Novel Treatments (novel + treatment)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Novel Treatments

  • novel treatment approach
  • novel treatment modality
  • novel treatment option
  • novel treatment strategy

  • Selected Abstracts


    Median Arcuate Ligament Syndrome,A Novel Treatment Using an Intrathecal Morphine Pump to Relieve Intractable Visceral Pain

    PAIN PRACTICE, Issue 2 2008
    Oren T. Guttman MD
    ,,Abstract Purpose: Median arcuate ligament syndrome, which presents with intractable visceral pain, is difficult to both diagnose and treat. This case report describes the first use of an intrathecal morphine pump as an effective therapeutic intervention. Clinical features: We describe a 39-year-old female who presented with a four-year history of misdiagnosed debilitating abdominal pain. After multiple failed attempts at medical management and surgeries, a trial of intrathecal narcotics provided significant relief. Six months after insertion of an intrathecal morphine pump, the patient was pain-free and had resumed all activities of daily living. Conclusion: The use of an intrathecal narcotic pump should be considered for treatment of patients with intractable visceral pain secondary to median arcuate ligament syndrome.,, [source]


    Botulinum Toxin Type A,A Novel Treatment for Provoked Vestibulodynia?

    THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2009
    Double Blinded Study, Placebo Controlled, Results from a Randomized
    ABSTRACT Introduction., Vestibulodynia is an increasingly recognized problem among women and is often difficult to treat. Aim., This randomized, double blinded, placebo-controlled study aimed to evaluate the efficacy of Botox in the treatment of vestibulodynia. Methods., Sixty-four women were randomized to receive Botox (N = 32) or saline placebo (N = 32). Botulinum toxin A (20 I.E.) diluted in 0.5 mL saline or 0.5 mL saline was injected in the musculus bulbospongiosus at baseline. Main Outcome Measures., Pain was measured monthly on a visual analog scale (VAS) Likert scale. Sexual function was measured using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale at baseline and at 3 and 6 months follow up. Quality of life was measured using the 36-item short-form (SF-36). Results., Sixty women (94%) completed the 6 months follow up. Both Botox and placebo produced significantly pain reduction (P < 0.001). There was no significant difference in the median VAS score between the groups at 6 months follow up (P = 0.984). An improvement on the FSFI full score from baseline until 6 months was not significantly different between the groups (P = 0.635). In the placebo group a statistical significant larger reduction in sexual distress was observed from baseline until 6 months follow up compared to the Botox group (P = 0.044). No statistical significant differences were observed between the B- and P-groups in regard to the SF-36 scores. Conclusion., Injection of 20 I.E. Botox in the vestibule of women diagnosed with vestibulodynia does not reduce pain, improve sexual functioning, or impact the quality of life compared to placebo and evaluated at 3 and 6 moths follow up. Both the Botox group and the placebo groups experienced a reduction in pain on the VAS Likert scale at 6 months follow up. Women with vestibulodynia have difficulty with sexual function and present with sexual distress, which has to be addressed in conjunction with pain to eliminate the disorder. Petersen CD, Giraldi A, Lundvall L, and Kristensen E. Botulinum toxin Type A,A novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study. J Sex Med 2009;6:2523,2537. [source]


    Novel treatment of first bite syndrome using botulinum toxin type A

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2009
    Byung-Joo Lee MD
    Abstract Background First bite syndrome is the development of pain in the parotid region after the first bite of each meal and can be seen after surgery of the parapharyngeal space. The purpose of this study is to evaluate the efficacy of intraglandular injection of botulinum toxin type A (BTA) in patients with first bite syndrome. Methods Five patients with first bite syndrome developed after head and neck surgery were treated by injection of BTA into parotid gland. All patients completed a 4-item quality-of-life survey with a 10-point response scale designed to measure outcome of intraglandular injection of BTA. Results The first bite syndrome without or with sialogogue and degree of interference with daily activity with or without eating or drinking improved significantly at 1 and 3 month after injection (p < .05). Conclusion The BTA injection into affected parotid gland produces a decrease in the severity of first bite syndrome and improves the patient's quality of life. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source]


