Assessment of refinery effluents and receiving waters using biologically-based effect methods

International Nuclear Information System (INIS)

2012-01-01

Within the EU it is apparent that the regulatory focus on the use of biologically-based effects methods in the assessment of refinery effluents and receiving waters has increased in the past decade. This has been reflected in a recent refinery survey which revealed an increased use of such methods for assessing the quality of refinery effluents and their receiving waters. This report provides an overview of recent techniques used for this purpose. Several case studies provided by CONCAWE member companies describe the application of biological methods to effluent discharge assessment and surface water monitoring. The case studies show that when biological methods are applied to refinery effluents and receiving waters they raise different questions compared with those obtained using physical and chemical methods. Although direct measurement of the toxicity of effluent and receiving to aquatic organisms is the most cited technique, more recent efforts include tests that also address the persistence of effluent toxicity once discharged into the receiving water. Similarly, ecological monitoring of receiving waters can identify effects of effluent inputs arising from species interactions and other secondary effects that would not always be apparent from the results of biological tests conducted on single aquatic organisms. In light of recent and proposed regulatory developments the objectives of this report are therefore to: Discuss the application of biologically-based effects methods (including ecological monitoring) to refinery discharges and receiving waters; Assess the implications of such methods for future regulation of refinery discharges; and Provide guidance on good practice that can be used by refineries and the downstream oil industry to carry out and interpret data obtained using biologically-based effects methods. While the emphasis is on the toxic effects of effluents, other properties will also be covered because of their interdependency in determining

Assessment of refinery effluents and receiving waters using biologically-based effect methods

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-01-15

Within the EU it is apparent that the regulatory focus on the use of biologically-based effects methods in the assessment of refinery effluents and receiving waters has increased in the past decade. This has been reflected in a recent refinery survey which revealed an increased use of such methods for assessing the quality of refinery effluents and their receiving waters. This report provides an overview of recent techniques used for this purpose. Several case studies provided by CONCAWE member companies describe the application of biological methods to effluent discharge assessment and surface water monitoring. The case studies show that when biological methods are applied to refinery effluents and receiving waters they raise different questions compared with those obtained using physical and chemical methods. Although direct measurement of the toxicity of effluent and receiving to aquatic organisms is the most cited technique, more recent efforts include tests that also address the persistence of effluent toxicity once discharged into the receiving water. Similarly, ecological monitoring of receiving waters can identify effects of effluent inputs arising from species interactions and other secondary effects that would not always be apparent from the results of biological tests conducted on single aquatic organisms. In light of recent and proposed regulatory developments the objectives of this report are therefore to: Discuss the application of biologically-based effects methods (including ecological monitoring) to refinery discharges and receiving waters; Assess the implications of such methods for future regulation of refinery discharges; and Provide guidance on good practice that can be used by refineries and the downstream oil industry to carry out and interpret data obtained using biologically-based effects methods. While the emphasis is on the toxic effects of effluents, other properties will also be covered because of their interdependency in determining

EUD-based biological optimization for carbon ion therapy

International Nuclear Information System (INIS)

Brüningk, Sarah C.; Kamp, Florian; Wilkens, Jan J.

2015-01-01

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon

Radiation biology and radiation therapy

International Nuclear Information System (INIS)

Wideroee, R.

1975-01-01

Radiation biology and radiation therapy can be compared with investigations in different layers of earth. Radiation biology works upwards from the elementary foundations, therapy works downwards with roots to secure and improve the clinical 'surface work'. The Ellis formula (Strandquist), which is a collection of clinical experience, is suited to form connections with radiobiology in the middle layers, and cooperation can give impulses for research. The structure and conditions of tumours and the complicated problems met with are discussed, based on the Carmel symposium of 1969. The oxygen problem in anoxic tumours is not yet solved. Experimental investigations of the effect itself give partly contradictory results. From a clinical viewpoint reoxygenation is of the utmost significance for obtaining control over the primary tumour, and advanced irradiation programmes will here give better results than the traditional ones. New chemicals, e.g. R 0 -07-0582, appear to reduce the OER value to 1.5, thereby making neutron therapy superfluous. Finally a problem from fundamental research is dealt with, wherein two hypotheses explaining the β-effect are described. The repair hypothesis gives a simple explanation but leaves many questions unanswered. The other hypothesis explains the β-effect as two neighbouring single breaks of the DNA molecule. It still presents difficulties, and is scarcely the correct explanation. (JIW)

Biological Considerations When Comparing Proton Therapy. With Photon Therapy

NARCIS (Netherlands)

Paganetti, Harald; van Luijk, Peter

Owing to the limited availability of data on the outcome of proton therapy, treatments are generally optimized based on broadly available data on photon-based treatments. However, the microscopic pattern of energy deposition of protons differs from that of photons, leading to a different biological

Antipsychotic Polypharmacy in a Treatment-Refractory Schizophrenia Population Receiving Adjunctive Treatment With Electroconvulsive Therapy

DEFF Research Database (Denmark)

Kristensen, Diana; Hageman, Ida; Bauer, Jeanett

2013-01-01

Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT).......Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT)....

Symptomatic burden of COPD for patients receiving dual or triple therapy

Directory of Open Access Journals (Sweden)

Chen S

2018-04-01

Full Text Available Stephanie Chen,1 Mark Small,2 Leandro Lindner,3 Xiao Xu1,4 1Health Economics and Payer Analytics, AstraZeneca, Gaithersburg, MD, USA; 2Respiratory, Adelphi Real World, Bollington, UK; 3Global Payer Evidence and Pricing, AstraZeneca, Cambridge, UK; 4Global Payer Evidence and Pricing, AstraZeneca, Gaithersburg, MD, USA Background: COPD is associated with a large disease burden. The use of dual (two maintenance treatments and triple (combination of any three treatments therapy has shown efficacy for symptom relief; however, some patients with COPD remain symptomatic despite these therapies. This study assessed the scope and magnitude of the symptomatic burden for patients with COPD receiving dual or triple therapy. Patients and methods: Cross-sectional data from three Adelphi COPD surveys (2013–2016 conducted in the USA, Europe, Japan, and China were analyzed for patients with COPD and forced expiratory volume in 1 second ≤65% receiving dual or triple therapy for ≥3 months. Physicians completed clinical and disease characteristic forms for identified patients. Corresponding patients completed questionnaires that included validated survey instruments to assess adherence and symptom impact. Descriptive statistics are reported. Results: Our analysis included 690 patients (mean age 68.2 years; 73.3% male; 41.4% and 58.6% were receiving dual and triple therapy, respectively. Most patients had dyspnea with substantial disability (modified Medical Research Council dyspnea scale rating ≥2, 56.3%; large health status impairment from symptoms, COPD Assessment Test score >20, 64.4%. A large symptom burden was observed, even for patients highly adherent to treatment (Morisky Medication Adherence Scale 8, 30.3% [185/612], of whom 62.1% still had a COPD Assessment Test score >20. Sensitivity analyses of patients regardless of their forced expiratory volume in 1 second status and of those receiving treatment for >6 months both reported similar results

Malfunctions of Implantable Cardiac Devices in Patients Receiving Proton Beam Therapy: Incidence and Predictors

International Nuclear Information System (INIS)

Gomez, Daniel R.; Poenisch, Falk; Pinnix, Chelsea C.; Sheu, Tommy; Chang, Joe Y.; Memon, Nada; Mohan, Radhe; Rozner, Marc A.; Dougherty, Anne H.

2013-01-01

Purpose: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. Methods and Materials: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. Results: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. Conclusions: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving

Opportunity of interventional radiology: advantages and application of interventional technique in biological target therapy

International Nuclear Information System (INIS)

Teng Gaojun; Lu Qin

2007-01-01

Interventional techniques not only provide opportunity of treatment for many diseases, but also alter the traditional therapeutic pattern. With the new century of wide application of biological therapies, interventional technique also shows extensive roles. The current biological therapy, including gene therapy, cell transplantation therapy, immunobiologic molecule therapy containing cell factors, tumor antibody or vaccine, recombined proteins, radioactive-particles and targeting materials therapy, can be locally administrated by interventional techniques. The combination of targeting biological therapies and high-targeted interventional technique holds advantages of minimal invasion, accurate delivery, vigorous local effect, and less systemic adverse reactions. Authors believe that the biological therapy may arise a great opportunity for interventional radiology, therefore interventional colleagues should grasp firmly and promptly for the development and extension in this field. (authors)

The Effects of Music Therapy on the Physiological Response of Asthmatic Children Receiving Inhalation Therapy.

Science.gov (United States)

Roslita, Riau; Nurhaeni, Nani; Wanda, Dessie

The clinical manifestation of asthma in children can interfere with their daily activities. Music therapy may become one of the alternative approaches to making children feel comfortable during inhalation therapy. The aim of the study was to identify the effects of music therapy on the physiological response of asthmatic preschool and school-age children receiving inhalation therapy. This study used a quasi-experimental, nonequivalent control group with a pre-test-post-test design. The 44 respondents consisted of preschool and school-age children assigned to intervention and control groups. The results showed a significant difference in average oxygen saturation, heart rate, and respiratory rate between the control and intervention groups before and after intervention (p Music therapy can be used as a nursing intervention to improve the physiological response of children with breathing problems.

New perspectives on biological HDL-targeted therapies

OpenAIRE

Muthuramu, Ilayaraja; Amin, Md Ruhul; De Geest, Bart

2017-01-01

According to a modified high-density lipoprotein (HDL) hypothesis, improving HDL function will lead to a decrease of coronary events. The stringent requirement for proving or refuting this hypothesis is that the causal pathway between the therapeutic intervention and a clinically meaningful endpoint obligatory passes through HDL. Infusion therapy of reconstituted HDL particles and human apolipoprotein A-I gene transfer are biological HDL-targeted therapies that are distinguished by HDL specif...

Optimizing biological therapy in Crohn's disease.

Science.gov (United States)

Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

2016-01-01

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

Where Do Patients With Cancer in Iowa Receive Radiation Therapy?

Science.gov (United States)

Ward, Marcia M.; Ullrich, Fred; Matthews, Kevin; Rushton, Gerard; Tracy, Roger; Goldstein, Michael A.; Bajorin, Dean F.; Kosty, Michael P.; Bruinooge, Suanna S.; Hanley, Amy; Jacobson, Geraldine M.; Lynch, Charles F.

2014-01-01

Purpose: Multiple studies have shown survival benefits in patients with cancer treated with radiation therapy, but access to treatment facilities has been found to limit its use. This study was undertaken to examine access issues in Iowa and determine a methodology for conducting a similar national analysis. Patients and Methods: All Iowa residents who received radiation therapy regardless of where they were diagnosed or treated were identified through the Iowa Cancer Registry (ICR). Radiation oncologists were identified through the Iowa Physician Information System (IPIS). Radiation facilities were identified through IPIS and classified using the Commission on Cancer accreditation standard. Results: Between 2004 and 2010, 113,885 invasive cancers in 106,603 patients, 28.5% of whom received radiation treatment, were entered in ICR. Mean and median travel times were 25.8 and 20.1 minutes, respectively, to the nearest facility but 42.4 and 29.1 minutes, respectively, to the patient's chosen treatment facility. Multivariable analysis predicting travel time showed significant relationships for disease site, age, residence location, and facility category. Residents of small and isolated rural towns traveled nearly 3× longer than urban residents to receive radiation therapy, as did patients using certain categories of facilities. Conclusion: Half of Iowa patients could reach their nearest facility in 20 minutes, but instead, they traveled 30 minutes on average to receive treatment. The findings identified certain groups of patients with cancer who chose more distant facilities. However, other groups of patients with cancer, namely those residing in rural areas, had less choice, and some had to travel considerably farther to radiation facilities than urban patients. PMID:24443730

Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

Science.gov (United States)

Strober, Bruce; Gooderham, Melinda; de Jong, Elke M G J; Kimball, Alexa B; Langley, Richard G; Lakdawala, Nikita; Goyal, Kavitha; Lawson, Fabio; Langholff, Wayne; Hopkins, Lori; Fakharzadeh, Steve; Srivastava, Bhaskar; Menter, Alan

2018-01-01

Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. Incomplete capture of depression and confounders in the patients on registry. Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

CEFTRIAXONE EFFICIENCY AMONG PATIENTS, SUFFERING FROM JUVENILE ARTHRITIS AND RECEIVING IMMUNOSUPPRESSIVE THERAPY

Directory of Open Access Journals (Sweden)

A.M. Chomakhidze

2007-01-01

Full Text Available The article is dedicated to diagnostics and treatment of infectious complications among children with juvenile rheumatoid arthritis, receiving immunosuppressive therapy. The research involves 92 children with different variants of the illness run, who received immunosuppressive therapy. All the patients showed development of the systemic inflammatory response manifestations. The researchers used the definition of the procalcytonine levels as a marker for the bacterial infectiondevelopment. All the patients showed it higher than 0,5 ng/ml, while 7 patients — higher than 10 ng/ml. keeping in mind several courses of the antibacterial therapy in the anamnesis and presence of the combined bacterial infection, ceftriaxone was prescribed to all the children. As a result of the ceftriaxone based therapy, reduction of the clinical and laboratory manifestations of the bacterial infection was noted among more than 90% of patients. The development of the allergic reaction was noted in 1 case, and leukopenia was also found in 1 patient.Key words: children, juvenile rheumatoid arthritis, ceftriaxone.

Biologic therapies for chronic inflammatory bowel disease

Directory of Open Access Journals (Sweden)

M. P. Martínez-Montiel

Full Text Available Crohn's disease (CD and ulcerative colitis (UC make up the so-called chronic inflammatory bowel disease (IBD. Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Anti-integrin α4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors. Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab, T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.

Cardiovascular safety of biologic therapies for the treatment of RA.

Science.gov (United States)

Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

2011-11-15

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Top-down approach to biological therapy of Crohn's disease.

Science.gov (United States)

Hirschmann, Simon; Neurath, Markus F

2017-03-01

Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.

Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry.

Science.gov (United States)

Strand, Vibeke; Miller, Paul; Williams, Setareh A; Saunders, Katherine; Grant, Shannon; Kremer, Joel

2017-12-01

Despite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation. Inclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002-2011); age of RA onset: ≥16 years; ≥6 months' follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire. Overall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007-2010 versus 2002-2003, and Clinical Disease Activity Index scores. Almost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy. Corrona LLC and MedImmune.

Biological basis of heavy ion beams for cancer therapy

International Nuclear Information System (INIS)

Sakamoto, Kiyohiko

1985-01-01

Fast neutron therapy has started firstly and proton therapy has commenced secondly, fast neutron shows better biological effects compared to conventional radiations but its dose distribution is not good, and proton demonstrates excellent dose distribution but its biological effects are almost the same as that of conventional radiations. On the other hand, negative pi-mesons and heavy ions indicate high radiobiological effect and excellent dose distribution, therefore these particle radiations is considered to be more attractive for radiotherapeutic radiations to enhance cure rate of cancers. The biological strong points of these particles are as follows : 1) cells exposed to these particle radiations shows less recovery after irradiation compared to conventional radiations, 2) these radiations show high biological effects (high value of relative biological effectiveness = RBE) when the same dose is given, 3) big effects on hypoxic cells which exsist in tumor, i.e. the value of oxygen enhancement ratio (OER) is low, 4) the differences in radiosensitivity by stages of cell cycle are not so great (data was not shown in present paper), 5) biological effects at prepeak plateau region in depth dose curve formed by these particle radiations is less than that at peak region (therefore, if beam is modulated to cover tumor at spraed out broad peak, tumors is given more biological effect compared to normal tissues which is to be exposed to radiations at prepaeak region). Clinical trial using heavy ions are being performed at Lawrence Berkeley Laboratory which is only one facility to be able to try clinical trial. The results of clinical trials at Lawrence Berkeley Laboratory suggest to be very prospective to enhance tumor cure rate, however it is too early to estimate the effect of heavy ion therapy. (J.P.N.)

Phage Therapy in the Era of Synthetic Biology.

Science.gov (United States)

Barbu, E Magda; Cady, Kyle C; Hubby, Bolyn

2016-10-03

For more than a century, bacteriophage (or phage) research has enabled some of the most important discoveries in biological sciences and has equipped scientists with many of the molecular biology tools that have advanced our understanding of replication, maintenance, and expression of genetic material. Phages have also been recognized and exploited as natural antimicrobial agents and nanovectors for gene therapy, but their potential as therapeutics has not been fully exploited in Western medicine because of challenges such as narrow host range, bacterial resistance, and unique pharmacokinetics. However, increasing concern related to the emergence of bacteria resistant to multiple antibiotics has heightened interest in phage therapy and the development of strategies to overcome hurdles associated with bacteriophage therapeutics. Recent progress in sequencing technologies, DNA manipulation, and synthetic biology allowed scientists to refactor the entire bacterial genome of Mycoplasma mycoides, thereby creating the first synthetic cell. These new strategies for engineering genomes may have the potential to accelerate the construction of designer phage genomes with superior therapeutic potential. Here, we discuss the use of phage as therapeutics, as well as how synthetic biology can create bacteriophage with desirable attributes. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Predicting dropout in adolescents receiving therapy for depression.

Science.gov (United States)

O'Keeffe, Sally; Martin, Peter; Goodyer, Ian M; Wilkinson, Paul; Consortium, Impact; Midgley, Nick

2017-10-30

Therapy dropout is a common occurrence, especially in adolescence. This study investigated whether dropout could be predicted from a range of child, family, and treatment factors in a sample of adolescents receiving therapy for depression. This study draws on data from 406 participants of the IMPACT study, a randomized controlled trial, investigating three types of therapy in the treatment of adolescent depression. Logistic regression was used to estimate the effects of predictors on the odds of dropout. Few pre-treatment predictors of dropout were found, with the only significant predictors being older age, antisocial behaviour, and lower scores of verbal intelligence. Missed sessions and poorer therapeutic alliance early in treatment also predicted dropout. Most child and family factors investigated were not significantly associated with dropout. There may be little about depressed adolescents' presentation prior to therapy starting that indicates their risk of dropout. However, within-treatment factors indicated that warning signs of dropout may be identifiable during the initial phase of therapy. Identifying and targeting early treatment indicators of dropout may provide possibilities for improving engagement. Clinical and methodological significance of this article: In the literature, a great deal of attention has been paid to child and family factors that predict therapy dropout, yet in this study, few pre-treatment characteristics were predictive of dropout. However, findings revealed possible warning signs of dropout in the early part of treatment, as poor therapeutic alliance and missed sessions were both found to be predictive of dropout. These findings call for therapists to be aware of such warning signs and clinical guidelines for managing cases at risk of dropout are warranted.

Radiation biology as a basis for multidisciplinary cancer therapy

International Nuclear Information System (INIS)

Hosoya, N.

2017-01-01

The research field of radiation biology has progressed greatly thanks to the advances in molecular biology. DNA in the cell nucleus is the principal target of radiation. The biological effect of radiation can be determined by how the DNA damage is processed in the cell. In order to prevent deleterious biological effects due to DNA damage, the cells possess a system termed 'DNA damage response'. The DNA damage response finally induces cell cycle arrest, activation of DNA repair pathways, or cell death. If accurately repaired, DNA damage will result in survival of cells with no biological effects. If inaccurately repaired, DNA damage may result in survival of cells exhibiting genetic alterations, which can lead to the development of various diseases including cancer. If unrepaired, fatal DNA damage such as the DNA double-strand break will result in cell depth. Since radiation therapy and chemotherapy are designed to specifically kill cancer cells by inducing DNA double-strand breaks, it is important to take advantage of cancer-specific abnormalities in DNA damage response. In this review, I describe the impact of targeting DNA damage response in cancer therapy and show how progress in radiation biology has contributed to the development of novel therapeutic strategies. (author)

One-appointment endodontic therapy: biological considerations.

Science.gov (United States)

Lin, Louis M; Lin, Jarshen; Rosenberg, Paul A

2007-11-01

The authors conducted a literature review to present the best available biological evidence concerning one-appointment endodontic therapy for asymptomatic teeth with apical periodontitis. Because of recent advances in technology, such as rotary engines and nickel-titanium instruments, some practitioners are performing one-appointment endodontic therapy for asymptomatic teeth with apical periodontitis. The authors reviewed the literature, which revealed only a small number of randomized, controlled clinical trials that have been conducted on one-appointment versus multiple-appointment endodontic therapy. As the apical canal preparation is enlarged, a greater percentage of bacteria is eradicated from infected root canals. In addition, sufficiently large apical root canal enlargement facilitates the delivery of antimicrobial irrigant to the apical portion of the canal. However, an association between positive or negative preobturation root canal culture results and the outcome of endodontic treatment has not been well-established. The best available evidence, based on a systematic literature review, indicates that one-appointment endodontic therapy may be feasible in selected cases of apical periodontitis in asymptomatic teeth. However, additional randomized, controlled clinical trials are required.

The Use of Biologic Therapies in Uveitis.

Science.gov (United States)

Schwartzman, Sergio; Schwartzman, Monica

2015-12-01

Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective

Building for Biology: A Gene Therapy Trial Infrastructure

Directory of Open Access Journals (Sweden)

Samuel Taylor-Alexander

2017-06-01

Full Text Available In this article, we examine the construction of the infrastructure for a Phase II gene therapy trial for Cystic Fibrosis (CF. Tracing the development of the material technologies and physical spaces used in the trial, we show how the trial infrastructure took form at the uncertain intersection of scientific norms, built environments, regulatory negotiations, patienthood, and the biologies of both disease and therapy. We define infrastructures as material and immaterial (including symbols and affect composites that serve a selective distributive purpose and facilitate projects of making and doing. There is a politics to this distributive action, which is itself twofold, because whilst infrastructures enable and delimit the movement of matter, they also mediate the very activity for which they provide the grounds. An infrastructural focus allows us to show how purposeful connections are made in a context of epistemic and regulatory uncertainty. The gene therapy researchers were working in a context of multiple uncertainties, regarding not only how to do gene therapy, but also how to anticipate and enact ambiguous regulatory requirements in a context of limited resources (technical, spatial, and financial. At the same time, the trial infrastructure had to accommodate Cystic Fibrosis biology by bridging the gap between pathology and therapy. The consortium’s approach to treating CF required that they address concerns about contamination and safety while finding a way of getting a modified gene product into the lungs of the trial participants.

Tumor biology and cancer therapy – an evolving relationship

Directory of Open Access Journals (Sweden)

Lother Ulrike

2009-08-01

Full Text Available Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.

Nursing care of patients receiving interventional therapy for hepatic artery stenosis after liver transplantation

International Nuclear Information System (INIS)

Wei Lin; Liu Shiguang

2009-01-01

Objective: To discuss the perioperative nursing care of patients who is going to receive interventional therapy for hepatic artery stenosis after liver transplantation and to provide useful reference for reducing surgery-related complication and for improving the prognosis of patients. Methods: Based on the patient's condition and operative requirement,we provided effective nursing care for 20 patients who were admitted to receive the interventional therapy for hepatic artery stenosis after liver transplantation. The nursing care included preoperative preparation,postoperative nursing and medical guidance at the time of discharge. Results: Interventional therapy was successfully performed in all 20 cases, and no hemorrhagic tendency or acute thrombosis occurred. Marked symptomatic improvement was obtained in all patients. Conclusion: The interventional therapy is an effective treatment for hepatic artery stenosis after liver transplantation. Intensive perioperative nursing care can well prevent the occurrence of surgery-related complications and can surely improve the therapeutic results. (authors)

Characteristics of Hemorrhagic Peptic Ulcers in Patients Receiving Antithrombotic/Nonsteroidal Antiinflammatory Drug Therapy

OpenAIRE

Nakamura, Kazuhiko; Akahoshi, Kazuya; Ochiai, Toshiaki; Komori, Keishi; Haraguchi, Kazuhiro; Tanaka, Munehiro; Nakamura, Norimoto; Tanaka, Yoshimasa; Kakigao, Kana; Ogino, Haruei; Ihara, Eikichi; Akiho, Hirotada; Motomura, Yasuaki; Kabemura, Teppei; Harada, Naohiko

2012-01-01

Background/Aims Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were c...

Metastasis in renal cell carcinoma: Biology and implications for therapy

Directory of Open Access Journals (Sweden)

Jun Gong

2016-10-01

Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

Osteoporosis prophylaxis in patients receiving chronic glucocorticoid therapy

International Nuclear Information System (INIS)

Ali, Mir Sadat; AlElq, Abdulmohsen H.; AlShafei, Badar A.; AbuJubarac, Mohammed A.; AlTurki, Haifa A.

2009-01-01

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, yet few patients receive proper measures to prevent its development. We retrospectively searched prescription records to determine if patients receiving oral prednisolone were receiving prophylaxis or treatment for osteopenia and osteoporosis. Patients who were prescribed greater or equal to 7.5 milligrams of prednisolone for 6 months or longer during a 6- month period were identified through the prescription monitoring system. Demographic and clinical data were extracted from the patient records, and dual energy x-ray absorptiometry (DEXA) scans were retrieved, when available. Use of oral calcium, vitamin D and anti-resorptives was recorded. One hundred males and 65 females were receiving oral prednisolone for a mean (SD) duration of 40.4 (29.9) months in males and 41.2 (36.4) months in females. Twenty-one females (12.7%) and 5 (3%) males had bone mineral density measured by DEXA. Of those, 10 (47.6%) females and 3 (50%) males were osteoporotic and 11(52.4%) females and 2 (40%) males were osteopenic. Calcium and vitamin D were prescribed to the majority of patients (60% to 80%), but none were prescribed antiresorptive/anabolic therapy. Patients in this study were neither investigated properly nor treated according to the minimum recommendations for the management of GIOP. Physician awareness about the prevention and treatment of GIOP should be a priority for the local health care system. (author)

Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

Science.gov (United States)

Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

2017-05-01

Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

Challenges of biological therapy in patients with pustular psoriasis coexisting with psoriatic arthritis

Directory of Open Access Journals (Sweden)

Joanna Narbutt

2017-04-01

Full Text Available Introduction . Psoriasis is a chronic inflammatory skin disease affecting approximately 2–3% of the general population. It is a condition with immunological and genetic background, coexisting with psoriatic arthritis in about 25% of cases. Biologic drugs have brought a significant improvement in managing the disease, however they are not approved for the treatment of pustular psoriasis. An increasing number of reports indicate the efficacy of biological drugs in pustular psoriasis. In some patients there are factors responsible for a worse clinical response to biologic therapy. Objective . Presentation of therapeutic difficulties identified in a patient with pustular psoriasis and psoriatic arthritis. Case report . We report a case of a 48-year-old man with generalized pustular psoriasis coexisting with psoriatic arthritis in whom therapy with multiple biologic drugs (adalimumab, infliximab, golimumab, ustekinumab has failed to bring a satisfactory improvement. Conclusions . Further studies are needed to verify the efficacy and pos­sibly approve biological drugs for the treatment of pustular psoriasis. Also, attempts should be made to identify predictors of poorer response to treatment in order to individualize therapy and prevent the loss of efficacy of biologic drugs during prolonged use.

Skeletal mass in patients receiving chronic anticonvulsant therapy

Energy Technology Data Exchange (ETDEWEB)

Zanzi, I.; Roginsky, M.S.; Rosen, A.; Cohn, S.H.

1981-01-01

The technique of in vivo total body neutron activation analysis was used to measure total body calcium (TBCa), a sensitive and precise index of skeletal mass, expressed as the Ca ratio (TBCa observed/TBCa predicted). 23 unselected, ambulatory, noninstitutionalized, adult epileptic patients under long-term anticonvulsant therapy were studied. Ca ratio was normal in 20 of the patients, low in only 2 and borderline in 1 patient. Plasma alkaline phosphatase values were elevated in half the subjects. Plasma Ca (uncorrected) was in the normal range in all. Serum 25-hydroxvitamin D (25-OHD) was low in 67% of the subjects, but only 1 patient had a value below 5 ng/ml. There was no correlation between the Ca ratio and the alkaline phosphatase or 25-OHD values. No radiographic or other evidences of osteomalacia were observed. This study does not support the notion of a prevalence of osteopenia in ambulatory, noninstitutionalized, adult epileptic patients receiving chronic anticonvulsant therapy in this geographical area despite the frequent findings of biochemical abnormalities.

Stent patency in patients with distal malignant biliary obstruction receiving chemo(radio)therapy

Science.gov (United States)

Haal, Sylke; van Hooft, Jeanin E.; Rauws, Erik A. J.; Fockens, Paul; Voermans, Rogier P.

2017-01-01

Background and study aims  Recent literature suggests that chemo(radio)therapy might reduce the patency of plastic stents in patients with malignant biliary obstruction. Whether this might also be valid for other types of stents is unknown. The aim of this study was to determine the influence of chemo(radio)therapy on the patency of fully-covered self-expandable metal stents (FCSEMSs) and plastic stents. Patients and methods  We retrospectively reviewed the electronic medical records of patients with distal malignant biliary obstruction who underwent biliary stent placement between April 2001 and July 2015. Primary outcome was duration of stent patency. Secondary outcome was stent patency at 3 and 6 months. We used Kaplan–Meier survival analyses to compare stent patency rates between patients who received chemo(radio)therapy and patients who did not. Results  A total of 291 biliary stents (151 metal and 140 plastic) were identified. The median cumulative stent patency of FCSEMSs did not differ between patients receiving chemo(radio)therapy (n = 51) and those (n = 100) who did not ( P  = 0.70, log-rank test). The estimated cumulative stent patency of plastic stents was also comparable in 99 patients without and 41 patients with chemo(radio)therapy ( P  = 0.73, log-rank test). At 3 and 6 months, FCSEMS patency rates were 87 % and 83 % in patients without chemo(radio)therapy and 96 % and 83 % in patients with therapy, respectively. Plastic patency rates were 69 % and 55 % in patients without and 85 % and 39 % in patients with therapy, respectively. After 1 year, 78 % of the FCSEMSs were still patent in patients without chemo(radio)therapy and 69 % of the FCSEMSs were still patent in patients with therapy. Conclusion  Our data indicate that chemo(radio)therapy does not reduce the patency of biliary fully-covered metal and plastic stents. PMID:29090242

WE-FG-BRB-03: Challenges and Opportunities for Implementing Biological Optimization in Particle Therapy

Energy Technology Data Exchange (ETDEWEB)

Carlson, D. [Yale University School of Medicine (United States)

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

Discussion: DMARDs and biologic therapies in the management of inflammatory joint diseases.

Science.gov (United States)

Vaz, Austin; Lisse, Jeffrey; Rizzo, Warren; Albani, Salvatore

2009-05-01

Therapy for inflammatory joint diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, includes various conventional disease-modifying antirheumatic drugs (DMARDs). These therapeutic agents are termed DMARDs because they have the potential to reduce or prevent joint damage and preserve joint integrity and function. Conventional DMARDs are used as monotherapy or in combination and include methotrexate, leflunomide, azathioprine, ciclosporin, hydroxychloroquine, sulfasalazine, gold and minocycline. Biologic response modifiers, which are based on proteins made by living cells, are newer agents available for the treatment of various inflammatory joint diseases. Biologic therapies now approved for use in inflammatory joint diseases are TNF inhibitors, T-cell modulators and B-cell depleters. They have all been shown to have clinical efficacy and are able to retard structural damage. However, all current immune-modulating therapies also have potential side effects, and the decision to use a particular agent for treatment should be based on a thorough discussion of the benefits and risks with the patient. Newer biologic response modifiers and other immunologic therapies are currently being developed for the treatment of inflammatory joint diseases and are discussed in this review.

Reiki Therapy for Symptom Management in Children Receiving Palliative Care: A Pilot Study.

Science.gov (United States)

Thrane, Susan E; Maurer, Scott H; Ren, Dianxu; Danford, Cynthia A; Cohen, Susan M

2017-05-01

Pain may be reported in one-half to three-fourths of children with cancer and other terminal conditions and anxiety in about one-third of them. Pharmacologic methods do not always give satisfactory symptom relief. Complementary therapies such as Reiki may help children manage symptoms. This pre-post mixed-methods single group pilot study examined feasibility, acceptability, and the outcomes of pain, anxiety, and relaxation using Reiki therapy with children receiving palliative care. A convenience sample of children ages 7 to 16 and their parents were recruited from a palliative care service. Two 24-minute Reiki sessions were completed at the children's home. Paired t tests or Wilcoxon signed-rank tests were calculated to compare change from pre to post for outcome variables. Significance was set at P Reiki therapy did decrease pain, anxiety, heart, and respiratory rates, but small sample size deterred statistical significance. This preliminary work suggests that complementary methods of treatment such as Reiki may be beneficial to support traditional methods to manage pain and anxiety in children receiving palliative care.

A pilot study of exercise in men with prostate cancer receiving androgen deprivation therapy

International Nuclear Information System (INIS)

Lee, C Ellen; Leslie, William D; Lau, YK James

2012-01-01

Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT. A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data. Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical

Music Therapy is Associated With Family Perception of More Spiritual Support and Decreased Breathing Problems in Cancer Patients Receiving Hospice Care.

Science.gov (United States)

Burns, Debra S; Perkins, Susan M; Tong, Yan; Hilliard, Russell E; Cripe, Larry D

2015-08-01

Music therapy is a common discretionary service offered within hospice; however, there are critical gaps in understanding the effects of music therapy on hospice quality indicators, such as family satisfaction with care. The purpose of this study was to examine whether music therapy affected family perception of patients' symptoms and family satisfaction with hospice care. This was a retrospective, cross-sectional analysis of electronic medical records from 10,534 cancer patients cared for between 2006 and 2010 by a large national hospice. Logistic regression was used to estimate the effect of music therapy using propensity scores to adjust for non-random assignment. Overall, those receiving music therapy had higher odds of being female, having longer lengths of stay, and receiving more services other than music therapy, and lower odds of being married/partnered or receiving home care. Family satisfaction data were available for 1495 (14%) and were more likely available if the patient received music therapy (16% vs. 12%, P music therapy vs. those not. Patients who received music therapy were more likely to report discussions about spirituality (odds ratio [OR] = 1.59, P = 0.01), had marginally less trouble breathing (OR = 0.77, P = 0.06), and were marginally more likely to receive the right amount of spiritual support (OR = 1.59, P = 0.06). Music therapy was associated with perceptions of meaningful spiritual support and less trouble breathing. The results provide preliminary data for a prospective trial to optimize music therapy interventions for integration into clinical practice. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A systematic review of oral fungal infections in patients receiving cancer therapy

NARCIS (Netherlands)

Lalla, Rajesh V.; Latortue, Marie C.; Hong, Catherine H.; Ariyawardana, Anura; D'Amato-Palumbo, Sandra; Fischer, Dena J.; Martof, Andrew; Nicolatou-Galitis, Ourania; Patton, Lauren L.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.

Quality of life, treatment satisfaction and efficacy of non-biological systemic therapies in patients with plaque psoriasis: study protocol for a prospective observational study.

