While the two groups both received normal medications, the intervention group also attended horticultural therapy. Patients in the intervention group were led by a rehabilitation therapist who had obtained the level II psychological counselor qualification (the standard qualification for counselors in China). The treatment period lasted for 12 weeks. Treatment was held 3 times every week and each session lasted for 90 minutes. The specific contents included ridging, planting, watering, fertilizing and pruning of flowers; plowing, sowing, watering, fertilizing, weeding and catching pests for gardens; appreciating, collecting vegetables, cooking and tasting for flowers and grasses. During the final 10 minutes of every session, patients mutually expressed their thoughts and experiences and the rehabilitation therapist concluded the session. The two groups were measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, the end of the 4th week and the end of the 12th week. Results There was no statistically significant difference in gender, age, course of disease, marital status, mean dosage of antipsychotic medications and PANSS score before the intervention among two groups. The PANSS score in the

  4. A Galleria mellonella infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Pseudomonas aeruginosa.

    PubMed

    Krezdorn, Jessica; Adams, Sophie; Coote, Peter J

    2014-07-01

    The aim of this study was to compare the inhibitory effect of antibiotic combinations in vitro with efficacy in Galleria mellonella larvae in vivo to identify efficacious combinations that target Pseudomonas aeruginosa. P. aeruginosa NCTC 13437, a multidrug-resistant strain resistant to β-lactams and aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem, amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was measured in vitro via a 24 h time-kill assay. In vitro results were then compared with the efficacy of the same dual or triple antibiotic combinations versus G. mellonella larvae infected with P. aeruginosa. G. mellonella haemolymph burden of P. aeruginosa was determined over 96 h post-infection and treatment with the most potent combination therapies. Many dual and triple combinations of antibiotics displayed synergistic inhibition of multidrug-resistant P. aeruginosa in vitro. There was little correlation between combinations that were synergistic in vitro and those that showed enhanced efficacy in vivo versus infected G. mellonella larvae. The most potent dual and triple combinations in vivo were cefotaxime plus piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer combinations were found to offer enhanced therapeutic benefit in vivo compared with in vitro. The therapeutic benefit arising from treatment with antibiotic combinations in vivo correlated with reduced larval burden of P. aeruginosa. This study has identified antibiotic combinations that merit further investigation for their clinical potential and has demonstrated the utility of using G. mellonella to screen for novel antibiotic treatments that demonstrate efficacy in vivo.

  5. Radial extracorporeal shock-wave therapy in patients with chronic rotator cuff tendinitis: a prospective randomised double-blind placebo-controlled multicentre trial.

    PubMed

    Kolk, A; Yang, K G Auw; Tamminga, R; van der Hoeven, H

    2013-11-01

    The aim of this study was to determine the effect of radial extracorporeal shock-wave therapy (rESWT) on patients with chronic tendinitis of the rotator cuff. This was a randomised controlled trial in which 82 patients (mean age 47 years (24 to 67)) with chronic tendinitis diagnosed clinically were randomly allocated to a treatment group who received low-dose rESWT (three sessions at an interval 10 to 14 days, 2000 pulses, 0.11 mJ/mm(2), 8 Hz) or to a placebo group, with a follow-up of six months. The patients and the treating orthopaedic surgeon, who were both blinded to the treatment, evaluated the results. A total of 44 patients were allocated to the rESWT group and 38 patients to the placebo group. A visual analogue scale (VAS) score for pain, a Constant-Murley (CMS) score and a simple shoulder test (SST) score significantly improved in both groups at three and six months compared with baseline (all p ≤ 0.012). The mean VAS was similar in both groups at three (p = 0.43) and six months (p = 0.262). Also, the mean CMS and SST scores were similar in both groups at six months (p = 0.815 and p = 0.834, respectively). It would thus seem that low-dose rESWT does not reduce pain or improve function in patients chronic rotator cuff tendinitis compared with placebo treatment.