    Novel treatment of chronic severe hand dermatitis with bexarotene gel

    BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004
    J.M. Hanifin
    Summary Background Hand dermatitis is an eczematous inflammation of the hands that is related to occupation or to routine activities. It often becomes chronic, and in some patients may become severe and disabling. Topical corticosteroids are effective treatment, particularly for milder forms, but they often lose effectiveness with time and can produce skin atrophy. Objectives To evaluate bexarotene gel topical therapy for safety, tolerability and efficacy in patients with chronic hand dermatitis. Methods A phase I,II open-label randomized clinical study of bexarotene gel, alone and in combination with a low- and a mid-potency steroid, was conducted in 55 patients with chronic severe hand dermatitis at two academic clinics. Results Patients using bexarotene gel monotherapy reached a 79% response rate for ,,50% clinical improvement and a 39% response rate for ,,90% clearance of hands. Adverse events possibly related to treatment in all patients were stinging or burning (15%), flare of dermatitis (16%) and irritation (29%). Thirteen patients (24%) withdrew early, including two for related adverse events and five for inadequate response. Conclusions Bexarotene gel appears to be safe, tolerated by most patients, with useful therapeutic activity in chronic severe hand dermatitis. [source]


    Novel treatments for autistic spectrum disorders

    DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2005
    Susan E. Levy
    Abstract In no area of developmental pediatric practice is there more controversy regarding the choice of treatment than related to children with autistic spectrum disorders (ASD). Complementary and alternative medical therapies (CAM) are often elected because they are perceived as treating the cause of symptoms rather than the symptoms themselves. CAM used for autism can be divided by proposed mechanism: immune modulation, gastrointestinal, supplements that affect neurotransmitter function, and nonbiologic intervention. Secretin as a therapy for autism is discussed as an example of how a clinical observation rapidly grew to a widespread treatment before well-designed studies demonstrated absence of effect. The plausibility for behavioral effect was not substantiated by clinical studies. CAM used for treatment of autism is examined in terms of rationale, evidence of efficacy, side effects, and additional commentary. Families and clinicians need access to well-designed clinical evidence to assist them in choice of therapies. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:131,142. [source]


    Cognitive enhancement as a pharmacotherapy target for stimulant addiction

    ADDICTION, Issue 1 2010
    Mehmet Sofuoglu
    ABSTRACT Background No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. Aim To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Methods Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Results and conclusions Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha2 -adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction. [source]


    Botulinum Neurotoxin for the Treatment of Migraine and Other Primary Headache Disorders: From Bench to Bedside

    HEADACHE, Issue 2003
    David W. Dodick MD
    Botulinum toxin type A, a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction including cervical dystonia, blepharospasm, and hemifacial spasm. It inhibits neuromuscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient, with normal neuronal signaling returning within approximately 3 to 6 months postinjection. Recent clinical findings suggest that botulinum toxin type A may inhibit pain associated with migraine and other types of headache. However, the mechanism by which this toxin inhibits pain is not fully understood and is under investigation. Research findings suggest that botulinum toxin type A inhibits the release of neurotransmitters from nociceptive nerve terminals and, in this way, may possess an analgesic effect. A number of retrospective open-label chart reviews and 3 double-blind, placebo-controlled trials have demonstrated that localized injections of botulinum toxin type A significantly reduce the frequency, severity, and disability associated with migraine headaches. Although the majority of patients in these studies experienced no botulinum toxin type A-mediated side effects, a small percentage of patients did report transient minor side effects including blepharoptosis, diplopia, and injection-site weakness. Currently, 4 randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A as a novel treatment for migraine and other types of headache. These studies may provide further evidence that botulinum toxin type A is an effective option for the preventive treatment of migraine. [source]


    Platinum Surface Modification of SBA-15 by ,-Radiation Treatment,

    ADVANCED MATERIALS, Issue 6 2003
    T. Yamada
    Modification of the mesoporous surface of SBA-15 with platinum has been successfully carried out by means of ,-radiation treatment. This novel treatment allows the selective growth of platinum in the SBA-15 micropores (see Figure). This is in contrast to traditional temperature treatment, in which platinum particles or rods also grow in the mesopores. [source]