Science.gov (United States)

Fink, Christine; Schank, Timo E; Trenkler, Nina; Uhlmann, Lorenz; Schäkel, Knut

2017-06-30

Psoriasis vulgaris often leads to a significant impaired quality of life and dissatisfaction with the existing therapeutic approaches. However, patients' quality of life and treatment satisfaction are of utmost importance, since it is positively related to therapy adherence and encourages patient's compliance. The study described herein evaluates the quality of life, treatment satisfaction and efficacy during the initial 6 months of treatment with a non-biological systemic agent in a real-life clinical setting. This observational study compares quality of life, treatment satisfaction and the efficacy of non-biological systemic therapy between 60 patients suffering from plaque psoriasis receiving the non-biological systemic therapies with apremilast, methotrexate and fumaric acid esters. Ethics approval was provided by the ethics committee of the medical faculty of the University of Heidelberg. Ethics approval number is S-298/2015. The design and the final results of the study will be published and made available to the public. German Clinical Trial Register (DRKS): DRKS00008721 (https://www.germanctr.de/). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Listeria monocytogenes meningitis in an atomic bomb survivor receiving corticosteroid therapy for aplastic anemia

Energy Technology Data Exchange (ETDEWEB)

Fujihara, Kazuo; Shida, Norihiko; Ohta, Michiya [Hiroshima Atomic Bomb Hospital (Japan)

1995-12-01

We report a case of successfully treated Listeria monocytogenes (Lm) meningitis in a atomic bomb survivor receiving steroid therapy for aplastic anemia. The patient was a 62-year-old woman and the past medical history included hypothyroidism due to radioiodide therapy for Basedow disease, breast cancer, aplastic anemia, steroid-induced diabetes mellitus, and pulmonary tuberculosis. At the time of onset, she was receiving corticosteroid, anabolic steroid, an H{sub 2}-blocker (famotidine), and other medication. Since she developed symptoms of meningitis when she visited our hospital for regular medical check-up for aplastic anemia, she was hospitalized and given antibiotic therapy, including ABPC, without delay. With this effective antibiotic therapy and successful management of the co-existing medical conditions, she was cured except for being a little euphoric. Lm meningitis is known to occur in aged and immunocompromised patients. Since most of the atomic bomb survivors are now aged and the prevalence of malignancy, diabetes mellitus, and other diseases which cause immunodeficiency have been rising year by year, Lm meningitis is one of the emergency neurologic conditions whose diagnosis should not be delayed in this population. (author).

Listeria monocytogenes meningitis in an atomic bomb survivor receiving corticosteroid therapy for aplastic anemia

International Nuclear Information System (INIS)

Fujihara, Kazuo; Shida, Norihiko; Ohta, Michiya

1995-01-01

We report a case of successfully treated Listeria monocytogenes (Lm) meningitis in a atomic bomb survivor receiving steroid therapy for aplastic anemia. The patient was a 62-year-old woman and the past medical history included hypothyroidism due to radioiodide therapy for Basedow disease, breast cancer, aplastic anemia, steroid-induced diabetes mellitus, and pulmonary tuberculosis. At the time of onset, she was receiving corticosteroid, anabolic steroid, an H 2 -blocker (famotidine), and other medication. Since she developed symptoms of meningitis when she visited our hospital for regular medical check-up for aplastic anemia, she was hospitalized and given antibiotic therapy, including ABPC, without delay. With this effective antibiotic therapy and successful management of the co-existing medical conditions, she was cured except for being a little euphoric. Lm meningitis is known to occur in aged and immunocompromised patients. Since most of the atomic bomb survivors are now aged and the prevalence of malignancy, diabetes mellitus, and other diseases which cause immunodeficiency have been rising year by year, Lm meningitis is one of the emergency neurologic conditions whose diagnosis should not be delayed in this population. (author)

Language Profile in Congenital Hypothyroid Children Receiving Replacement Therapy.

Science.gov (United States)

Soliman, Hend; Abdel Hady, Aisha Fawzy; Abdel Hamid, Asmaa; Mahmoud, Heba

2016-01-01

The aim of this work was to evaluate receptive and expressive language skills in children with congenital hypothyroidism receiving early hormonal replacement treatment before the age of 3 months and to identify any subtle areas of weaknesses in their language development to check the necessity for future language intervention. The study was conducted on 30 hypothyroid children receiving hormonal replacement. They were subdivided into group I (5-8 years 11 months; 12 cases) and group II (9-12 years 11 months; 18 cases). All patients were subjected to a protocol of assessment applied in the Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU) and evaluation of language skills by the REAL scale. The younger group reached average Arabic language scores, while the older group showed moderate language delay. Early replacement therapy supports language development in young children. However, longitudinal and follow-up studies are required to identify difficulties presenting at older ages that may affect children in the academic settings. © 2016 S. Karger AG, Basel.

em>In vivoem> biological response to extracorporeal shockwave therapy in human tendinopathy

DEFF Research Database (Denmark)

Waugh, C. M.; Morrissey, D.; Jones, E.

2015-01-01

Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session...

Cost-effectiveness of abiraterone treatment in patients with castration-resistant prostate cancer who previously received docetaxel therapy

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2014-01-01

Full Text Available Background. Therapy for metastatic castration-resistant prostate cancer (CRPC is a serious problem that requires significant public health care expenditures.Objective: to evaluate the cost-effectiveness of abiraterone treatment in patients with metastatic CRPC who previously received docetaxel under the conditions of the budgetary public health system of the Russian Federation.Material and methods. Markovian simulation based on the COU-AA-301 randomized placebo-controlled Phase III study was used. Survival analysis was made in 70-year-old patients. The cost of abiraterone therapy corresponded to that of the 2013 auctions.Results. Abiraterone therapy in patients who have previously received docetaxel therapy causes an increase in average life expectancy by an average of 4.6 months and progression-free survival by 2.0 months. Moreover, the cost calculated with reference to one year of additional life will account for about 3.6 million rubles and that to one additional quality-adjusted life year will be about 5.45 million rubles.Conclusion. The cost-effectiveness of abiraterone therapy for metastatic CRPC in patients who have previously received docetaxel therapy is similar to that of other medicaments used in oncological practice under the conditions of the budgetary public health system of the Russian Federation. In this connection, abiraterone may be considered as an economically acceptable medical intervention in this clinical situation.

Cost-effectiveness of abiraterone treatment in patients with castration-resistant prostate cancer who previously received docetaxel therapy

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2014-11-01

Full Text Available Background. Therapy for metastatic castration-resistant prostate cancer (CRPC is a serious problem that requires significant public health care expenditures.Objective: to evaluate the cost-effectiveness of abiraterone treatment in patients with metastatic CRPC who previously received docetaxel under the conditions of the budgetary public health system of the Russian Federation.Material and methods. Markovian simulation based on the COU-AA-301 randomized placebo-controlled Phase III study was used. Survival analysis was made in 70-year-old patients. The cost of abiraterone therapy corresponded to that of the 2013 auctions.Results. Abiraterone therapy in patients who have previously received docetaxel therapy causes an increase in average life expectancy by an average of 4.6 months and progression-free survival by 2.0 months. Moreover, the cost calculated with reference to one year of additional life will account for about 3.6 million rubles and that to one additional quality-adjusted life year will be about 5.45 million rubles.Conclusion. The cost-effectiveness of abiraterone therapy for metastatic CRPC in patients who have previously received docetaxel therapy is similar to that of other medicaments used in oncological practice under the conditions of the budgetary public health system of the Russian Federation. In this connection, abiraterone may be considered as an economically acceptable medical intervention in this clinical situation.

Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

2006-03-15

Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

Science.gov (United States)

Xu, Zhenhua; Davis, Hugh M; Zhou, Honghui

2015-03-01

Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents. © 2015, The American College of Clinical Pharmacology.

Biologic Drugs: A New Target Therapy in COPD?

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Yousuf, Ahmed; Brightling, Christopher E

2018-04-23

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Current diagnostic criteria based on the presence of fixed airflow obstruction and symptoms do not integrate the complex pathological changes occurring within the lung and they do not define different airway inflammatory patterns. The current management of COPD is based on 'one size fits all' approach and does not take the importance of heterogeneity in COPD population into account. The available treatments aim to alleviate symptoms and reduce exacerbation frequency but do not alter the course of the disease. Recent advances in molecular biology have furthered our understanding of inflammatory pathways in pathogenesis of COPD and have led to development of targeted therapies (biologics and small molecules) based on predefined biomarkers. Herein we shall review the trials of biologics in COPD and potential future drug developments in the field.

Towards biologically conformal radiation therapy (BCRT): Selective IMRT dose escalation under the guidance of spatial biology distribution

International Nuclear Information System (INIS)

Yang Yong; Xing Lei

2005-01-01

It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT

Physics fundamentals and biological effects of synchrotron radiation therapy

International Nuclear Information System (INIS)

Prezado, Y.

2010-01-01

The main goal of radiation therapy is to deposit a curative dose in the tumor without exceeding the tolerances in the nearby healthy tissues. For some radioresistant tumors, like gliomas, requiring high doses for complete sterilization, the major obstacle for curative treatment with ionizing radiation remains the limited tolerance of the surrounding healthy tissue. This limitation is particularly severe for brain tumors and, especially important in children, due to the high risk of complications in the development of the central nervous system. In addition, the treatment of tumors close to an organ at risk, like the spinal cord, is also restricted. One possible solution is the development of new radiation therapy techniques exploiting radically different irradiation modes and modifying, in this way, the biological equivalent doses. This is the case of synchrotron radiation therapy (SRT). In this work the three new radiation therapy techniques under development at the European Synchrotron Radiation Facility (ESRF), in Grenoble (France) will be described, namely: synchrotron stereotactic radiation therapy (SSRT), microbeam radiation therapy (MRT) and minibeam radiation therapy. The promising results in the treatment of the high grade brain tumors obtained in preclinical studies have paved the way to the clinical trials. The first patients are expected in the fall of 2010. (Author).

Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

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Hisanao Akiyama

Full Text Available The first non-vitamin K antagonist oral anticoagulant (NOAC introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH.We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014.ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years. Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset.Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy.

The effect of music therapy on physiological signs of anxiety in patients receiving mechanical ventilatory support.

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Korhan, Esra Akin; Khorshid, Leyla; Uyar, Mehmet

2011-04-01

The aim of this study was to investigate if relaxing music is an effective method of reducing the physiological signs of anxiety in patients receiving mechanical ventilatory support. Few studies have focused on the effect of music on physiological signs of anxiety in patients receiving mechanical ventilatory support. A study-case-control, experimental repeated measures design was used. Sixty patients aged 18-70 years, receiving mechanical ventilatory support and hospitalised in the intensive care unit, were taken as a convenience sample. Participants were randomised to a control group or intervention group, who received 60 minutes of music therapy. Classical music was played to patients using media player (MP3) and headphones. Subjects had physiological signs taken immediately before the intervention and at the 30th, 60th and 90th minutes of the intervention. Physiological signs of anxiety assessed in this study were mean systolic and diastolic blood pressure, pulse rate, respiratory rate and oxygen saturation in blood measured by pulse oxymetry. Data were collected over eight months in 2006-2007. The music group had significantly lower respiratory rates, and systolic and diastolic blood pressure, than the control group. This decrease improved progressively in the 30th, 60th and 90th minutes of the intervention, indicating a cumulative dose effect. Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety. As indicated by the results of this study, music therapy can be supplied to allay anxiety in patients receiving mechanical ventilation. Nurses may include music therapy in the routine care of patients receiving mechanical ventilation. © 2011 Blackwell Publishing Ltd.

Safety and immunogenicity of yellow fever 17D vaccine in adults receiving systemic corticosteroid therapy: an observational cohort study.

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Kernéis, Solen; Launay, Odile; Ancelle, Thierry; Iordache, Laura; Naneix-Laroche, Véronique; Méchaï, Frédéric; Fehr, Thierry; Leroy, Jean-Philippe; Issartel, Bertrand; Dunand, Jean; van der Vliet, Diane; Wyplosz, Benjamin; Consigny, Paul-Henri; Hanslik, Thomas

2013-09-01

To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy. All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids. Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination. After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results. Copyright © 2013 by the American College of Rheumatology.

The prognostic value of electrodiagnostic testing in patients with sciatica receiving physical therapy.

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Savage, Nathan J; Fritz, Julie M; Kircher, John C; Thackeray, Anne

2015-03-01

To investigate the prognostic value of electrodiagnostic testing in patients with sciatica receiving physical therapy. Electrodiagnostic testing was performed on 38 patients with sciatica participating in a randomized trial comparing different physical therapy interventions. Patients were grouped and analyzed according to the presence or absence of radiculopathy based on electrodiagnostic testing. Longitudinal data analysis was conducted using multilevel growth modeling with ten waves of data collected from baseline through the treatment and post-treatment periods up to 6 months. The primary outcome measure was changes in low back pain-related disability assessed using the Roland and Morris disability questionnaire (RMDQ). Patients with radiculopathy (n = 19) had statistically significant and clinically meaningful improvements in RMDQ scores at every post-treatment follow-up occasion regardless of treatment received. The final multilevel growth model revealed improvements in RMDQ scores in patients with radiculopathy at the 6-week (-8.1, 95 % CI -12.6 to -2.6; P = 0.006) and 6-month (-4.1, 95 % CI -7.4 to -0.7; P = 0.020) follow-up occasions compared to patients without radiculopathy. Treatment group was not a significant predictive factor at any follow-up occasion. An interaction between electrodiagnostic status and time revealed faster weekly improvements in RMDQ scores in patients with radiculopathy at the 6-week (-0.72, 95 % CI -1.4 to -0.04; P = 0.040) through the 16-week (-0.30, 95 % CI, -0.57 to -0.04; P = 0.028) follow-up occasions compared to patients without radiculopathy. The presence of lumbosacral radiculopathy identified with electrodiagnostic testing is a favorable prognostic factor for recovery in low back pain-related disability regardless of physical therapy treatment received.

METHODS OF ASSESSMENT OF THE RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS IN NEUTRON THERAPY

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V. A. Lisin

2017-01-01

Full Text Available The relative biological effectiveness (RBE of fast neutrons is an important factor influencing the quality of neutron therapy therefore, the assessment of RBE is of great importance. Experimental and clinical studies as well as different mathematical and radiobiological models are used for assessing RBE. Research is conducted for neutron sources differing in the method of producing particles, energy and energy spectrum. Purpose: to find and analyze the dose-dependence of fast neutron RBE in neutron therapy using the U-120 cyclotron and NG-12I generator. Material and methods: The optimal method for assessing the relative biological effectiveness of neutrons for neutron therapy was described. To analyze the dependence of the RBE on neutron dose, the multi-target model of cell survival was applied. Results: The dependence of the RBE of neutrons produced from the U-120 cyclotron and NG-120 generator on the dose level was found for a single irradiation of biological objects. It was shown that the function of neutron dose was consistent with similar dependencies found by other authors in the experimental and clinical studies.

Summary of the primer on tumor immunology and the biological therapy of cancer

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Margolin Kim

2009-01-01

Full Text Available Abstract The International Society for Biological Therapy of Cancer (iSBTc is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1 cytokines in cancer immunology; (2 anti-angiogenic therapy; (3 end stage: immune killing of tumors; (4 blocking T cell checkpoints; (5 approach to identification and therapeutic exploitation of tumor antigens; (6 T regulatory cells; (7 adoptive T cell therapy; (8 immune monitoring of cancer immunotherapy; and (9 immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis.

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Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

DEFF Research Database (Denmark)

Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis – 2016 update

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Pedro Machado

2017-07-01

Full Text Available Objective: To update the recommendations for the treatment of axial spondyloarthritis (axSpA with biological therapies, endorsed by the Portuguese Society of Rheumatology. Methods: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. Results: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment, assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%, and strategy in the presence of an inadequate response (where switching is recommended or in the presence of long-term remission (where a process of biological therapy optimization can be

A prospective observational study of pigmented naevi changes in psoriasis patients on biologic therapy.

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Choi, Seohee Deanne; D'Souza, Mario I; Menzies, Scott W; Weninger, Wolfgang

2018-05-23

Patients on biologic therapy are thought to be at increased risk of developing non-melanoma skin cancers and melanomas. It is unknown whether biologic therapy alters the natural history of melanocytic naevi. Therefore, a prospective observational study was conducted to determine whether psoriasis patients on biologic therapy develop changes in naevi. Clinical and dermoscopic assessment of all melanocytic naevi was performed in 45 psoriasis patients on biologic therapy versus a control cohort of 43 subjects, using sequential digital dermoscopic imaging and total body photography. The mean follow-up period was 1.5 years. The study and control patients had comparable age, gender, previous and family history of non-melanoma skin cancers and melanomas, as well as previous sun exposure and total number of naevi. The number of naevi with major dermoscopic changes was 3% in the study and 1.9% in the control group, with an adjusted incidence rate ratio of 1.45 (95% confidence interval 0.90-2.33; P = 0.125). The rate of minor changes was 15.9% in the study group versus 19.4% in the control (adjusted incidence rate ratio 0.77, 95% confidence interval 0.57-1.08; P = 0.14). There were six new dysplastic naevi in 4/45 biologic patients and four in 4/43 controls; however, the difference was not significant (relative risk 0.96, 95% confidence interval -0.12 to 0.12; P = 0.95). There were no melanomas in either group. Over a mean follow-up period of 1.5 years there was no evidence of significantly different changes in naevi or development of new dysplastic naevi in psoriasis patients on biologic treatment compared to controls. © 2018 The Australasian College of Dermatologists.

Cortical thickness in children receiving intensive therapy for idiopathic apraxia of speech.

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Kadis, Darren S; Goshulak, Debra; Namasivayam, Aravind; Pukonen, Margit; Kroll, Robert; De Nil, Luc F; Pang, Elizabeth W; Lerch, Jason P

2014-03-01

Children with idiopathic apraxia experience difficulties planning the movements necessary for intelligible speech. There is increasing evidence that targeted early interventions, such as Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT), can be effective in treating these disorders. In this study, we investigate possible cortical thickness correlates of idiopathic apraxia of speech in childhood, and changes associated with participation in an 8-week block of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged 3-6 years, had significantly thicker left supramarginal gyri than a group of typically-developing age-matched controls (n = 11), t(20) = 2.84, p ≤ 0.05. Over the course of therapy, the children with apraxia (n = 9) experienced significant thinning of the left posterior superior temporal gyrus (canonical Wernicke's area), t(8) = 2.42, p ≤ 0.05. This is the first study to demonstrate experience-dependent structural plasticity in children receiving therapy for speech sound disorders.

Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications.

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Carney, R M; Rich, M W; teVelde, A; Saini, J; Clark, K; Freedland, K E

1987-08-01

Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.

Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease.

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Waterman, Matti; Xu, Wei; Dinani, Amreen; Steinhart, A Hillary; Croitoru, Kenneth; Nguyen, Geoffrey C; McLeod, Robin S; Greenberg, Gordon R; Cohen, Zane; Silverberg, Mark S

2013-03-01

Previous investigations of short-term outcomes after preoperative exposure to biological therapy in inflammatory bowel disease (IBD) were conflicting. The authors aimed to assess postoperative outcomes in patients who underwent abdominal surgery with recent exposure to anti-tumour necrosis factor therapy. A retrospective case-control study with detailed matching was performed for subjects with IBD with and without exposure to biologics within 180 days of abdominal surgery. Postoperative outcomes were compared between the groups. 473 procedures were reviewed consisting of 195 patients with exposure to biologics and 278 matched controls. There were no significant differences in most postoperative outcomes such as: length of stay, fever (≥ 38.5°C), urinary tract infection, pneumonia, bacteraemia, readmission, reoperations and mortality. On univariate analysis, procedures on biologics had more wound infections compared with controls (19% vs 11%; p=0.008), but this was not significant in multivariate analysis. Concomitant therapy with biologics and thiopurines was associated with increased frequencies of urinary tract infections (p=0.0007) and wound infections (p=0.0045). Operations performed ≤ 14 days from last biologic dose had similar rates of infections and other outcomes when compared with those performed within 15-30 days or 31-180 days. Patients with detectable preoperative infliximab levels had similar rates of wound infection compared with those with undetectable levels (3/10 vs 0/9; p=0.21). Preoperative treatment with TNF-α antagonists in patients with IBD is not associated with most early postoperative complications. A shorter time interval from last biological dose is not associated with increased postoperative complications. In most cases, surgery should not be delayed, and appropriate biological therapy may be continued perioperatively.

Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

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Joanna Świdrowska

2015-04-01

Full Text Available Objectives: Connective tissue diseases (CTD are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA. Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient’s clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS, it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods: Data from 24 patients with CTD treated with tumor necrosis factor--blockers (etanercept, adalimumab, golimumab and an interleukin-6 receptor blocker (tocilizumab were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results : Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1% during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions : In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS

Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

International Nuclear Information System (INIS)

Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

2014-01-01

Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

Predictors of mortality in patients with extensively drug-resistant Acinetobacter baumannii pneumonia receiving colistin therapy.

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Choi, Ik Sung; Lee, Yu Ji; Wi, Yu Mi; Kwan, Byung Soo; Jung, Kae Hwa; Hong, Woong Pyo; Kim, June Myong

2016-08-01

The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

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Kawara, Fumiaki; Fujita, Tsuyoshi; Morita, Yoshinori; Uda, Atsushi; Masuda, Atsuhiro; Saito, Masaya; Ooi, Makoto; Ishida, Tsukasa; Kondo, Yasuyuki; Yoshida, Shiei; Okuno, Tatsuya; Yano, Yoshihiko; Yoshida, Masaru; Kutsumi, Hiromu; Hayakumo, Takanobu; Yamashita, Kazuhiko; Hirano, Takeshi; Hirai, Midori; Azuma, Takeshi

2017-03-21

To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.

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Noujaim, Jonathan; Thway, Khin; Bajwa, Zia; Bajwa, Ayeza; Maki, Robert G; Jones, Robin L; Keller, Charles

2015-01-01

Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.

Does hormonal therapy influence sexual function in men receiving 3D conformal radiation therapy for prostate cancer?

International Nuclear Information System (INIS)

Chen, Christopher T.; Valicenti, Richard K.; Lu Jiandong; Derose, Troy; Dicker, Adam P.; Strup, Stephen E.; Mulholland, S. Grant; Hirsch, Irvin H.; McGinnis, David E.; Gomella, Leonard G.

2001-01-01

Purpose: We evaluated the effect of three-dimensional conformal radiation therapy (3D-CRT) with or without hormonal therapy (HT) on sexual function (SF) in prostate cancer patients whose SF was known before all treatment. Methods and Materials: Between March 1996 and March 1999, 144 patients received 3D-CRT (median dose = 70.2 Gy, range 66.6-79.2 Gy) for prostate cancer and had pre- and post-therapy SF data. All SF data were obtained with the O'Leary Brief SF Inventory, a self-administered, multidimensional, validated instrument. We defined total sexual potency as erections firm enough for penetration during intercourse. Mean follow-up time was 21 months (SD ± 11 months). The Wilcoxon signed-rank test was used to test for significance of the change from baseline. Results: Before 3D-CRT, 87 (60%) of 144 men were totally potent as compared to only 47 (47%) of 101 at 1-year follow-up. Of the 60 men totally potent at baseline and followed for at least 1 year, 35 (58%) remained totally potent. These changes corresponded to a significant reduction in SF (p<0.05). Patients who had 3D-CRT alone were more likely to be totally potent at 1 year than those receiving 3D-CRT with HT (56% vs. 31%, p=0.012); however, they were also more likely to be potent at baseline (71% vs. 44%, p=0.001). Although these two groups had a significant reduction in SF from baseline, their change was not significantly different from each other. Conclusion: These data indicate that 3D-CRT causes a significant reduction in total sexual potency as compared to pretreatment baseline. The addition of HT does not appear to increase the risk of sexual dysfunction

The incidence of dysphagia in patients receiving cerebral reperfusion therapy poststroke.

Science.gov (United States)

Ribeiro, Priscila W; Cola, Paula C; Gatto, Ana R; da Silva, Roberta G; Luvizutto, Gustavo J; Braga, Gabriel P; Schelp, Arthur O; de Arruda Henry, Maria A C; Bazan, Rodrigo

2014-07-01

The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann-Whitney test and considered significant if P is less than .05. The moderate and severe degrees of dysphagia were more frequent (P=.013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P=.045). We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Pannus growth regulators as potential targets for biological therapy in rheumatoid arthritis

Directory of Open Access Journals (Sweden)

A. S. Mikhaylova

2018-01-01

Full Text Available The main goal of treatment for rheumatoid arthritis (RA is to suppress inflammation using basic and symptomatic therapies. At the same time, the above strategy does not significantly stop joint  destruction that leads to disability in patients. The review analyzes  publications dealing with a search for intercellular interaction  regulators among the main effector cells in the pannus – fibroblast- like synoviocytes (FLSs. It assesses the influence of FLS aggression  factors on invasive pannus behavior, the possibility of their targeted deactivation during biological therapy, and the preliminary  results of similar treatment by the examples of animal models. It is  shown that the most promising targets for biological therapy may be FLS adhesion molecules, such as transmembrane receptor cadherin  11, integrins α5/β1, and VCAM1, ICAM1, which actively participate in the attachment of FLSs to the cartilage surface and activate their production of cytokines, growth factors and aggression factors.

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

International Nuclear Information System (INIS)

Orton, C; Borras, C; Carlson, D

2014-01-01

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

Energy Technology Data Exchange (ETDEWEB)

Orton, C [Wayne State University, Grosse Pointe, MI (United States); Borras, C [Radiological Physics and Health Services, Washington, DC (United States); Carlson, D [Yale University School of Medicine, New Haven, CT (United States)

2014-06-15

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

Bleeding-related admissions in patients with atrial fibrillation receiving antithrombotic therapy: results from the Tasmanian Atrial Fibrillation (TAF) study.

Science.gov (United States)

Admassie, Endalkachew; Chalmers, Leanne; Bereznicki, Luke R

2017-12-01

Limited data are available from the Australian setting regarding bleeding in patients with atrial fibrillation (AF) receiving antithrombotic therapy. We aimed to investigate the incidence of hospital admissions due to bleeding and factors associated with bleeding in patients with AF who received antithrombotic therapy. A retrospective cohort study was conducted involving all patients with AF admitted to the Royal Hobart Hospital, Tasmania, Australia, between January 2011 and July 2015. Bleeding rates were calculated per 100 patient-years (PY) of follow-up, and multivariable modelling was used to identify predictors of bleeding. Of 2202 patients receiving antithrombotic therapy, 113 presented to the hospital with a major or minor bleeding event. These patients were older, had higher stroke and bleeding risk scores and were more often treated with warfarin and multiple antithrombotic therapies than patients who did not experience bleeding. The combined incidence of major and minor bleeding was significantly higher in warfarin- versus direct-acting oral anticoagulants (DOAC)- and antiplatelet-treated patients (4.1 vs 3.0 vs 1.2 per 100 PY, respectively; p = 0.002). Similarly, the rate of major bleeding was higher in patients who received warfarin than in the DOAC and antiplatelet cohorts (2.4 vs 0.4 vs 0.6 per 100 PY, respectively; p = 0.001). In multivariate analysis, increasing age, prior bleeding, warfarin and multiple antithrombotic therapies were independently associated with bleeding. The overall rate of bleeding in this cohort was low relative to similar observational studies. The rate of major bleeding was higher in patients prescribed warfarin compared to DOACs, with a similar rate of major bleeding for DOACs and antiplatelet agents. Our findings suggest potential to strategies to reduce bleeding include using DOACs in preference to warfarin, and avoiding multiple antithrombotic therapies in patients with AF.

Epithelioid Sarcoma: Opportunities for Biology-driven Targeted Therapy

Directory of Open Access Journals (Sweden)

Jonathan eNoujaim

2015-08-01

Full Text Available Epithelioid sarcoma is a soft tissue sarcoma of children and young adults for which the preferred treatment for localised disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review we will summarize clinically-relevant biomarkers (e.g., SMARCB1, CA125, dysadherin and others with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR and polykinase inhibitors (e.g., sunitinib in the management of local and disseminated disease. Towards building a consortium of pharmaceutical, academic and non-profit collaborators, we will discuss the state of resources for investigating epithelioid sarcoma with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed towards effective biology-driven therapies.

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

Energy Technology Data Exchange (ETDEWEB)

Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, M. Alma [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); and others

2015-05-01

Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed

Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies.

Science.gov (United States)

Wu, Eric Q; Birnbaum, Howard G; Zhang, Huabin F; Ivanova, Jasmina I; Yang, Elaine; Mallet, David

2007-09-01

2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index. Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD. After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on

Biologic Treatments for Sports Injuries II Think Tank-Current Concepts, Future Research, and Barriers to Advancement, Part 1: Biologics Overview, Ligament Injury, Tendinopathy.

Science.gov (United States)

LaPrade, Robert F; Geeslin, Andrew G; Murray, Iain R; Musahl, Volker; Zlotnicki, Jason P; Petrigliano, Frank; Mann, Barton J

2016-12-01

Biologic therapies, including stem cells, platelet-rich plasma, growth factors, and other biologically active adjuncts, have recently received increased attention in the basic science and clinical literature. At the 2015 AOSSM Biologics II Think Tank held in Colorado Springs, Colorado, a group of orthopaedic surgeons, basic scientists, veterinarians, and other investigators gathered to review the state of the science for biologics and barriers to implementation of biologics for the treatment of sports medicine injuries. This series of current concepts reviews reports the summary of the scientific presentations, roundtable discussions, and recommendations from this think tank. © 2016 The Author(s).

Biological Therapy for Pyoderma Gangrenosum

Directory of Open Access Journals (Sweden)

Naw Ally Krüger

2013-10-01

Full Text Available Introduction: pyoderma gangrenosum (PG is a rare and severe neutrophilic dermatosis asso- ciated with inflammatory bowel disease (IBD and other systemic diseases such as rheu- matoid arthritis and hematological malignancies. Diagnosis is based on clinical criteria and exclusion of other skin disorders. There is no gold standard for the treatment of PG; traditionally intravenous corticosteroids are used, but recently the use of drugs that in- hibit tumor necrosis factor alpha (TNF-alpha has changed the management of PG, showing great effectiveness.Case report: female patient, 23 years old, diagnosed with severe nonspecific ulcerative colitis (UC three years ago, undergoing treatment with oral mesalamine and azathioprine. She developed PG fourteen days after hospital discharge; hospitalization was due to worsening of intestinal disease symptoms. She was successfully treated using biological therapy after unfavorable evolution with corticosteroid therapy.Conclusion: PG, a rare extraintestinal manifestation of IBD of difficult resolution that has significant impact on patient quality of life. The use of biological therapy for PG has higher efficacy in the treatment of patients decreasing wound healing time and return to daily activities. Resumo: Introdução: pioderma gangrenoso (PG é uma rara e grave dermatose neutrofílica associada a doença inflamatória intestinal (DII e a outras doenças sistêmicas como a artrite reumatoi- de e neoplasias hematológicas. O diagnóstico é baseado em critérios clínicos e exclusão de outras desordens da pele. Ainda não há padrão ouro para o tratamento do PG, tradicional- mente usa-se corticoides endovenosos, porém recentemente o uso de fármacos inibidores do fator de necrose tumoral alfa (TNF-alfa tem mudado o manejo do PG mostrando grande efetividade.Relato do caso: paciente feminina, 23 anos, com diagnóstico de retocolite ulcerativa inespe- cífica (RCUI severa há três anos, em tratamento com

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator.

Science.gov (United States)

Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J; Jordaens, Luc; Pedersen, Susanne S

2012-01-01

Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD. Between 2003 and 2010, 448 consecutively implanted ICD patients were enrolled in the prospective Mood and personality as precipitants of arrhythmia in patients with an Implantable cardioverter Defibrillator: A prospective Study (MIDAS), of which 429 completed the Hospital Anxiety and Depression Scale (HADS) and the ICD Patient Concerns questionnaire (ICDC) at baseline. Eighty per cent of all patients received beta-blocker therapy. In univariate analysis, beta-blocker therapy was not significantly associated with symptoms of anxiety, depression, and ICD concerns (β = -0.030, β = 0.007, and β = -0.045, respectively; all P's >0.36). Type of beta-blocker showed a trend towards significance for mean levels of ICD concerns (P = 0.09). No association was found between dosage and emotional distress (all P's >0.21). After adjustment for relevant clinical and demographic variables, the association of beta-blocker therapy and symptoms of anxiety, depression, and ICD concerns remained non-significant (β = 0.009, β = 0.037, and β = 0.019, respectively; all P's >0.47). In patients receiving an ICD, beta-blocker therapy was not associated with symptoms of anxiety, depression, and ICD concerns. Research is warranted that further elucidates the link between beta-blocker therapy and emotional distress in this vulnerable patient group.

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

Science.gov (United States)

Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L

2015-01-01

Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe

DEFF Research Database (Denmark)

Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein

2017-01-01

HR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. FINDINGS: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate......BACKGROUND: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. METHODS: In this registry analysis, we extracted...... patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (a...

Dominican Children with HIV Not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development

Directory of Open Access Journals (Sweden)

Maria Hernandez-Reif

2008-01-01

Full Text Available Forty-eight children (M age = 4.8 years infected with HIV/AIDS and living in the Dominican Republic were randomly assigned to a massage therapy or a play session control group. The children in the massage therapy group received two weekly 20-min massages for 12 weeks; the children in the control group participated in a play session (coloring, playing with blocks for the same duration and length as the massage therapy group. Overall, the children in the massage therapy group improved in self-help abilities and communication, suggesting that massage therapy may enhance daily functioning for children with HIV/AIDS. Moreover, the HIV infected children who were six or older also showed a decrease in internalizing behaviors; specifically depressive/anxious behaviors and negative thoughts were reduced. Additionally, baseline assessments revealed IQ equivalence below normal functioning for 70% of the HIV infected children and very high incidences of mood problems (depression, withdrawn for 40% of the children and anxiety problems for 20% of the children, suggesting the need for better monitoring and alternative interventions in countries with limited resources to improve cognition and the mental health status of children infected with HIV/AIDS.

Microbeam radiation therapy. Physical and biological aspects of a new cancer therapy and development of a treatment planning system

Energy Technology Data Exchange (ETDEWEB)

Bartzsch, Stefan

2014-11-05

Microbeam Radiation Therapy (MRT) is a novel treatment strategy against cancer. Highly brilliant synchrotron radiation is collimated to parallel, a few micrometre wide, planar beams and used to irradiate malignant tissues with high doses. The applied peak doses are considerably higher than in conventional radiotherapy, but valley doses between the beams remain underneath the established tissue tolerance. Previous research has shown that these beam geometries spare normal tissue, while being effective in tumour ablation. In this work physical and biological aspects of the therapy were investigated. A therapy planning system was developed for the first clinical treatments at the European Synchrotron Radiation Facility in Grenoble (France) and a dosimetry method based on radiochromic films was created to validate planned doses with measurements on a micrometre scale. Finally, experiments were carried out on a cellular level in order to correlate the physically planned doses with the biological damage caused in the tissue. The differences between Monte Carlo dose and dosimetry are less than 10% in the valley and 5% in the peak regions. Developed alternative faster dose calculation methods deviate from the computational intensive MC simulations by less than 15% and are able to determine the dose within a few minutes. The experiments in cell biology revealed an significant influence of intercellular signalling on the survival of cells close to radiation boundaries. These observations may not only be important for MRT but also for conventional radiotherapy.