  6. Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial

    PubMed Central

    Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício

    2015-01-01

    Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Results Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Significance Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by

  7. Effect of Ruxolitinib Therapy on Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in COMFORT-I: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Mesa, Ruben A.; Gotlib, Jason; Gupta, Vikas; Catalano, John V.; Deininger, Michael W.; Shields, Alan L.; Miller, Carole B.; Silver, Richard T.; Talpaz, Moshe; Winton, Elliott F.; Harvey, Jimmie H.; Hare, Thomas; Erickson-Viitanen, Susan; Sun, William; Sandor, Victor; Levy, Richard S.; Kantarjian, Hagop M.; Verstovsek, Srdan

    2013-01-01

    Purpose To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis. Patients and Methods COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment–I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC). Results Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms, although patients receiving placebo experienced worsening (P < .001). The majority (91%) of ruxolitinib-treated patients designated as ≥ 50% TSS responders (≥ 50% TSS improvement) self-reported their condition as either “Much improved” or “Very much improved” on the PGIC. These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo, who experienced worsening on these measures (P ≤ .0135). Ruxolitinib-treated patients with a lesser degree of symptom improvement (< 50% TSS responders) also achieved improvements over placebo on these measures. The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS, PGIC, PROMIS Fatigue Scale, and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in these PROs. Conclusion

  8. Triple therapy with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide in adult patients with hypertension: The TRINITY multicenter, randomized, double-blind, 12-week, parallel-group study.

    PubMed

    Oparil, Suzanne; Melino, Michael; Lee, James; Fernandez, Victor; Heyrman, Reinilde

    2010-07-01

    Patients with hypertension may require a combination of > or =2 antihypertensive agents to achieve blood pressure (BP) control. The aim of this study was to determine whether a triple combination of olmesartan medoxomil (OM), amlodipine besylate (AML), and hydrochlorothiazide (HCTZ) had a clinically significant benefit compared with dual combinations of the individual components in patients with moderate to severe hypertension. This was a multicenter, randomized, doubleblind, parallel-group study in which triple combination treatment with OM 40 mg + AML 10 mg + HCTZ 25 mg was compared with dual combinations of the individual components-OM 40 mg/AML 10 mg in fixed-dose combination, OM 40 mg/HCTZ 25 mg in fixed-dose combination, and AML 10 mg + HCTZ 25 mg-in patients aged > or =18 years who had a mean seated BP > or =140/100 mm Hg or > or =160/90 mm Hg. The study consisted of a 3-week washout period with no study medication and a 12-week double-blind treatment period. In the first 2 weeks of the double-blind treatment period, all patients were randomized to receive dual combination treatment or placebo. All patients assigned to a dual combination treatment group continued the assigned treatment until week 4, and all patients assigned to placebo were switched at week 2 to receive 1 of the dual combination treatments until week 4. At week 4, patients either continued dual combination treatment or switched to triple combination treatment until week 12. The primary end point was the change in seated diastolic BP (SeDBP) from baseline to week 12; SeDBP reduction of > or =2 mm Hg was considered a clinically significant benefit. Secondary efficacy end points included the change in seated systolic BP (SeSBP) at week 12 and the percentages of patients achieving BP targets of <140/90 mm Hg, <120/80 mm Hg, SeSBP <140 mm Hg, and SeDBP <90 mm Hg at week 12. The tolerability of the treatments was also evaluated based on adverse events (AEs), clinical laboratory evaluations

  9. Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

    PubMed

    Möller, Hans-Jürgen; Demyttenaere, Koen; Olausson, Bengt; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Tummala, Raj; Eriksson, Hans

    2015-10-01

    To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.

  10. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial.

    PubMed

    Wherrett, Diane K; Bundy, Brian; Becker, Dorothy J; DiMeglio, Linda A; Gitelman, Stephen E; Goland, Robin; Gottlieb, Peter A; Greenbaum, Carla J; Herold, Kevan C; Marks, Jennifer B; Monzavi, Roshanak; Moran, Antoinette; Orban, Tihamer; Palmer, Jerry P; Raskin, Philip; Rodriguez, Henry; Schatz, Desmond; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S

    2011-07-23

    the occurrence and severity of adverse events did not differ between groups. Antigen-based immunotherapy therapy with two or three doses of subcutaneous GAD-alum across 4-12 weeks does not alter the course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigen-based therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune disease remains a challenge. US National Institutes of Health. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Long-term effects of pulsed high-intensity laser therapy in the treatment of post-burn pruritus: a double-blind, placebo-controlled, randomized study.