    Ecabet sodium promotes the healing of trinitrobenzene-sulfonic-acid-induced ulceration by enhanced restitution of intestinal epithelial cells

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2010
    Tomohisa Takagi
    Abstract Background and Aims:, Ecabet sodium (ES) is a gastric mucosal protective and ulcer-healing agent. Recently enema therapy with ES was found to be effective for the treatment of human ulcerative colitis as well as experimental colitis in an animal model. Whereas ES possesses potential as a novel treatment for ulcerative colitis, its precise mechanism of action remains to be elucidated. In this study, we investigated the therapeutic efficacy of ES in an experimental rat model of colitis, and evaluated the restitution of intestinal epithelial cells treated with ES in vitro. Methods:, Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal treatment with ES daily starting on day 7 and were sacrificed on day 14 after the administration of TNBS. The distal colon was removed to evaluate various parameters of inflammation. Moreover, wound-healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with ES. Results:, Intracolonic administration of ES accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by ES treatment. The wound assay revealed ES enhancement of the migration of RIE cells migration through the phosphorylation of extracellular signal-regulated kinase. Conclusion:, Daily administration of an ES enema promoted the healing of intestinal mucosal injury, in part by the enhanced restitution of intestinal epithelial cells via extracellular signal-regulated kinase activation. ES may thus represent a novel therapeutic approach for the treatment of inflammatory bowel disease. [source]


    Personal view: a potential novel treatment for fatigue complicating chronic liver disease , how should its efficacy be evaluated?

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006
    E. A. JONES
    Summary Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease. However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue. Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated. [source]


    Pathology of soft-tissue tumors: Daily diagnosis, molecular cytogenetics and experimental approach

    PATHOLOGY INTERNATIONAL, Issue 8 2009
    Hiroshi Iwasaki
    This article reviews problems in diagnostic pathology and molecular cytogenetics of soft-tissue tumors. Also discussed are the origin of soft-tissue sarcomas and the molecular basis of effective target therapy for sarcomas. Molecular cytogenetic analysis of tumor-specific chromosomal translocations and associated fusion gene transcripts offers a useful adjunct to the diagnosis of soft-tissue tumors, but recent studies have indicated a growing number of fusion gene variations in each tumor type. In pleomorphic sarcoma/malignant fibrous histiocytoma, the alternative lengthening of telomeres (ALT) mechanism may result in formation of anaphase bridges and marked nuclear pleomorphism. The histogenesis of soft-tissue sarcomas has been a matter of controversy. In the present experimental model using s.c. injection of 3-methylcholanthrene in C57BL/6 mice pretreated with bone marrow-transplantation from green fluorescent protein (GFP)-positive green mice, the bone marrow-derived mesenchymal stem cells as well as the tissue-resident mesenchymal cells in the peripheral soft tissues are possible originators of sarcomagenesis. Little is known about a molecular basis of target therapy for sarcomas. Platelet-derived growth factor-BB (PDGF-BB) enhances the invasive activity of malignant peripheral nerve sheath tumor (MPNST) cells through platelet-derived growth factor receptor (PDGFR) phosphorylation, whereas imatinib mesylate inhibited such activity, suggesting that targeting PDGFR-, may result in the establishment of novel treatment for MPNST. In addition, emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMP), playing a crucial role in tumor progression, invasion and metastasis. The MMP upregulation mechanism mediated by tumor-associated emmprin may be a potentially useful target in anti-tumor invasion therapy for sarcomas. [source]


    How do we identify novel treatment for childhood cancer?