Biologic targets identified from dynamic 18FDG-PET and implications for image-guided therapy

International Nuclear Information System (INIS)

Rusten, Espen; Malinen, Eirik; Roedal, Jan; Bruland, Oeyvind S.

2013-01-01

Purpose: The outcome of biologic image-guided radiotherapy depends on the definition of the biologic target. The purpose of the current work was to extract hyper perfused and hypermetabolic regions from dynamic positron emission tomography (D-PET) images, to dose escalate either region and to discuss implications of such image guided strategies. Methods: Eleven patients with soft tissue sarcomas were investigated with D-PET. The images were analyzed using a two-compartment model producing parametric maps of perfusion and metabolic rate. The two image series were segmented and exported to a treatment planning system, and biological target volumes BTV per and BTV met (perfusion and metabolism, respectively) were generated. Dice's similarity coefficient was used to compare the two biologic targets. Intensity-modulated radiation therapy (IMRT) plans were generated for a dose painting by contours regime, where planning target volume (PTV) was planned to 60 Gy and BTV to 70 Gy. Thus, two separate plans were created for each patient with dose escalation of either BTV per or BTV met . Results: BTV per was somewhat smaller than BTV met (209 ±170 cm 3 against 243 ±143 cm 3 , respectively; population-based mean and s.d.). Dice's coefficient depended on the applied margin, and was 0.72 ±0.10 for a margin of 10 mm. Boosting BTV per resulted in mean dose of 69 ±1.0 Gy to this region, while BTV met received 67 ±3.2 Gy. Boosting BTV met gave smaller dose differences between the respective non-boost DVHs (such as D 98 ). Conclusions: Dose escalation of one of the BTVs results in a partial dose escalation of the other BTV as well. If tumor aggressiveness is equally pronounced in hyper perfused and hypermetabolic regions, this should be taken into account in the treatment planning

Perspectives of newly diagnosed advanced cancer patients receiving dignity therapy during cancer treatment.

Science.gov (United States)

Dose, Ann Marie; Rhudy, Lori M

2018-01-01

Dignity therapy is a psychosocial intervention that has been used primarily at the end of life to improve quality of life and other patient outcomes, but many individuals are unable to complete it due to health decline and death. The purpose of this study was to identify what individuals with advanced pancreatic or lung cancer with limited life expectancy, undergoing active cancer treatment describe during the dignity therapy intervention as important to them when not immediately facing end of life. Twenty patients undergoing chemotherapy for advanced cancer participated in a dignity therapy intervention study. Initial interviews were analyzed using descriptive content analysis. Family provided the overall context and background for emerging themes of defining events, accomplishments, and God's plan, which led to lessons learned, and resulted in messages of hope. Interviews were often autobiographical in nature and contained much reminiscence, consistent with dignity therapy's intent. Few participants spoke about their cancer diagnoses during the interview. This study adds unique insight into the use of dignity therapy for those still receiving active cancer treatment, different from work by others in which it was offered only at end of life. As part of supportive care, clinicians need to validate the importance of family to those with advanced cancer and to provide opportunities for patients to share what they have learned throughout life and to impart messages of hope to those closest to them.

DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy.

Science.gov (United States)

Wang, Arthur; Pednekar, Noorie; Lehrer, Rachel; Todo, Akira; Sahni, Ramandeep; Marks, Stephen; Stiefel, Michael F

2017-01-01

The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy. A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3. Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3-8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS ( P DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively. The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.

Science.gov (United States)

Rowland, Nathan C; Starr, Philip A; Larson, Paul S; Ostrem, Jill L; Marks, William J; Lim, Daniel A

2015-02-01

Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain. © 2014 International Parkinson and Movement Disorder Society.

Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs.

Science.gov (United States)

Taroumian, Sara; Knowles, Susan L; Lisse, Jeffrey R; Yanes, James; Ampel, Neil M; Vaz, Austin; Galgiani, John N; Hoover, Susan E

2012-12-01

Coccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona. A retrospective chart review identified patients who developed coccidioidomycosis during treatment with DMARDs or BRMs. Patients were seen at least once in a university-affiliated or Veterans Affairs outpatient rheumatology clinic in Tucson, Arizona, between 2007 and 2009. Forty-four patients were identified. Rheumatologic treatment included a BRM alone (n = 11), a DMARD alone (n = 8), or combination therapy (n = 25). Manifestations of coccidioidomycosis included pulmonary infection (n = 29), disseminated disease (n = 9), and asymptomatic positive coccidioidal serologies (n = 6). After the diagnosis of coccidioidomycosis, 26 patients had BRMs and DMARDs stopped, 8 patients had BRMs stopped but DMARD therapy continued, and 10 patients had no change in their immunosuppressive therapy. Forty-one patients had antifungal therapy initiated for 1 month or longer. Followup data were available for 38 patients. BRM and/or DMARD therapy was continued or resumed in 33 patients, only 16 of whom continued concurrent antifungal therapy. None of the patients have had subsequent dissemination or complications of coccidioidomycosis. Re-treating rheumatic disease patients with a BRM and/or a DMARD after coccidioidomycosis appears to be safe in some patients. We propose a management strategy based on coccidioidomycosis disease activity. Copyright © 2012 by the American College of Rheumatology.

Biological imaging in radiation therapy: role of positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Nestle, Ursula; Hentschel, Michael; Grosu, Anca-Ligia [Departments of Radiation Oncology, University of Freiburg, Robert Koch Str. 3, 79106 Freiburg (Germany); Weber, Wolfgang [Nuclear Medicine, University of Freiburg, Robert Koch Str. 3, 79106 Freiburg (Germany)], E-mail: ursula.nestle@uniklinik-freiburg.de

2009-01-07

In radiation therapy (RT), staging, treatment planning, monitoring and evaluation of response are traditionally based on computed tomography (CT) and magnetic resonance imaging (MRI). These radiological investigations have the significant advantage to show the anatomy with a high resolution, being also called anatomical imaging. In recent years, so called biological imaging methods which visualize metabolic pathways have been developed. These methods offer complementary imaging of various aspects of tumour biology. To date, the most prominent biological imaging system in use is positron emission tomography (PET), whose diagnostic properties have clinically been evaluated for years. The aim of this review is to discuss the valences and implications of PET in RT. We will focus our evaluation on the following topics: the role of biological imaging for tumour tissue detection/delineation of the gross tumour volume (GTV) and for the visualization of heterogeneous tumour biology. We will discuss the role of fluorodeoxyglucose-PET in lung and head and neck cancer and the impact of amino acids (AA)-PET in target volume delineation of brain gliomas. Furthermore, we summarize the data of the literature about tumour hypoxia and proliferation visualized by PET. We conclude that, regarding treatment planning in radiotherapy, PET offers advantages in terms of tumour delineation and the description of biological processes. However, to define the real impact of biological imaging on clinical outcome after radiotherapy, further experimental, clinical and cost/benefit analyses are required. (topical review)

Biological imaging in radiation therapy: role of positron emission tomography.

Science.gov (United States)

Nestle, Ursula; Weber, Wolfgang; Hentschel, Michael; Grosu, Anca-Ligia

2009-01-07

In radiation therapy (RT), staging, treatment planning, monitoring and evaluation of response are traditionally based on computed tomography (CT) and magnetic resonance imaging (MRI). These radiological investigations have the significant advantage to show the anatomy with a high resolution, being also called anatomical imaging. In recent years, so called biological imaging methods which visualize metabolic pathways have been developed. These methods offer complementary imaging of various aspects of tumour biology. To date, the most prominent biological imaging system in use is positron emission tomography (PET), whose diagnostic properties have clinically been evaluated for years. The aim of this review is to discuss the valences and implications of PET in RT. We will focus our evaluation on the following topics: the role of biological imaging for tumour tissue detection/delineation of the gross tumour volume (GTV) and for the visualization of heterogeneous tumour biology. We will discuss the role of fluorodeoxyglucose-PET in lung and head and neck cancer and the impact of amino acids (AA)-PET in target volume delineation of brain gliomas. Furthermore, we summarize the data of the literature about tumour hypoxia and proliferation visualized by PET. We conclude that, regarding treatment planning in radiotherapy, PET offers advantages in terms of tumour delineation and the description of biological processes. However, to define the real impact of biological imaging on clinical outcome after radiotherapy, further experimental, clinical and cost/benefit analyses are required.

Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review.

Science.gov (United States)

Streed, Carl G; Harfouch, Omar; Marvel, Francoise; Blumenthal, Roger S; Martin, Seth S; Mukherjee, Monica

2017-08-15

Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy

Directory of Open Access Journals (Sweden)

Megan E. Kunka

2015-01-01

Full Text Available Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours, which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient’s actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Cognitive Behavioral Therapy for Psychosis (CBT-p) Delivered in a Community Mental Health Setting: A Case Comparison of Clients Receiving CBT Informed Strategies by Case Managers Prior to Therapy.

Science.gov (United States)

Sivec, Harry J; Montesano, Vicki L; Skubby, David; Knepp, Kristen A; Munetz, Mark R

2017-02-01

This exploratory case comparison examines the influence of case management activities on engagement and progress in psychotherapy for clients with schizophrenia. Six clients were recruited to participate in ten sessions of Cognitive Behavioral Therapy for psychosis (CBT-p). Three clients who had received Cognitive Behavioral techniques for psychosis (CBt-p, a low-intensity case management intervention) prior to receiving therapy were selected from referrals. A comparison group of three clients who had received standard case management services was selected from referrals. Cases within and across groups were compared on outcome measures and observations from case review were offered to inform future research. Delivering CBT-p services on a continuum from low- to high-intensity is discussed.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

Science.gov (United States)

Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

2014-01-01

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy

DEFF Research Database (Denmark)

Rask Lage-Hansen, Philip; Chrysidis, S; Lage-Hansen, M

2016-01-01

identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2......OBJECTIVES: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups. METHOD: Questionnaires developed to diagnose FM were...... applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate. RESULTS: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were...

Is exercise training safe and beneficial in patients receiving left ventricular assist device therapy?

Science.gov (United States)

Alsara, Osama; Perez-Terzic, Carmen; Squires, Ray W; Dandamudi, Sanjay; Miranda, William R; Park, Soon J; Thomas, Randal J

2014-01-01

Because a limited number of patients receive heart transplantation, alternative therapies, such as left ventricular assist device (LVAD) therapy, have emerged. Published studies have shown that LVAD implantation, by itself, improves exercise tolerance to the point where it is comparable to those with mild heart failure. The improvement in exercise capacity is maximally achieved 12 weeks after LVAD therapy and can continue even after explantation of the device. This effect varies, depending on the type of LVAD and exercise training. The available data in the literature on safety and benefits of exercise training in patients after LVAD implantation are limited, but the data that are available suggest that training trends to be safe and have an impact on exercise capacity in LVAD patients. Although no studies were identified on the role of cardiac rehabilitation programs in the management of LVAD patients, it appears that cardiac rehabilitation programs offer an ideal setting for the provision of supervised exercise training in this patient group.

Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study

NARCIS (Netherlands)

van der Have, Mike; Belderbos, Tim D. G.; Fidder, Herma H.; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P.; Eshuis, Emma J.; Ponsioen, Cyriel Y.; Siersema, Peter D.; van Oijen, Martijn G. H.; Oldenburg, Bas

2014-01-01

Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre

Screening prior to biological therapy in Crohn's disease : Adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study

NARCIS (Netherlands)

van der Have, Mike; Belderbos, Tim D. G.; Fidder, Herma H.; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P.; Eshuis, Emma J.; Ponsioen, Cyriel Y.; Siersema, Peter D.; van Oijen, Martijn G. H.; Oldenburg, Bas

2014-01-01

Background: Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. Aims: To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield.

Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

Directory of Open Access Journals (Sweden)

Elizabeth A Brezinski

Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa

NARCIS (Netherlands)

Mekuria, Legese A.; Sprangers, Mirjam A. G.; Prins, Jan M.; Yalew, Alemayehu W.; Nieuwkerk, Pythia T.

2015-01-01

Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

2016-03-15

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Dikken, Johan L. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Coit, Daniel G. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Baser, Raymond E.; Gönen, Mithat [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brennan, Murray F. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jansen, Edwin P.M. [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Boot, Henk [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Velde, Cornelis J.H. van de [Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Cats, Annemieke [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verheij, Marcel, E-mail: m.verheij@nki.nl [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

2014-03-01

Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy

Directory of Open Access Journals (Sweden)

Sandra López-Verdín

2013-01-01

Full Text Available Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV, and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow.

Biological basis of combination therapy with radiation and bleomycin

International Nuclear Information System (INIS)

Fukuda, Hiroshi; Matsuzawa, Taiju; Yokoyama, Kumiko; Okuyama, Shinichi; Yamaura, Hiroshi

1976-01-01

The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C 2 W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C 2 W cells were irradiated, incubated at 37 0 C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

Biological basis of combination therapy with radiation and bleomycin

Energy Technology Data Exchange (ETDEWEB)

Fukuda, H; Matsuzawa, T; Yokoyama, K; Okuyama, S; Yamaura, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1976-01-01

The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C/sub 2/W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C/sub 2/W cells were irradiated, incubated at 37/sup 0/C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising.

Virtual reality-based therapy for the treatment of balance deficits in patients receiving inpatient rehabilitation for traumatic brain injury.

Science.gov (United States)

Cuthbert, Jeffrey P; Staniszewski, Kristi; Hays, Kaitlin; Gerber, Don; Natale, Audrey; O'Dell, Denise

2014-01-01

To evaluate the feasibility and safety of utilizing a commercially available virtual reality gaming system as a treatment intervention for balance training. A randomized controlled trial in which assessment and analysis were blinded. An inpatient rehabilitation facility. Interventions included balance-based physical therapy using a Nintendo Wii, as monitored by a physical therapist, and receipt of one-on-one balance-based physical therapy using standard physical therapy modalities available for use in the therapy gym. Participants in the standard physical therapy group were found to have slightly higher enjoyment at mid-intervention, while those receiving the virtual reality-based balance intervention were found to have higher enjoyment at study completion. Both groups demonstrated improved static and dynamic balance over the course of the study, with no significant differences between groups. Correlational analyses suggest a relationship exists between Wii balance board game scores and BBS scores for measures taken beyond the baseline assessment. This study provides a modest level of evidence to support using commercially available VR gaming systems for the treatment of balance deficits in patients with a primary diagnosis of TBI receiving inpatient rehabilitation. Additional research of these types of interventions for the treatment of balance deficits is warranted.

The impact of religiosity and individual prayer activities on advanced cancer patients' health: is there any difference in function of whether or not receiving palliative anti-neoplastic therapy?

Science.gov (United States)

Paiva, Carlos Eduardo; Paiva, Bianca Sakamoto Ribeiro; Yennurajalingam, Sriram; Hui, David

2014-12-01

Consecutive patients (n = 221) presenting for initial consultation at a palliative care outpatient clinic were prospectively interviewed and then followed until death. Individual prayer activity (IPA) and global religion scores were associated with quality of life, symptoms, inflammatory markers, and survival. Analyses were adjusted for whether patients were still receiving anti-neoplastic therapies (ANTs) or not. Higher religion scores were associated with lower levels of inflammation in advanced cancer patients still undergoing ANTs. Additionally, higher IPA was an independent good prognostic factor in patients on active ANTs. Further studies are necessary to confirm these findings and to investigate possible biological mechanisms involved.

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

Science.gov (United States)

Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

2018-01-01

The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

Mind-body therapies and control of inflammatory biology: A descriptive review.

Science.gov (United States)

Bower, Julienne E; Irwin, Michael R

2016-01-01

The use of mind-body therapies, including Tai Chi, Qigong, yoga, and meditation, has grown steadily in recent years. These approaches have been shown to be effective in reducing symptoms and improving quality of life, and research has begun to examine the impact of these therapies on biological processes, including inflammation. A review of 26 randomized controlled trials was conducted to describe the effects of mind-body therapies (MBTs) on circulating, cellular, and genomic markers of inflammation. This qualitative evaluation showed mixed effects of MBTs on circulating inflammatory markers, including CRP and IL-6, and on measures of stimulated cytokine production. More consistent findings were seen for genomic markers, with trials showing decreased expression of inflammation-related genes and reduced signaling through the proinflammatory transcription factor NF-κB. Potential mechanisms for these effects are discussed, including alterations in neuroendocrine, neural, and psychological and behavioral processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy

DEFF Research Database (Denmark)

Ostrowski, Sisse R; Katzenstein, Terese L; Thim, Per T.

2005-01-01

Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined....

Use of artificial neural networks to predict biological outcomes for patients receiving radical radiotherapy of the prostate

International Nuclear Information System (INIS)

Gulliford, Sarah L.; Webb, Steve; Rowbottom, Carl G.; Corne, David W.; Dearnaley, David P.

2004-01-01

Background and purpose: This paper discusses the application of artificial neural networks (ANN) in predicting biological outcomes following prostate radiotherapy. A number of model-based methods have been developed to correlate the dose distributions calculated for a patient receiving radiotherapy and the radiobiological effect this will produce. Most widely used are the normal tissue complication probability and tumour control probability models. An alternative method for predicting specific examples of tumour control and normal tissue complications is to use an ANN. One of the advantages of this method is that there is no need for a priori information regarding the relationship between the data being correlated. Patients and methods: A set of retrospective clinical data from patients who received radical prostate radiotherapy was used to train ANNs to predict specific biological outcomes by learning the relationship between the treatment plan prescription, dose distribution and the corresponding biological effect. The dose and volume were included as a differential dose-volume histogram in order to provide a holistic description of the available data. Results: It was shown that the ANNs were able to predict biochemical control and specific bladder and rectum complications with sensitivity and specificity of above 55% when the outcomes were dichotomised. It was also possible to analyse information from the ANNs to investigate the effect of individual treatment parameters on the outcome. Conclusion: ANNs have been shown to learn something of the complex relationship between treatment parameters and outcome which, if developed further, may prove to be a useful tool in predicting biological outcomes

Targeted alpha therapy using Radium-223: From physics to biological effects.

Science.gov (United States)

Marques, I A; Neves, A R; Abrantes, A M; Pires, A S; Tavares-da-Silva, E; Figueiredo, A; Botelho, M F

2018-05-25

With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 ( 223 Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223 Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

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D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

DEFF Research Database (Denmark)

Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J

2012-01-01

Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We...... investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD....

Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

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Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

2012-01-01

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

Retrospective chart review of elderly patients receiving electroconvulsive therapy in a tertiary general hospital

OpenAIRE

Mosam Phirke; Harshal Sathe; Nilesh Shah; Sushma Sonavane; Anup Bharati; Avinash DeSousa

2015-01-01

Background: Electroconvulsive therapy (ECT) is the one of the oldest and effective treatments in psychiatry today. It has been used in a wide variety of psychiatric disorders in both young and old patients. Aims of the study: The present study is a retrospective chart review of geriatric patients receiving ECT as a treatment option in a tertiary care general hospital psychiatry setting. Methodology: The study evaluated ECT records over a 5-year period between the years 2010 and 2014...

Reasons for not receiving thrombolytic therapy in patients with acute myocardial infarction admitted to Bu-Ali Sina Hospital in Qazvin (2013-14

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MM. Daei

2017-04-01

Full Text Available This hospital-based cross-sectional study was conducted in 2013-14 in Qazvin Bu-Ali Sina Hospital. 170 patients with acute myocardial infarction who not receiving thrombolytic therapy entered the study and were analyzed. Medical history, physical examination, twelve lead ECG and cardiac biomarkers were obtained. The mean age of the patients was 63.4±14.4 years (from 19 to 90 years. 110 (64.7% of the patients were male and 48 (28.2% were diabetic. 86 (50% of patients due to late presentation and 47 (28% due to lack of diagnosis and 29 (17% due to contraindication and 8 (5% due to autolysis or coronary spam were not received thrombolytic therapy. We could reduce failure of receiving thrombolytic therapy more than seventy five percent with increasing people's awareness about the symptoms of myocardial infarction and skills of health staff in relation to the proper and timely diagnosis of myocardial infarction.

Impairments in static standing balance are highly prevalent among older adults receiving home-based physical therapy.

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Bohannon, Richard W

2012-01-01

Measures of balance are an important component of the physical therapist examination. This study investigated the usefulness of timed static stance durations for identifying balance impairments among patients receiving home-based physical therapy. This study involved the retrospective retrieval of data from the records of 48 patients at least 60 years of age. Their balance was measured under 3 foot configurations; that is, feet apart, feet together, and on each foot. Every patient demonstrated impaired standing balance. Most, but not all could balance 30 seconds with the feet apart or together. Only 19 could maintain balance on each of both feet. Of those who could so balance, none was able to achieve the average time of normal individuals of comparable age. Although not able to identify all aspects of balance, timed durations of stance under different configurations demonstrate a high prevalence of balance impairments among patients receiving home-based physical therapy. As the tests are objective, fast, and require little space, they can be advocated in such a setting.

Factors Associated with Quality of Life in Chronic Hepatitis C Patients Who Received Interferon Plus Ribavirin Therapy

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Shu-Chuan Chang

2008-06-01

Conclusion: The study found that patients with chronic hepatitis C who received interferon plus ribavirin therapy had poor quality of life during the treatment period. There was significant difference among patients with different financial stress, and a negative relationship between tangible support and hepatitis quality of life. Financial stress and tangible support are predictors of quality of life for all subjects. The results of this study might assist healthcare personnel to comprehend the quality of life and its related factors in patients with chronic hepatitis C treated with antiviral therapy.

Relationship between social support and the nutritional status of patients receiving radiation therapy for cancer

International Nuclear Information System (INIS)

Pulliam, L.W.

1985-01-01

The purpose of this descriptive, correlational study was to ascertain if there is a relationship between social support and the nutritional status of patients receiving radiation therapy for cancer. The data collection instruments used included the Norbeck Social Support Questionnaire (NSSQ), the Personal Characteristics Form, the abbreviated Health History, the Flow Sheet for Nutritional Data, and the Interview Schedule. For the analysis of data descriptive statistics were utilized to provide a profile of subjects, and correlational statistics were used to ascertain if there were relationships among the indicators of nutritional status and the social support variables. A convenience sample was comprised of 50 cancer patients deemed curable by radiation therapy. Findings included significant decreases in anthropometric measurements and biochemical tests during therapy. Serial assessments of nutritional status, therefore, are recommended for all cancer patients during therapy in order to plan and implement strategies for meeting the self-care requisites for food and water. No statistically significant relationships were found between the social support variables as measured by the NSSQ and the indicators of nutritional status. This suggests that nurses can assist patients by fostering support from actual and potential nutritional confidants

Denosumab for bone diseases: translating bone biology into targeted therapy.

Science.gov (United States)

Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

2011-12-01

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

Long-term changes in the quality of life of patients with rheumatoid arthritis treated with biological therapies.

Science.gov (United States)

Ortega-Valín, Luis; Mayorga-Bajo, Isabel; Prieto-Fernández, Carolina; Del Pozo-Ruiz, Javier; Gutiérrez-Gutiérrez, Esperanza; Pérez-Sandoval, Trinidad

2017-02-27

To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The iSBTc/SITC primer on tumor immunology and biological therapy of cancer: a summary of the 2010 program

Directory of Open Access Journals (Sweden)

Urba Walter J

2011-01-01

Full Text Available Abstract The Society for Immunotherapy of Cancer, SITC (formerly the International Society for Biological Therapy of Cancer, iSBTc, aims to improve cancer patient outcomes by advancing the science, development and application of biological therapy and immunotherapy. The society and its educational programs have become premier destinations for interaction and innovation in the cancer biologics community. For over a decade, the society has offered the Primer on Tumor Immunology and Biological Therapy of Cancer™ in conjunction with its Annual Scientific Meeting. This report summarizes the 2010 Primer that took place October 1, 2010 in Washington, D.C. as part of the educational offerings associated with the society's 25th anniversary. The target audience was basic and clinical investigators from academia, industry and regulatory agencies, and included clinicians, post-doctoral fellows, students, and allied health professionals. Attendees were provided a review of basic immunology and educated on the current status and most recent advances in tumor immunology and clinical/translational caner immunology. Ten prominent investigators presented on the following topics: innate immunity and inflammation; an overview of adaptive immunity; dendritic cells; tumor microenvironment; regulatory immune cells; immune monitoring; cytokines in cancer immunotherapy; immune modulating antibodies; cancer vaccines; and adoptive T cell therapy. Presentation slides, a Primer webinar and additional program information are available online on the society's website.

Predictors of receiving therapy among very low birth weight 2-year olds eligible for Part C early intervention in Wisconsin.

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McManus, Beth Marie; Robert, Stephanie; Albanese, Aggie; Sadek-Badawi, Mona; Palta, Mari

2013-07-11

The Individuals with Disabilities Education Act (Part C) authorizes states to establish systems to provide early intervention services (e.g., therapy) for children at risk, with the incentive of federal financial support. This study examines family and neighborhood characteristics associated with currently utilizing physical, occupational, or speech therapy among very low birthweight (VLBW) 2-year-old children who meet Wisconsin eligibility requirements for early intervention services (EI) due to developmental delay. This cross-sectional analysis used data from the Newborn Lung Project, a regional cohort study of VLBW infants hospitalized in Wisconsin's newborn intensive care units during 2003-2004. We included the 176 children who were age two at follow-up, and met Wisconsin state eligibility requirements for EI based on developmental delay. Exact logistic regression was used to describe child and neighborhood socio-demographic correlates of parent-reported receipt of therapy. Among VLBW children with developmental delay, currently utilizing therapy was higher among children with Medicaid (aOR = 5.3, 95% CI: 1.3, 28.3) and concomitant developmental disability (aOR = 5.2, 95% CI: 2.1, 13.3) and lower for those living in a socially more disadvantaged neighborhood (aOR=0.48, 95% CI: 0.21, 0.98, per tertile). Among a sample of VLBW 2-year olds with developmental delays who are EI-eligible in WI, 4 out of 5 were currently receiving therapy, per parent report. Participation in Medicaid positively influences therapy utilization. Children with developmental difficulties who live in socially disadvantaged neighborhoods are at highest risk for not receiving therapy.

A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study

DEFF Research Database (Denmark)

Lundgren, Jens Dilling; Mocroft, Amanda; Gatell, Jose M

2002-01-01

The risk of clinical progression for human immunodeficiency virus (HIV)-infected persons receiving treatment with highly active antiretroviral therapy (HAART) is poorly defined. From an inception cohort of 8457 HIV-infected persons, 2027 patients who started HAART during prospective follow-up wer...

[Biologics and mycobacterial diseases].

Science.gov (United States)

Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

2013-03-01

developing TB. Lastly, Dr. Matsumoto stressed the risk of discontinuing TNF-alpha inhibitor during treatment for tuberculosis. He showed from his clinical experience that TNF-alpha inhibitor can be safely used in active TB patient receiving effective antituberculosis chemotherapy and it is even more effective for prevention of paradoxical response. Active discussion was done about the four topics, including the matter beyond present guidelines. We hope these discussions will form the basis for the establishment of new guideline for the management of mycobacterial disease when using immunosuppressive agents including biologics. 1. The risk of developing tuberculosis (TB) and situations of screening for TB risk at administration of biologics-the case of rheumatoid arthritis: Shigeto TOHMA (Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital) We calculated the standardized incidence ratio (SIR) of TB from the clinical data on National Database of Rheumatic Diseases by iR-net in Japan (NinJa) and compared with the SIR of TB from the data of the post-marketing surveillances of five biologics. Among 43584 patient-years, forty patients developed TB. The SIR of TB in NinJa was 4.34 (95%CI: 3.00-5.69). According to the post-marketing surveillances of 5 biologics, the SIR of TB were 3.62-34.4. The incidence of TB in patients with RA was higher than general population in Japan, and was increased more by some biologics. We have to recognize the risk of TB when we start biologics therapy to patients with RA. Although the frequency of implementation of QuantiFERON test (QFT) had gradually increased, it was still limited to 41%. In order to predict the risk of developing TB and to prevent TB, it might be better to check all RA patients by QFT at time time of biologics administration. 2. Biologics and nontuberculous mycobacterial diseases: Hitoshi TOKUDA (Social Insurance Central General Hospital) Several topics about the

Biological therapy in inflammatory bowel diseases: Access in Central and Eastern Europe

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Rencz, Fanni; Péntek, Márta; Bortlik, Martin; Zagorowicz, Edyta; Hlavaty, Tibor; Śliwczyński, Andrzej; Diculescu, Mihai M; Kupcinskas, Limas; Gecse, Krisztina B; Gulácsi, László; Lakatos, Peter L

2015-01-01

Biological drugs opened up new horizons in the management of inflammatory bowel diseases (IBD). This study focuses on access to biological therapy in IBD patients across 9 selected Central and Eastern European (CEE) countries, namely Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovakia. Literature data on the epidemiology and disease burden of IBD in CEE countries was systematically reviewed. Moreover, we provide an estimation on prevalence of IBD as well as biological treatment rates. In all countries with the exception of Romania, lower biological treatment rates were observed in ulcerative colitis (UC) compared to Crohn’s disease despite the higher prevalence of UC. Great heterogeneity (up to 96-fold) was found in access to biologicals across the CEE countries. Poland, Bulgaria, Romania and the Baltic States are lagging behind Hungary, Slovakia and the Czech Republic in their access to biologicals. Variations of reimbursement policy may be one of the factors explaining the differences to a certain extent in Bulgaria, Latvia, Lithuania, and Poland, but association with other possible determinants (differences in prevalence and incidence, price of biologicals, total expenditure on health, geographical access, and cost-effectiveness results) was not proven. We assume, nevertheless, that health deterioration linked to IBD might be valued differently against other systemic inflammatory conditions in distinct countries and which may contribute to the immense diversity in the utilization of biological drugs for IBD. In conclusion, access to biologicals varies widely among CEE countries and this difference cannot be explained by epidemiological factors, drug prices or total health expenditure. Changes in reimbursement policy could contribute to better access to biologicals in some countries. PMID:25684937

H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

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Rahier, Jean-François; Papay, Pavol; Salleron, Julia; Sebastian, Shaji; Marzo, Manuela; Peyrin-Biroulet, Laurent; Garcia-Sanchez, Valle; Fries, Walter; van Asseldonk, Dirk P; Farkas, Klaudia; de Boer, Nanne K; Sipponen, Taina; Ellul, Pierre; Louis, Edouard; Peake, Simon T C; Kopylov, Uri; Maul, Jochen; Makhoul, Badira; Fiorino, Gionata; Yazdanpanah, Yazdan; Chaparro, Maria

2011-04-01

Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy. The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

Energy Technology Data Exchange (ETDEWEB)

Taleei, R; Qin, N; Jiang, S [UT Southwestern Medical Center, Dallas, TX (United States); Peeler, C [UT MD Anderson Cancer Center, Houston, TX (United States); Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relative Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.

Biosimilars: A new scenario in biologic therapies.

Science.gov (United States)

Serra López-Matencio, José M; Morell Baladrón, Alberto; Castañeda, Santos

There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Risk factors for death in HIV-infected adult African patients receiving anti-retroviral therapy.

Science.gov (United States)

Siika, A M; Wools-Kaloustian, K; Mwangi, A W; Kimaiyo, S N; Diero, L O; Ayuo, P O; Owino-Ong'or, W D; Sidle, J E; Einterz, R M; Yiannoutsos, C T; Musick, B; Tierney, W M

2010-11-01

To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART). Retrospective Case-control study. The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya. Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p<0.003). Patients attending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p<0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level <10 grams% were associated with time to death while age, marital status, educational level, employment status and weight were not. Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital.

Retrospective chart review of elderly patients receiving electroconvulsive therapy in a tertiary general hospital

Directory of Open Access Journals (Sweden)

Mosam Phirke

2015-01-01

Full Text Available Background: Electroconvulsive therapy (ECT is the one of the oldest and effective treatments in psychiatry today. It has been used in a wide variety of psychiatric disorders in both young and old patients. Aims of the study: The present study is a retrospective chart review of geriatric patients receiving ECT as a treatment option in a tertiary care general hospital psychiatry setting. Methodology: The study evaluated ECT records over a 5-year period between the years 2010 and 2014, and it was observed that 23 elderly patients (aged ≥60 years had received ECT. Results: The patients received modified bitemporal ECT using a brief pulse ECT machine and had no major complications. A total of 184 ECT treatments were administered at an average of 8 treatments per case. The major diagnoses of patients were schizophrenia and major depression. The main indications of ECT were intolerance to medication, suicidal behavior and aggression. Out of the 23 elderly patients, 18 (78.26% showed a good response to ECT. The only complication noted was memory loss and confusion in 3 cases. Patients with medical illnesses like hypertension, diabetes and both together received ECT without any complications. Conclusions: This study adds to the scarce database on the use of ECT in elderly patients in India and adds evidence to the fact that ECT is a safe and effective treatment in the elderly.

Predictors of psychological well-being in a diverse sample of HIV-positive patients receiving highly active antiretroviral therapy.

Science.gov (United States)

Safren, Steven A; Radomsky, Adam S; Otto, Michael W; Salomon, Elizabeth

2002-01-01

The purpose of the present study was to identify variables relevant to psychological well-being in HIV patients receiving highly active antiretroviral therapy (HAART). Multiple stressors accompany living with HIV while managing a HAART regimen. However, a variety of cognitive and behavioral variables can protect against or augment the deleterious effects of stress in this population. The authors hypothesized that satisfaction with social support, coping styles, and maladaptive attributions about HIV would explain more variance in psychological well-being than stressful life events per se. Participants were individuals with HIV receiving antiretroviral therapy-either starting a new HAART regimen or having difficulties adhering to their current regimen. Satisfaction with social support, coping styles, and punishment beliefs about HIV were uniquely associated with depression, quality of life, and self-esteem over and above the effects of stressful life events. These results provide support for continued psychosocial interventions that target these variables among patients with HIV.