    PubMed

    Ebid, Anwar Abdelgayed; Ibrahim, Abeer Ramadan; Omar, Mohammed Taher; El Baky, Amal Mohamed Abd

    2017-04-01

    We assessed the long-term effects of pulsed high-intensity laser therapy (HILT) in post-burn pruritus treatment. A total of 49 adult burn patients with mean age of 31.53 ± 10.14 years participated, with 24 patients randomly assigned to the active laser group (ALG) and 25 in the placebo laser group (PLG). The ALG received HILT three times per week for 6 weeks, while the PLG received placebo HILT. Both groups received 10-mg cetirizine tablets twice daily and 10 mg at bedtime. All patients were advised to massage their burn scars with coconut oil for 5 min four times daily. The outcomes measured were the itch severity scale (ISS), impairment of pruritus-related quality of life (QoL), pain level by the visual analog scale (VAS), hand grip strength by handheld dynamometer, and daily cetirizine intake. Repeated-measures ANOVA was used to compare the baseline and post-treatment measurements and after 12 weeks of follow-up. Statistical significance was set at P < 0.05. ISS decreased significantly in the ALG after 6 weeks of treatment and after 12 weeks of follow-up compared with the PLG. The QoL results showed a significant improvement in the ALG compared with the PLG, which continued after 12 weeks. VAS results significantly decrease, hand grip strength significantly improved, and cetirizine intake significantly decreased post-treatment in the ALG relative to the PLG. HILT combined with cetirizine seems more effective in patients with post-burn pruritus than a placebo laser procedure with cetirizine.

  12. Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer.

    PubMed

    de la Cruz, Maxine; Hui, David; Parsons, Henrique A; Bruera, Eduardo

    2010-02-01

    A significant response to placebo in randomized controlled trials of treatments for cancer-related fatigue (CRF) had been reported. A retrospective study was conducted to determine the frequency and predictors of response to placebo effect and nocebo effects in patients with CRF treated in those trials. The records of 105 patients who received placebo in 2 previous randomized clinical trials conducted by this group were reviewed. The proportion of patients who demonstrated clinical response to fatigue, defined as an increase in Functional Assessment of Chronic Illness Therapy-Fatigue score of > or = 7 from baseline to Day 8, and the proportion of patients with a nocebo effect, defined as those reporting >2 side effects, were determined. Baseline patient characteristics and symptoms recorded using the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. Fifty-nine (56%) patients had a placebo response. Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate) were significantly associated with placebo response. Commonly reported side effects were insomnia (79%), anorexia (53%), nausea (38%), and restlessness (34%). Multivariate analysis indicated that worse baseline (ESAS) sleep, appetite, and nausea were associated with increased reporting of the corresponding side effects. Greater than half of advanced cancer patients enrolled in CRF trials had a placebo response. Worse baseline physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in the design of future CRF trials. Copyright 2009 American Cancer Society.

  13. Comparison of ischemic compression and lumbopelvic manipulation as trigger point therapy for patellofemoral pain syndrome in young adults: A double-blind randomized clinical trial.

    PubMed

    Behrangrad, Shabnam; Kamali, Fahimeh

    2017-07-01

    To compare the effectiveness of ischemic compression (IC) directly to the vastus medialis obliquus (VMO) versus lumbopelvic manipulation (LPM) in improving pain, functional status and sensitivity to mechanical stimulation of the VMO trigger point in patients with patellofemoral pain syndrome (PFPS). 40 patients with unilateral PFPS aged 20-30 years were selected randomly among patients with unilateral PFPS referred to physical therapy clinics of Shiraz University of Medical Sciences in Shiraz, Iran, between March 2014 and July 2014. 30 young adults participated. Participants were blinded to treatment allocation, and 15 patients were allocated to either IC or LPM. Patients in both groups were treated in three sessions per week. IC consisted of three sets of continuous pressure applied for on the myofascial trigger point (MTrP) of VMO. LPM consisted of supine rotational glide manipulation of the ipsilateral lumbopelvic region of the involved knee. Numeric pain rating scale (VAS) for pain intensity, Kujala questionnaire for functional status, and pressure pain threshold (PPT) for sensitivity to mechanical stimulation. All three were recorded before treatment, 1 week, 1 month and 3 months after the last session. Both groups showed significant improvement (p < 0.05, 95% confidence interval) in pain, functional status and PPT values. However, the IC group showed greater improvements, and outcome measures remained significantly better than in the LPM group during post-intervention follow-up. Both groups showed improvements throughout the study and follow-up period. However, the IC showed better short-term and long-term effectiveness than LPM for treating PFPS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Min, Kyunghoon; Song, Junyoung; Kang, Jin Young; Ko, Jooyeon; Ryu, Ju Seok; Kang, Myung Seo; Jang, Su Jin; Kim, Sang Heum; Oh, Doyeun; Kim, Moon Kyu; Kim, Sung Soo; Kim, Minyoung