    PEDIATRIC BLOOD & CANCER, Issue 3 2009
    Peter J. Houghton PhD
    No abstract is available for this article. [source]


    Noninvasive ventilation in the pediatric intensive care unit for children with acute respiratory failure,,

    PEDIATRIC PULMONOLOGY, Issue 6 2003
    W. Gerald Teague MD
    Abstract Noninvasive ventilation, a novel treatment to increase alveolar ventilation, is accomplished with either subatmospheric or positive pressure administered via an external interface. In adults with acute respiratory failure, noninvasive positive pressure ventilation (NPPV) is superior to standard therapy in preventing intubation and reducing mortality. The role of NPPV in pediatric-age patients with acute respiratory distress is not as well established. Early case reports showed that NPPV treatment does acutely improve both the clinical manifestations of respiratory distress and respiratory gas exchange in children with respiratory distress. However, it is not clear whether NPPV in this setting can prevent vs. delay endotracheal intubation. Other uses of NPPV in the pediatric intensive care unit include the treatment of upper airway obstruction, atelectasis, and exacerbations of neuromuscular disorders, and to facilitate weaning from invasive mechanical ventilation. Successful use of NPPV in young infants with respiratory distress is impeded by the lack of suitable size interfaces, and the response characteristics of commercially available bilevel ventilators. Despite these challenges, NPPV is a promising alternate to standard therapies in the treatment of acute respiratory distress in the pediatric-age patient. Pediatr Pulmonol. 2003; 35:418,426. © 2003 Wiley-Liss, Inc. [source]


    Unmet need in inadequately controlled asthma

    RESPIROLOGY, Issue 2007
    Richard BEASLEY
    Abstract: Over the last 20 years in Australia, outcomes have improved for patients with asthma. With the advent of inhaled corticosteroids and long-acting beta agonists, and improvements in management including implementation of the guided self-management plan system of care, the mortality rate for asthma has fallen by almost half. However, despite huge improvements, there remains a small but significant cohort of patients with inadequately controlled severe persistent asthma. This group of patients consumes a substantial proportion of public health resources. Patients who have poorly controlled asthma, despite receiving ,optimal' treatment, are the ones most likely to benefit from new therapies such as those that target IgE. This presentation provides an overview of severe asthma in terms of prevalence and morbidity, mortality, economic costs and then considers a way forward in terms of identifying patients in greatest need of novel treatment such as omalizumab. [source]


    Vascular Changes in Hepatocellular Carcinoma

    THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 6 2008
    Zhen Fan Yang
    Abstract Hepatocellular carcinoma (HCC) is one of the most vascular solid tumors, in which angiogenesis plays an important role. The status of angiogenesis in HCC correlates with the disease progression and prognosis, and thus provides a potential therapeutic target. This review summarizes the vascular changes and molecular and cellular basis of angiogenesis in HCC. Development of HCC is characterized by arterialization of its blood supply and sinusoidal capillarization. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a critical role in mediating angiogenesis in HCC. The VEGF can function on various types of cells, such as endothelial cells, hepatic stellate cells, endothelial progenitor cells and hemangiocytes, to induce vascular changes in HCC. Therefore, blockade of VEGF-mediated pathways, either by anti-VEGF neutralizing antibody or tyrosine kinase inhibitors that target VEGF receptors, suppresses carcinogenesis and angiogenesis in HCC. In addition to VEGF, several other angiogenic factors in HCC have recently been identified. These factors can also regulate angiogenic processes through interaction with VEGF or VEGF-independent pathways. Despite the fact that treatment of HCC remains a tough task due to lack of effective systemic therapy, antiangiogenic therapy has already entered clinical trials in HCC patients and sheds light on a promising novel treatment for this disease. Anat Rec, 291:721,734, 2008. © 2008 Wiley-Liss, Inc. [source]


    Research Review: attention bias modification (ABM): a novel treatment for anxiety disorders

    THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 8 2010
    Yair Bar-Haim
    Attention bias modification (ABM) is a newly emerging therapy for anxiety disorders that is rooted in current cognitive models of anxiety and in established experimental data on threat-related attentional biases in anxiety. This review describes the evidence indicating that ABM has the potential to become an enhancing tool for current psychological and pharmacological treatments for anxiety or even a novel standalone treatment. The review also outlines the gaps in need of bridging before ABM techniques could be routinely applied and incorporated into standard treatment protocols. [source]


    X-ray fluorescence holography: a novel treatment for crystal structure determination