An analysis of the incidence and related factors for radiation dermatitis in breast cancer patients who receive radiation therapy

International Nuclear Information System (INIS)

Lee, Sun Young; Kwon, Hyoung Cheol; Kim, Jung Soo; Lee, Heui Kwan

2010-01-01

We analyzed the incidence and related factors of radiation dermatitis; at first, to recognize whether a decrease in radiation dermatitis is possible or not in breast cancer patients who received radiation therapy. Of 338 patients, 284 with invasive breast cancer who received breast conservation surgery with radiotherapy at Chonbuk National University Hospital from January 2007 to June 2009 were evaluated. Patients who also underwent bolus, previous contralateral breast irradiation and irradiation on both breasts were excluded. For patients who appeared to have greater than moderate radiation dermatitis, the incidence and relating factors for radiation dermatitis were analyzed retrospectively. A total of 207 and 77 patients appeared to have RTOG grade 0/1 or above RTOG grade 2 radiation dermatitis, respectively. The factors found to be statistically significant for the 77 patients who appeared to have greater than moderate radiation dermatitis include the presence of lymphocele due to the stasis of lymph and lymph edema which affect the healing disturbance of radiation dermatitis (p=0.003, p=0.001). Moreover, an allergic reaction to plaster due to the immune cells of skin and the activation of cytokine and concomitant hormonal therapy were also statistically significant factors (p=0.001, p=0.025). Most of the breast cancer patients who received radiation therapy appeared to have a greater than mild case of radiation dermatitis. Lymphocele, lymphedema, an allergy to plaster and concomitant hormonal therapy which affect radiation dermatitis were found to be significant factors. Consequently, we should eliminate lymphocele prior to radiation treatment for patients who appear to have an allergic reaction to plaster. We should also instruct patients of methods to maintain skin moisture if they appear to have a greater than moderate case of radiation dermatitis.

Energy expenditure in growing preterm infants receiving massage therapy.

Science.gov (United States)

Lahat, Sharon; Mimouni, Francis B; Ashbel, Gina; Dollberg, Shaul

2007-08-01

Massage therapy has been consistently shown to increase weight gain in preterm infants. The mechanism of this presumed improved metabolic efficiency is unknown. We conducted the following trial to test the hypothesis that massage therapy reduces energy expenditure in growing healthy preterm infants. A prospective, randomized, cross-over design study was conducted in 10 healthy, appropriate weights for gestational age, gavage fed preterm infants. Each infant was studied twice: after a period of either 5 days of massage therapy, or after a period of 5 days without massage therapy. Infants were randomized to 5 days of massage followed by 5 days of no massage (n = 5) or the opposite sequence (n = 5). During the massage therapy period, massage was provided daily for three 15 minute periods at the beginning of each 3 hour period every morning. Metabolic measurements were performed by indirect calorimetry, using the Deltatrac II Metabolic cart. Energy expenditure was significantly lower in infants after the 5 day massage therapy period (59.6 +/- 3.6 Kcal/Kg/ 24 hours) than after the period without (63.1 +/- 5.4 Kcal/Kg/ 24 hours) (p = 0.05). Energy expenditure is significantly lowered by 5 days of massage therapy in metabolically and thermally stable preterm infants. This decrease in energy expenditure may be in part responsible for the enhanced growth caused by massage therapy.

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

Energy Technology Data Exchange (ETDEWEB)

Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-04-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

International Nuclear Information System (INIS)

Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-01-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

No Evidence for Decay of the Latent Reservoir in HIV-1–Infected Patients Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy

Science.gov (United States)

Gandhi, Rajesh T.; Bosch, Ronald J.; Aga, Evgenia; Albrecht, Mary; Demeter, Lisa M.; Dykes, Carrie; Bastow, Barbara; Para, Michael; Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.; Eron, Joseph J.

2010-01-01

Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. PMID:20001856

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet.

Science.gov (United States)

Chauveau, Philippe; Couzi, Lionel; Vendrely, Benoit; de Précigout, Valérie; Combe, Christian; Fouque, Denis; Aparicio, Michel

2009-10-01

The consequences of a supplemented very-low-protein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for >3 mo (inclusion period: 1985-2000) and started dialysis after a mean diet duration of 33.1 mo (4-230 mo). The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy.

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab

Directory of Open Access Journals (Sweden)

Suenaga M

2015-01-01

Full Text Available Mitsukuni Suenaga, Nobuyuki Mizunuma, Eiji Shinozaki, Satoshi Matsusaka, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Background: Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev. We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings.Methods: Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E, thrombus >40 mm in diameter (S, thrombus involving the superior vena cava (C, and decreased blood flow (V.Results: Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9% by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%. Of these 56 patients, 11 (19.6% received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%, as well as V in two (18.2%, S + V + C in one (9.1%, E + S + V in one (9.1%, E + C in one (9.1%, E in one (9.1%, and C in one (9.1%. All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%. Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%, but there were no treatment

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders

Directory of Open Access Journals (Sweden)

D'Angelo S

2017-03-01

Full Text Available Salvatore D’Angelo,1 Giuseppina Tramontano,1 Michele Gilio,1 Pietro Leccese,1 Ignazio Olivieri1,2 1Rheumatology Institute of Lucania (IRel - Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza and Matera, 2Basilicata Ricerca Biomedica (BRB Foundation, Potenza, Italy Abstract: Psoriatic arthritis (PsA is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab as well as interleukin (IL-12/23 (ustekinumab and IL-17 (secukinumab inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient’s preferences (e.g., administration route, and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed. Keywords: psoriatic arthritis, treatment, biological drugs, TNF inhibitors, ustekinumab, secukinumab

New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

Science.gov (United States)

Carrascosa, J M; Del-Alcazar, E

2018-04-01

Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

Reactivation of BK polyomavirus in patients with multiple sclerosis receiving natalizumab therapy.

LENUS (Irish Health Repository)

Lonergan, Roisin M

2012-02-01

Natalizumab therapy in multiple sclerosis has been associated with JC polyomavirus-induced progressive multifocal leucoencephalopathy. We hypothesized that natalizumab may also lead to reactivation of BK, a related human polyomavirus capable of causing morbidity in immunosuppressed groups. Patients with relapsing remitting multiple sclerosis treated with natalizumab were prospectively monitored for reactivation of BK virus in blood and urine samples, and for evidence of associated renal dysfunction. In this cohort, JC and BK DNA in blood and urine; cytomegalovirus (CMV) DNA in blood and urine; CD4 and CD8 T-lymphocyte counts and ratios in peripheral blood; and renal function were monitored at regular intervals. BK subtyping and noncoding control region sequencing was performed on samples demonstrating reactivation. Prior to commencement of natalizumab therapy, 3 of 36 patients with multiple sclerosis (8.3%) had BK viruria and BK reactivation occurred in 12 of 54 patients (22.2%). BK viruria was transient in 7, continuous in 2 patients, and persistent viruria was associated with transient viremia. Concomitant JC and CMV viral loads were undetectable. CD4:CD8 ratios fluctuated, but absolute CD4 counts did not fall below normal limits. In four of seven patients with BK virus reactivation, transient reductions in CD4 counts were observed at onset of BK viruria: these resolved in three of four patients on resuppression of BK replication. No renal dysfunction was observed in the cohort. BK virus reactivation can occur during natalizumab therapy; however, the significance in the absence of renal dysfunction is unclear. We propose regular monitoring for BK reactivation or at least for evidence of renal dysfunction in patients receiving natalizumab.

Should over-treatment of axial spondyloarthritis with biologics remain a concern after the issue of the new ASAS criteria? Data from REGISPONSERBIO (Spanish Register of Biological Therapy in Spondyloarthritides).

Science.gov (United States)

Moreno, Mireia; Gratacós, Jordi; Navarro-Compán, Victoria; de Miguel, Eugenio; Font, Pilar; Clavaguera, Teresa; Linares, Luis Francisco; Joven, Beatriz; Juanola, Xavier

2018-05-08

To study whether disease status at treatment initiation has changed after the issue of the ASAS classification criteria. REGISPONSERBIO registers patients with axial spondyloarthritis (axSpA) on biological treatment since 2013. It includes patients starting biological treatment (incident) or already on biological therapies (prevalent). Patients in both groups were compared in terms of: age at disease onset and at treatment start, disease duration, gender, HLA-B27, body mass index (BMI), BASDAI, BASFI, C-reactive protein, ESR, metrological data, ASQoL, WAPAI, extra-articular manifestations, comorbidities, radiological study, type of biological treatment and concomitant treatments. 256 patients were included, of whom 174 (65%) were already on biologic therapy. Compared to incident patients, prevalent patients started treatment with longer disease duration (15 vs. 8.6 years; p<0.001), a higher proportion of them were men (83% vs. 67%; p=0.01), a smaller proportion of them showed non-radiographic axial spondylarthritis (nr-axSpA)(17% vs. 32%; p<0.01), and a higher proportion had HLAB27 (85% vs. 73%; p=0.02). There were no statistically significant differences in terms of disease activity, degree of disability, quality of life, or prevalence of extra-articular manifestations. Data suggest that, after the issue of the new classification criteria for SpA, biological therapy is being administered earlier than previously in SpA patients and in a higher proportion of patients with nr-axSpA. However, this change in prescribing profile, apparently, has not caused an over-treatment, as patients do not seem to have a lower disease burden than prior to the issue of the criteria.

Cost-utility Analysis: Thiopurines Plus Endoscopy-guided Biological Step-up Therapy is the Optimal Management of Postoperative Crohn's Disease.

Science.gov (United States)

Candia, Roberto; Naimark, David; Sander, Beate; Nguyen, Geoffrey C

2017-11-01

Postoperative recurrence of Crohn's disease is common. This study sought to assess whether the postoperative management should be based on biological therapy alone or combined with thiopurines and whether the therapy should be started immediately after surgery or guided by either endoscopic or clinical recurrence. A Markov model was developed to estimate expected health outcomes in quality-adjusted life years (QALYs) and costs in Canadian dollars (CAD$) accrued by hypothetical patients with high recurrence risk after ileocolic resection. Eight strategies of postoperative management were evaluated. A lifetime time horizon, an annual discount rate of 5%, a societal perspective, and a cost-effectiveness threshold of 50,000 CAD$/QALY were assumed. Deterministic and probabilistic sensitivity analyses were conducted. The model was validated against randomized trials and historical cohorts. Three strategies dominated the others: endoscopy-guided full step-up therapy (14.80 QALYs, CAD$ 462,180), thiopurines immediately post-surgery plus endoscopy-guided biological step-up therapy (14.89 QALYs, CAD$ 464,099) and combination therapy immediately post-surgery (14.94 QALYs, CAD$ 483,685). The second strategy was the most cost-effective, assuming a cost-effectiveness threshold of 50,000 CAD$/QALY. Probabilistic sensitivity analysis showed that the second strategy has the highest probability of being the optimal alternative in all comparisons at cost-effectiveness thresholds from 30,000 to 100,000 CAD$/QALY. The strategies guided only by clinical recurrence and those using biologics alone were dominated. According to this decision analysis, thiopurines immediately after surgery and addition of biologics guided by endoscopic recurrence is the optimal strategy of postoperative management in patients with Crohn's disease with high risk of recurrence (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B654).

Biological effectiveness and application of heavy ions in radiation therapy described by a physical and biological model

International Nuclear Information System (INIS)

Olsen, K.J.; Hansen, J.W.

1982-12-01

A description is given of the physical basis for applying track structure theory in the determination of the effectiveness of heavy-ion irradiation of single- and multi-hit target systems. It will be shown that for applying the theory to biological systems the effectiveness of heavy-ion irradiation is inadequately described by an RBE-factor, whereas the complete formulation of the probability of survival must be used, as survival depends on both radiation quality and dose. The theoretical model of track structure can be used in dose-effect calculations for neutron-, high-LET, and low-LET radiation applied simultaneously in therapy. (author)

Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

Science.gov (United States)

Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

2014-05-01

Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (Pstatistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including

WE-E-17A-07: Patient-Specific Mathematical Neuro-Oncology: Biologically-Informed Radiation Therapy and Imaging Physics

Energy Technology Data Exchange (ETDEWEB)

Swanson, K; Corwin, D [Northwestern University, Chicago, IL (United States); Rockne, R

2014-06-15

Purpose: To demonstrate a method of generating patient-specific, biologically-guided radiation therapy (RT) plans and to quantify and predict response to RT in glioblastoma. We investigate the biological correlates and imaging physics driving T2-MRI based response to radiation therapy using an MRI simulator. Methods: We have integrated a patient-specific biomathematical model of glioblastoma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated RT optimization to construct individualized, biologically-guided plans. Patient-individualized simulations of the standard-of-care and optimized plans are compared in terms of several biological metrics quantified on MRI. An extension of the PI model is used to investigate the role of angiogenesis and its correlates in glioma response to therapy with the Proliferation-Invasion-Hypoxia- Necrosis-Angiogenesis model (PIHNA). The PIHNA model is used with a brain tissue phantom to predict tumor-induced vasogenic edema, tumor and tissue density that is used in a multi-compartmental MRI signal equation for generation of simulated T2- weighted MRIs. Results: Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized RT plans would have a significant impact on delaying tumor progression, with Days Gained increases from 21% to 105%. For the T2- MRI simulations, initial validation tests compared average simulated T2 values for white matter, tumor, and peripheral edema to values cited in the literature. Simulated results closely match the characteristic T2 value for each tissue. Conclusion: Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for RT generated biologically-guided doses that decreased normal tissue dose and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma. Simulated T2-MRI

WE-E-17A-07: Patient-Specific Mathematical Neuro-Oncology: Biologically-Informed Radiation Therapy and Imaging Physics

International Nuclear Information System (INIS)

Swanson, K; Corwin, D; Rockne, R

2014-01-01

Purpose: To demonstrate a method of generating patient-specific, biologically-guided radiation therapy (RT) plans and to quantify and predict response to RT in glioblastoma. We investigate the biological correlates and imaging physics driving T2-MRI based response to radiation therapy using an MRI simulator. Methods: We have integrated a patient-specific biomathematical model of glioblastoma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated RT optimization to construct individualized, biologically-guided plans. Patient-individualized simulations of the standard-of-care and optimized plans are compared in terms of several biological metrics quantified on MRI. An extension of the PI model is used to investigate the role of angiogenesis and its correlates in glioma response to therapy with the Proliferation-Invasion-Hypoxia- Necrosis-Angiogenesis model (PIHNA). The PIHNA model is used with a brain tissue phantom to predict tumor-induced vasogenic edema, tumor and tissue density that is used in a multi-compartmental MRI signal equation for generation of simulated T2- weighted MRIs. Results: Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized RT plans would have a significant impact on delaying tumor progression, with Days Gained increases from 21% to 105%. For the T2- MRI simulations, initial validation tests compared average simulated T2 values for white matter, tumor, and peripheral edema to values cited in the literature. Simulated results closely match the characteristic T2 value for each tissue. Conclusion: Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for RT generated biologically-guided doses that decreased normal tissue dose and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma. Simulated T2-MRI

A Randomized Controlled Trial of Lorazepam to Reduce Liver Motion in Patients Receiving Upper Abdominal Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Tsang, Derek S.; Voncken, Francine E.M.; Tse, Regina V. [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada); Sykes, Jenna [Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto (Canada); Wong, Rebecca K.S.; Dinniwell, Rob E.; Kim, John; Ringash, Jolie; Brierley, James D.; Cummings, Bernard J.; Brade, Anthony [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada); Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada)

2013-12-01

Purpose: Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion. Methods and Materials: Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy. Results: Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant. Conclusions: Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm.

Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

International Nuclear Information System (INIS)

Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

2010-01-01

Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

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Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

2015-01-01

In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

Energy Technology Data Exchange (ETDEWEB)

Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Podoloff, Donald A. [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Medeiros, L. Jeffrey [Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Arzu, Isidora [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E. [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reed, Valerie K.; Kedir, Aziza; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Office of the Executive Vice President and Physician-in-Chief, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-06-01

Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

Significant renoprotective effect of telbivudine during preemptive antiviral therapy in advanced liver cancer patients receiving cisplatin-based chemotherapy: a case-control study.

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Lin, Chih-Lang; Chien, Rong-Nan; Yeh, Charisse; Hsu, Chao-Wei; Chang, Ming-Ling; Chen, Yi-Cheng; Yeh, Chau-Ting

2014-12-01

Cisplatin is a known nephrotoxic agent requiring vigorous hydration before use. However, aggressive hydration could be life-threatening. Therefore, in cirrhotic patients with advanced hepatocellular carcinoma (HCC) under cisplatin-based chemotherapy, the risk of nephrotoxicity increased. Because previous studies showed that long-term telbivudine treatment improved renal function in chronic hepatitis B virus (HBV) infected patients, we conducted a case-control study to evaluate the clinical outcome of telbivudine preemptive therapy in HBV-related advanced HCC patients treated by combination chemotherapy comprising 5-fluorouracil, mitoxantrone and cisplatin (FMP). From June 2007 to March 2012, 60 patients with HBV-related advanced HCC, all receiving the same FMP chemotherapy protocol, were enrolled. Of them, 20 did not receive any antiviral therapy, whereas the remaining 40 patients (sex and age matched) received telbivudine preemptive therapy. Progressive decrease of aminotransferase levels (p 100 ml/min (n = 34), the median overall survival was significantly longer in the telbivudine-treated group (12.1 vs. 4.9 months; p = 0.042). Preemptive use of telbivudine significantly prevented eGFR deterioration caused by cisplatin-based chemotherapy in HBV-related advanced HCC. In patients with initially sufficient eGFR level, telbivudine treatment was associated with a longer overall survival.

Feasibility of Using the Helping Alliance Questionnaire II as a Self-Report Measure for Individuals with a Psychiatric Disorder Receiving Music Therapy.

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Hannibal, Niels; Domingo, Maria Rodrigo; Valentin, Jan B; Licht, Rasmus W

2017-11-01

No specific instrument has been developed for measuring alliance during music therapy. To evaluate the feasibility of using the Helping Alliance Questionnaire II (HAq-II) as a self-report measure for individuals receiving treatment for a psychiatric disorder. Specifically, we examined the percent of patients who filled out the questionnaire, and when completed, whether there were any missing items. We also examined internal consistency and associations between patient variables and HAq-II scores. Between October 2013 and April 2014, we invited 45 individuals with a psychiatric disorder, who were also receiving music therapy, to fill out the HAq-II. We also collected clinical data from each person's record. Thirty-one (69%) of the 45 invited patients filled out the HAq-II, and of those completed, only three had missing items. Of the 45 invited patients, thirty (67%) had a diagnosis of schizophrenia or other psychotic disorders, and 11 (24%) were diagnosed with other psychiatric disorders. In terms of diagnosis and other clinical variables, no statistically significant differences were found between the 31 patients who filled out the HAq-II and the 14 patients who did not return the questionnaire. The median HAq-II score was 5.11 (range 3.74-6.00), indicating a relatively high alliance. We did not find any statistically significant associations between the HAq-II scores and potential predictors of interest. The Cronbach's alpha was 0.85. Completion of the HAq-II was fairly high in this group of individuals with psychiatric diagnoses who were receiving music therapy. Internal consistency of the HAq-II was acceptable. Relatively high HAq-II scores suggest a high degree of therapeutic alliance, but the external validity of the HAq-II and the relationship between scores and therapy needs further evaluation. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Palliative medicine consultation for preparedness planning in patients receiving left ventricular assist devices as destination therapy.

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Swetz, Keith M; Freeman, Monica R; AbouEzzeddine, Omar F; Carter, Kari A; Boilson, Barry A; Ottenberg, Abigale L; Park, Soon J; Mueller, Paul S

2011-06-01

To assess the benefit of proactive palliative medicine consultation for delineation of goals of care and quality-of-life preferences before implantation of left ventricular assist devices as destination therapy (DT). We retrospectively reviewed the cases of patients who received DT between January 15, 2009, and January 1, 2010. Of 19 patients identified, 13 (68%) received proactive palliative medicine consultation. Median time of palliative medicine consultation was 1 day before DT implantation (range, 5 days before to 16 days after). Thirteen patients (68%) completed advance directives. The DT implantation team and families reported that preimplantation discussions and goals of care planning made postoperative care more clear and that adverse events were handled more effectively. Currently, palliative medicine involvement in patients receiving DT is viewed as routine by cardiac care specialists. Proactive palliative medicine consultation for patients being considered for or being treated with DT improves advance care planning and thus contributes to better overall care of these patients. Our experience highlights focused advance care planning, thorough exploration of goals of care, and expert symptom management and end-of-life care when appropriate.

The use of biologically related model (Eclipse for the intensity-modulated radiation therapy planning of nasopharyngeal carcinomas.

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Monica W K Kan

Full Text Available Intensity-modulated radiation therapy (IMRT is the most common treatment technique for nasopharyngeal carcinoma (NPC. Physical quantities such as dose/dose-volume parameters are used conventionally for IMRT optimization. The use of biological related models has been proposed and can be a new trend. This work was to assess the performance of the biologically based IMRT optimization model installed in a popular commercial treatment planning system (Eclipse as compared to its dose/dose volume optimization model when employed in the clinical environment for NPC cases.Ten patients of early stage NPC and ten of advanced stage NPC were selected for this study. IMRT plans optimized using biological related approach (BBTP were compared to their corresponding plans optimized using the dose/dose volume based approach (DVTP. Plan evaluation was performed using both biological indices and physical dose indices such as tumor control probability (TCP, normal tissue complication probability (NTCP, target coverage, conformity, dose homogeneity and doses to organs at risk. The comparison results of the more complex advanced stage cases were reported separately from those of the simpler early stage cases.The target coverage and conformity were comparable between the two approaches, with BBTP plans producing more hot spots. For the primary targets, BBTP plans produced comparable TCP for the early stage cases and higher TCP for the advanced stage cases. BBTP plans reduced the volume of parotid glands receiving doses of above 40 Gy compared to DVTP plans. The NTCP of parotid glands produced by BBTP were 8.0 ± 5.8 and 7.9 ± 8.7 for early and advanced stage cases, respectively, while those of DVTP were 21.3 ± 8.3 and 24.4 ± 12.8, respectively. There were no significant differences in the NTCP values between the two approaches for the serial organs.Our results showed that the BBTP approach could be a potential alternative approach to the DVTP approach for NPC.

Caregiver Burden in Patients Receiving Ranibizumab Therapy for Neovascular Age Related Macular Degeneration.

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Rishma Gohil

Full Text Available To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD.This is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA. Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient's visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model.The mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient's visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively.Ranibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

The effect of geriatric intervention in frail elderly patients receiving chemotherapy for colorectal cancer

DEFF Research Database (Denmark)

Lund, C M; Vistisen, K K; Dehlendorff, C

2017-01-01

patients are offered inclusion and are then randomized to two groups (the intervention group and the control group). Patients in the intervention group receive a full geriatric assessment of comorbidity, medication, psycho-cognitive function, physical, functional and nutrition status, and interventions......BACKGROUND: Better surgical techniques, chemotherapy and biological therapy have improved survival in patients with colorectal cancer (CRC), most markedly in younger patients. About half of patients over 70 years receive dose reductions or early treatment discontinuation of the planned adjuvant...... or first-line treatment due to side effects. The Comprehensive Geriatric Assessment (CGA) is a multidisciplinary evaluation of an elderly individual's health status. This assessment in older patients with cancer can predict survival, chemotherapy toxicity and morbidity. METHODS: This randomized phase II...

Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy.

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Li, Xiaolin; Wu, Tong; Jiang, Yongjun; Zhang, Zining; Han, Xiaoxu; Geng, Wenqing; Ding, Haibo; Kang, Jing; Wang, Qi; Shang, Hong

2018-05-16

The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART. Copyright © 2018 Elsevier Ltd. All rights reserved.

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

International Nuclear Information System (INIS)

Stauder, Michael C.; Caudle, Abigail S.; Allen, Pamela K.; Shaitelman, Simona F.; Smith, Benjamin D.; Hoffman, Karen E.; Buchholz, Thomas A.; Chavez-Macgregor, Mariana; Hunt, Kelly K.; Meric-Bernstam, Funda; Woodward, Wendy A.

2016-01-01

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

Energy Technology Data Exchange (ETDEWEB)

Stauder, Michael C., E-mail: mstauder@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Caudle, Abigail S. [Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Shaitelman, Simona F.; Smith, Benjamin D.; Hoffman, Karen E.; Buchholz, Thomas A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chavez-Macgregor, Mariana [Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hunt, Kelly K.; Meric-Bernstam, Funda [Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-11-01

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

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Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes

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Faiman B

2016-05-01

Full Text Available Beth Faiman, Jason Valent Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA Abstract: Improved understanding as to the biology of multiple myeloma (MM and the bone marrow microenvironment has led to the development of new drugs to treat MM. This explosion of new and highly effective drugs has led to dramatic advances in the management of MM and underscores the need for supportive care. Impressive and deep response rates to chemotherapy, monoclonal antibodies, and small molecule drugs provide hope of a cure or prolonged remission for the majority of individuals. For most patients, long-term, continuous therapy is often required to suppress the malignant plasma cell clone, thus requiring clinicians to become more astute in assessment, monitoring, and intervention of side effects as well as monitoring response to therapy. Appropriate diagnosis and monitoring strategies are essential to ensure that patients receive the appropriate chemotherapy and supportive therapy at relapse, and that side effects are appropriately managed to allow for continued therapy and adherence to the regimen. Multiple drugs with complex regimens are currently available with varying side effect profiles. Knowledge of the drugs used to treat MM and the common adverse events will allow for preventative strategies to mitigate adverse events and prompt intervention. The purpose of this paper is to review updates in the diagnosis and management of MM, and to provide strategies for assessment and monitoring of patients receiving chemotherapy for MM. Keywords: multiple myeloma, treatment, symptoms, assessment, monitoring, symptom management, targeted therapies

Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

International Nuclear Information System (INIS)

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

2009-01-01

High-energy heavy ions (HZE particles) have become widely used for radiotherapy of tumors owing to their high biological effectiveness. In the treatment planning of such charged-particle therapy, it is necessary to estimate not only physical but also biological dose, which is the product of physical dose and relative biological effectiveness (RBE). In the Heavy-ion Medical Accelerator in Chiba (HIMAC), the biological dose is estimated by a method proposed by Kanai et al., which is based on the linear-quadratic (LQ) model with its parameters α and β determined by the dose distribution in terms of the unrestricted linear energy transfer (LET). Thus, RBE is simply expressed as a function of LET in their model. However, RBE of HZE particles cannot be uniquely determined from their LET because of their large cross sections for high-energy δ-ray production. Hence, development of a biological dose estimation model that can explicitly consider the track structure of δ-rays around the trajectory of HZE particles is urgently needed. Microdosimetric quantities such as lineal energy y are better indexes for representing RBE of HZE particles in comparison to LET, since they can express the decrease of ionization densities around their trajectories due to the production of δ-rays. The difference of the concept between LET and y is illustrated in Figure 1. However, the use of microdosimetric quantities in computational dosimetry was severely limited because of the difficulty in calculating their probability densities (PDs) in macroscopic matter. We therefore improved the 3-dimensional particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric PDs in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the PDs around the trajectory of HZE particles with precision equivalent to a microscopic track-structure simulation. A new method for estimating biological dose from charged

Prevalence and correlates of cigarette smoking among Chinese schizophrenia inpatients receiving antipsychotic mono-therapy.

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Yan-Min Xu

Full Text Available OBJECTIVE: To investigate the prevalence rate of cigarette smoking and its socio-demographic and clinical correlates in Chinese schizophrenia inpatients receiving antipsychotic mono-therapy. METHODS: This study was a cross-sectional, two-site, hospital-based survey. Four hundred and twenty-nine schizophrenia patients (male/female: 66.9% vs. 33.1% were consecutively recruited from psychosis inpatient wards of two large specialty psychiatric hospitals in mainland China. Patients were assessed using a cigarette smoking questionnaire, the Positive and Negative Symptom Scale, the Simpson Angus Scale, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale. Socio-demographic and other clinical data were also collected. We calculated the prevalence of current smoking in our sample as well as its indirectly standardized prevalence ratio (ISPR using data from the 2010 Global Adult Tobacco Survey in China. RESULTS: The prevalence rate of current smoking was 40.6% in our sample, and 57.5% in males and 6.3% in females. The ISPRs of all patients, men and women were 1.11(95%CI: 0.95 ∼ 1.29, 1.07(95%CI = 0.91 ∼ 1.24 and 4.64(95% CI = 2.12 ∼ 8.82, respectively. The overall and male-specific prevalence of current smoking did not differ significantly between patients and the general population. In multiple logistic regression analysis, male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking. CONCLUSION: Male Chinese inpatients with schizophrenia who received a mono-therapy of antipsychotics were not more likely to smoke than the general population. Cigarette smoking is more common in schizophrenia patients with more severe illness.

Synthetic Biology: Advancing Biological Frontiers by Building Synthetic Systems

OpenAIRE

Chen, Yvonne Yu-Hsuan; Galloway, Kate E; Smolke, Christina D

2012-01-01

Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

OpenAIRE

Lesiuk, Teresa

2016-01-01

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attent...

Biology and therapy of inherited retinal degenerative disease: insights from mouse models

Science.gov (United States)

Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

2015-01-01

Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

Depressive symptomatology in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison.

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Lee, Morgan; Jim, Heather S; Fishman, Mayer; Zachariah, Babu; Heysek, Randy; Biagioli, Matthew; Jacobsen, Paul B

2015-04-01

Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared with two groups of matched controls. Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT- group; n = 61), and no-cancer controls (CA- group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again 6 months later. Differences in depressive symptomatology and rates of clinically significant depressive symptomatology were analyzed between groups at each time point and within groups over time. Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically significant depressive symptomatology (ps depressive symptomatology than both control groups at follow-up (ps depressive symptomatology were higher in the ADT+ group than the ADT- and CA- groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%). Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT's association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Biologic Therapy and Asthma.

Science.gov (United States)

Viswanathan, Ravi K; Busse, William W

2018-02-01

Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Patient Understanding of the Risks and Benefits of Biologic Therapies in Inflammatory Bowel Disease: Insights from a Large-scale Analysis of Social Media Platforms.

Science.gov (United States)

Martinez, Bibiana; Dailey, Francis; Almario, Christopher V; Keller, Michelle S; Desai, Mansee; Dupuy, Taylor; Mosadeghi, Sasan; Whitman, Cynthia; Lasch, Karen; Ursos, Lyann; Spiegel, Brennan M R

2017-07-01

Few studies have examined inflammatory bowel disease (IBD) patients' knowledge and understanding of biologic therapies outside traditional surveys. Here, we used social media data to examine IBD patients' understanding of the risks and benefits associated with biologic therapies and how this affects decision-making. We collected posts from Twitter and e-forum discussions from >3000 social media sites posted between June 27, 2012 and June 27, 2015. Guided by natural language processing, we identified posts with specific IBD keywords that discussed the risks and/or benefits of biologics. We then manually coded the resulting posts and performed qualitative analysis using ATLAS.ti software. A hierarchical coding structure was developed based on the keyword list and relevant themes were identified through manual coding. We examined 1598 IBD-related posts, of which 452 (28.3%) centered on the risks and/or benefits of biologics. There were 5 main themes: negative experiences and concerns with biologics (n = 247; 54.6%), decision-making surrounding biologic use (n = 169; 37.4%), positive experiences with biologics (n = 168; 37.2%), information seeking from peers (n = 125; 27.7%), and cost (n = 38; 8.4%). Posts describing negative experiences primarily commented on side effects from biologics, concerns about potential side effects and increased cancer risk, and pregnancy safety concerns. Posts on decision-making focused on nonbiologic treatment options, hesitation to initiate biologics, and concerns about changing or discontinuing regimens. Social media reveals a wide range of themes governing patients' experience and choice with IBD biologics. The complexity of navigating their risk-benefit profiles suggests merit in creating online tailored decision tools to support IBD patients' decision-making with biologic therapies.

Oral care of the cancer patient receiving radiation therapy

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Holtzhausen, T [Medical Univ. of Southern Africa, Pretoria (South Africa). Dept. of Community Dentistry

1982-07-01

Radiation therapy is frequently being used for the patient with oral cancer. The survival rate is increasing, due to more effective treatment technique. The question of whether any teeth should be extracted, the mode of therapy and the side effects of radiation like Xerostomia, caries, stomatitis, trismus and osteo-radionecrosis and also post radiation care are discussed.

Low Risk of Pneumonia From Pneumocystis jirovecii Infection in Patients With Inflammatory Bowel Disease Receiving Immune Suppression.

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Cotter, Thomas G; Gathaiya, Nicola; Catania, Jelena; Loftus, Edward V; Tremaine, William J; Baddour, Larry M; Harmsen, W Scott; Zinsmeister, Alan R; Sandborn, William J; Limper, Andrew H; Pardi, Darrell S

2017-06-01

-years of exposure to triple therapy. Primary prophylaxis for PJP was prescribed to 37 patients, for a total of 24.9 patient-years of exposure. In a population-based cohort of patients with IBD treated with corticosteroids, immunosuppressants, and biologics, there were only 3 cases of PJP, despite the uncommon use of PJP prophylaxis. Routine administration of PJP prophylaxis in these patients may not be warranted, although it should be considered for high-risk groups, such as patients receiving triple therapy. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Factors associated with interest in receiving prison-based methadone maintenance therapy in Malaysia.

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Mukherjee, Trena I; Wickersham, Jeffrey A; Desai, Mayur M; Pillai, Veena; Kamarulzaman, Adeeba; Altice, Frederick L

2016-07-01

Methadone maintenance therapy (MMT) is crucial for HIV prevention and treatment in people who inject opioids. In Malaysia, a large proportion of the prison population is affected by both HIV and opioid use disorders. This study assessed individual preferences and factors associated with interest in receiving MMT among male prisoners meeting criteria for opioid dependence in Malaysia. A convenience sample of 96 HIV-positive and 104 HIV-negative incarcerated men who met pre-incarceration criteria for opioid dependence was interviewed using a structured questionnaire to examine participant characteristics and attitudes toward MMT. Factors associated with interest in prison-based MMT initiation were identified using logistic regression analysis. Among all participants, 85 (42.5%) were interested in receiving MMT within prison. Independent correlates of interest in prison-based MMT were being previously married (AOR=4.15, 95% CI: 1.15, 15.02), previously incarcerated (AOR=5.68, 95% CI: 1.54, 21.02), depression (AOR=3.66, 95% CI: 1.68, 7.98), daily heroin use in the 30days prior to incarceration (AOR=5.53, 95% CI: 1.65, 18.58), and more favorable attitudes toward MMT (AOR=19.82, 95% CI: 6.07, 64.74). Overall, interest in receiving prison-based MMT was low, and was associated with adverse social, mental health, and drug use consequences. Incarceration provides a unique opportunity to initiate MMT for those who need it, however, optimal scale-up efforts must be systemic and address modifiable factors like improving attitudes toward and motivation for MMT. Informed or shared decision-making tools may be useful in improving expectations and acceptability of MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Depressive features among adult patients receiving antiretroviral therapy for HIV in Rustenburg district, SA

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T Bongongo

2013-06-01

Full Text Available Background. Globally, it is estimated that depressive features occur in 15 - 36% of people suffering from chronic diseases and 60% of people with HIV/AIDS. A high prevalence of mental disorders among HIV-infected individuals has been shown in South Africa and other parts of sub-Saharan Africa. Untreated depression leads to poor adherence to treatment and poor quality of life for patients with chronic diseases. Methods. Using the Zung self-rating scale, we screened for depressive features among adult patients receiving highly active antiretroviral therapy (HAART who attended primary healthcare facilities in the Rustenburg district of North West Province in South Africa during December 2009. Results. Among 117 participants, 81 (69.2 % had mild depressive features, 2 (1.7% had moderate depressive features, 1 (0.9 % had severe depressive features and 33 (28.2% did not have depressive features. Depressive features were more common in males (77.1% than in females (69.5%, and were most common in patients taking the combination of efavirenz, lamivudine and stavudine. Conclusion. Depressive features seem to be common among adult patients receiving HAART and attending primary healthcare facilities in the Rustenburg district.