    2013-03-01

    Allogeneic umbilical cord blood (UCB) has therapeutic potential for cerebral palsy (CP). Concomitant administration of recombinant human erythropoietin (rhEPO) may boost the efficacy of UCB, as it has neurotrophic effects. The objectives of this study were to assess the safety and efficacy of allogeneic UCB potentiated with rhEPO in children with CP. Children with CP were randomly assigned to one of three parallel groups: the pUCB group, which received allogeneic UCB potentiated with rhEPO; the EPO group, which received rhEPO and placebo UCB; and the Control group, which received placebo UCB and placebo rhEPO. All participants received rehabilitation therapy. The main outcomes were changes in scores on the following measures during the 6 months treatment period: the gross motor performance measure (GMPM), gross motor function measure, and Bayley scales of infant development-II (BSID-II) Mental and Motor scales (18). F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images (DTI) were acquired at baseline and followed up to detect changes in the brain. In total, 96 subjects completed the study. Compared with the EPO (n = 33) and Control (n = 32) groups, the pUCB (n = 31) group had significantly higher scores on the GMPM and BSID-II Mental and Motor scales at 6 months. DTI revealed significant correlations between the GMPM increment and changes in fractional anisotropy in the pUCB group. 18F-FDG-PET/CT showed differential activation and deactivation patterns between the three groups. The incidence of serious adverse events did not differ between groups. In conclusion, UCB treatment ameliorated motor and cognitive dysfunction in children with CP undergoing active rehabilitation, accompanied by structural and metabolic changes in the brain. Copyright © 2012 AlphaMed Press.

  15. Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study.

    PubMed

    Wildermuth, Brett E; Griffin, Craig E; Rosenkrantz, Wayne S

    2012-04-01

    In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate-potassium clavulanate (Clavamox(®); Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were photographed and their areas measured in square centimetres before and after 21 days of therapy with either flavoured amoxicillin-clavulanate suspension or flavoured placebo suspension. Sixteen cats completed the study, with nine plaque lesions (four treatment and five placebo) and eight lip ulcer lesions (four treatment and four placebo) included in the analysis. All lesions were shown to have infection, with bacterial phagocytosis present on cytological examination. Coagulase-positive staphylococci were the most commonly isolated bacteria. The amoxicillin-clavulanate-treated eosinophilic plaque group had a statistically significant 96.2% reduction in mean lesion size (-7.60 cm(2), P = 0.0078) and an 80% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), whereas the placebo group did not. The amoxicillin-clavulanate-treated lip ulcer group had a 42.6% decrease in mean lesion size (-0.25 cm(2), P = 0.4125) and the placebo group a 36.6% increase (+0.49 cm(2), P = 0.1575), although neither change was statistically significant. The amoxicillin-clavulanate-treated lip ulcer group had a statistically significant 65.0% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P < 0.0001), while no significant reduction was observed in the placebo group. A suspension of amoxicillin trihydrate-potassium clavulanate is an effective monotherapy for the treatment of feline eosinophilic plaques.

  16. A feasibility double-blind randomized placebo-controlled trial of extracorporeal shockwave therapy as a novel treatment for intermittent claudication.

    PubMed

    Harwood, Amy Elizabeth; Green, Jordan; Cayton, Thomas; Raza, Ali; Wallace, Tom; Carradice, Daniel; Chetter, Ian Clifford; Smith, George Edward