    ACTA CRYSTALLOGRAPHICA SECTION A, Issue 2 2003
    F. N. Chukhovskii
    It is shown that it is possible to use a linear regression algorithm direct method to solve crystal structures from X-ray fluorescence holography (XFH) data. It is found that, in contrast to conventional X-ray structure determination methods, which do not always work unambiguously, the sustainable method utilizing the XFH data generally provides the unique phase-retrieval structure solution and is able, in many cases, to replace the above for determining both the absolute values (moduli) and phases of structure factors. The XFH scan with a fluorescing Cu atom from a spherical cluster of a Cu3Au single crystal, at an energy of 10,keV for the incident unpolarized plane-wave X-radiation, is numerically simulated to test the performance of the method in finding a unique solution for the structure factors involved in the restoration procedure using the linear regression algorithm. [source]


    Botulinum Toxin Type A,A Novel Treatment for Provoked Vestibulodynia?

    THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2009
    Double Blinded Study, Placebo Controlled, Results from a Randomized
    ABSTRACT Introduction., Vestibulodynia is an increasingly recognized problem among women and is often difficult to treat. Aim., This randomized, double blinded, placebo-controlled study aimed to evaluate the efficacy of Botox in the treatment of vestibulodynia. Methods., Sixty-four women were randomized to receive Botox (N = 32) or saline placebo (N = 32). Botulinum toxin A (20 I.E.) diluted in 0.5 mL saline or 0.5 mL saline was injected in the musculus bulbospongiosus at baseline. Main Outcome Measures., Pain was measured monthly on a visual analog scale (VAS) Likert scale. Sexual function was measured using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale at baseline and at 3 and 6 months follow up. Quality of life was measured using the 36-item short-form (SF-36). Results., Sixty women (94%) completed the 6 months follow up. Both Botox and placebo produced significantly pain reduction (P < 0.001). There was no significant difference in the median VAS score between the groups at 6 months follow up (P = 0.984). An improvement on the FSFI full score from baseline until 6 months was not significantly different between the groups (P = 0.635). In the placebo group a statistical significant larger reduction in sexual distress was observed from baseline until 6 months follow up compared to the Botox group (P = 0.044). No statistical significant differences were observed between the B- and P-groups in regard to the SF-36 scores. Conclusion., Injection of 20 I.E. Botox in the vestibule of women diagnosed with vestibulodynia does not reduce pain, improve sexual functioning, or impact the quality of life compared to placebo and evaluated at 3 and 6 moths follow up. Both the Botox group and the placebo groups experienced a reduction in pain on the VAS Likert scale at 6 months follow up. Women with vestibulodynia have difficulty with sexual function and present with sexual distress, which has to be addressed in conjunction with pain to eliminate the disorder. Petersen CD, Giraldi A, Lundvall L, and Kristensen E. Botulinum toxin Type A,A novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study. J Sex Med 2009;6:2523,2537. [source]


    Anti-PSMA immunotoxin as novel treatment for prostate cancer?

    THE PROSTATE, Issue 2 2008
    specific antitumor activity on human prostate xenograft tumors in SCID mice
    Abstract BACKGROUND Expression of the prostate specific membrane antigen (PSMA) is highly restricted to prostate epithelial cells. Therefore, toxin-based immunotherapy against this antigen may represent an alternative therapeutic option for prostate cancer. For these purposes, the effects of the recombinant anti-PSMA immunotoxin A5-PE40 on prostate tumor growth were investigated in vitro and in vivo. METHODS The in vitro binding and cytotoxicity of A5-PE40 were tested on the PSMA-expressing prostate cancer cell line C4-2 and on the PSMA-negative cell line DU145 by flow cytometry and WST assays. The binding of the immunotoxin to SCID mouse xenografts and to various mouse organs was examined by Western blot analysis. In vivo, the antitumor activity of the immunotoxin was tested by injecting A5-PE40 in mice bearing C4-2 or DU145 xenografts. RESULTS In vitro, a specific binding of A5-PE40 to C4-2 cells could be shown with a concentration-dependent cytotoxicity (IC50 value,=,220 pM). In the next step, a specific binding of the immunotoxin to C4-2 xenografts could be demonstrated. In contrast, no binding on mouse organs expressing high homologous mouse PSMA was found. The treatment of mice with C4-2 tumors caused a significant inhibition of tumor growth in vivo, whereas DU145 xenografts remained totally unaffected. CONCLUSIONS A5-PE40 represents a recombinant anti-PSMA immunotoxin with potent antitumor activity in mice bearing human prostate cancer xenograft tumors. Therefore, A5-PE40 could be a promising candidate for therapeutic applications in patients with prostate cancer. Prostate 68: 129,138, 2008. © 2007 Wiley-Liss, Inc. [source]