The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

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Lesiuk, Teresa

2016-01-01

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

Salivary oxytocin concentrations in seven boys with autism spectrum disorder received massage from their mothers: a pilot study

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Shuji eTsuji

2015-04-01

Full Text Available Seven male children with autism spectrum disorder (ASD, aged 8 – 12 years, attending special education classrooms for ASD and disabled children, were assigned to receive touch therapy. Their mothers were instructed to provide gentle touch in the massage style of the International Liddle Kidz Association. The mothers gave massages to their child for 20 minutes every day over a period of 3 months followed by no massage for 4 months. To assess the biological effects of such touch therapy, saliva was collected before and 20 minutes after a single session of massage for 20 minutes from the children and mothers every 3 weeks during the massage period and every 4 weeks during the non-massage period, when they visited a community meeting room. Salivary oxytocin levels were measured using an enzyme immunoassay kit. During the period of massage therapy, the children and mothers exhibited higher oxytocin concentrations compared those during the non-massage period. The changes in oxytocin levels before and after a single massage session were not significantly changed in children and mothers. The results suggested that the ASD children (massage receivers and their mothers (massage givers show touch therapy-dependent changes in salivary oxytocin concentrations.

Oral candidiasis in patients receiving radiation therapy for head and neck cancer.

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Deng, Zeyi; Kiyuna, Asanori; Hasegawa, Masahiro; Nakasone, Isamu; Hosokawa, Atsushi; Suzuki, Mikio

2010-08-01

To investigate oral candidiasis in patients with head and neck cancer before, during, and after radiation therapy, and to explore its association with clinical oropharyngeal symptoms. A cohort study. University hospital. Subjects who received radiation therapy (RT) for the treatment of head and neck cancer were divided into two groups: an oral cavity irradiated group (OIRR group, n = 29) and an oral cavity nonirradiated group (ONIRR group, n = 17). A control group consisted of 18 healthy subjects. Patients were examined for signs of oral candidiasis before, during, immediately after, and one month after RT. Mouth and throat soreness (MTS), dysphagia, and xerostomia were evaluated by self-reported questionnaires, and associations between oral candidiasis and these symptoms were analyzed. The incidence of oral candidiasis during RT was significantly higher in the OIRR group (55.2%) than in the ONIRR group (11.8%). Similarly, the occurrence of xerostomia during RT was significantly higher in the OIRR group (86.2%) than in the ONIRR group (52.9%). In the OIRR group, the mean MTS score at the 20th fraction of RT was significantly higher in patients with candidiasis (mean +/- SD, 5.8 +/- 2.1) than in those with RT-induced mucositis without candidiasis (3.7 +/- 2.0). In the OIRR group, 65.2 percent of patients who experienced dysphagia developed oral candidiasis, compared with only 10 percent in the ONIRR group. Oral candidiasis concurrent with oral mucositis due to RT may increase oropharyngeal discomfort during RT. Copyright (c) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Psychological therapy for inpatients receiving acute mental health care: A systematic review and meta-analysis of controlled trials.

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Paterson, Charlotte; Karatzias, Thanos; Dickson, Adele; Harper, Sean; Dougall, Nadine; Hutton, Paul

2018-04-16

The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta-analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. A systematic review and meta-analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms 'inpatient', 'psychological therapy', and 'acute'. No restriction was placed on diagnosis. The moderating effect of the use of assessor-blind RCT methodology was examined via subgroup and sensitivity analyses. Overall, psychological therapy was associated with small-to-moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow-up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single-blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single-blind RCT methodology was associated with reduced therapy-attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and

Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

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Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

2018-01-01

One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease.

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Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-07-28

To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 +/- 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 +/- 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

Estimate of neutron secondary doses received by patients in proton therapy: cases of ophthalmologic treatments

International Nuclear Information System (INIS)

Martinetti, F.

2009-12-01

This research thesis aims at assessing doses due to secondary neutrons and received by the organs of a patient which are located outside of the treatment field. The study focused on ophthalmological treatments performed at the Orsay proton therapy centre. A 75 eV beam line model has first been developed with the MCNPX Monte Carlo code. Several experimental validations of this model have been performed: proton dose distribution in a water phantom, ambient equivalent dose due to secondary neutrons and neutron spectra in the treatment room, and doses deposited by secondary neutrons in an anthropomorphous phantom. Simulations and measurements are in correct agreement. Then, a numeric assessment of secondary doses received by the patient's organs has been performed by using a MIRD-type mathematical phantom. These doses have been computed for several organs: the non-treated eye, the brain, the thyroid, and other parts of the body situated either in the front part of the body (the one directly exposed to neutrons generated in the treatment line) or deeper and further from the treatment field

Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis.

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Farahani, Mansour; Mulinder, Holly; Farahani, Alexander; Marlink, Richard

2017-06-01

The advent of antiretroviral therapy has significantly improved AIDS-related morbidity and mortality. Yet, among people living with HIV, deaths due to non-AIDS-defining illnesses have been on the rise. The objective of this study was to provide information about the global prevalence and distribution of non-AIDS causes of death in the last ten years among people living with HIV receiving antiretroviral therapy, by income levels of countries. We used broad search terms in Google Scholar, PubMed, and EMBASE to identify all studies that investigated the cause of death among people living with HIV receiving antiretroviral therapy, published after January 1, 2005. References were also identified from review articles and reference lists. Inclusion criteria were English language, the study's end date was after 2005, all patients were HIV-positive, at least two-thirds of the patients were receiving antiretroviral therapy, at least one patient died of non-AIDS causes of death. Titles, abstracts, and articles were reviewed by at least two independent readers. Of 2951 titles identified in our original search, 151 articles were selected for further screening. We identified 19 studies meeting our full criteria, with patients from 55 different nations. Pooled non-AIDS causes of death prevalence estimates in high-income countries were 53.0% (95% confidence interval, 43.6-62.3), in developing countries 34.0% (95% confidence interval, 20.3-49.1), and in sub-Saharan countries 18.5% (95% confidence interval, 13.8-23.7). Statistically significant variation was noted within and between categories. Our findings show that a significant number of people living with HIV across the world die from cardiovascular disease, non-AIDS malignancies, and liver disease. There is a global need for further scrutiny in all regions to improve preventive measures and early detection according to distinct causes of death patterns.

Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.

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Delea, Thomas E; Hagiwara, May; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

2008-04-01

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. (c) 2007 Wiley-Liss, Inc.

Correlation of microdosimetric measurements with relative biological effectiveness from clinical experience for two neutron therapy beams

International Nuclear Information System (INIS)

Stinchcomb, T.G.; Kuchnir, F.T.; Myrianthopoulos, L.C.; Horton, J.L. Jr.; Roberts, W.K.

1986-01-01

Microdosimetric measurements were made for the neutron therapy beams at the University of Chicago and at the Cleveland Clinic with the same geometry and phantom material using the same tissue-equivalent spherical proportional counter and standard techniques. The energy deposition spectra (dose distributions in lineal energy) are compared for these beams and for their scattered components (direct beam blocked). The model of dual radiation action (DRA) of Kellerer and Rossi is employed to interpret these data in terms of biological effectiveness over this limited range of radiation qualities. The site-diameter parameter of the DRA theory is determined for the Cleveland beam by setting the biological effectiveness (relative to 60 Co gamma radiation) equal to the relative biological effectiveness value deduced from radiobiology experiments and clinical experience. The resulting value of this site-diameter parameter is then used to predict the biological effectiveness of the Chicago beam. The prediction agrees with the value deduced from radiobiology and clinical experience. The biological effectiveness of the scattered components of both beams is also estimated using the model

Biological effects of radiation

International Nuclear Information System (INIS)

2013-01-01

This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

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Hwang, Jessica P; Suarez-Almazor, Maria E; Cantor, Scott B; Barbo, Andrea; Lin, Heather Y; Ahmed, Sairah; Chavez-MacGregor, Mariana; Donato-Santana, Christian; Eng, Cathy; Ferrajoli, Alessandra; Fisch, Michael J; McLaughlin, Peter; Simon, George R; Rondon, Gabriela; Shpall, Elizabeth J; Lok, Anna S

2017-09-01

Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients

Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review

International Nuclear Information System (INIS)

Bonan, Paulo Rogerio Ferreti; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de; Alves, Fabio de Abreu

2005-01-01

The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

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Nadia E. Aikawa

Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

Spinal cordd biological safety comparison of intensity modulated radiotherapy and conventional radiation therapy

International Nuclear Information System (INIS)

Xilinbaoleri; Xu Wanlong; Chen Gang; Liu Hao; Wang Ruozheng; Bai Jingping

2010-01-01

Objective: To compare the spine intensity modulated radiation therapy (IMRT) and the conventional radiation therapy on the beagle spinal cord neurons, in order to prove the biological safety of IMRT of the spinal cord. Methods: Twelve selected purebred beagles were randomly divided into 2 groups. A beagle clinical model of tumor was mimiced in the ninth and tenth thoracic vertebrae. Then the beagles were irradiated by 2 different models of intensity modulated radiotherapy and conventional radiation therapy, with the total irradiation doses of 50 and 70 Gy. The samples of spinal cord were taken out from the same position of the nine and tenth thoracic vertebrae at the third month after radiation.All the samples were observed by the electron microscope, and the Fas and HSP70 expression in spinal cord neurons were evaluated by immunohistochemistry method. Terminal deoxynucleatidyl transferase mediated dUTP nick and labeling (TUNEL) technique was used to examine the apoptotic cells in the spinal cord. Results: The neurons in the spinal cord of IMRT group were mainly reversible injury, and those in the conventional radiation therapy were mainly apoptosis. Compared with the conventional radiation therapy group [50 Gy group, (7.3 ± 1.1)%; 70 Gy group, (11.3 ± 1.4)%], the apoptosis rate of the spinal cord neurons of the intensity modulated radiotherapy group [50 Gy group, (1.2 ± 0.7)%; 70 Gy group (2.5 ± 0.8)%] was much lower[(50 Gy group, t=0.022, P<0.05; 70 Gy group, t=0.017, P<0.05)]. The expression levels of Fas in the IMPT group (50 Gy group, 4.6 ± 0.8; 70 Gy group, 7.4 ± 1.1) were also much lowerthan those in the other group (50 Gy group, 15.1 ± 6.4; 70 Gy group, 19.3 ± 7.6. 50 Gy group, t=0.231, P<0.05; 70 Gy group, t=0.457, P<0.05), while the expression levels of HSP70 in the IMPT group (50 Gy group, 9.1 ± 0.8; 70 Gy group, 7.3 ± 1.4)were much higher than those in the conventional radiation therapy group (50 Gy group, 2.1 ± 0.9; 70 Gy group, 1.7 ± 0

Supporting Treatment Decisions in Patients with Differentiated Thyroid Carcinoma (DTC) under Radioiodine-131 Therapy: Role of Biological Dosimetry Assessment

International Nuclear Information System (INIS)

Fadel, A.M.; Chebel, G.M.; Di Giorgio, M.; Vallerga, M.B.; Taja, M.R.; Radl, A.; Bubniak, R.V.; Oneto, A.

2010-01-01

Radioiodine-131 therapy is applied in patients with differentiated thyroid carcinoma (DTC), within the therapeutic scheme following thyroidectomy, for the ablation of thyroid remnants and treatment of metastatic disease. Several approaches for the selection of a therapeutic dose were applied. The aim of this therapy is to achieve a lethal dose in the tumor tissue, without exceeding the dose of tolerance in healthy tissues (doses greater than 2 Gy in bone marrow could lead to myelotoxicity). In this work, the treatment protocol used incorporates the assessment by biological dosimetry (BD) for estimating doses to whole body and bone marrow, to tailor patient's treatment. Biological Dosimetry prospective studies conducted on samples from patients with cumulative activities, before and after each therapeutic administration, allows to evaluate DNA damage and repair capacity in peripheral blood lymphocytes. (authors)

Latent tuberculosis infection screening prior to biological treatment in Tunisian patients.

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Slouma, Marwa; Mahmoud, Ines; Saidane, Olfa; Bouden, Selma; Abdelmoula, Leila

2017-10-01

The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months. The screening of LTBI was performed according to national Tunisian guidelines. There were 35 men and 78 women. The mean age was 47.67±13.50 years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91 years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Evaluating changes in stable chromosomal translocation frequency in patients receiving radioimmunotherapy

International Nuclear Information System (INIS)

Wong, Jeffrey Y.C.; Wang Jianyi; Liu An; Odom-Maryon, Tamara; Shively, John E.; Raubitschek, Andrew A.; Williams, Lawrence E.

2000-01-01

Purpose: The lack of any consistent correlation between radioimmunotherapy (RIT) dose and observed hematologic toxicity has made it difficult to validate RIT radiation dose estimates to marrow. Stable chromosomal translocations (SCT) which result after radiation exposure may be a biologic parameter that more closely correlates with RIT radiation dose. Increases in the frequency of SCT are observed after radiation exposure and are highly correlated with absorbed radiation dose. SCT are cumulative after multiple radiation doses and conserved through an extended number of cell divisions. The purpose of this study was to evaluate whether increases in SCT frequency were detectable in peripheral lymphocytes after RIT and whether the magnitude of these increases correlated with estimated radiation dose to marrow and whole body. Methods and Materials: Patients entered in a Phase I dose escalation therapy trial each received 1-3 intravenous cycles of the radiolabeled anti-carcinoembryonic antigen (CEA) monoclonal antibody, 90 Y-chimeric T84.66. Five mCi of 111 In-chimeric T84.66 was co-administered for imaging and biodistribution purposes. Blood samples were collected immediately prior to the start of therapy and 5-6 weeks after each therapy cycle. Peripheral lymphocytes were harvested after 72 hours of phytohemagglutinin stimulation and metaphase spreads prepared. Spreads were then stained by fluorescence in situ hybridization (FISH) using commercially available chromosome paint probes to chromosomes 3 and 4. Approximately 1000 spreads were evaluated for each chromosome sample. Red marrow radiation doses were estimated using the AAPM algorithm and blood clearance curves. Results: Eighteen patients were studied, each receiving at least one cycle of therapy ranging from 5-22 mCi/m 2 . Three patients received 2 cycles and two patients received 3 cycles of therapy. Cumulative estimated marrow doses ranged from 9.2 to 310 cGy. Increases in SCT frequencies were observed after

Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease

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Tetsuya Ishida

2014-01-01

Full Text Available We report a 45-year-old female patient who developed acute hepatic disorder during anti-tumor necrosis factor α therapy for the treatment of Crohn's disease (CD. She was diagnosed as colonic CD and placed on infliximab (IFX. She was negative for hepatitis B surface antigen at the initiation of IFX therapy, but developed acute hepatitis after the 30th administration of IFX 4 years and 1 month after the first administration. She was suspected to have had occult hepatitis B virus infection before IFX therapy, and de novo hepatitis B was considered the most likely diagnosis. Hepatitis subsided after discontinuation of anti-tumor necrosis factor α therapy and initiation of treatment with entecavir. She started to receive adalimumab to prevent relapse of CD. She has continued maintenance therapy with entecavir and adalimumab and has since been asymptomatic. As de novo hepatitis B may be fatal, virological testing for hepatitis B is essential for patients who are being considered for treatment that may weaken the immune system.

Ethnographic Observational Study of the Biologic Initiation Conversation Between Rheumatologists and Biologic-Naive Rheumatoid Arthritis Patients.

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Kottak, Nicholas; Tesser, John; Leibowitz, Evan; Rosenberg, Melissa; Parenti, Dennis; DeHoratius, Raphael

2018-01-30

This ethnographic market research study investigated the biologic initiation conversation between rheumatologists and biologic-naive patients with rheumatoid arthritis to assess how therapy options, particularly mode of administration, were discussed. Consenting rheumatologists (n = 16) and patients (n = 48) were videotaped during medical visits and interviewed by a trained ethnographer. The content, structure, and timing of conversations regarding biologic initiation were analyzed. The mean duration of physician-patient visits was approximately 15 minutes; biologic therapies were discussed for a mean of 5.6 minutes. Subcutaneous (SC) and intravenous (IV) therapy options were mentioned in 45 and 35 visits, respectively, out of a total of 48 visits. All patients had some familiarity with SC administration, but nearly half of patients (22 of 48) were unfamiliar with IV therapy going into the visit. IV administration was not defined or described by rheumatologists in 77% of visits (27 of 35) mentioning IV therapy. Thus, 19 of 22 patients who were initially unfamiliar with IV therapy remained unfamiliar after the visit. Disparities in physician-patient perceptions were revealed, as all rheumatologists (16 of 16) believed IV therapy would be less convenient than SC therapy for patients, while 46% of patients (22 of 48) felt this way. In post-visit interviews, some patients seemed confused and overwhelmed, particularly when presented with many treatment choices in a visit. Some patients stated they would benefit from visual aids or summary sheets of key points. This study revealed significant educational opportunities to improve the biologic initiation conversation and indicated a disparity between patients' and rheumatologists' perception of IV therapy. © 2018 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Psychometric properties of the PROMIS Physical Function item bank in patients receiving physical therapy.

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Martine H P Crins

Full Text Available The Patient-Reported Outcomes Measurement Information System (PROMIS is a universally applicable set of instruments, including item banks, short forms and computer adaptive tests (CATs, measuring patient-reported health across different patient populations. PROMIS CATs are highly efficient and the use in practice is considered feasible with little administration time, offering standardized and routine patient monitoring. Before an item bank can be used as CAT, the psychometric properties of the item bank have to be examined. Therefore, the objective was to assess the psychometric properties of the Dutch-Flemish PROMIS Physical Function item bank (DF-PROMIS-PF in Dutch patients receiving physical therapy.Cross-sectional study.805 patients >18 years, who received any kind of physical therapy in primary care in the past year, completed the full DF-PROMIS-PF (121 items.Unidimensionality was examined by Confirmatory Factor Analysis and local dependence and monotonicity were evaluated. A Graded Response Model was fitted. Construct validity was examined with correlations between DF-PROMIS-PF T-scores and scores on two legacy instruments (SF-36 Health Survey Physical Functioning scale [SF36-PF10] and the Health Assessment Questionnaire Disability-Index [HAQ-DI]. Reliability (standard errors of theta was assessed.The results for unidimensionality were mixed (scaled CFI = 0.924, TLI = 0.923, RMSEA = 0.045, 1th factor explained 61.5% of variance. Some local dependence was found (8.2% of item pairs. The item bank showed a broad coverage of the physical function construct (threshold-parameters range: -4.28-2.33 and good construct validity (correlation with SF36-PF10 = 0.84 and HAQ-DI = -0.85. Furthermore, the DF-PROMIS-PF showed greater reliability over a broader score-range than the SF36-PF10 and HAQ-DI.The psychometric properties of the DF-PROMIS-PF item bank are sufficient. The DF-PROMIS-PF can now be used as short forms or CAT to measure the level of

Efficacy of walking exercise in promoting cognitive-psychosocial functions in men with prostate cancer receiving androgen deprivation therapy

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Lee C

2012-07-01

Full Text Available Abstract Background Prostate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT. Methods A 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale. Discussion The significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately

Biology and therapy of inherited retinal degenerative disease: insights from mouse models

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Shobi Veleri

2015-02-01

Full Text Available Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

Patients with schizophrenia or schizoaffective disorder who receive multiple electroconvulsive therapy sessions: characteristics, indications, and results

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Iancu I

2015-03-01

Full Text Available Iulian Iancu,* Nimrod Pick,* Orit Seener-Lorsh, Pinhas Dannon Be’er Ya’akov Mental Health Center, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel *These authors share first authorship of this paper Background: While electroconvulsive therapy (ECT has been used for many years, there is insufficient research regarding the indications for continuation/maintenance (C/M-ECT, its safety and efficacy, and the characteristics of patients with schizophrenia or schizoaffective disorder who receive multiple ECT sessions. The aims of this study were to characterize a series of patients who received 30 ECT sessions or more, to describe treatment regimens in actual practice, and to examine the results of C/M-ECT in terms of safety and efficacy, especially the effect on aggression and functioning.Methods: We performed a retrospective chart review of 20 consecutive patients (mean age 64.6 years with schizophrenia (n=16 or schizoaffective disorder (n=4 who received at least 30 ECT sessions at our ECT unit, and also interviewed the treating physician and filled out the Clinical Global Impression-Severity, Global Assessment of Functioning, and the Staff Observation Aggression Scale-Revised.Results: Patients received a mean of 91.3 ECT sessions at a mean interval of 2.6 weeks. All had been hospitalized for most or all of the previous 3 years. There were no major adverse effects, and cognitive side effects were relatively minimal (cognitive deficit present for several hours after treatment. We found that ECT significantly reduced scores on the Staff Observation Aggression Scale-Revised subscales for verbal aggression and self-harm, and improved Global Assessment of Functioning scores. There were reductions in total aggression scores, subscale scores for harm to objects and to others, and Clinical Global Impression-Severity scores, these were not statistically significant.Conclusion: C/M-ECT is safe and effective for

Vaginal dilator therapy for women receiving pelvic radiotherapy.

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Miles, Tracie; Johnson, Nick

2014-09-08

Vaginal dilation therapy is advocated after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina), but can be uncomfortable and psychologically distressing. To assess the benefits and harms of different types of vaginal dilation methods offered to women treated by pelvic radiotherapy for cancer. Searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 5), MEDLINE (1950 to June week 2, 2013), EMBASE (1980 to 2013 week 24) and CINAHL (1982 to 2013). Comparative data of any type, which evaluated dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and therefore analysed no data. We identified no studies for inclusion in the original review or for this update. However, we felt that some studies that were excluded warranted discussion. These included one randomised trial (RCT), which showed no improvement in sexual scores associated with encouraging women to practise dilation therapy; a recent small RCT that did not show any advantage to dilation over vibration therapy during radiotherapy; two non-randomised comparative studies; and five correlation studies. One of these showed that objective measurements of vaginal elasticity and length were not linked to dilation during radiotherapy, but the study lacked power. One study showed that women who dilated tolerated a larger dilator, but the risk of objectivity and bias with historical controls was high. Another study showed that the vaginal measurements increased in length by a mean of 3 cm after dilation was introduced 6 to 10 weeks after radiotherapy, but there was no control group; another case series showed the opposite. Three recent studies showed less stenosis associated with prophylactic dilation after radiotherapy. One small case series suggested that dilation years after radiotherapy might restore the

Interactions between physical, chemical and biological processes in aquatic systems - impacts on receiving waters with different contents of treated wastewater

International Nuclear Information System (INIS)

Kreuzinger, N.

2000-08-01

Two scenarios have be chosen within this PhD Thesis to describe the integrative key-significance of interactions between most relevant physical, chemical and biological processes in aquatic systems. These two case studies are used to illustrate and describe the importance of a detailed synthesis of biological, physical and chemical interactions in aquatic systems in order to provide relevant protection of water resources and to perform a sound water management. Methods are described to allow a detailed assessment of particular aspects within the complexity of the overall integration and therefore serve as a basis to determine the eventual necessity of proposed water management measures. Regarding the anthropogenic influence of treated wastewater on aquatic systems, one case study focuses on the interactions between emitted waters from a wastewater treatment plant and the resulting immission situation of its receiving water (The receiving water is quantitatively influenced by the treated wastewater by 95 %). This thesis proves that the effluent of wastewater treatment plants operated by best available technology meets the quality standards of running waters for the nutrients nitrogen and phosphorus, carbon-parameters, oxygen-regime and ecotoxicology. Within the second case study the focus is put on interactions between immissions and water usage. The general importance of biological phosphorus precipitation on the trophic situation of aquatic systems is described. Nevertheless, this generally known but within the field of applied limnology so far unrespected process of immobilization of phosphorus could be shown to represent a significant and major impact on phytoplannctotic development and eutrification. (author)

Clinically Applicable Monte Carlo–based Biological Dose Optimization for the Treatment of Head and Neck Cancers With Spot-Scanning Proton Therapy

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Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.; Ma, Daniel J.; Beltran, Chris

2016-08-01

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of this novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for

Gene therapy for cartilage and bone tissue engineering

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Hu, Yu-Chen

2014-01-01

"Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

Fatal Candida septic shock during systemic chemotherapy in lung cancer patient receiving corticosteroid replacement therapy for hypopituitarism. A case report

International Nuclear Information System (INIS)

Morichika, Daisuke; Sato-Hisamoto, Akiko; Hotta, Katsuyuki

2014-01-01

Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage 3A. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (1) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (2) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome. (author)

Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

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Simone Mocellin

Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

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Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-08-10

The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

Physical, biological and clinical basis of light ions using in radiotherapy: EULIMA project

International Nuclear Information System (INIS)

Chauvel, P.

1991-01-01

Improving the efficiency of radiotherapy is a constant concern in oncology: more than half of the patients who contract cancer receive radiotherapy at some stage. Use of charged particles in radiotherapy represents indisputable progress in localization of the dose delivered to tumour masses, thereby allowing reduction of dose received by adjacent healthy tissues. Protons improve the physical selectivity of the irradiation, i.e. the dose distribution. High-LET (Linear Energy Transfer) radiations produce different biological effects, decreasing the differences in radiosensitivity, and allowing radiation therapy to control radioresistant tumours. Fast neutrons represent the most known of these high-LET particles, but they suffer of a relatively poor physical selectivity. The two approaches (physical selectivity and biological advantages) are joined in by light ions (Carbon, Oxygen, Neon). Highly selective high-LET radiation therapy can be performed for radioresistant tumours without damage to healthy tissues. Preliminary results obtained in Berkeley (USA) demonstrate an improved local control of unresectable, slowly growing tumours, confirming what could be extrapolated from proton and neutrontherapy. Furthermore, radioactive light ion beams can be used to verify the accuracy of treatment planning by checking the range of the particle with a PET camera, and in the future for the treatment itself. In the framework of its programme Europe against Cancer, the Commission of the European Communities participates in the funding of the EULIMA (European Light Ion Medical Accelerator) project feasibility study, aiming to design an hospital-based light ion therapy facility in Europe [fr

Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

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Turner, Bruce; Ali, Sacha; Pati, Jhumur; Nargund, Vinod; Ali, Enamul; Cheng, Leo; Wells, Paula

2016-01-01

Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

Secondary neutron doses received by patients of different ages during intracranial proton therapy treatments

International Nuclear Information System (INIS)

Sayah, R.

2012-01-01

Proton therapy is an advanced radiation therapy technique that allows delivering high doses to the tumor while saving the healthy surrounding tissues due to the protons' ballistic properties. However, secondary particles, especially neutrons, are created during protons' nuclear reactions in the beam-line and the treatment room components, as well as inside the patient. Those secondary neutrons lead to unwanted dose deposition to the healthy tissues located at distance from the target, which may increase the secondary cancer risks to the patients, especially the pediatric ones. The aim of this work was to calculate the neutron secondary doses received by patients of different ages treated at the Institut Curie-centre de Protontherapie d'Orsay (ICPO) for intracranial tumors, using a 178 MeV proton beam. The treatments are undertaken at the new ICPO room equipped with an IBA gantry. The treatment room and the beam-line components, as well as the proton source were modeled using the Monte Carlo code MCNPX. The obtained model was then validated by a series of comparisons between model calculations and experimental measurements. The comparisons concerned: a) depth and lateral proton dose distributions in a water phantom, b) neutron spectrometry at one position in the treatment room, c) ambient dose equivalents at different positions in the treatment room and d) secondary absorbed doses inside a physical anthropomorphic phantom. A general good agreement was found between calculations and measurements, thus our model was considered as validated. The University of Florida hybrid voxelized phantoms of different ages were introduced into the MCNPX validated model, and secondary neutron doses were calculated to many of these phantoms' organs. The calculated doses were found to decrease as the organ's distance to the treatment field increases and as the patient's age increases. The secondary doses received by a one year-old patient may be two times higher than the doses

Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

International Nuclear Information System (INIS)

Hindley, Andrew; Zain, Zakiyah; Wood, Lisa; Whitehead, Anne; Sanneh, Alison; Barber, David; Hornsby, Ruth

2014-01-01

Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected

Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

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Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom); Zain, Zakiyah [College of Arts and Sciences, Universiti Utara Malaysia, Kedah (Malaysia); Wood, Lisa [Department of Social Sciences, Lancaster Medical School, Lancaster (United Kingdom); Whitehead, Anne [Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster (United Kingdom); Sanneh, Alison; Barber, David; Hornsby, Ruth [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom)

2014-11-15

Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

Is refractory angina pectoris a form of chronic pain? A comparison of two patient groups receiving spinal cord stimulation therapy.

Science.gov (United States)

Pak, Nick; Devcich, Daniel A; Johnson, Malcolm H; Merry, Alan F

2014-03-28

To compare psychological and pain-related characteristics of patients with chronic pain and patients with refractory angina pectoris who had been treated with spinal cord stimulation (SCS) therapy. Twenty-four patients receiving SCS therapy were interviewed. Four psychological variables were assessed using standardised questionnaires for pain catastrophising, health locus of control, anxiety sensitivity, and self-efficacy. Patients also completed the revised version of the Short-Form McGill Pain Questionnaire, the Short-Form Health Survey, and self-reported measures of global perceived effect, pain, functionality, and satisfaction with SCS therapy. Most patients reported improvements in pain, functionality, and improvement overall. Some health locus of control dimensions were significantly higher for the angina group than the chronic pain group, and chronic angina patients reported significantly lower levels of intermittent pain. Virtually all patients reported being satisfied with SCS therapy. Most self-rated psychological and pain-related characteristics were no different between the two groups, which gives some support to the view that refractory angina is a form of chronic pain. The results also add to evidence supporting the use of SCS therapy for refractory angina pectoris; however, differences observed on a few variables may indicate points of focus for the assessment and treatment of such patients.

Stimulant use and its impact on growth in children receiving growth hormone therapy: an analysis of the KIGS International Growth Database.

Science.gov (United States)

Miller, Bradley S; Aydin, Ferah; Lundgren, Frida; Lindberg, Anders; Geffner, Mitchell E

2014-01-01

Children receiving stimulants for attention deficit hyperactivity disorder (ADHD) frequently present to pediatric endocrinology clinics for evaluation and treatment of growth disorders. The worldwide prevalence of stimulant use in children with ADHD also receiving recombinant human growth hormone (rhGH) and the impact on response to rhGH are unknown. Data on children enrolled in the KIGS® (Pfizer International Growth Study) registry were evaluated for the associated diagnosis of ADHD prior to initiation of Genotropin® rhGH. Concomitant stimulant medications and auxological information were captured. Response to rhGH was evaluated using established growth prediction models. The prevalence of ADHD in KIGS was 2.3% (1,748/75,251), with stimulants used in 1.8% (1,326/75,251). Children with idiopathic growth hormone deficiency (IGHD) who received stimulants grew significantly less (1.1 cm) in the first year of rhGH therapy than expected for rhGH-treated non-ADHD IGHD children. After one year of rhGH, idiopathic short stature (ISS) children with ADHD were significantly shorter [0.74 cm (with stimulants) and 0.69 cm (without stimulants)] than non-ADHD ISS children. We demonstrated an impaired response to rhGH in IGHD and ISS children with ADHD. Our findings suggest that the ADHD phenotype, alone or in conjunction with stimulant therapy, may impair the short-term growth response to rhGH.

Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence.

Science.gov (United States)

Ramdurg, Santosh; Ambekar, Atul; Lal, Rakesh

2015-01-01

People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn’s disease

Science.gov (United States)

Lakatos, Peter Laszlo; Czegledi, Zsofia; Szamosi, Tamas; Banai, Janos; David, Gyula; Zsigmond, Ferenc; Pandur, Tunde; Erdelyi, Zsuzsanna; Gemela, Orsolya; Papp, Janos; Lakatos, Laszlo

2009-01-01

AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn’s disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location (P = 0.001), presence of perianal disease (P < 0.001), prior steroid use (P = 0.006), early AZA (P = 0.005) or AZA/biological therapy (P = 0.002), or smoking (P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients. PMID:19630105

SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

International Nuclear Information System (INIS)

Oesten, H; Loeck, S; Wohlfahrt, P; Helmbrecht, S; Tillner, F; Schuemann, J; Luehr, A

2016-01-01

Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam

SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

Energy Technology Data Exchange (ETDEWEB)

Oesten, H [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Massachusetts General Hospital, Boston, MA (Germany); Loeck, S; Wohlfahrt, P [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Helmbrecht, S [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf (Germany); Tillner, F [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States); Luehr, A [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

2016-06-15

Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam

Patients receiving anti-TNF therapies experience clinically important improvements in RA-related fatigue: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Science.gov (United States)

Druce, Katie L; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

2015-06-01

Pro-inflammatory cytokines such as TNF-α are important in the pathogenesis of fatigue in conditions such as RA. This study aimed to determine whether fatigue improved in a cohort of RA patients with clinically relevant fatigue commencing anti-TNF-α therapy and, if so, to identify predictors of improvement. Participants recruited to a long-term observational cohort study (the British Society for Rheumatology Biologics Register for RA) provided information on fatigue using the 36-item Short Form Health Survey (SF-36) vitality subscale. The prevalence of severe baseline fatigue (SF-36 vitality ≤12.5) was calculated and improvements, considered as (i) absolute values and (ii) improvement from severe to non-severe fatigue (SF-36 vitality >12.5), were examined 6 months subsequently. A comprehensive set of putative predictors of fatigue improvement were evaluated using multivariable logistic regression. In 6835 participants the prevalence of severe baseline fatigue was 38.8%. Of those with severe fatigue, 70% reported clinically relevant improvement and 66% moved to the non-severe fatigue category (i.e. improvers). The mean change for improvers was three times the minimum clinically important difference for improvement (33.0 U). Independent baseline predictors of improvement were female sex [odds ratio (OR) 1.3 (95% CI 1.1, 1.7)], not being unemployed due to ill health [OR 1.5 (95% CI 1.2, 1.7)], low disability [OR 1.2 (95% CI 1.001, 1.5)], seropositivity [OR 1.2 (95% CI 0.98, 1.4)], not using steroids [OR 1.2 (95% CI 1.03, 1.5)], no history of hypertension [OR 1.4 (95% CI 1.1, 1.6)] or depression [OR 1.3 (95% CI 1.1, 1.5)] and good mental health [SF-36 mental health subscale >35; OR 1.4 (95% CI 1.2, 1.7)]. Fatigued RA patients reported substantial improvement in their fatigue after commencing anti-TNF-α therapy. Further, a number of clinical and psychosocial baseline factors identified those most likely to improve, supporting future stratified approaches to RA

Hadron Therapy for Cancer Treatment

International Nuclear Information System (INIS)

Lennox, Arlene

2003-01-01

The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.