    2017-09-21

    Intermittent claudication is the most common symptom of peripheral arterial disease. Previous research has suggested that extracorporeal shockwave therapy (ESWT) may induce angiogenesis in treated tissue. The objective of this feasibility pilot trial was to assess the safety, tolerability, and efficacy of ESWT as a novel treatment. Patients with unilateral claudication were randomized to receive ESWT or sham treatment to the calf muscle three times per week for 3 weeks. Primary outcomes were pain-free walking distance (PFWD) and maximum walking distance (MWD). Secondary outcomes included safety and tolerability of ESWT treatment, ankle-brachial index before and after exercise, and quality of life assessed using generic (36-Item Short Form Health Survey, EuroQol-5 Dimension 3-Level) and disease-specific (Vascular Quality of Life) instruments. Participants were assessed at baseline and 4, 8, and 12 weeks after treatment. Feasibility outcomes included recruitment and attendance rates for treatment and follow-up. Thirty patients were recruited in total. Statistically significant (P < .05) improvements at all time points were observed in the active treatment group for both MWD and PFWD compared with the sham treatment group. PFWD improved by 276% in the active group and MWD improved by 167% in the active group at 12 weeks after treatment. There were no immediate or delayed treatment safety concerns or documented adverse effects of treatment with ESWT in this trial. ESWT is safe and well tolerated when it is applied to the calf and demonstrated significant improvements in walking distances. Current conservative management of intermittent claudication includes supervised exercise. The early results with ESWT as an alternative, noninvasive treatment option show great potential. The mechanism of action, durability of the clinical effect, and cost-effectiveness of ESWT for claudication require further investigation. Copyright © 2017 Society for Vascular Surgery

  17. Effect of low-level laser therapy irradiation and Bio-Oss graft material on the osteogenesis process in rabbit calvarium defects: a double blind experimental study.

    PubMed

    Rasouli Ghahroudi, Amir Alireza; Rokn, Amir Reza; Kalhori, Katayoun A M; Khorsand, Afshin; Pournabi, Alireza; Pinheiro, A L B; Fekrazad, Reza

    2014-05-01

    This study aims to assess the effect of low-level laser therapy (LLLT) irradiation and Bio-Oss graft material on the osteogenesis process in the rabbit calvarium defects. Twelve white male New Zealand rabbits were included in this study. Four 8-mm diameter identical defects were prepared on each rabbit's calvarium. One site was left as an untreated control (C), the second site was filled with Bio-Oss (B), the third site was treated with laser irradiation (L), and the fourth site treated with Bio-Oss and laser irradiation (B + L). In the laser group, a diode laser (wavelength 810 nm, output power 300 mW, irradiation mode CW, energy density 4 J/cm2) was applied immediately after surgery and then one other day for the next 20 days. After 4 and 8 weeks, the animals were sacrificed and histological and histomorphometric examinations were performed and the data were subjected to Friedman and repeated measurements ANOVA tests. Significant differences were not found regarding inflammation severity, foreign body reactions, and vitality of newly formed bone on 4th and 8th week after operation. The mean amount of new bone was 15.83 and 18.5% in the controls on the 4th and 8th week; 27.66 and 25.16% in the laser-irradiated group; 35.0 and 41.83% in Bio-Oss and 41.83 and 47.0% in the laser + Bio-Oss treated specimens with significant statistical differences (p <0.05). Application of LLLT in combination with Bio-Oss® can promote bone healing. Therefore, LLLT may be clinically beneficial in promoting bone formation in skeletal defects.

  18. Does photobiomodulation therapy is better than cryotherapy in muscle recovery after a high-intensity exercise? A randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    De Marchi, Thiago; Schmitt, Vinicius Mazzochi; Machado, Guilherme Pinheiro; de Sene, Juliane Souza; de Col, Camila Dallavechia; Tairova, Olga; Salvador, Mirian; Leal-Junior, Ernesto Cesar Pinto

    2017-02-01

    This study aimed to determine the effectiveness of photobiomodulation therapy (PBMT) and cryotherapy, in isolated and combined forms, as muscle recovery techniques after muscle fatigue-inducing protocol. Forty volunteers were randomly divided into five groups: a placebo group (PG); a PBMT group (PBMT); a cryotherapy group (CG); a cryotherapy-PBMT group (CPG); and a PBMT-cryotherapy group (PCG). All subjects performed four sessions at 24-h intervals, during which they submitted to isometric assessment (MVC) and blood collection in the pre-exercise period, and 5 and 60 min post-exercise, while the muscle fatigue induction protocol occurred after the pre-exercise collections. In the remaining sessions performed 24, 48, and 72 h later, only blood collections and MVCs were performed. A single treatment with PBMT and/or cryotherapy was applied after only 2 min of completing the post-5-min MVC test at the first session. In the intragroup comparison, it was found that exercise led to a significant decrease (p < 0.05) in the production of MVC in all groups. Comparing the results of MVCs between groups, we observed significant increases in the MVC capacity of the PBMT, CPG, and PCG volunteers in comparison with both PG and CG (p < 0.05). We observed a significant decrease in the concentrations of the biochemical markers of oxidative damage (TBARS and PC) in all groups and muscle damage (creatine kinase-CK) in the PBMT, PCG, and CPG compared with the PG (p < 0.01). The clinical impact of these findings is clear because they demonstrate that the use of phototherapy is more effective than the use of cryotherapy for muscle recovery, additionally cryotherapy decreases PBMT efficacy.