    Re-Formulating Non-inferiority Trials as Superiority Trials: The Case of Binary Outcomes

    BIOMETRICAL JOURNAL, Issue 1 2009
    Valerie L. Durkalski
    Abstract Non-inferiority trials are conducted for a variety of reasons including to show that a new treatment has a negligible reduction in efficacy or safety when compared to the current standard treatment, or a more complex setting of showing that a new treatment has a negligible reduction in efficacy when compared to the current standard yet is superior in terms of other treatment characteristics. The latter reason for conducting a non-inferiority trial presents the challenge of deciding on a balance between a suitable reduction in efficacy, known as the non-inferiority margin, in return for a gain in other important treatment characteristics/findings. It would be ideal to alleviate the dilemma on the choice of margin in this setting by reverting to a traditional superiority trial design where a single p -value for superiority of both the most important endpoint (efficacy) and the most important finding (treatment characteristic) is provided. We discuss how this can be done using the information-preserving composite endpoint (IPCE) approach and consider binary outcome cases in which the combination of efficacy and treatment characteristics, but not one itself, paints a clear picture that the novel treatment is superior to the active control (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


    Angiographic subsegmentectomy for the treatment of patients with small hepatocellular carcinoma

    CANCER, Issue 4 2003
    Shozo Iwamoto M.D.
    Abstract BACKGROUND The therapeutic results of nonsurgical treatment for patients with hepatocellular carcinoma (HCC) have been poor, and improved treatments are needed. The authors recently developed a new technique called angiographic subsegmentectomy for the treatment of patients with small HCC. METHODS The technique includes confirming the diagnosis of small HCC using a helical computed tomography (CT) scan combined with an angiography system for identifying the tumor-feeding subsegmental hepatic artery, injecting lipiodol containing farmorubicin until it enters the portal vein in sufficient amounts, and injecting sponge particles into the hepatic artery for embolization. Occlusion of the hepatic artery with gel particles and occlusion of the portal vein by lipiodol induce infarction necrosis, which encompasses the entire tumor and the surrounding liver parenchyma. RESULTS The treatment was given to 23 patients with 30 HCC tumors that measured < 20 mm in greatest dimension. It was successful in all 23 patients. Serum alanine aminotransferase levels were elevated to a significant level in the majority of patients after treatment, mild ascites developed in three patients, and the patients complained of pain and fever posttreatment that were controlled readily. No patients developed hepatic failure. Only one patient developed recurrent disease posttreatment at 1.5 years, for a recurrence rate of 5% at 1 year and 6.6% at 1.5 years, a rate that has never been achieved with other treatment modalities. CONCLUSIONS Angiographic subsegmentectomy is a novel treatment for patients with small HCC. The results indicated that it is equivalent to undergoing small resection and is superior to conventional arterial chemoembolization. Cancer 2003;97:1051,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11106 [source]


    Treatment of severe scleroderma skin ulcers with recombinant human erythropoietin

    CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2007
    C. Ferri
    Summary Systemic sclerosis (SSc) is frequently complicated by skin ulcers, often unresponsive to traditional treatments. A preliminary evaluation of the effects of recombinant human erythropoietin (rHuEPO) was carried out in 14 patients with SSc with nonhealing, severe cutaneous ulcers. Patients received rHuEPO subcutaneously at a dosage of 150 IU/kg 3 times weekly for 2 weeks, twice weekly for the next 2 weeks, and then once weekly for 1 month. At follow-up 3,6 months from the beginning of the treatment, six patients showed complete resolution of the skin ulcers, while a significant reduction (> 60%) in lesional areas was obtained in the other eight patients (mean ± SD ulcer area reduced from 27.6 ± 28 to 5.3 ± 7.8 cm2; P < 0.005). Moreover, patients' quality of life significantly improved (pain, as measured on visual analogue scale reduced from 96 ± 5 to 46 ± 17 points; P = 0.0001; disability as measured by the Health Assessment Questionnaire,Disability Index reduced from 1.6 ± 0.5 to 0.9 ± 0.4 points; P = 0.0001). The rHuEPO may represent a novel treatment of nonhealing scleroderma skin ulcers, suggesting some important aetiopathological implications. [source]