CAM therapies among primary care patients using opioid therapy for chronic pain

OpenAIRE

Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F

2007-01-01

Abstract Background Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to as...

Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

DEFF Research Database (Denmark)

Becker, Juergen C.; Stang, Andreas; zur Hausen, Axel

2018-01-01

Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations...... knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC....

Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

Energy Technology Data Exchange (ETDEWEB)

Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tran, David D.; Linette, Gerry [Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Jalalizadeh, Rohan [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Dacey, Ralph; Rich, Keith M.; Chicoine, Michael R.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

2014-11-15

Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

Cost-of-illness in psoriasis: comparing inpatient and outpatient therapy.

Directory of Open Access Journals (Sweden)

Sabine I B Steinke

Full Text Available Treatment modalities of chronic plaque psoriasis have dramatically changed over the past ten years with a still continuing shift from inpatient to outpatient treatment. This development is mainly caused by outpatient availability of highly efficient and relatively well-tolerated systemic treatments, in particular BioLogicals. In addition, inpatient treatment is time- and cost-intense, conflicting with the actual burst of health expenses and with patient preferences. Nevertheless, inpatient treatment with dithranol and UV light still is a major mainstay of psoriasis treatment in Germany. The current study aims at comparing the total costs of inpatient treatment and outpatient follow-up to mere outpatient therapy with different modalities (topical treatment, phototherapy, classic systemic therapy or BioLogicals over a period of 12 months. To this end, a retrospective cost-of-illness study was conducted on 120 patients treated at the University Medical Centre Mannheim between 2005 and 2006. Inpatient therapy caused significantly higher direct medical, indirect and total annual costs than outpatient treatment (13,042 € versus 2,984 €. Its strong influence on cost levels was confirmed by regression analysis, with total costs rising by 104.3% in case of inpatient treatment. Patients receiving BioLogicals produced the overall highest costs, whereas outpatient treatment with classic systemic antipsoriatic medications was less cost-intense than other alternatives.

Matching Biological Mesh and Negative Pressure Wound Therapy in Reconstructing an Open Abdomen Defect

Directory of Open Access Journals (Sweden)

Fabio Caviggioli

2014-01-01

Full Text Available Reconstruction of open abdominal defects is a clinical problem which general and plastic surgeons have to address in cooperation. We report the case of a 66-year-old man who presented an abdominal dehiscence after multiple laparotomies for a sigmoid-rectal adenocarcinoma that infiltrated into the abdominal wall, subsequently complicated by peritonitis and enteric fistula. A cutaneous dehiscence and an incontinent abdominal wall resulted after the last surgery. The abdominal wall was reconstructed using a biological porcine cross-linked mesh Permacol (Covidien Inc., Norwalk, CT. Negative Pressure Wound Therapy (NPWT, instead, was used on the mesh in order to reduce wound dimensions, promote granulation tissue formation, and obtain secondary closure of cutaneous dehiscence which was finally achieved with a split-thickness skin graft. Biological mesh behaved like a scaffold for the granulation tissue that was stimulated by the negative pressure. The biological mesh was rapidly integrated in the abdominal wall restoring abdominal wall continence, while the small dehiscence, still present in the central area, was subsequently covered with a split-thickness skin graft. The combination of these different procedures led us to solve this complicated case obtaining complete wound closure after less than 2 months.

Radiation therapy in old patients. Side effects and results of radiation therapy in old patients

International Nuclear Information System (INIS)

Geinitz, H.; Zimmermann, F.B.; Molls, M.

1999-01-01

Background: Despite a growing number of elderly patients receiving radiation therapy little is known about side effects and outcome of irradiation in this section of the population. Methods: In a review article epidemiologic data, aspects of radiation-biology as well as side effects and outcome of radiation therapy of elderly patients are discussed. Results: Cancer incidence rises with age and is exceeding 3.5% for males older than 85 years. With a life expectancy of more than 4 years, curative therapy is indicated even at this age. Furthermore, several retrospective studies indicate that local control and disease-Specific survival after radiation therapy of elderly patients is comparable with that of younger persons. The exception contains elderly patients with grade-III to IV gliomas or with rectal carcinoma who show a reduced survival which is perhaps caused by less aggressive combined treatment (tumor resection). Although some biological and molecular data indicate a rise in radiation sensitivity with growing age like the reduction of the capacity of some DNA-repair enzymes, there is no convincing evidence in animal studies or in retrospective clinical studies that radiation therapy is generally less well tolerated by older individuals. Some age-depending differences in organ toxicities are described in 3 large studies, which evaluate the data of patients who were enrolled in different EORTC-trials: Older patients suffer more of functional mucositis in case of radiation therapy to the head and neck, they have an increased weight loss and a higher frequency of late esophageal damage when irradiated in the thorax, and they show a higher prevalence of sexual dysfunction when treated with radiation therapy to the pelvis. On the other hand younger patients suffer more from acute toxicity like skin damage, nausea, and deterioration of the performance status during pelvic radiotherapy. When discussing the dose intensity of radiation therapy concomitant disease which

Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review

Directory of Open Access Journals (Sweden)

Vanessa Patricia L. Pereira

Full Text Available Abstract Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

Sick leave and disability pension before and after initiation of antirheumatic therapies in clinical practice.

Science.gov (United States)

Neovius, M; Simard, J F; Klareskog, L; Askling, J

2011-08-01

To investigate sick leave and disability pension in rheumatoid arthritis (RA) in relation to the initiation of biological and non-biological antirheumatic therapies in clinical practice. Patients aged 19-60 years initiating non-biological mono (n=2796) or combination disease-modifying antirheumatic drug (DMARD) therapy (n=973), or biological agents (n=4787) were identified in the Swedish Rheumatology Quality Register between 1999 and 2007. Sick leave and disability pension data (1995-2010) were retrieved from national registers. During the year before the start of mono DMARD, combination DMARD and biological treatment, 10%, 12% and 43% of patients received disability pension benefits, respectively. The corresponding combined annual sick leave and disability pension days were 78 (54+25), 132 (105+27) and 190 (79+111). Irrespective of treatment type, initiators were characterised by a history of increasing sick leave and disability pension. Treatment start was associated with a break in this trajectory: sick leave decreased while disability pension increased, resulting in a net stabilisation of total days. Higher levels of days on sick leave and disability pension at treatment start were observed in patients initiating biologics in 1999 (236 days/year) compared with 2007 (150 days/year; ppension increased rapidly before the initiation of antirheumatic therapy, which was associated with a halt but not a reversal of this development. Work ability is a metric of importance for clinical practice, signalling large remaining needs in the RA population, and the need for intervention earlier in the disease process.

FUNCTIONAL ABILITY AND QUALITY OF LIFE IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING TOCILIZUMAB THERAPY

Directory of Open Access Journals (Sweden)

Anna Sergeyevna Starkova

2013-01-01

Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory joint disease causing joint dysfunction; reduction of quality of life (QoL; loss of work ability, self-care ability, and executing daily routines in most patients 5–10 years after the disease onset.Objective. To study QoL and the functional status (FS of Russian RA patients receiving tocilizumab (TCZ.Material and Methods. The study involved 42 patients with verified RA diagnosis (moderate or high activity who had earlier undergone inefficient therapy with basic anti-inflammatory medications. The limitation of the FS of the RA patients was determined quantitatively using the Russian-language version of the HAQ questionnaire. QoL was evaluated using the EuroQol-5D (EQ-5D Quality of Life questionnaire prior to treatment and after 4, 8, 12, 16, 20, and 24 weeks.Results. TCZ therapy demonstrated a rapid improvement of the FS of RA patients with a 64% decrease in the HAQ index (ΔHAQ=1.12, which corresponded to a 50% improvement of the health status of patients according to the ACR criteria.The median value [25th; 75th percentile] of the EQ-5D index was 0.52 [-0.02; 0.52]; 27.7% patients assessed their QoL as “worse than death”. The index reliably increased by week 8 of therapy; there were no patients with the negative EQ-5D index by week 24. Depending on QoL, all the patients were subdivided into two groups. Group 1 (n=12 comprised the patients with the EQ-5D no higher than 0; in group 2 patients (n=30, it was higher than 0. The groups were comparable in terms of disease duration, age, disease activity indices, and the previous treatment. The low QoL index in all 12 patients in group 1 was attributed to the infeasibility of performing daily activities and the reliably higher pain level (75.0 [61.0; 86.0] and 66.0 [48.0; 71.0] in groups 1 and 2, respectively; p=0.02. Improved QoL and reduced pain level were observed in both groups as early as after the first TCZ infusion. By week 24

Gait and physical impairments in patients with acute ankle sprains who did not receive physical therapy.

Science.gov (United States)

Punt, Ilona M; Ziltener, Jean-Luc; Laidet, Magali; Armand, Stéphane; Allet, Lara

2015-01-01

To assess ankle function 4 weeks after conservative management and to examine the correlation of function with gait. A prospective comparison study. Thirty patients with grade I or II acute ankle sprains were followed up after 4 weeks of conservative management not involving physical therapy. Participants underwent a clinical assessment and had to walk at a normal self-selected walking speed. Their results were compared with the data of 15 healthy subjects. Participants' joint swelling, muscle strength, passive mobility, and pain were assessed. In addition, patients' temporal-spatial, kinematic, and kinetic gait data were measured while walking. Muscle strength and passive mobility were significantly reduced on the injured side compared with the noninjured side (P ankle sprains showed slower walking speed, shorter step length, shorter single support time, reduced and delayed maximum plantar flexion, decreased maximum power, and decreased maximum moment (P ankle sprain, patients who did not receive physical therapy showed physical impairments of the ankle that were correlated with gait parameters. These findings might help fine-tune rehabilitation protocols. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

Energy Technology Data Exchange (ETDEWEB)

Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C. [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States); Gaspar, Laurie E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Camidge, D. Ross [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States)

2014-03-15

Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

Switching of biologics in psoriasis: Reasons and results.

Science.gov (United States)

Honda, Hiromi; Umezawa, Yoshinori; Kikuchi, Sota; Yanaba, Koichi; Fukuchi, Osamu; Ito, Toshihiro; Nobeyama, Yoshimasa; Asahina, Akihiko; Nakagawa, Hidemi

2017-09-01

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second-line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis. © 2017 Japanese Dermatological Association.

Comparison of the effect of Olanzapine and Sertraline on patients suffering from personality disorder, receiving methadone maintenance therapy

Directory of Open Access Journals (Sweden)

mozhgan Jariani

2009-03-01

Full Text Available Background: Borderline Personality disorder is a disabling disease affecting 2% of general population. Various drugs have been suggested for treatment of borderline Personality disorder. If a drug could alleviate a wide range of symptoms, it would be more suitable. In these disorders drug addiction is very common. This fact makes the symptoms complicated and the treatment more difficult. This study is designed to evaluate the effect of Olanzapine and Sertraline in patients suffering from personality disorders who are on methadone maintenance therapy. Materials and Methods: This clinical trial study was carried out on 120 male and female cases chosen for methadone maintenance therapy through interview by a psychiatrist based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly divided into two groups. These groups separately received Olanzapine (5-10 mg daily and Sertraline (50-100 mg daily therapy. The SCL-90 questionnaire was filled out by the participants before treatment and at the 4th, 8th and 12th weeks of the treatment. Results: According to this clinical trial, Olanzapine and Sertraline were effective in ameliorating symptoms of depression, anxiety and aggression, reducing sensitivity in interpersonal relationship and alleviating obsessive symptoms, pessimistic behaviors and somatization disorders in patients with personality disorders on methadone maintenance therapy. Conclusion: As results of this study stated that Olanzapine and Sertraline are definitely effective in alleviating symptoms of patients with personality disorder, prescribing theses drugs are highly recommended for these patients. .

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response

NARCIS (Netherlands)

D'Haens, Geert R.; Panaccione, Remo; Higgins, Peter D. R.; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B.; Herfarth, Hans; Hommes, Daan W.; Kamm, Michael; Löfberg, Robert; Quary, A.; Sands, Bruce; Sood, A.; Watermayer, G.; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M.; Feagan, Brian; Sandborn, William J.; Colombel, Jean Frédéric; Travis, Simon

2011-01-01

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability,

Clinical response to anti-TNFα therapy in patients with rheumatoid arthritis faulted or intolerance in non-biological DMARD in the Hospital San Juan de Dios in the period January 2006 to December 2011

International Nuclear Information System (INIS)

Salas Mena, Claudio

2014-01-01

Various clinical studies are performed globally using anti-TNFα therapy and has proven its clinical effectiveness in the management of rheumatoid arthritis patients, that have failed or have presented intolerance to the use of non-biological DMARDs. The clinical response to treatment of anti-TNFα was determined in patients with rheumatoid arthritis who have presented without respond, have showed intolerance or secondary effects to DMARDs no biological, in the Servicio de Reumatologia del Hospital San Juan de Dios, in the period January 2006 to December 2011. Study has been descriptive, retrospective, observational, by reviewing dossiers of patients with rheumatoid arthritis to initiate anti-TNFα therapy where has valued the DAS28 and initial VES, then at 6 months and 12 months after starting treatment. In the period analyzed, 47 patients evaluated with traditional DMARD failure who have received anti-TNFα therapy, according to DAS28, 32 patients were cataloged as severe activity and 15 of them with moderate activity. A total of 41 patients have used etanercept, with adalimumab 6 patients. The DAS28 initial average was 5,63 in all patients, 6,16 in the subgroup of patients with severe activity, and 4,49 in the subgroup of moderate activity. After 6 months of treatment, the DAS28 has descended to 3,25 in all patients, with 3,67 in the subgroup of severe clinical activity, and 2,35 in the subgroup of moderate clinical activity. One year after treatment values DAS28 have been 3,13 for all patients, 3,53 in severe activity and 2,28 in the subgroup of activity clinical moderate. In all groups and subgroups of patients, difference was demonstrated statistically significant at p less than 0,05. Between the subgroups of patients according to clinical activity is keeped without significant difference, or the type of anti-TNFα therapy employed. The anti-TNFα therapy has proven to be effective for improvement of clinical activity of rheumatoid arthritis, regardless of

Basic radiotherapy physics and biology

CERN Document Server

Chang, David S; Das, Indra J; Mendonca, Marc S; Dynlacht, Joseph R

2014-01-01

This book is a concise and well-illustrated review of the physics and biology of radiation therapy intended for radiation oncology residents, radiation therapists, dosimetrists, and physicists. It presents topics that are included on the Radiation Therapy Physics and Biology examinations and is designed with the intent of presenting information in an easily digestible format with maximum retention in mind. The inclusion of mnemonics, rules of thumb, and reader-friendly illustrations throughout the book help to make difficult concepts easier to grasp. Basic Radiotherapy Physics and Biology is a

[Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis].

Science.gov (United States)

Salinas-Escudero, Guillermo; Vargas-Valencia, Juan; García-García, Erika Gabriela; Munciño-Ortega, Emilio; Galindo-Suárez, Rosa María

2013-01-01

to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

Comparison of the efficacy of biologics versus conventional systemic therapies in the treatment of psoriasis at a comprehensive psoriasis care center.

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Au, Shiu-Chung; Madani, Abdulaziz; Alhaddad, Marwan; Alkofide, Maha; Gottlieb, Alice B

2013-08-01

The efficacy of biologic treatment for psoriasis has not been compared to that of conventional systemic therapies and phototherapy outside of clinical trial settings. Retrospective, cross-sectional. All patient visits with a code for psoriasis (ICD-9 696.1) in the clinical practice of two dermatologists with a high percentage (over 70% of chief complaints) of psoriasis patients from Jan 1, 2008 to Jan 4, 2012 inclusive were included in this retrospective data analysis. Patients were excluded if the baseline Physician's Global Assessment (PGA) at start of treatment was unknown, or less than 3 (moderate). The practice is a comprehensive psoriasis care center in the Northeastern United States serving a metropolitan population of over 4 million people. Patients were divided by treatment type (biologic, conventional systemic or both) and history of previous treatments. Patients were evaluated by Body Surface Area (BSA), PGA, Simple-Measure for Assessing Psoriasis Activity (S-MAPA, calculated by BSA multiplied by PGA). Patients were evaluated at baseline, 8, 12, 16, and 24 weeks after start of treatment. Patients must have completed at least 8 weeks on a single treatment in order to be included. 46 courses of biologics, 12 courses of conventional systemic therapies, and 18 courses of both together were identified with PGA 3 or greater at baseline. Baseline S-MAPA for biologics was 74, for non-biologic systemics was 62.25. At week 24, S-MAPA improved 70.2% over baseline in patients treated with biologics, patients treated with non-biologic systemics improved by only 40.4% (PMAPA (PGA multiplied by BSA) at week 24. These results were observed despite the fact that patients on biologics had a greater baseline severity and had a greater number of previous treatments.

Molecular biology-based diagnosis and therapy for pancreatic cancer

International Nuclear Information System (INIS)

Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

2011-01-01

Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs.

Science.gov (United States)

Edwards, Beatrice J; Hellstein, John W; Jacobsen, Peter L; Kaltman, Steven; Mariotti, Angelo; Migliorati, Cesar A

2008-12-01

and Overview. In 2005, the American Dental Association (ADA) Council on Scientific Affairs convened an expert panel to develop clinical recommendations for dentists treating patients who are receiving oral bisphosphonate therapy. The Journal of the American Dental Association published the resulting report in 2006. This 2008 advisory statement is the first of projected periodic updates of the 2006 clinical recommendations. This 2008 advisory statement concludes, on the basis of a review of the current literature, that for patients receiving bisphosphonate therapy, the risk of developing bisphosphonate-associated osteonecrosis (BON) of the jaw apparently remains low. It also newly concludes that current screening and diagnostic tests are unreliable for predicting a patient's risk of developing the condition. This statement updates the 2006 recommendations regarding general dentistry, management of periodontal diseases, implant placement and maintenance, oral and maxillofacial surgery, endodontics, restorative dentistry and prosthodontics, and orthodontics.

Assessment of satisfaction with pharmaceutical services in patients receiving antiretroviral therapy in outpatient HIV treatment setting.

Science.gov (United States)

Agu, Kenneth Anene; Oqua, Dorothy; Agada, Peter; Ohiaeri, Samuel I; Adesina, Afusat; Abdulkareem, Mohammed Habeeb; King, Rosalyn C; Wutoh, Anthony K

2014-06-01

The patient's perception and satisfaction are increasingly considered as a useful factor in the assessment of competency of health care providers and quality of care. However, these patient focused assessments are largely ignored when assessing health care outcomes. The study assessed the perception and satisfaction of patients receiving antiretroviral therapy (ART) with pharmaceutical services received in outpatient HIV treatment settings. Seventeen HIV treatment centres in Nigeria. This cross-sectional survey included 2,700 patients randomly selected from 26,319 HIV patients on ART, who received pharmaceutical services in the study setting. A study-specific Likert-type instrument was administered to the participants at point of exit from the pharmacy. Midpoint of the 5-point scale was computed and scores above it were regarded as positive while below as negative. Chi-square was used for inferential statistics. All reported p values were 2-sided at 95 % confidence interval (CI). Patient satisfaction with pharmaceutical services. Of 2,700 patients sampled, data from 1,617 (59.9 %) were valid for analysis; 62.3 % were aged 26-40 years and 65.4 % were females. The participants had received pharmaceutical services for a mean duration of 25.2 (95 % CI 24.3-26.1) months. Perception of participants regarding the appearance of pharmacy was positive while that regarding the pharmacists' efforts to solve patients' medication related problems was negative. The participants' rating of satisfaction with the waiting time to access pharmaceutical services was negative; the satisfaction decreases with increasing waiting time. However, the satisfaction with the overall quality of pharmaceutical services received was rated as positive; 90.0 % reported that they got the kind of pharmaceutical services they wanted; 98.2 % would come back to the pharmacy if they were to seek help again and would recommend services to others. The level of satisfaction was found to be associated with

Biological treatments in Behçet's disease: beyond anti-TNF therapy.

Science.gov (United States)

Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

Impact of ECG findings and process-of-care characteristics on the likelihood of not receiving reperfusion therapy in patients with ST-elevation myocardial infarction: results of a field evaluation.

Directory of Open Access Journals (Sweden)

Kevin A Brown

Full Text Available BACKGROUND: Many patients with ST-elevation myocardial infarction (STEMI do not receive reperfusion therapy and are known to have poorer outcomes. We aimed to perform the first population-level, integrated analysis of clinical, ECG and hospital characteristics associated with non-receipt of reperfusion therapy in patients with STEMI. METHODS AND RESULTS: This systematic evaluation of STEMI care in 82 hospitals in Quebec included all patients with a discharge diagnosis of myocardial infarction, presenting with characteristic symptoms and an ECG showing STEMI as attested by at least one of two study cardiologists or left bundle branch block (LBBB. Excluding LBBB, an ECG was considered a definite STEMI diagnosis if both cardiologists scored 'certain STEMI' and ambiguous if one scored 'uncertain' or 'not STEMI'. Centers were classified according to accessibility to primary percutaneous coronary intervention (PPCI: 1 on-site PPCI; 2 routine transfer for PPCI; 3 varying mix of PPCI transfer and on-site fibrinolysis; and 4 routine on-site fibrinolysis. Of 3730 STEMI/LBBB patients, 812 (21.8% did not receive reperfusion therapy. In multivariate analysis, likelihood of no reperfusion therapy was a function of PPCI accessibility (odds ratio [OR] for fibrinolysis versus PPCI centers = 3.1; 95% CI: 2.2-4.4, presence of LBBB (OR = 24.1; 95% CI: 17.8-32.9 and an ECG ambiguous for STEMI (OR = 4.1; 95% CI: 3.3-5.1. When the ECG was ambiguous, likelihood of no reperfusion therapy was highest in hospitals most distant from PPCI centers. CONCLUSIONS: ECG diagnostic ambiguity, LBBB and PPCI accessibility are important predictors of not receiving reperfusion therapy, suggesting opportunities for improving outcomes.

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

Science.gov (United States)

Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

2017-01-01

Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

Patients with schizophrenia or schizoaffective disorder who receive multiple electroconvulsive therapy sessions: characteristics, indications, and results.

Science.gov (United States)

Iancu, Iulian; Pick, Nimrod; Seener-Lorsh, Orit; Dannon, Pinhas

2015-01-01

While electroconvulsive therapy (ECT) has been used for many years, there is insufficient research regarding the indications for continuation/maintenance (C/M)-ECT, its safety and efficacy, and the characteristics of patients with schizophrenia or schizoaffective disorder who receive multiple ECT sessions. The aims of this study were to characterize a series of patients who received 30 ECT sessions or more, to describe treatment regimens in actual practice, and to examine the results of C/M-ECT in terms of safety and efficacy, especially the effect on aggression and functioning. We performed a retrospective chart review of 20 consecutive patients (mean age 64.6 years) with schizophrenia (n=16) or schizoaffective disorder (n=4) who received at least 30 ECT sessions at our ECT unit, and also interviewed the treating physician and filled out the Clinical Global Impression-Severity, Global Assessment of Functioning, and the Staff Observation Aggression Scale-Revised. Patients received a mean of 91.3 ECT sessions at a mean interval of 2.6 weeks. All had been hospitalized for most or all of the previous 3 years. There were no major adverse effects, and cognitive side effects were relatively minimal (cognitive deficit present for several hours after treatment). We found that ECT significantly reduced scores on the Staff Observation Aggression Scale-Revised subscales for verbal aggression and self-harm, and improved Global Assessment of Functioning scores. There were reductions in total aggression scores, subscale scores for harm to objects and to others, and Clinical Global Impression-Severity scores, these were not statistically significant. C/M-ECT is safe and effective for chronically hospitalized patients. It improves general functioning and reduces verbal aggression and self-harm. More research using other aggression tools is needed to determine its effects and to reproduce our findings in prospective and controlled studies.

Low cost biological lung volume reduction therapy for advanced emphysema

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Bakeer M

2016-08-01

Full Text Available Mostafa Bakeer,1 Taha Taha Abdelgawad,1 Raed El-Metwaly,1 Ahmed El-Morsi,1 Mohammad Khairy El-Badrawy,1 Solafa El-Sharawy2 1Chest Medicine Department, 2Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt Background: Bronchoscopic lung volume reduction (BLVR, using biological agents, is one of the new alternatives to lung volume reduction surgery.Objectives: To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue.Methods: Enrolled patients were divided into two groups: group A (seven patients in which autologous blood was used and group B (eight patients in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications.Results: In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted (P-value: <0.001 and 0.038, respectively. In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted (P-value: 0.005 and 0.004, respectively. All patients tolerated the procedure with no mortality.Conclusion: BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. Keywords: BLVR, bronchoscopy, COPD, interventional pulmonology

Brief Report: Risk of Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologic Treatments.

Science.gov (United States)

Xie, Fenglong; Yun, Huifeng; Bernatsky, Sasha; Curtis, Jeffrey R

2016-11-01

To evaluate gastrointestinal (GI) perforation in rheumatoid arthritis (RA) patients receiving tofacitinib, tocilizumab, or other biologic agents. Using health plan data from 2006 through 2014, RA patients without prior GI perforation were identified. Those in whom treatment with tofacitinib or a biologic agent was being initiated were followed up for incident GI perforation with hospitalization. Crude incidence rates were calculated by exposure. Adjusted Cox proportional hazards models were used to evaluate the association between GI perforation and exposures. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. A cohort of 167,113 RA patients was analyzed. Among them, 4,755 began treatment with tofacitinib, 11,705 with tocilizumab, 115,047 with a tumor necrosis factor inhibitor (TNFi), 31,214 with abatacept, and 4,392 with rituximab. Compared to TNFi recipients, abatacept recipients were older, tofacitinib and rituximab recipients were younger, and tocilizumab recipients were similar in age. Patients beginning treatment with a non-TNFi agent were more likely to have previously received biologic agents than patients beginning treatment with a TNFi. The incidence of GI perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.55 (tocilizumab), 1.07 (abatacept), 0.73 (rituximab), and 0.83 (TNFi). Most perforations occurred in the lower GI tract: the incidence of lower GI tract perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.26 (tocilizumab), 0.76 (abatacept), 0.48 (rituximab), and 0.46 (TNFi). Lower GI tract perforation risk was significantly elevated with tocilizumab treatment, and numerically elevated with tofacitinib treatment, versus treatment with TNFi. Adjusted HRs were 2.51 (95% CI 1.31-4.80) for tocilizumab and 1.94 (95% CI 0.49-7.65) for tofacitinib. Older age (HR 1.16 per 5 years [95% CI 1.10-1.22]), diverticulitis/other GI conditions (HR 3.25 [95% CI 1.62-6.50]), and prednisone use at >7.5 mg/day (HR 2.29 [95% CI 1

Assessment of doses due to secondary neutrons received by patient treated by proton therapy

International Nuclear Information System (INIS)

Sayah, R.; Martinetti, F.; Donadille, L.; Clairand, I.; Delacroix, S.; De Oliveira, A.; Herault, J.

2010-01-01

Proton therapy is a specific technique of radiotherapy which aims at destroying cancerous cells by irradiating them with a proton beam. Nuclear reactions in the device and in the patient himself induce secondary radiations involving mainly neutrons which contribute to an additional dose for the patient. The author reports a study aimed at the assessment of these doses due to secondary neutrons in the case of ophthalmological and intra-cranial treatments. He presents a Monte Carlo simulation of the room and of the apparatus, reports the experimental validation of the model (dose deposited by protons in a water phantom, ambient dose equivalent due to neutrons in the treatment room, absorbed dose due to secondary particles in an anthropomorphic phantom), and the assessment with a mathematical phantom of doses dues to secondary neutrons received by organs during an ophthalmological treatment. He finally evokes current works of calculation of doses due to secondary neutrons in the case of intra-cranial treatments

Biomedicines—Moving Biologic Agents into Approved Treatment Options

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Kenneth Cornetta

2013-03-01

Full Text Available The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and Europe. Bioengineering of new agents capitalizing on microRNA biology, nanoparticle technology, stem cell biology, and an increasing understanding of immunology predict a rich future for product development. [...

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

Science.gov (United States)

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

Directory of Open Access Journals (Sweden)

Santosh Ramdurg

2015-01-01

Full Text Available Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30 and naltrexone (n = 30 maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05 there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

Pancreatic cancer stromal biology and therapy

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Xie, Dacheng; Xie, Keping

2015-01-01

Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

Impact of biological therapy on body composition of patients with Chron's disease

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Julianne Campos dos Santos

Full Text Available Summary Introduction: Protein-energy malnutrition in Crohn's disease (CD has been reported in 20 to 92% of patients, and is associated with increased morbidity and mortality and higher costs for the health system. Anti-TNF drugs are a landmark in the clinical management, promoting prolonged remission in patients with CD. It is believed that the remission of this disease leads to nutritional recovery. The effect of biological therapy on body composition and nutritional status is unclear. Method: Prospective study of body assessment by bioelectrical impedance method in patients with moderate to severe CD undergoing treatment with infliximab. The main outcome was the body composition before and after 6 months of anti-TNF therapy. Results: There was a predominance of females (52% with a mean age of 42±12 years. Most patients were eutrophic at baseline and remained so. There was an increase in all parameters of body composition after anti-TNF treatment: BMI (22.9±3.2 versus 25±3.8; p=0.005, waist circumference (88.1±6.7 versus 93.9±7.7; p=0.002, lean mass index (17.5±2.2 versus 18.2±2.3; p=0.000 and fat mass index (5.5±2.3 versus 6.8±2.3; p=0.000. Phase angle remained unchanged (6.2 versus 6.8; p=0.94. Conclusion: After therapy with IFX, all components of body composition increased, except for phase angle. The substantial increase in fat mass index and waist circumference led to concern regarding cardiovascular risk and, thus, to the need for further studies.

Validation of the quality of life-radiation therapy instrument (QOL-RTI) in patients receiving definitive radiation therapy for locally advanced prostate cancer

International Nuclear Information System (INIS)

Gwede, Clement; Friedland, Jay L.; Johnson, Darlene J.; Casey, Linda; Cantor, Alan; Sauder, Bonnie; Beres, Kathleen L.

1996-01-01

Purpose/Objective: The incidence of prostate cancer has tripled over the last 10 years, doubled over the last four years and continues to increase. A common method of treating prostate cancer is with external beam radiotherapy with or without hormones. Accurate and comprehensive documentation through prospective studies with long term follow-up is necessary to reduce the negative impact of treatment on a patient's quality of life. While it is increasingly recognized that radiation therapy treatment for prostate cancer may result in permanent alteration of the patient's quality of life, the extent and timing of this change in quality of life has not been adequately investigated in a comprehensive and prospective manner. Furthermore, there are limited instruments developed for use with patients undergoing definitive radiotherapy. The purpose of this paper is to report on the validation of the Quality of Life Radiation Therapy Instrument (QOL-RTI), a 24-item visual analogue general quality of life tool developed for use with patients receiving radiotherapy. Materials and Methods: Health related quality of life was assessed in a prospective study of 62 patients treated with either combined hormonal therapy (HT) plus external beam radiotherapy (EBRT) or EBRT alone for locally advanced prostate cancer. Quality life was measured prospectively before, during, and after radiation therapy. Results: The estimated reliability of the subscales was assessed with coefficient alpha which ranged from 0.57 to 0.68. Internal consistency was calculated using initial questionnaires for the entire sample, yielding a Cronbach's alpha of 0.82. Test-retest produced a correlation coefficient of 0.75 (p<0.0001) [n=60]. Construct validity was assessed by a repeated measures design to look for time effect, group effect, group and time interaction effect. We examined quality of life total scores, subscale total scores and performance status scores for patients who were treated with HT+ EBRT and

Biology of radiation therapy

International Nuclear Information System (INIS)

Peters, L.J.

1987-01-01

A working knowledge of the biologic principles underlying radiotherapy for head and neck tumors is desirable for all the disciplines involved in the management of patients with these cancers. Clinical practice is certainly possible without this basic understanding, and historically most clinical advances have been made empirically. However, an understanding of the basic concepts permits a better appreciation of the strengths and weaknesses of various treatment strategies and offers a rational approach for future modifications of techniques so as to improve the outcome of treatment

Race/Ethnic differences in the risk of hemorrhagic complications among patients with ischemic stroke receiving thrombolytic therapy.

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Mehta, Rajendra H; Cox, Margueritte; Smith, Eric E; Xian, Ying; Bhatt, Deepak L; Fonarow, Gregg C; Peterson, Eric D

2014-08-01

Race/ethnic-related differences in safety of intravenous thrombolytic therapy have been shown in patients with myocardial infarction, but not studied in ischemic stroke. Using data from the Get With The Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk-adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH], serious life-threatening [excluding sICH], or other) and mortality in white (n=40 411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke. Compared with white patients, overall adjusted hemorrhagic complications after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04-1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14-1.61) patients. Overall adjusted bleeding complications in Hispanics were similar to those of whites. Increased risk of overall bleeding in Asians was related to higher risk of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19-1.82), whereas in blacks, it was related to higher risk of other bleeding. No significant race-related difference was noted in risk of serious or life-threatening bleeding or in overall mortality or death in patients with sICH or any hemorrhagic complications. In patients with stroke receiving tPA, hemorrhagic complications were slightly higher in blacks and Asians, but not in Hispanics compared with whites. Asians also faced significantly higher risk for sICH relative to other race/ethnic groups. Future studies are needed to evaluate whether reduction in tPA dose similar to that used in many Asian countries could improve the safety of tPA therapy in Asians in the United States with acute ischemic strokes while maintaining efficacy. © 2014 American Heart Association, Inc.

Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

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Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

2003-01-01

Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

Biological models in vivo for boron neutronic capture studies as tumors therapy

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Kreimann, Erica L.; Dagrosa, Maria A.; Schwint, Amanda E.; Itoiz, Maria E.; Pisarev, Mario A.; Farias, Silvia S.; Garavaglia, Ricardo N.; Batistoni, Daniel A.