  19. Local adjunct effect of antimicrobial photodynamic therapy for the treatment of chronic periodontitis in type 2 diabetics: split-mouth double-blind randomized controlled clinical trial.

    PubMed

    Castro Dos Santos, Nídia Cristina; Andere, Naira Maria Rebelatto Bechara; Araujo, Cássia Fernandes; de Marco, Andrea Carvalho; Dos Santos, Lúcio Murilo; Jardini, Maria Aparecida Neves; Santamaria, Mauro Pedrine

    2016-11-01

    Diabetes has become a global epidemic. Its complications can have a significant impact on quality of life, longevity, and public health costs. The presence of diabetes might impair the prognosis of periodontal treatments due to its negative influence on wound healing. Antimicrobial photodynamic therapy (aPDT) is a local approach that can promote bacterial decontamination in periodontal pockets. The aim of this study was to investigate the local effect of adjunct aPDT to ultrasonic periodontal debridement (UPD) and compare it to UD only for the treatment of chronic periodontitis in type 2 diabetic patients. Twenty type 2 diabetic patients with moderate to severe generalized chronic periodontitis were selected. Two periodontal pockets with probing depth (PD) and clinical attachment level (CAL) ≥5 mm received UPD only (UPD group) or UPD plus adjunct aPDT (UPD + aPDT group). Periodontal clinical measures were collected and compared at baseline and 30, 90, and 180 days. After 180 days of follow-up, there were statistically significant reductions in PD from 5.75 ± 0.91 to 3.47 ± 0.97 mm in the UPD group and from 6.15 ± 1.27 to 3.71 ± 1.63 mm in the UPD + aPDT group. However, intergroup analysis did not reveal statistically significant differences in any of the evaluated clinical parameters (p > 0.05). The adjunct application of aPDT to UPD did not present additional benefits for the treatment of chronic periodontitis in type 2 diabetic patients. The ClinicalTrials.gov identifier of the present study is NCT02627534.

  20. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner.

    PubMed

    Ferraresi, Cleber; Beltrame, Thomas; Fabrizzi, Fernando; do Nascimento, Eduardo Sanches Pereira; Karsten, Marlus; Francisco, Cristina de Oliveira; Borghi-Silva, Audrey; Catai, Aparecida Maria; Cardoso, Daniel Rodrigues; Ferreira, Antonio Gilberto; Hamblin, Michael R; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-07-01

    Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase--CK and alanine), and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy ((1)H NMR). A LED cluster with 50 LEDs (λ = 850 nm; 50 mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (∼-9 s), decreased O2 deficit (∼-10 L), increased the VO2 from the slow component phase (∼+348 ml min(-1)), and increased the time limit of exercise (∼+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance.

  1. A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy

    PubMed Central

    Choe, Jung-Yoon; Prodanovic, Nenad; Niebrzydowski, Jaroslaw; Staykov, Ivan; Dokoupilova, Eva; Baranauskaite, Asta; Yatsyshyn, Roman; Mekic, Mevludin; Porawska, Wieskawa; Ciferska, Hana; Jedrychowicz-Rosiak, Krystyna; Zielinska, Agnieszka; Choi, Jasmine; Rho, Young Hee; Smolen, Josef S

    2017-01-01

    Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. Trial registration number NCT01936181. PMID:26318384

  2. Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: a four-week, randomized, double-blinded, placebo-controlled study.