    Therapeutic approaches to epileptogenesis,Hope on the horizon

    EPILEPSIA, Issue 2010
    Asla Pitkänen
    Summary Prevention of epileptogenesis is an unmet need in medicine. During the last 3 years, however, several preclinical studies have demonstrated remarkable favorable effects of novel treatments on genetic and acquired epileptogenesis. These include the use of immunosuppressants and treatments that modify cellular adhesion, proliferation, and/or plasticity. In addition, the use of antiepileptic drugs in rats with genetic epilepsy or proconvulsants in acquired epilepsy models has provided somewhat unexpected favorable effects. This review summarizes these studies, and introduces some caveats when interpreting the data. In particular, the effect of genetic background, the severity of epileptogenic insult, the method and duration of seizure monitoring, and size of animal population are discussed. Furthermore, a novel scheme for defining epileptogenesis-related terms is presented. [source]


    Analysing the effect of novel therapies on cytokine expression in experimental arthritis

    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2005
    Richard O. Williams
    Summary Type II collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis that has been used extensively to address questions of disease pathogenesis and to validate novel therapeutic targets. Susceptibility to CIA is strongly associated with major histocompatibility complex class II genes, and the development of arthritis is accompanied by a robust T- and B-cell response to type II collagen. The main pathological features of CIA include proliferative synovitis with infiltration of inflammatory cells, pannus formation, cartilage degradation, erosion of bone and fibrosis. Pro-inflammatory cytokines, such as tumour necrosis factor , and interleukin-1,, are expressed in the arthritic joints in both murine CIA and human rheumatoid arthritis, and blockade of these molecules results in amelioration of disease. Hence, there is a great deal of interest in the development of small-molecular-weight inhibitors of pro-inflammatory cytokines. There is also interest in the development and testing of drugs with the capacity to modulate the immune pathways involved in driving the inflammatory response in arthritis. For these reasons, there is a need to monitor the effect of novel treatments on cytokine expression in vivo. In this review, we outline the various techniques used to detect cytokines in experimental arthritis and describe how these techniques have been used to quantify changes in cytokine expression following therapeutic intervention. [source]


    A model for intervention research in late-life depression

    INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 12 2009
    George S. Alexopoulos
    Abstract Objective To serve as a conceptual map of the role of new interventions designed to reduce the burden of late-life depression. Methods We identified three needs to be addressed by intervention research: (1) the need for novel interventions given that the existing treatments leave many older adults depressed and disabled; (2) the need for procedures enabling community-based agencies to offer interventions of known efficacy with fidelity; and (3) the need to increase access of depressed older adults to care. Results Our model orders novel interventions according to their role in serving depressed older adults and according to their position in the efficacy, effectiveness, implementation, and dissemination testing continuum. We describe three interventions designed by our institute to exemplify intervention research at different level of the model. A common element is that each intervention personalizes care both at the level of the individuals served and the level of community agencies providing care. To this end, each intervention is designed to accommodate the strengths and limitations of both patients and agencies and introduces changes in the patients' environment and community agencies needed in order to assimilate the new intervention. Conclusions We suggest that this model provides conceptual guidance on how to shorten the testing cycle and bring urgently needed novel treatments and implementation approaches to the community. While replication studies are important, propose that most of the support should be directed to those projects that take rational risks, and after adequate preliminary evidence, make the next step along the testing continuum. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depression

    INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2003
    Alan J. Thomas
    Abstract Background Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Methods We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n,=,20) and control (n,=,20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). Results We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p,=,0.01) and a trend towards an increase for VCAM-1 (p,=,0.10). In the gyral white matter there was a trend towards significance for both molecules (p,=,0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. Conclusions These findings are consistent with white matter ischemia in the DLPFC and lend support to the ,vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future. Copyright © 2002 John Wiley & Sons, Ltd. [source]


    An Ovine Model of Chronic Heart Failure: Echocardiographic and Tissue Doppler Imaging Characterization

    JOURNAL OF CARDIAC SURGERY, Issue 1 2006
    M.Sc., Nicolas Borenstein D.V.M.
    In order to validate novel surgical or pharmacological treatments, reproducible animal models of left ventricular dysfunction are necessary. In the current study, we report our data and experience with a model of toxin-induced heart failure in the sheep. Methods: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until standard echocardiographic and tissue Doppler imaging detection of myocardial systolic dysfunction. The animals were assessed 1 month later and harvested. Indices of cardiac function from baseline to last day of protocol were recorded and their differences were evaluated by a Wilcoxon rank test for paired data. Results: Ten sheep received 2.5 ± 0.7 intracoronary injections of a cumulative dose of 88.8 ± 25 mg/m2 doxorubicin. All available parameters demonstrated signs of severe cardiac dysfunction with statistical significance. All hearts demonstrated severe histological lesions, some of which were consistent with doxorubicin-induced toxicity. Conclusions: The present study shows that this ovine model is reproducible and stable. It can therefore be relevant to the study of chronic heart failure. It will be incorporated in our future studies concerning novel treatments (such as cell therapy) of nonischemic dilated cardiomyopathy. [source]


    Brain regulation of food intake and appetite: molecules and networks

    JOURNAL OF INTERNAL MEDICINE, Issue 4 2005
    C. BROBERGER
    Abstract. In the clinic, obesity and anorexia constitute prevalent problems whose manifestations are encountered in virtually every field of medicine. However, as the command centre for regulating food intake and energy metabolism is located in the brain, the basic neuroscientist sees in the same disorders malfunctions of a model network for how integration of diverse sensory inputs leads to a coordinated behavioural, endocrine and autonomic response. The two approaches are not mutually exclusive; rather, much can be gained by combining both perspectives to understand the pathophysiology of over- and underweight. The present review summarizes recent advances in this field including the characterization of peripheral metabolic signals to the brain such as leptin, insulin, peptide YY, ghrelin and lipid mediators as well as the vagus nerve; signalling of the metabolic sensors in the brainstem and hypothalamus via, e.g. neuropeptide Y and melanocortin peptides; integration and coordination of brain-mediated responses to nutritional challenges; the organization of food intake in simple model organisms; the mechanisms underlying food reward and processing of the sensory and metabolic properties of food in the cerebral cortex; and the development of the central metabolic system, as well as its pathological regulation in cancer and infections. Finally, recent findings on the genetics of human obesity are summarized, as well as the potential for novel treatments of body weight disorders. [source]


    Where are clinical trials going?

    JOURNAL OF INTERNAL MEDICINE, Issue 2 2004
    Society, clinical trials
    Abstract. Clinical trials now increasingly impinge on society at large. First there is growing emphasis from health organizations on the need for unbiased evidence about the effectiveness of promoted remedies. Second, as most novel treatments accrue increased costs to society, these need to be evaluated in terms of value for money. Third, there has been confusion and concern about the resolution of conflicting evidence, especially the role of advertising and commercial pressures from a powerful pharmaceutical industry motivated by profit. Fourth, there is concern about research fraud and the ethics of clinical trials. Fifth, there is increasing suspicion of political advice, which sometimes has sought to reassure an anxious public on the basis of complex and possibly inadequate scientific information. Some of these issues are addressed by truly independent and properly constituted data and safety monitoring committees, which are of particular importance when academic investigators or universities have a large financial conflict of interest. This is now more problematic with the current encouragement of investigator-led spin-off companies. These issues are best resolved by independent financial support (from government or other institutions) rather than relying on the commercial sponsor. [source]


    Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2008
    M. CHAPARRO
    Summary Background, Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC. Aim, To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease. Methods, A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. Results, Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor , tyrosine kinases. Conclusions, Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients. [source]