1999-01-01

The use of experimental models for Boron Neutronic Capture studies as Tumors Therapy have as two main objectives: 1) To contribute to the basic knowledge of the biological mechanisms involved to increase the method therapeutical advantage, and 2) To explore the possible application of this therapeutic method to other pathologies. In this frame it was studied the carcinogenesis model of hamster cheek pouch, a type of human buccal cancer. Biodistribution studies of boron compound were performed in tumor, blood and in different precancerous and normal tissues as well as BNCT studies. Results validated this method for BNCT studies and show the capacity of the oral mucosa tumors of selectively concentrate the boron compound, showing a deleterious clear effect on the tumor after 24 hours with BNCT treatment. (author)

Anti-inflammatory therapy for urinary tract infection in children

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A. A. Vyalkova

2015-01-01

Full Text Available Objective: to substantiate the importance of an etiological approach to diagnosing urinary tract infection in children in terms of the species and biological properties of an infectious agent and to evaluate the efficiency of anti-inflammatory therapy. The study included 116 patients aged 3-15 years with chronic pyelonephritis (Group 1 and isolated bacteriuria (Group 2. After 10-14-day antibiotic therapy, Group 1 patients were allocated to two subgroups: Subgroup la («=30 took furamag 5 mg/kg/day; Subgroup lb («=30 received furamag at the same dose in combination with canephron. The treatment cycle lasted 10-14 days. Subgroup 2a («=26 children had furamag 5 mgДg/day and Subgroup 2b (« =30 took furamag in combination with canephron. The duration of treatment was 14 days. The investigators established the high efficiency of therapy with furamag for renal infection in the children with the active and decrement phases and that of the drug of choice for its monotherapy of isolated highly virulent bacteriuria. Therapeutic efficiency was proven to be related to the species and biological characteristics of an infectious agent. Anti-inflammatory therapy for pyelonephritis in terms of the species of pathogenic bacteria was ascertained to improve the efficiency of treatment. A rationale was provided for the individual choice of antibiotics, followed by the use of furamag, eubiotics, and drugs aimed at inhibiting virulence factors and persistence of the pathogen to sanitize the primary focus of infection.

A pharmacogenetics study to predict outcome in patients receiving anti-VEGF therapy in age related macular degeneration

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Kitchens, John W; Kassem, Nawal; Wood, William; Stone, Thomas W; Isernhagen, Rick; Wood, Edward; Hancock, Brad A; Radovich, Milan; Waymire, Josh; Li, Lang; Schneider, Bryan P

2013-01-01

Purpose To ascertain whether single nucleotide polymorphisms (SNPs) in the Vascular Endothelial Growth factor (VEGFA), Complement Factor H (CFH), and LOC387715 genes could predict outcome to anti-VEGF therapy for patients with age related macular degeneration (AMD). Methods Patients with “wet” AMD were identified by chart review. Baseline optical coherence tomography (OCT) and visual acuity (VA) data, and at least 6 months of clinical follow up after 3 initial monthly injections of bevacizumab or ranibizumab were required for inclusion. Based on OCT and VA, patients were categorized into two possible clinical outcomes: (a) responders and (b) non-responders. DNA was extracted from saliva and genotyped for candidate SNPs in the VEGFA, LOC387715, and CFH genes. Clinical outcomes were statistically compared to patient genotypes. Results 101 patients were recruited, and one eye from each patient was included in the analysis. 97% of samples were successfully genotyped for all SNPs. We found a statistically significant association between the LOC387715 A69S TT genotype and outcome based on OCT. Conclusion Genetic variation may be associated with outcome in patients receiving anti-VEGF therapy. PMID:24143065

Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

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Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

2015-01-01

Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients

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de Iudicibus, Gianfranco; Cremer, Olaf L.; Ong, David S. Y.; van der Poll, Tom; Bos, Lieuwe D.; Schultz, Marcus J.

2018-01-01

Background Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). Methods This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers. Results In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1–4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% vs. 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43–0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% vs. 32.9%; OR, 0.62 (interquartile range, 0.39–0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS vs. pulmonary ARDS and also varied by biological phenotype. Conclusions These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS. PMID:29430441

Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients.

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Simonis, Fabienne D; de Iudicibus, Gianfranco; Cremer, Olaf L; Ong, David S Y; van der Poll, Tom; Bos, Lieuwe D; Schultz, Marcus J

2018-01-01

Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers. In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1-4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% vs. 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43-0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% vs. 32.9%; OR, 0.62 (interquartile range, 0.39-0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS vs. pulmonary ARDS and also varied by biological phenotype. These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS.

Reduction of perception of chronic fatigue in an observational study of patients receiving 12 weeks of Kampo therapy.

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Sekiya, Nobuyasu; Shimada, Yutaka; Shintani, Takahiro; Tahara, Eiichi; Kouta, Kazufumi; Shibahara, Naotoshi; Terasawa, Katsutoshi

2005-10-01

The aim of this study was to observe the influence of Kampo therapy on latent chronic fatigue of patients with chronic diseases. One hundred and seventy-three (173) consecutive patients with chronic diseases came to our department for the first time. This was a prospective study. Patients were divided into two groups: a chronic fatigue group (CFG) and a nonchronic fatigue group (NCFG). Based on Kampo diagnosis, both groups were prescribed Kampo formulae as an extract or decoction for 12 weeks. By using questionnaires, patients were assessed concerning their physical and mental types of fatigue, their sleep situation, and their attitude toward work or housekeeping, both before and after 12 weeks of treatment, according to Kampo diagnosis. The mental fatigue, physical fatigue, and sleep scores of both groups, and the work score of CFG, were decreased. The rate of reduction of the fatigue score was significantly greater in CFG than in NCFG. The factor responsible for this difference in fatigue score was physical fatigue. A reduction of the perception of chronic fatigue was observed in patients receiving 12 weeks of Kampo therapy.

Biological effective dose studies in carcinoma of uterine cervix

International Nuclear Information System (INIS)

Yadav, Poonam; Ramasubramanian, V.

2008-01-01

Cancer of cervix is the second most common cancer worldwide among women. Several treatments related protocols of radiotherapy have been followed over few decades in its treatment for evaluating the response. These physical doses varying on the basics of fractionation size, dose rate and total dose needed to be indicated as biological effective dose (BED) to rationalize these treatments. The curative potential of radiation therapy in the management of carcinoma of the cervix is greatly enhanced by the use of intracavitary brachytherapy. Successful brachytherapy requires the high radiation dose to be delivered to the tumor where as minimum radiation dose reach to surrounding normal tissue. Present study is aimed to evaluate biologically effective dose in patients receiving high dose-rate brachytherapy plus external beam radiotherapy based on tumor cell proliferation values in cancer of the cervix patients. The study includes 30 patients' data as a retrospective analysis. In addition determine extent of a dose-response relationship existing between the biological effective dose at Point A and the bladder and rectum and the clinical outcomes

Induced hemocompatibility and bone formation as biological scaffold for cell therapy implant

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Keng-Liang Ou

2016-06-01

Full Text Available Although stem cells can become almost any type of specialized cell in the human body and may have the potential to generate replacement cells for tissues and organs, the transplantation of these cells are hindered by immune rejection and teratoma formation. However, scientists have found a promising solution for these problems-they have discovered the ability to isolate stem cells from a patient’s umbilical cord blood or bone marrow. Even more recently, small stem cells, such as spore-like stem cells, Blastomere-Like Stem Cells (BLSCs, and Very-Small Embryonic-Like stem cells (VSELs isolated directly from the peripheral blood have beeninvestigated as a novel approach to stem cell therapy as they can be isolated directly from the peripheral blood. A newly-discovered population of multipotent stem cells in this class has been dubbed StemBios (SB cells. The potential therapeutic uses of such stem cells have been explored in many ways, one of which includes dental remodeling and construction. Using adult stem cells, scientists have engineered and cultivated teeth in mice that may one day be used for human implantation.It follows that such regeneration may be possible, to a certain degree, in human patients as well. This idea leads to the present study on the effect of SB cell therapy on early osseointegrationof dental implants. Titanium (Ti dental implants have been proven to be a reliable and predictable treatment for restoration of edentulous regions. The osseointegration process can be described in two stages: primary stability (mechanical stability and secondary stability (biological stability. The mechanical stabilization of the implant reflects the interaction between the bone density and the features of the implant designs and can be determined after implant insertion. Alternatively,the biological stabilization of the implant is a physiologic healing process. It is couple to the biological interaction between the external surface of the

Determination of production biology of cladocera in a reservoir receiving hyperthermal effluents from a nuclear production reactor

International Nuclear Information System (INIS)

Vigerstad, T.J.

1980-01-01

The effects on zooplankton of residence in a cooling reservoir receiving hyperthermal effluents directly from a nuclear-production-reactor were studied. Rates of cladoceran population production were compared at two stations in the winter and summer of 1976 on Par Pond located on the Savannah River Plant, Aiken, SC. One station was located in an area of the reservoir directly receiving hyperthermal effluent (Station MAS) and the second was located about 4 km away in an area where surface temperatures were normal for reservoirs in the general geographical region (Station CAS). A non-parametric comparison between stations of standing stock and fecundity data for Bosmina longirostris, taken for the egg ratio model, was used to observe potential hyperthermal effluent effects. There was a statistically higher incidence of deformed eggs in the Bosmina population at Station MAS in the summer. Bosmina standing stock underwent two large oscillations in the winter and three large oscillations in the summer at Station MAS compared with two in the winter and one in the summer at Station CAS. These results are consistent with almost all other Par Pond studies which have found the two stations to be essentially similar in spectra composition but with some statistically significant differences in various aspects of the biology of the species

Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

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Jones G

2012-07-01

Full Text Available Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression. A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference and abatacept (no effect on odds of progression. This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

Peptic ulcer disease and other complications in patients receiving dexamethasone palliation for brain metastasis

International Nuclear Information System (INIS)

Penzner, R.D.; Lipsett, J.A.

1982-01-01

A retrospective analysis was done of 106 patients who received radiation therapy for brain metastasis. Dexamethasone therapy was instituted in 97 patients. Peptic ulcer disease developed in 5 of 89 patients (5.6 percent) who received a dosage of at least 12 mg a day, but did not occur in patients who received a lower dose or in those who did not receive steroids. The interval between institution of dexamethasone therapy and the development of peptic ulcer disease ranged from three to nine weeks. Two patients had perforated ulcers, one of whom required surgical resection. Peptic ulcer disease contributed to the general deterioration and death of three of the five patients. Overall, in 14 of the 89 patients (15.7 percent) a complication of steroid therapy developed in the form of peptic ulcer disease, steroid myopathy or diabetes mellitus (or a combination of these)

[Acupuncture therapy for the improvement of sleep quality of outpatients receiving methadone maintenance treatment: a randomized controlled trial].

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Li, Yi; Liu, Xue-bing; Zhang, Yao

2012-08-01

To study the efficacy and safety of acupuncture therapy for the improvement of sleep quality of outpatients receiving methadone maintenance treatment (MMT). Using randomized double-blinded controlled design, seventy-five MMT outpatients with low sleep quality [score of Pittsburgh sleep quality index (PSQI) > or = 8], were randomly assigned to the acupuncture group (38 cases) and the sham-acupuncture group (37 cases). All patients maintained previous MMT. Acupuncture was applied to Baihui (GV20), Shenmen (bilateral, TF4), Shenting (GV24), Sanyinjiao (bilateral, SP6), and Sishencong (EX-HN1) in the acupuncture group. The same procedures were performed in the sham-acupuncture group, but not to the acupoints (5 mm lateral to the acupoints selected in the acupuncture group) with shallow needling technique. The treatment was performed 5 times each week for 8 successive weeks. The PSQI was assessed before treatment, at the end of the 2nd, 4th, 6th, and 8th week of the treatment. The detection ratio of low sleep quality and the incidence of adverse acupuncture reactions were compared between the two groups at the end of the 8th week. The overall PSQI score was obviously higher in the acupuncture group than in the sham-acupuncture group with statistical difference (P acupuncture group (60.53%, 23/38 cases) than in the sham-acupuncture group (83.78%, 31/37 cases) with statistical difference (P acupuncture reaction was 5.26% (2/38 cases) in the acupuncture group and 2.70% (1/37 cases) in the sham-acupuncture group respectively, showing no statistical difference (P > 0.05). Acupuncture therapy could effectively and safely improve the sleep quality of outpatients receiving MMT.

Evaluation of anxiety and salivary chromogranin a secretion in women receiving breast conserving surgery followed by radiation therapy

International Nuclear Information System (INIS)

Seki-Nakamura, Kaori; Maebayashi, Katsuya; Nasu-Izumi, Sachiko; Akimoto, Tetsuo; Mitsuhashi, Norio

2011-01-01

We conducted a prospective study to assess the anxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received whole-breast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34±1.56 at 3 months after RT (p<0.0001). The mean trait anxiety score for all patients was 43.10±1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p=0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p=0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by State Trait Anxiety Inventory (STAI) showed no positive correlation with salivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery. (author)

Radon therapy; Radon in der Therapie

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Spruck, Kaija [Technische Hochschule Mittelhessen, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

2017-04-01

Radon therapies are used since more than 100 years in human medicine. Today this method is controversially discussed due to the possible increase of ionizing radiation induced tumor risk. Although the exact mode of biological radiation effect on the cell level is still not known new studies show the efficiency of the radon therapy without side effect for instance for rheumatic/inflammatory or respiratory disorders.

Combined tumor therapy

International Nuclear Information System (INIS)

Wrba, H.

1990-01-01

This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

Psoriasis : implications of biologics

NARCIS (Netherlands)

Lecluse, L.L.A.

2010-01-01

Since the end of 2004 several specific immunomodulating therapies: ‘biologic response modifiers’ or ‘biologics’ have been registered for moderate to severe psoriasis in Europe. This thesis is considering the implications of the introduction of the biologics for psoriasis patients, focusing on safety

Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

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Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Kataoka, Saki; Hashinokuchi, Shinichi

2017-12-01

There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7-14.7), 8.8 (7.1-12.1), and 7.6 (6.3-10.3) kPa, respectively (P liver) and Fibrosis-4 index > 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7-15.2), 9.2 (7.3-12.1), and 7.7 (6.3-10.1) kPa, respectively (P liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study

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Jiang SP

2014-06-01

Full Text Available Sai-Ping Jiang,1 Zheng-Yi Zhu,2 Xiao-Liang Wu,3 Xiao-Yang Lu,1 Xing-Guo Zhang,1 Bao-Hua Wu1 1Department of Pharmacy, the First Affiliated Hospital, 2Department of Pharmacy, Children’s Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China Background: The impact of continuous renal replacement therapy (CRRT on drug removal is complicated; pharmacist dosing adjustment for these patients may be advantageous. This study aims to describe the development and implementation of pharmacist dosing adjustment for critically ill patients receiving CRRT and to examine the effectiveness of pharmacist interventions. Methods: A comparative study was conducted in an intensive care unit (ICU of a university-affiliated hospital. Patients receiving CRRT in the intervention group received specialized pharmacy dosing service from pharmacists, whereas patients in the no-intervention group received routine medical care without pharmacist involvement. The two phases were compared to evaluate the outcome of pharmacist dosing adjustment. Results: The pharmacist carried out 233 dosing adjustment recommendations for patients receiving CRRT, and 212 (90.98% of the recommendations were well accepted by the physicians. Changes in CRRT-related variables (n=144, 61.81% were the most common risk factors for dosing errors, whereas antibiotics (n=168, 72.10% were the medications most commonly associated with dosing errors. Pharmacist dosing adjustment resulted in a US$2,345.98 ICU cost savings per critically ill patient receiving CRRT. Suspected adverse drug events in the intervention group were significantly lower than those in the preintervention group (35 in 27 patients versus [vs] 18 in eleven patients, P<0.001. However, there was no significant difference between length of ICU stay and mortality after pharmacist dosing adjustment, which

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

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D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

2011-02-01

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

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Francesco Caso

2014-01-01

Full Text Available Behçet’s disease (BD is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF- α, interleukin- (IL- 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

[Dr. Sklenar's Kombucha mushroom infusion--a biological cancer therapy. Documentation No. 18].

Science.gov (United States)

Hauser, S P

1990-02-27

Kombucha, a fungal infusion, is a 'symbiotic mixture' of bacteria, yeasts, tea and sugar. A number of components are listed, but exact analyses are not published. On the basis of 'thorough detoxification', Kombucha is claimed to be a prophylactic and therapeutic agent in countless diseases, such as rheumatism, intestinal disorders, ageing and cancer. All 'stages of the Sklenar blood picture' have to be treated with Kombucha Drink, Kombucha Drops, coli preparations and Gelum oral-rd for a period of months. A litre-bottle costs 13 DM, the blood analysis 150 Sfr. In the 1960's Dr. R. Sklenar developed a 'biological cancer therapy with Kombucha as the main agent' and his own system of diagnosing cancer. Sklenar's diagnosis of cancer is based on iris diagnosis and demonstration of the causative organism by means of a 'Blood picture according to Dr. Sklenar'. He claims, on one hand, that cancer is only one of the many metabolic diseases and, on the other, that viruses, in his view parasitic microorganisms in general, are responsible for the pathogenesis of cancer. No preclinical and nor investigations are available, as 'success has proved him (Dr. Sklenar) to be right'. The seven 'case histories' described have no solid medical data. There is so far no evidence to support the claim that Kombucha offers 'effective biological treatment of cancer'.

Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

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Allan W. Taylor

2013-01-01

Full Text Available Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART are not established in human-immunodeficiency-virus-(HIV- infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6% were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095 of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.. Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

CAM therapies among primary care patients using opioid therapy for chronic pain

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Mundt Marlon P

2007-05-01

Full Text Available Abstract Background Complementary and alternative medicine (CAM is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Results Patients were treated for a variety of pain problems including low back pain (38.4%, headaches (9.9%, and knee pain (6.5%; the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248, chiropractic treatment (17.8%, n = 162, acupuncture (7.6%, n = 69, yoga (6.1%, n = 55, herbs and supplements (6.8%, n = 62, and prolotherapy (5.9%, n = 54. CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8% and prolotherapy (87.7%, whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. Conclusion This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.

CAM therapies among primary care patients using opioid therapy for chronic pain.

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Fleming, Sara; Rabago, David P; Mundt, Marlon P; Fleming, Michael F

2007-05-16

Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.

Severe and acute complications of biologics in psoriasis.

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Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

2017-12-01

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

Biomedicines?Moving Biologic Agents into Approved Treatment Options

OpenAIRE

Cornetta, Kenneth

2013-01-01

The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and...

Can We Advance Proton Therapy for Prostate? Considering Alternative Beam Angles and Relative Biological Effectiveness Variations When Comparing Against Intensity Modulated Radiation Therapy

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Underwood, Tracy, E-mail: tunderwood@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Department of Medical Physics and Bioengineering, University College London, London (United Kingdom); Giantsoudi, Drosoula; Moteabbed, Maryam; Zietman, Anthony; Efstathiou, Jason; Paganetti, Harald; Lu, Hsiao-Ming [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

2016-05-01

Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions were simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.

Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter?

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Curkendall, S; Patel, V; Gleeson, M; Campbell, R S; Zagari, M; Dubois, R

2008-10-15

To assess the impact of patient out-of-pocket (OOP) expenditures on adherence and persistence with biologics in patients with rheumatoid arthritis (RA). An inception cohort of RA patients with pharmacy claims for etanercept or adalimumab during 2002-2004 was selected from an insurance claims database of self-insured employer health plans (n=2,285) in the US. Adherence was defined as medication possession ratio (MPR): the proportion of the 365 followup days covered by days supply. Persistence was determined using a survival analysis of therapy discontinuation during followup. Patient OOP cost was measured as the patient's coinsurance and copayments per week of therapy, and as the proportion of the total medication charges paid by the patient. Multivariate linear regression models of MPR and proportional hazards models of persistence were used to estimate the impact of cost, adjusting for insurance type and demographic and clinical variables. Mean +/- SD OOP expenditures averaged $7.84+/-$14.15 per week. Most patients (92%) paid less than $20 OOP for therapy/week. The mean +/- SD MPR was 0.52+/-0.31. Adherence significantly decreased with increased weekly OOP (coeff= -0.0035, Pcosts paid by patients (coeff= -0.8794, Pcost exceeded $50 were more likely to discontinue than patients with lower costs (hazard ratio 1.58, Pcompliance. The adverse impact of high OOP costs on adherence, persistence, and outcomes must be considered when making decisions about increasing copayments.

The future of cytotoxic therapy: selective cytotoxicity based on biology is the key

International Nuclear Information System (INIS)

Bono, Johann S de; Tolcher, Anthony W; Rowinsky, Eric K

2003-01-01

Although mortality from breast cancer is decreasing, 15% or more of all patients ultimately develop incurable metastatic disease. It is hoped that new classes of target-based cytotoxic therapeutics will significantly improve the outcome for these patients. Many of these novel agents have displayed cytotoxic activity in preclinical and clinical evaluations, with little toxicity. Such preferential cytotoxicity against malignant tissues will remain tantamount to the Holy Grail in oncologic therapeutics because this portends improved patient tolerance and overall quality of life, and the capacity to deliver combination therapy. Combinations of such rationally designed target-based therapies are likely to be increasingly important in treating patients with breast carcinoma. The anticancer efficacy of these agents will, however, remain dependent on the involvement of the targets of these agents in the biology of the individual patient's disease. Results of DNA microarray analyses have raised high hopes that the analyses of RNA expression levels can successfully predict patient prognosis, and indicate that the ability to rapidly 'fingerprint' the oncogenic profile of a patient's tumor is now possible. It is hoped that these studies will support the identification of the molecules driving a tumor's growth, and the selection of the appropriate combination of targeted agents in the near future

Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

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Mario Degli Stefani

2016-10-01

Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

Science.gov (United States)

Degli Stefani, Mario; Biasutti, Michele

2016-01-01

Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.

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Negahban, Hossein; Rezaie, Solmaz; Goharpey, Shahin

2013-12-01

The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis. The secondary aim was to investigate whether combination of both massage and exercise has an additive effect. Randomized controlled pilot trial with repeated measurements and blinded assessments. Local Multiple Sclerosis Society. A total of 48 patients with multiple sclerosis were randomly assigned to four equal subgroups labelled as massage therapy, exercise therapy, combined massage-exercise therapy and control group. The treatment group received 15 sessions of supervised intervention for five weeks. The massage therapy group received a standard Swedish massage. The exercise therapy group was given a combined set of strength, stretch, endurance and balance exercises. Patients in the massage-exercise therapy received a combined set of massage and exercise treatments. Patients in the control group were asked to continue their standard medical care. Pain, fatigue, spasticity, balance, gait and quality of life were assessed before and after intervention. Massage therapy resulted in significantly larger improvement in pain reduction (mean change 2.75 points, P = 0.001), dynamic balance (mean change, 3.69 seconds, P = 0.009) and walking speed (mean change, 7.84 seconds, P = 0.007) than exercise therapy. Patients involved in the combined massage-exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy (mean change, 1.67 points, P = 0.001). Massage therapy could be more effective than exercise therapy. Moreover, the combination of massage and exercise therapy may be a little more effective than exercise therapy alone.

Comparison of steroid pulse therapy and conventional oral steroid therapy as initial treatment for autoimmune pancreatitis

International Nuclear Information System (INIS)

Tomiyama, Takashi; Uchida, Kazushige; Matsushita, Mitsunobu; Ikeura, Tsukasa; Fukui, Toshiro; Takaoka, Makoto; Nishio, Akiyoshi; Okazaki, Kazuichi

2011-01-01

The efficacy of oral steroid therapy for autoimmune pancreatitis (AIP) is well known, and oral prednisolone treatment is most usually commenced at 30-40 mg/day, but there have been few reports about comparative studies of oral steroid therapy and steroid pulse therapy as the initial treatment for AIP. We studied the clinical course and image findings to estimate the utility of steroid pulse therapy for AIP, comparing it with oral steroid therapy. Laboratory and image findings were assessed retrospectively in 11 patients who received steroid pulse therapy, and the findings were compared to those in 10 patients who received conventional oral steroid therapy. Change in pancreatic size showed no significant difference between the therapies after 2 weeks of treatment. Significant improvement of lower bile duct strictures after 2 weeks of treatment and that of immunoglobulin values within 6 months were shown with both therapies. However, steroid pulse therapy showed significant improvement of γ-guanosine triphosphate (GTP) in 2 weeks and of alanine aminotransferase (ALT) in 2 and 8 weeks, compared with oral steroid therapy. Moreover, there was one patient in whom the lower bile duct stricture was not improved by oral steroid therapy, but it did show improvement with steroid pulse therapy. Initial steroid pulse therapy is a beneficial alternative to oral steroid therapy for the improvement of bile duct lesions. In future, the accumulation of a larger number of patients receiving steroid pulse therapy is needed, and prospective studies will be required. (author)

Impact of therapist change after initial contact and traumatic burden on dropout in a naturalistic sample of inpatients with borderline pathology receiving dialectical behavior therapy.

Science.gov (United States)

Steuwe, Carolin; Berg, Michaela; Driessen, Martin; Beblo, Thomas

2017-01-01

This study focused on the predictors of therapy dropout in a naturalistic sample of patients with borderline pathology receiving dialectical behavior therapy (DBT) in an inpatient setting. We assumed that the change of the therapist between DBT-briefing and start of DBT-treatment as well as comorbid posttraumatic stress disorder (PTSD) and childhood trauma history were associated with elevated dropout. Eighty-nine participants with borderline pathology (≥ 3 borderline personality disorder criteria) receiving an inpatient DBT program completed a quality assurance questionnaire set assessing demographic information and pretreatment psychopathology during the days of their inpatient stay. Beyond that, changes of therapists were documented. The predictor analyses were investigated with generalized estimating equations. The dropout rate was 24.7%. A change of therapist between DBT-briefing and treatment as well as high childhood emotional abuse was associated with premature termination of treatment. Higher values of physical neglect during childhood were associated with a protective effect on treatment dropout. Surprisingly, this was also true for comorbid PTSD. This study supports the importance of therapy process variables as predictors of therapy dropout in borderline pathology. A change of therapist between DBT-briefing and treatment was associated with an increased vulnerability for dropping out of treatment and should therefore be avoided if possible. Against our hypotheses, a comorbid PTSD was even protective with regard to DBT dropout. Therefore, this severely suffering patient group should not be rejected from treatment assuming them to be too unstable for psychotherapy. However, results need to be replicated. ClinicalTrials.gov Identifier: NCT03018639, retrospectively registered on January 9, 2017.

Longitudinal analysis of quality of life in patients receiving conformal radiation therapy for prostate cancer

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Geinitz, Hans; Thamm, Reinhard; Scholz, Christian; Heinrich, Christine; Prause, Nina; Kerndl, Simone; Molls, Michael; Zimmermann, Frank B. [Dept. of Radiotherapy and Radiooncology, Technische Univ. Muenchen (Germany); Keller, Monika [Psychooncology Section, Dept. of Psychosomatic and General Clinical Medicine, Univ. Hospital, Heidelberg (Germany); Busch, Raymonde [Inst. of Medical Statistics and Epidemiology, Technische Univ. Muenchen (Germany)

2010-01-15

Purpose: To prospectively assess quality of life (QoL) in patients receiving conformal radiation therapy (CRT) for prostate cancer. Patients and Methods: 78 men with definitive CRT for prostate cancer were entered into the study. Patients were assessed before CRT, at 40 and 60 Gy, and 2, 12 and 24 months after the end of treatment. QoL was assessed using the EORTC Quality of Life Questionnaire C30 and the prostate module PR25. Changes in mean QoL scores with time of {>=} 10 points were considered clinically relevant. Results: Global QoL did not change statistically significant during CRT and was slightly above baseline levels during follow-up. CRT had a statistically significant negative short-term impact on role functioning, fatigue, and PR25 urinary symptoms. The scores recovered within 2 months to 1 year after CRT. Emotional functioning and social functioning scores slightly increased during and after CRT. Role functioning decreased by > 10 points at 60 Gy and urinary symptoms decreased by > 10 points at 40 and 60 Gy. All other differences were < 10 points. A high number of concomitant diseases and having no children were negative pretreatment predictors for long-term global QoL. Conclusion: Definitive CRT for prostate cancer does not compromise global QoL during therapy and up to 2 years after treatment. It has a limited negative effect on role functioning, urinary symptoms and, to a lesser extent, on fatigue with restitution within 2 months to 1 year after treatment. (orig.)

Longitudinal analysis of quality of life in patients receiving conformal radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Geinitz, Hans; Thamm, Reinhard; Scholz, Christian; Heinrich, Christine; Prause, Nina; Kerndl, Simone; Molls, Michael; Zimmermann, Frank B.; Keller, Monika; Busch, Raymonde

2010-01-01

Purpose: To prospectively assess quality of life (QoL) in patients receiving conformal radiation therapy (CRT) for prostate cancer. Patients and Methods: 78 men with definitive CRT for prostate cancer were entered into the study. Patients were assessed before CRT, at 40 and 60 Gy, and 2, 12 and 24 months after the end of treatment. QoL was assessed using the EORTC Quality of Life Questionnaire C30 and the prostate module PR25. Changes in mean QoL scores with time of ≥ 10 points were considered clinically relevant. Results: Global QoL did not change statistically significant during CRT and was slightly above baseline levels during follow-up. CRT had a statistically significant negative short-term impact on role functioning, fatigue, and PR25 urinary symptoms. The scores recovered within 2 months to 1 year after CRT. Emotional functioning and social functioning scores slightly increased during and after CRT. Role functioning decreased by > 10 points at 60 Gy and urinary symptoms decreased by > 10 points at 40 and 60 Gy. All other differences were < 10 points. A high number of concomitant diseases and having no children were negative pretreatment predictors for long-term global QoL. Conclusion: Definitive CRT for prostate cancer does not compromise global QoL during therapy and up to 2 years after treatment. It has a limited negative effect on role functioning, urinary symptoms and, to a lesser extent, on fatigue with restitution within 2 months to 1 year after treatment. (orig.)

Technical basis of radiation therapy. Practical clinical applications. 5. ed.

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Levitt, Seymour H. [Karolinska Institutet Stockholm (Sweden). Dept. of Oncol-Pathol; Perez, Carlos A. [Washington Univ. Medical Center, St. Louis, MO (United States). Dept. of Radiation Oncology; Purdy, James A. [California Univ., Sacramento, CA (United States). Dept. of Radiation Oncology; Poortmans, Philip [Institute Verbeeten, Tilburg (Netherlands). Dept. of Radiation Oncology

2012-07-01

This well-received book, now in its fifth edition, is unique in providing a detailed description of the technological basis of radiation therapy. Another novel feature is the collaborative writing of the chapters by North American and European authors. This considerably broadens the book's perspective and increases its applicability in daily practice throughout the world. The book is divided into two sections. The first covers basic concepts in treatment planning, including essential physics and biological principles related to time-dose-fractionation, and explains the various technological approaches to radiation therapy, such as intensity-modulated radiation therapy, tomotherapy, stereotactic radiotherapy, and high and low dose rate brachytherapy. Issues relating to quality assurance, technology assessment, and cost-benefit analysis are also reviewed. The second part of the book discusses in depth the practical clinical applications of the different radiation therapy techniques in a wide range of cancer sites. All of the chapters have been written by leaders in the field. This book will serve to instruct and acquaint teachers, students, and practitioners in the various fields of oncology with the basic technological factors and approaches in radiation therapy. (orig.)

Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

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McDonald, Mark W., E-mail: mmcdona2@iuhealth.org [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Indiana University Health Proton Therapy Center, Bloomington, Indiana (United States); Linton, Okechuckwu R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Shah, Mitesh V. [Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, Indiana (United States)

2013-12-01

Purpose: To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. Methods and Materials: A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy). Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm{sup 3} (range, 0-701 cm{sup 3}). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). Results: The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Conclusions: Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional

Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

International Nuclear Information System (INIS)

McDonald, Mark W.; Linton, Okechuckwu R.; Shah, Mitesh V.

2013-01-01

Purpose: To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. Methods and Materials: A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy). Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm 3 (range, 0-701 cm 3 ). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). Results: The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Conclusions: Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional toxicities may

Early results of a prospective quality of life analysis using the lung cancer symptom scale (LCSS) in patients receiving radiation therapy (XRT) for lung cancer in the community hospital setting

International Nuclear Information System (INIS)

Lutz, Stephen T.; Norrell, Ruth; Johnson, Christopher R.; Kachnic, Lisa A.; Arthur, Douglas W.; Huang, David T.

1997-01-01

Purpose/Objective: To prospectively determine symptom response in patients receiving radiation therapy for primary lung cancer. Materials and Methods: Thirty-three consecutive lung cancer patients were evaluated between March 1996 and February 1997 at the Medical College of Virginia satellite facility which serves a local community hospital. The LCSS, a validated quality of life scale, was used prospectively during the consultation and upon subsequent follow-up. The scale allowed scoring of symptom improvement, worsening, or stability following therapy. One patient declined therapy, while another was not offered XRT. The 31 remaining patients received a median dose of 54 Gy. Eleven patients received radiotherapy with curative intent to doses between 60 and 70 Gy, 5 small cell lung carcinoma (SmCCa) patients received 54 Gy consolidative therapy, and 13 patients received 15 to 30 Gy with palliative intent. Eight patients received chemotherapy as part of their initial treatment course, including all of those diagnosed with SmCCa. Twenty-one patients completed the LCSS at least once in the three month interval after therapy, while 6 died prior to follow-up, 2 were under treatment at the time of this analysis, and 2 were lost to follow-up. Survival analysis was completed using the Kaplan-Meier method. Results: Median follow-up was 4 months (range = 1 to 14), with an estimated median survival of 5 months. Fourteen patients died of lung cancer, 12 are alive with disease, 6 are alive without disease, and 1 died without disease. Patient characteristics were median age of 69 years (range = 43 to 91), male to female ratio of 4.5 to 1, mean weight loss of 12 pounds (range = 0 to 27), and mean duration of symptoms of 3 months (range = 0 to 12). Stage was: I 9%, II = 0%, IIIA = 6%, IIIB = 43%, IV = 27%, and limited stage SmCCa = 15%. Histology was: squamous cell carcinoma = 21%, adenocarcinoma = 23%, large cell carcinoma = 23%, poorly differentiated carcinoma = 15%, mesothelioma

Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy.

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Esteva, Francisco J; Sahin, Aysegul A; Cristofanilli, Massimo; Coombes, Kevin; Lee, Sang-Joon; Baker, Joffre; Cronin, Maureen; Walker, Michael; Watson, Drew; Shak, Steven; Hortobagyi, Gabriel N

2005-05-01

To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-microm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.

Emerging biologic therapies for hypercholesterolaemia.