    PubMed

    Ng, Chong Guan; Boks, Marco P M; Roes, Kit C B; Zainal, Nor Zuraida; Sulaiman, Ahmad Hatim; Tan, Seng Beng; de Wit, Niek J

    2014-04-01

    This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83-6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54-1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  3. Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer

    PubMed Central

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2010-01-01

    Background Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. Purpose To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. Methods From 1998–2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. Results The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Limitations Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. Conclusions BIG 1-98 is an example of an enriched design, involving

  4. Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study.

    PubMed

    Amidfar, M; Khiabany, M; Kohi, A; Salardini, E; Arbabi, M; Roohi Azizi, M; Zarrindast, M-R; Mohammadinejad, P; Zeinoddini, A; Akhondzadeh, S

    2017-02-01

    Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P < 0·001, Cohen's d = 12·71) and placebo groups (P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing. © 2016 John Wiley & Sons Ltd.

  5. Preventive effect of Malva on urinary toxicity after radiation therapy in prostate cancer patients: A multi-centric, double-blind, randomized clinical trial

    PubMed Central

    Mofid, Bahram; Rezaeizadeh, Hossein; Jaladat, Amir Mohammad; Atarzadeh, Fatemeh; Moeini, Reihane; Motevalian, Abbas; Mosalaie, Ahmad; Farhan, Farshid; Rakhsha, Afshin; Kashi, Amir Shahram Yousefi

    2015-01-01

    Background: For patients receiving external beam radiation therapy (EBRT) after radical prostatectomy as adjuvant treatment or patients receiving EBRT as definitive treatment, partial irradiation of the urinary bladder is common. Many of such patients experience some degree of radiation-induced cystitis during or after EBRT. There is currently no efficient treatment for preventing radiation cystitis. Objective: The aim of this study was to evaluate the effectiveness of one of the safe mucilaginous herbs (Malva) in preventing radiation-induced dysuria in patients who are undergoing EBRT for prostate cancer. Methods: From April 2013 to August 2014, 68 patients were randomized into two groups using four block randomization, 34 to the drug (Malva) group and 34 to the placebo group. Of the 68 patients who began the study, 60 completed it. They were instructed to use the medication, i.e., Malva or the placebo, three times a day for six weeks. They were followed by a physician every two weeks for eight weeks, and urinary function was assessed in each visit by asking questions based on the Visual Prostate Symptom Score (VPSS) and a dysuria severity score. The changes in the VPSS and dysuria severity score between baseline and each follow-up visit were compared between the two groups in the study using repeated measures analysis of variance (ANOVA) and t-tests. Results: The median age of the 68 patients was 66. Twenty-one of 27 patients in the control group (77.7%) suffered from dysuria, while dysuria was detected in 23 of 33 patients (69.6%) who received Malva (odds ratio=2.70 for dysuria). After two weeks, four weeks, and six weeks of treatment with Malva, dysuria due to EBRT was milder in the treatment group than in the control group, and the differences were statistically significant (p = 0.005, p = 0.004, p = 0.001, respectively). Conclusion: To the best of our knowledge, our study is the first study to assess the protective effect of a mucilaginous herb (Malva

  6. A Double-blind, Randomized, Multicenter Clinical Trial Investigating the Efficacy and Safety of Esomeprazole Single Therapy Versus Mosapride and Esomeprazole Combined Therapy in Patients with Esophageal Reflux Disease

    PubMed Central

    Lee, Ju Yup; Kim, Sung Kook; Cho, Kwang Bum; Park, Kyung Sik; Kwon, Joong Goo; Jung, Jin Tae; Kim, Eun Young; Jang, Byung Ik; Lee, Si Hyung

    2017-01-01

    Background/Aims We aim to evaluate the efficacy and safety of combination therapy in erosive reflux disease (ERD) patients by comparing endoscopic healing rates according to the Los Angeles classification for esomeprazole alone, and esomeprazole plus mosapride. Methods A total of 116 ERD patients were randomized to receive esomeprazole 40 mg once daily plus mosapride 5 mg 3 times daily (E+M group), or esomeprazole plus placebo (E only group) for 8 weeks. Patients recorded gastroesophageal reflux disease (GERD) symptom questionnaire at weeks 4 and 8. The primary endpoint was the endoscopic healing rate of ERD after 8 weeks of treatment. Results Endoscopic healing rates according to the Los Angeles classification was 32 (66.7%) in the E+M group and 26 (60.5%) in the E only group, but there was no statistically significant difference between the groups. Only at 4 weeks, the total GERD symptom score changes relative to the baseline significantly improved in the E+M group than that of the E only group (−13.4 ± 14.7 vs −8.0 ± 12.3, P = 0.041), and upper abdominal pain and belching score changes showed significantly improved in the E+M group than that of the E only group (P = 0.018 and P = 0.013, respectively). Conclusions The combination of a proton pump inhibitor with mosapride shows a tendency for upper abdominal pain, belching, and total GERD symptoms scores to improve more rapidly. This suggests that combination therapy with esomeprazole and mosapride will be useful for rapid improvement of specific GERD symptoms, such as upper abdominal pain and belching in ERD patients. PMID:28192647

  7. Y2O3:Yb,Er@mSiO2-CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging

    NASA Astrophysics Data System (ADS)

    Yang, Dan; Yang, Guixin; Wang, Xingmei; Lv, Ruichan; Gai, Shili; He, Fei; Gulzar, Arif; Yang, Piaoping

    2015-07-01

    Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large specific surface area and uniform shape is composed of an inner shell of luminescent Y2O3:Yb,Er and an outer mesoporous silica shell. Ultra small CuxS nanoparticles (about 2.5 nm) served as photothermal agents, and a chemotherapeutic agent (doxorubicin, DOX) was then attached onto the surface of mesoporous silica, forming a DOX-DSHS-CuxS composite. The composite exhibits high anti-cancer efficacy due to the synergistic photothermal therapy (PTT) induced by the attached CuxS nanoparticles and the enhanced chemotherapy promoted by the heat from the CuxS-based PTT when irradiated by 980 nm near-infrared (NIR) light. Moreover, the composite shows excellent in vitro and in vivo X-ray computed tomography (CT) and up-conversion fluorescence (UCL) imaging properties owing to the doped rare earth ions, thus making it possible to achieve the target of imaging-guided synergistic therapy.Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large

  8. Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes.

    PubMed

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Pieters, Indra C; Cahen, Djuna L; Diamant, Michaela; van Raalte, Daniël H

    2015-11-19

    Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention). Secondary end points include

  9. Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes

    PubMed Central

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Pieters, Indra C; Cahen, Djuna L; Diamant, Michaela; van Raalte, Daniël H

    2015-01-01

    Introduction Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. Methods and analyses 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention

  10. What is the ideal dose and power output of low-level laser therapy (810 nm) on muscle performance and post-exercise recovery? Study protocol for a double-blind, randomized, placebo-controlled trial

    PubMed Central

    2014-01-01

    Background Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. Design and methods A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Discussion Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose–response pattern. Trial

  11. The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease

    PubMed Central

    Chen, Shi-Jian; Liu, Wei; Huang, Bao-Tao; Tsauo, Jia-Yu; Pu, Xiao-Bo; Peng, Yong; Chen, Mao; Huang, De-Jia

    2017-01-01

    Objective To analyze the current usage of optimal medical therapy (OMT), influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease (CAD) patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% (n = 1265) were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% (n = 217) of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45–0.95; P = 0.025). Sub-group analyses indicate that male acute coronary syndrome (ACS) patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was associated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics. PMID:28491084

  12. The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease.

    PubMed

    Chen, Shi-Jian; Liu, Wei; Huang, Bao-Tao; Tsauo, Jia-Yu; Pu, Xiao-Bo; Peng, Yong; Chen, Mao; Huang, De-Jia

    2017-02-01

    To analyze the current usage of optimal medical therapy (OMT), influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease (CAD) patients with different subgroups. A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Out of 3176 patients, only 39.8% (n = 1265) were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% (n = 217) of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45-0.95; P = 0.025). Sub-group analyses indicate that male acute coronary syndrome (ACS) patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. OMT was associated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.

  13. Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Patients With and Without Acute Coronary Syndrome: A Systematic Review of Randomized Controlled Trials.

    PubMed

    Sharma, Abhishek; Lavie, Carl J; Sharma, Samin K; Garg, Akash; Vallakati, Ajay; Mukherjee, Debabrata; Marmur, Jonathan D

    2016-08-01

    In this systemic review we evaluated the efficacy and safety of long duration dual anti-platelet therapy (DAPT) (L-DAPT) compared with sho