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Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Patency of the infarct-related coronary artery--a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

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Walamies, M; Virtanen, V; Koskinen, M; Uusitalo, A

1994-09-01

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarct-related coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-123I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (acid uptake was initially 20.2 +/- 4.7 (mean +/- SD) and was reduced to 11.3 +/- 6.1 during the follow-up (95% confidence interval of the decrease 16.0-1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7 +/- 13.1, initial test, and 21.3 +/- 13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of sequence and type of chemotherapy and radiation therapy on cosmesis and complications after breast conservation therapy

International Nuclear Information System (INIS)

Markiewicz, Deborah A.; Schultz, Delray J.; Haas, Jonathan A.; Harris, Eleanor E. R.; Fox, Kevin R.; Glick, John H.; Solin, Lawrence J.

1996-01-01

Purpose: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy. Methods and Materials: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy ± hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate(CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up. Results: The use of chemotherapy had an adverse effect

Proton therapy project at PSI

International Nuclear Information System (INIS)

Nakagawa, K.; Akanuma, A.; Karasawa, K.

1990-01-01

Particle radiation which might present steeper dose distribution has received much attention as the third particle facility at the Paul Scherrer Institute (PSI), Switzerland. Proton conformation with sharp fall-off is considered to be the radiation beam suitable for confining high doses to a target volume without complications and for verifying which factor out of high RBE or physical dose distribution is more essential for local control in malignant tumors. This paper discusses the current status of the spot scanning method, which allows three dimensional conformation radiotherapy, and preliminary results. Preliminary dose distribution with proton conformation technique was acquired by modifying a computer program for treatment planning in pion treatment. In a patient with prostate carcinoma receiving both proton and pion radiation therapy, proton conformation was found to confine high doses to the target area and spare both the bladder and rectum well; and pion therapy was found to deliver non-homogeneous radiation to these organs. Although there are some obstacles in the proton project at PSI, experimental investigations are encouraging. The dynamic spot scanning method with combination of the kicker magnet, wobbler magnet, range shifter, patient transporter, and position sensitive monitor provides highly confined dose distribution, making it possible to increase total doses and thus to improve local control rate. Proton confirmation is considered to be useful for verifying possible biological effectiveness of negative pion treatment of PSI as well. (N.K.)

Technical Stability and Biological Variability in MicroRNAs from Dried Blood Spots: A Lung Cancer Therapy-Monitoring Showcase.

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Kahraman, Mustafa; Laufer, Thomas; Backes, Christina; Schrörs, Hannah; Fehlmann, Tobias; Ludwig, Nicole; Kohlhaas, Jochen; Meese, Eckart; Wehler, Thomas; Bals, Robert; Keller, Andreas

2017-09-01

Different work flows have been proposed to use miRNAs as blood-borne biomarkers. In particular, the method used for collecting blood from patients can considerably influence the diagnostic results. We explored whether dried blood spots (DBSs) facilitate stable miRNA measurements and compared its technical stability with biological variability. First, we tested the stability of DBS samples by generating from 1 person 18 whole-genome-wide miRNA profiles of DBS samples that were exposed to different temperature and humidity conditions. Second, we investigated technical reproducibility by performing 7 replicates of DBS again from 1 person. Third, we investigated DBS samples from 53 patients with lung cancer undergoing different therapies. Across these 3 stages, 108 genome-wide miRNA profiles from DBS were generated and evaluated biostatistically. In the stability analysis, we observed that temperature and humidity had an overall limited influence on the miRNomes (average correlation between the different conditions of 0.993). Usage of a silica gel slightly diminished DBS' technical reproducibility. The 7 technical replicates had an average correlation of 0.996. The correlation with whole-blood PAXGene miRNomes of the same individual was remarkable (correlation of 0.88). Finally, evaluation of the samples from the 53 patients with lung cancer exposed to different therapies showed that the biological variations exceeded the technical variability significantly ( P work flow for profiling of whole miRNomes on the basis of samples collected from DBS. Biological variations exceeded technical variations significantly. DBS-based miRNA profiles will potentially further the translational character of miRNA biomarker studies. © 2017 American Association for Clinical Chemistry.

The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

Energy Technology Data Exchange (ETDEWEB)

Mairani, A [University of Pavia, Department of Nuclear and Theoretical Physics, and INFN, via Bassi 6, 27100 Pavia (Italy); Brons, S; Parodi, K [Heidelberg Ion Beam Therapy Center and Department of Radiation Oncology, Im Neuenheimer Feld 450, 69120 Heidelberg (Germany); Cerutti, F; Ferrari, A; Sommerer, F [CERN, 1211 Geneva 23 (Switzerland); Fasso, A [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Kraemer, M; Scholz, M, E-mail: Andrea.Mairani@mi.infn.i [GSI Biophysik, Planck-Str. 1, D-64291 Darmstadt (Germany)

2010-08-07

Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fuer Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed {sup 12}C ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-dose distributions in water used as input basic data in TRiP98 and the FLUKA recalculated ones. On the other hand, taking into account the differences in the physical beam modeling, the FLUKA-based biological calculations of the CHO cell survival profiles are found in good agreement with the experimental data as well with the TRiP98 predictions. The developed approach that combines the MC transport/interaction capability with the same biological model as in the treatment planning system (TPS) will be used at HIT to support validation/improvement of both dose and RBE-weighted dose calculations performed by the analytical TPS.

Evaluation of the effect of various parameters on the amount of radiation dose received by family members after 131-I therapy

International Nuclear Information System (INIS)

Sarkar, S.; Dehghanpour, M.; Saghari, M.; Ghiasinezhad, M.

2001-01-01

The main concern with respect to discharge of patients from hospital after 131-I therapy is contamination of their surroundings and exposure of people who are in close contact with them. In this study, we evaluated absorbed dose received by home mates of these patients within one week of discharge from hospital. This study was based on 100 patients (23 patients with thyroid cancer together with 70 members of their families and 2 hyperthyroid patients plus 5 of their family members). Measurements were performed by TLD. Patients were discharged from hospital if the dose rate from a meter distance of their thyroid was below 20 μSv/hr (ICRP-60). The hospitalization period for those patients with thyroid cancer varied between 2-3 days (depending on the amount of radioactivity received). Hyperthyroid patients were treated as outpatients. Our data indicate that although hyperthyroid patients received much less activity in comparison to those with thyroid cancer, but due to the slow iodine discharge rate from their bodies, they radiated more to their surroundings. For patients with thyroid cancer, when the given activity increased from 100 mCi to 150 mCi, the average dose absorbed by their family members increased by a factor of 3. The duration of hospitalization as well as the amount of activity given to the patients have a significant effect on the amount of radiation dose received by the family members. In a group of patients who received 100 mCi of 131-I, the average radiation dose received by the family members of those patients who were hospitalized for 2 days were 1.5 times more than of those patients who were hospitalized for 3 days, whereas following therapy with 150 mCi of 131-Iodine, the average radiation dose received by the family members of those patients who were hospitalized for 2 days were about 6.5 times more than that of those who were hospitalized for 3 days. The size of the patient's house and the time that family spends with the patient at house are

Initial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy Patients With Gynecologic Cancer

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Lin, Lilie L., E-mail: lin@xrt.upenn.edu; Kirk, Maura; Scholey, Jessica; Taku, Nicolette; Kiely, Janid B.; White, Benjamin; Both, Stefan

2016-05-01

Purpose: To report the acute toxicities associated with pencil beam scanning proton beam radiation therapy (PBS) for whole pelvis radiation therapy in women with gynecologic cancers and the results of a dosimetric comparison of PBS versus intensity modulated radiation therapy (IMRT) plans. Methods and Materials: Eleven patients with posthysterectomy gynecologic cancer received PBS to the whole pelvis. The patients received a dose of 45 to 50.4 Gy relative biological effectiveness (RBE) in 1.8 Gy (RBE) daily fractions. Acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 4. A dosimetric comparison between a 2-field posterior oblique beam PBS and an IMRT plan was conducted. The Wilcoxon signed rank test was used to assess the potential dosimetric differences between the 2 plans and PBS target coverage robustness relative to setup uncertainties. Results: The median patient age was 55 years (range 23-76). The primary site was cervical in 7, vaginal in 1, and endometrial in 3. Of the 11 patients, 7 received concurrent cisplatin, 1 each received sandwich carboplatin and paclitaxel chemotherapy, both sandwich and concurrent chemotherapy, and concurrent and adjuvant chemotherapy, and 1 received no chemotherapy. All patients completed treatment. Of the 9 patients who received concurrent chemotherapy, the rate of grade 2 and 3 hematologic toxicities was 33% and 11%, respectively. One patient (9%) developed grade 3 acute gastrointestinal toxicity; no patient developed grade ≥3 genitourinary toxicity. The volume of pelvic bone marrow, bladder, and small bowel receiving 10 to 30 Gy was significantly lower with PBS than with intensity modulated radiation therapy (P<.001). The target coverage for all PBS plans was robust relative to the setup uncertainties (P>.05) with the clinical target volume mean dose percentage received by 95% and 98% of the target volume coverage changes within 2% for the individual plans. Conclusions: Our

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

Science.gov (United States)

Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy.

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von Karstedt, Silvia; Montinaro, Antonella; Walczak, Henning

2017-05-24

The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL-TRAIL-R system to their own advantage. However, novel insight on two fronts - how resistance of cancer cells to TRAIL-based pro-apoptotic therapies might be overcome, and how the pro-tumorigenic effects of endogenous TRAIL might be countered - gives reasonable hope that the TRAIL system can be harnessed to treat cancer. In this Review we assess the status quo of our understanding of the biology of the TRAIL-TRAIL-R system - as well as the gaps therein - and discuss the opportunities and challenges in effectively targeting this pathway.

Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis.

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Youngstein, Taryn; Peters, James E; Hamdulay, Shahir S; Mewar, Devesh; Price-Forbes, Alec; Lloyd, Mark; Jeffery, Rachel; Kinderlerer, Anne R; Mason, Justin C

2014-01-01

We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease. Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated. Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-α therapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs. We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.

Biological assessment of aquaculture effects on effluent-receiving streams in Ghana using structural and functional composition of fish and macroinvertebrate assemblages.

Science.gov (United States)

Ansah, Yaw Boamah; Frimpong, Emmanuel A; Amisah, Stephen

2012-07-01

Biological assessment of aquatic ecosystems is widely employed as an alternative or complement to chemical and toxicity testing due to numerous advantages of using biota to determine ecosystem condition. These advantages, especially to developing countries, include the relatively low cost and technical requirements. This study was conducted to determine the biological impacts of aquaculture operations on effluent-receiving streams in the Ashanti Region of Ghana. We collected water, fish and benthic macroinvertebrate samples from 12 aquaculture effluent-receiving streams upstream and downstream of fish farms and 12 reference streams between May and August of 2009, and then calculated structural and functional metrics for biotic assemblages. Fish species with non-guarding mode of reproduction were more abundant in reference streams than downstream (P = 0.0214) and upstream (P = 0.0251), and sand-detritus spawning fish were less predominant in reference stream than upstream (P = 0.0222) and marginally less in downstream locations (P = 0.0539). A possible subsidy-stress response of macroinvertebrate family richness and abundance was also observed, with nutrient (nitrogen) augmentation from aquaculture and other farming activities likely. Generally, there were no, or only marginal differences among locations downstream and upstream of fish farms and in reference streams in terms of several other biotic metrics considered. Therefore, the scale of impact in the future will depend not only on the management of nutrient augmentation from pond effluents, but also on the consideration of nutrient discharges from other industries like fruit and vegetable farming within the study area.

Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

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Hossein Mozdarani

2012-01-01

Full Text Available Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity. It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation

Perioperative nursing for patients with diabetic foot receiving endovascular interventional therapy

International Nuclear Information System (INIS)

Yang Yang; Wang Feng; Li Ke; Li Cheng; Ji Donghua

2010-01-01

Objective: To study the effect of perioperative nursing on the living quality of patients with diabetic foot who are treated with endovascular interventional therapy. Methods: Specific perioperative nursing care plan was accordingly designed for 43 patients with diabetic foot. Endovascular balloon angioplasty and stent implantation were formed in these patients to treat their diabetic foot. The clinical results were observed. Results: Perioperative nursing effectively improved patient's limb blood supply, enhanced the healing of diabetic foot ulceration and increased the possibility of limb preservation. Conclusion: Endovascular therapy combined with corresponding perioperative nursing care can benefit more patients with diabetic foot. (authors)

Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study.

Science.gov (United States)

van der Have, Mike; Belderbos, Tim D G; Fidder, Herma H; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P; Eshuis, Emma J; Ponsioen, Cyriel Y; Siersema, Peter D; van Oijen, Martijn G H; Oldenburg, Bas

2014-10-01

Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Regenerative Therapy for Retinal Disorders

Directory of Open Access Journals (Sweden)

Narsis Daftarian

2010-01-01

Full Text Available Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.

Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study

DEFF Research Database (Denmark)

Lundgren, Jens; Emery, Sean; Neuhaus, Jacqueline A

2008-01-01

BACKGROUND: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group......, participants started ART when the CD4+ cell count was ART at entry inform the early use of ART. METHODS: Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following......). RESULTS: A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4...

Pilot study of sexual dysfunction in patients with psoriasis: Influence of biologic therapy

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Ricardo Ruiz-Villaverde

2011-01-01

Full Text Available Background: Psoriasis is a chronic skin disease that affects 1 to 3% of the population in most industrialized countries. It is commonly associated with a variety of psychological problems including low self-esteem, depression, suicidal thoughts, and sexual dysfunction. Materials and Methods : We have performed a pilot study in which we have tried to assess the impact on sexual dysfunction in patients with psoriasis who have started treatment with biological therapy using validated indexes in Spanish: International Index of Erectile Function for men and female sexual function index in women. Results : Considering the men and women from our study, an improvement in FSFI by an average of 9.5 and 6.3 points is observed, respectively. Conclusion: We considered our series as a first step for a more detailed approach to the study of sexual function in patients with psoriasis.

The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

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Lesiuk, Teresa

2015-05-01

To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

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Dgachi, Youssef; Ismaili, Lhassane; Knez, Damijan; Benchekroun, Mohamed; Martin, Hélène; Szałaj, Natalia; Wehle, Sarah; Bautista-Aguilera, Oscar M; Luzet, Vincent; Bonnet, Alexandre; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Decker, Michael; Chabchoub, Fakher; Marco-Contelles, José

2016-06-20

Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β-amyloid (Aβ1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36±0.02) μm], has strong antioxidant activity (3.61 μmol Trolox equivalents), and moderate Aβ1-42 antiaggregating power (40.3 %). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

Differences in major depressive disorder and generalised anxiety disorder symptomatology between prostate cancer patients receiving hormone therapy and those who are not.

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Sharpley, Christopher F; Bitsika, Vicki; Wootten, Addie C; Christie, David R H

2014-12-01

The aim of this study is to explore the associations between hormone treatment variables and depression, and the nature of depression in prostate cancer (PCa) patients by comparing the severity and symptom profile of anxiety and depression in men who were currently receiving hormone therapy (HT) versus those who were not. Self-reports of anxiety and depression on standardized scales of GAD and major depressive disorder (MDD) were collected from 156 PCa patients across two recruitment sites in Australia. Patients who were currently receiving HT were compared with patients not receiving HT for their severity and symptom profiles on GAD and MDD. Participants receiving HT had significantly higher GAD and MDD total scores than patients who were not receiving HT. In addition, the symptom profiles of these two HT subgroups were differentiated by significantly higher scores on the key criteria for GAD and MDD plus fatigue and sleeping difficulties but not the remaining symptoms of GAD and MDD. However, there were no significant differences between HT subgroups for the degree of functional impairment experienced by these symptoms. Although these data confirm the association between HT and anxiety/depression, the range of GAD and MDD symptoms influenced is relatively restricted. Moreover, functional ability does not appear to be impaired by HT. These findings clarify the ways in which HT affects PCa patients and suggests that a simple total scale score for anxiety and depression may not be as helpful in designing treatment as consideration of the symptomatic profiles of PCa patients receiving HT. Copyright © 2014 John Wiley & Sons, Ltd.

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab

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Insa Joost

2016-10-01

Full Text Available Abstract Background Ustekinumab (Stelara®, a human monoclonal antibody targeting the p40-subunit of interleukin (IL-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far. Case presentation Here, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers. She had received a third dose of ustekinumab due to psoriatic arthritis three days before admission. Blood cultures revealed growth of Staphylococcus aureus and imaging showed a thickening of the aortic wall ventral the bifurcation above the right internal iliac artery, resembling an acute bacterial endarteritis. Without the evidence of aneurysms and in absence of foreign bodies, the decision for conservative management was made. The patient received four weeks of antibiotic therapy with intravenous flucloxacillin, followed by an oral regime with levofloxacin and rifampicin for an additional four weeks. Inflammatory markers resolved promptly and the patient was discharged in good health. Conclusion To our knowledge, this is the first report of a severe S. aureus infection in a patient receiving ustekinumab. Albeit ustekinumab is generally regarded as a safe drug, severe bacterial infections should always be included in the differential diagnosis of elevated inflammatory markers in patients receiving biologicals as these might present with nonspecific symptoms and fever might be absent. Any effort to detect deep-seated or metastatic infections should be made to prevent complications and to secure appropriate treatment. Although other risk factors for an invasive staphylococcal infection like psoriasis, recent corticosteroid injection, or prior hospitalisations were present, and therefore a directive

Mediators and treatment matching in behavior therapy, cognitive therapy and cognitive behavior therapy for chronic insomnia.

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Harvey, Allison G; Dong, Lu; Bélanger, Lynda; Morin, Charles M

2017-10-01

To examine the mediators and the potential of treatment matching to improve outcome for cognitive behavior therapy (CBT) for insomnia. Participants were 188 adults (117 women; Mage = 47.4 years, SD = 12.6) meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; text rev.; DSM-IV-TR; American Psychiatric Association [APA], 2000) diagnostic criteria for chronic insomnia (Mduration: 14.5 years, SD: 12.8). Participants were randomized to behavior therapy (BT; n = 63), cognitive therapy (CT; n = 65), or CBT (n = 60). The outcome measure was the Insomnia Severity Index (ISI). Hypothesized BT mediators were sleep-incompatible behaviors, bedtime variability (BTv), risetime variability (RTv) and time in bed (TIB). Hypothesized CT mediators were worry, unhelpful beliefs, and monitoring for sleep-related threat. The behavioral processes mediated outcome for BT but not CT. The cognitive processes mediated outcome in both BT and CT. The subgroup scoring high on both behavioral and cognitive processes had a marginally significant better outcome if they received CBT relative to BT or CT. The subgroup scoring relatively high on behavioral but low on cognitive processes and received BT or CBT did not differ from those who received CT. The subgroup scoring relatively high on cognitive but low on behavioral processes and received CT or CBT did not differ from those who received BT. The behavioral mediators were specific to BT relative to CT. The cognitive mediators were significant for both BT and CT outcomes. Patients exhibiting high levels of both behavioral and cognitive processes achieve better outcome if they receive CBT relative to BT or CT alone. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Complementary Therapies for Pain Among Individuals Receiving Hemodialysis: A Systematic Review.

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Zins, Savannah; Gross, Cynthia R; Huff, Edwin D; Hooke, Mary Catherine

2018-01-01

Pain is a major problem for individuals undergoing hemodialysis and can lead to decreased quality of life when ineffectively managed. Pain is often reported as burdensome; thus, nurses must learn effective, nonpharmacological adjuncts to help care for symptomatic patients. The purpose of this review was to identify non-pharmacologic complementary therapies and evaluate their effectiveness in minimizing pain among individuals undergoing hemodialysis. Multiple complementary interventions were identified, and several reduced pain, but evidence is qualified by limitations in study methods. Complementary therapies have the potential to reduce pain among individuals undergoing hemodialysis; however, more research is needed. Copyright© by the American Nephrology Nurses Association.

Use of complementary and alternative medicine among patients with cancer receiving outpatient chemotherapy in Taiwan.

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Yang, Che; Chien, Li-Yin; Tai, Chen-Jei

2008-05-01

The objectives of this study were to describe the prevalence and types of complementary and alternative medicines (CAMs) used among patients with cancer receiving outpatient chemotherapy in Taiwan. This study was a cross-sectional survey. The study participants were 160 patients with cancer receiving outpatient chemotherapy at a medical center in northern Taiwan. The vast majority of the participants reported CAM use (n = 157, 98.1%). The two most common groups of CAM used were "biologically based therapies" (77.5%) and "mind-body interventions" (60.6%). Fifteen percent (15.3%) of patients took grapeseed and ginseng, which might affect the efficacy of some chemotherapy regimens. Fourteen percent (14.4%) of patients did not know the name of the herbs they took. The most commonly reported reasons for CAM use were to boost the immune system (55.4%) and relieve stress (53.5%). Approximately two thirds of patients (66.2%) had never informed their physicians of CAM use. This survey revealed a high prevalence of CAM use among patients with cancer receiving out-patient chemotherapy in Taiwan. The types of CAM used by patients with cancer in Taiwan differed from those in Western countries. Health professionals need to be cautious about the potential herb-drug interactions.

The radiation biology of Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Coderre, J.A.

2003-01-01

Boron Neutron Capture Therapy (BNCT) produces a complex mixture of high and low-LET radiations in tissue. Using data on the biological effectiveness of these various dose components, derived primarily in small animals irradiated with thermal neutrons, it has been possible to express clinical BNCT doses in photon-equivalent units. The accuracy of these calculated doses in normal tissue and tumor will be reviewed. Clinical trials are underway at a number of centers. There are differences in the neutron beams at these centers, and differences in the details of the clinical protocols. Ideally, data from all centers using similar boron compounds and treatment protocols should be compared and combined, if appropriate, in a multi-institutional study in order to strengthen statistical analysis. An international dosimetry exchange is underway that will allow the physical doses from the various treatment centers to be quantitatively compared. As a first step towards the comparison of the clinical data, the normal brain tolerance data from the patients treated in the initial Brookhaven National Laboratory and the Harvard/MIT BNCT clinical trials have been compared. The data provide a good estimate of the normal brain tolerance for a somnolence syndrome endpoint, and provide guidance for setting normal brain tolerance limits in ongoing and future clinical trials. Escalation of the dose in BNCT can be accomplished by increasing the amount of the boron compound administered, increasing the duration of the neutron exposure, or both. The dose escalations that have been carried out to date at the various treatment centers will be compared and contrasted. Possible future clinical trials using BNCT in combination with other modalities will be discussed

Adjuvant Biological Therapies in Chronic Leg Ulcers

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Natalia Burgos-Alonso

2017-11-01

Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

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Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein; Holman, Rebecca; Baiko, Sergey; Baskın, Esra; Bjerre, Anna; Cloarec, Sylvie; Cornelissen, Elisabeth A M; Espinosa, Laura; Heaf, James; Stone, Rosário; Shtiza, Diamant; Zagozdzon, Ilona; Harambat, Jérôme; Jager, Kitty J; Groothoff, Jaap W; van Stralen, Karlijn J

2017-05-27

We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4-16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52-0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 [95% CI 1·13-1·53], p=0·0005, to 1·21 [0·97-1·51], p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%. Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and

Altered growth and development of lower teeth in children receiving mantle therapy

International Nuclear Information System (INIS)

Lines, L.G.; Hazra, T.A.; Howells, R.; Shipman, B.

1979-01-01

The improvement in survival and local control rates in children with neoplasms in the head and neck region can be expected to demonstrate increased iatrogenic adverse effects of treatment. The authors report on mandibular growth and developmental abnormalities in 3 children with Hodgkin disease treated by external beam megavoltage therapy. Radiations to the mandible during mantle field therapy were measured and found to be significant. Possible methods of dose reduction are discussed

Evaluation of the vaginal flora in pregnant women receiving opioid maintenance therapy: a matched case-control study.

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Farr, Alex; Kiss, Herbert; Hagmann, Michael; Holzer, Iris; Kueronya, Verena; Husslein, Peter W; Petricevic, Ljubomir

2016-08-05

Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls. A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight. In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006]. Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.

Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.

Science.gov (United States)

Leal, A D; Kadakia, K C; Looker, S; Hilger, C; Sorgatz, K; Anderson, K; Jacobson, A; Grendahl, D; Seisler, D; Hobday, T; Loprinzi, Charles L

2014-05-01

The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Reasons for not receiving thrombolytic therapy in patients with acute myocardial infarction admitted to Bu-Ali Sina Hospital in Qazvin (2013-14)

OpenAIRE

MM. Daei; M. Karimi Rad; M. Khalaja

2017-01-01

This hospital-based cross-sectional study was conducted in 2013-14 in Qazvin Bu-Ali Sina Hospital. 170 patients with acute myocardial infarction who not receiving thrombolytic therapy entered the study and were analyzed. Medical history, physical examination, twelve lead ECG and cardiac biomarkers were obtained. The mean age of the patients was 63.4±14.4 years (from 19 to 90 years). 110 (64.7%) of the patients were male and 48 (28.2%) were diabetic. 86 (50%) of patients due to late present...

Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

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Sukhikh, E.; Sheino, I.; Vertinsky, A.

2017-09-01

Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

Nutritional status and CD4 cell counts in patients with HIV/AIDS receiving antiretroviral therapy

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Ana Celia Oliveira dos Santos

2013-12-01

Full Text Available Introduction Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4 cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Methods Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS 17.0 software for Windows. Results Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. Conclusions These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.

Basal cell carcinoma after radiation therapy

International Nuclear Information System (INIS)

Shimbo, Keisuke; Terashi, Hiroto; Ishida, Yasuhisa; Tahara, Shinya; Osaki, Takeo; Nomura, Tadashi; Ejiri, Hirotaka

2008-01-01

We reported two cases of basal cell carcinoma (BCC) that developed after radiation therapy. A 50-year-old woman, who had received an unknown amount of radiation therapy for the treatment of intracranial germinoma at the age of 22, presented with several tumors around the radiation ulcer. All tumors showed BCC. A 33-year-old woman, who had received an unknown amount of radiation therapy on the head for the treatment of leukemia at the age of 2, presented with a black nodule within the area of irradiation. The tumor showed BCC. We discuss the occurrence of BCC after radiation therapy. (author)

Practical Radiobiology for Proton Therapy Planning

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Jones, Bleddyn

2017-12-01

Practical Radiobiology for Proton Therapy Planning covers the principles, advantages and potential pitfalls that occur in proton therapy, especially its radiobiological modelling applications. This book is intended to educate, inform and to stimulate further research questions. Additionally, it will help proton therapy centres when designing new treatments or when unintended errors or delays occur. The clear descriptions of useful equations for high LET particle beam applications, worked examples of many important clinical situations, and discussion of how proton therapy may be optimized are all important features of the text. This important book blends the relevant physics, biology and medical aspects of this multidisciplinary subject. Part of Series in Physics and Engineering in Medicine and Biology.

Personality Patterns in Narcotics Anonymous Members versus Individuals with Addiction Receiving Methadone Maintenance Therapy.

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Akhondzadeh, Shahin; Shabrang, Moslem; Rezaei, Omid; Rezaei, Farzin

2014-07-01

Therapeutic interventions can be classified into two distinct approaches: abstinent and maintenance method. Currently, there are no clear criteria for referring addicted patients to one of these modalities. We aimed to compare the personality characteristics of individuals with addiction who attended narcotics anonymous sessions with those who received methadone maintenance therapy. This was a cross- sectional study. The participants were NA members and patients who were undergoing methadone maintenance treatment in outpatient clinics. Using the randomized cluster sampling method, 200 individuals with opioid dependence were selected (each group 100 persons). Data were collected through a demographic questionnaire and the five-factor personality inventory (NEO-FFI). Comparison of the mean scores of NEO-PPI in the two groups was performed by independent t test, and qualitative variables were compared using the Chi-square test. We found a significant difference between the MMT and NA groups with respect to neuroticism, extroversion, and agreeableness. No significant difference was found in the subscales of conscientious and openness. People who regularly attended the NA sessions had lower neuroticism and higher agreeableness than patients who were under the maintenance modality. Whether this is the cause or effect of attending NA sessions requires future large-scale cohort studies.

Personality Patterns in Narcotics Anonymous Members versus Individuals with Addiction Receiving Methadone Maintenance Therapy.

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Shahin Akhondzadeh

2014-09-01

Full Text Available Therapeutic interventions can be classified into two distinct approaches: abstinent and maintenance method. Currently, there are no clear criteria for referring addicted patients to one of these modalities. We aimed to compare the personality characteristics of individuals with addiction who attended narcotics anonymous sessions with those who received methadone maintenance therapy.This was a cross- sectional study. The participants were NA members and patients who were undergoing methadone maintenance treatment in outpatient clinics. Using the randomized cluster sampling method, 200 individuals with opioid dependence were selected (each group 100 persons. Data were collected through a demographic questionnaire and the five-factor personality inventory (NEO-FFI. Comparison of the mean scores of NEO-PPI in the two groups was performed by independent t test, and qualitative variables were compared using the Chi-square test.We found a significant difference between the MMT and NA groups with respect to neuroticism, extroversion, and agreeableness. No significant difference was found in the subscales of conscientious and openness.People who regularly attended the NA sessions had lower neuroticism and higher agreeableness than patients who were under the maintenance modality. Whether this is the cause or effect of attending NA sessions requires future large-scale cohort studies.

Biological Tests for Boron Neutron Capture Therapy Research at the TRIGA Mark II Reactor in Pavia

Energy Technology Data Exchange (ETDEWEB)

Protti, N.; Ballarini, F.; Bortolussi, S.; De Bari, A.; Stella, S.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Nuclear Physics National Institute (INFN), Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Bakeine, J.G.; Cansolino, L.; Clerici, A.M. [Laboratory of Experimental Surgery, Department of Surgery, University of Pavia, Pavia (Italy)

2011-07-01

The thermal column of the TRIGA Mark II reactor of the Pavia University is used as an irradiation facility to perform biological tests and irradiations of living systems for Boron Neutron Capture Therapy (BNCT) research. The suitability of the facility has been ensured by studying the neutron flux and the photon background in the irradiation chamber inside the thermal column. This characterization has been realized both by flux and dose measurements as well as by Monte Carlo simulations. The routine irradiations concern in vitro cells cultures and different tumor animal models to test the efficacy of the BNCT treatment. Some results about these experiments will be described. (author)

Photodynamic Therapy for Cancer

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... et al. Photodynamic therapy. Journal of the National Cancer Institute 1998; 90(12):889–905. [PubMed Abstract] Gudgin Dickson EF, Goyan RL, Pottier RH. New directions in photodynamic therapy. Cellular and Molecular Biology 2002; 48(8):939–954. [PubMed Abstract] Capella ...

Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of /ital Homo sapiens/

International Nuclear Information System (INIS)

1986-01-01

This volume is the second part of a collection of papers submitted by the participants to the 1986 Cold Spring Harbor Symposium on Quantitative Biology entitled Molecular Biology of /ital Homo sapiens/. The 49 papers included in this volume are grouped by subject into receptors, human cancer genes, and gene therapy. (DT)

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

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Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p 12 g/dl was a factor with an average association with the overall survival (p cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

Analytical dosimetry for spontaneous tumor dogs receiving boron neutron capture therapy

International Nuclear Information System (INIS)

Wheeler, F.J.; Atkinson, C.A.; Gavin, P.R.

1992-01-01

The dog irradiation project of the Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program is administered by Washington State University (WSU) with analytical and physical dosimetry provided by the Idaho National Engineering Laboratory (INEL). One subtask of this project includes BNCT safety studies for dogs with spontaneously-occurring brain tumors. The boron compound (Na 2 B 12 H 11 SH or BSH) was administered and single irradiations performed using the epithermal-neutron beam at the Brookhaven Medical Research Reactor (BMRR). The main goal of the study was not to provide therapy, but to determine tumorcidal effect while administering a subtolerance dose to healthy tissue. Irradiation times were based on delivery of 19 Gy peak physical dose to the blood

[A Case of HPN, In Which QOL Improvement Was Achieved by Combining Continuous Infusion with Once-Weekly Intermittent Infusion - Contribution of Pharmacists to Health Promotion among Home Patients Receiving Infusion Therapy].

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Takeda, Namihiro; Hamana, Tomoko; Oka, Toyoka; Hirohara, Masayoshi; Kushida, Kazuki

2016-12-01

Patients receiving parenteral nutrition at home have the following two options: 24-h continuous or intermittent infusion. To date, for patients with impaired glucose tolerance and/or other metabolic disorders or for those with decreased cardiac/ pulmonary/renal function, it is desirable to opt for continuous infusion to minimize the variance in the body's metabolic rate as much as possible. Furthermore, it should be noted that continuous infusion evokes a stronger feeling among patients of being constrained because it restricts their everyday activities. This case witnesses collaborations among the patient's doctor, dispensary's pharmacy, and patient's family. Because ofthe use ofintermittent infusion more or less once per week in addition to continuous infusion, significant improvement in quality of life was achieved, and the patient was able to enjoy taking a short trip. To assist a home patient receiving infusion therapy, it is essential that the pharmacist be equipped with skills to manage risks associated with infusion therapy and have knowledge about insurance to cover incidents concerning infusion fluids or medical materials. It will certainly depend on the degree ofindependence ofpatients and the level ofcare their families can provide; however, should we manage to use a similar medical procedure in at least a few cases in the future, we may be able to contribute to "joie de vivre" in home patients receiving infusion therapy.

THE EFFECTIVENESS OF PLAY THERAPY AND MUSICAL THERAPY IN REDUCING THE HOSPITALIZATION STRESS

Directory of Open Access Journals (Sweden)

Yuni Sufyanti Arief

2017-07-01

Full Text Available Introduction: Hospitalization in pediatric patients may caused an anxiety and stress in all age levels. Several techniques can be applied to reduced hospitalization stress in children, such as playing therapy and music therapy. The objective of this study was to analyze the difference of effectiveness between both therapies in reducing the hospitalization stress in 4-6 years old children. Method: A quasy-experimental pre-posttest design was used in this study. There were 18 respondents, divided into three groups, i.e. group one receiving playing therapy, group two receiving music therapy and the last group as control group. Data were collected by using observation sheet before and after intervention to recognize the hospitalization stress. Data were analyzed by using Wilcoxon Signed Rank Test and Mann Whitney U Test with significance level of α<0.05. Result: Result showed that playing therapy and music therapy had significant effect to reduce the hospitalization stress with p=0.027 for play therapy, p=0.024 for musical therapy, and p=0.068 for control. Mann Whitney U Test revealed that there were no difference in the effectiveness of play therapy and musical therapy in reducing the hospitalization stress with p=0.009 for play therapy and control group, p=0.012 for music therapy and control group, and p=0.684 for playing therapy and musical therapy. Discussion: It can be concluded that play therapy and musical therapy are equally effective to reduce the hospitalization stress in children. It’s recommended for nurses in pediatric ward to do  playg therapy and musical therapy periodically.

Selective use of adjuvant radiation therapy in resectable colorectal adenocarcinoma

International Nuclear Information System (INIS)

Cohen, A.M.; Gunderson, L.L.; Welch, C.E.

1981-01-01

Colorectal cancer recurs within the operative field in 10-20 per cent of patients undergoing potentially curative surgery. In certain subgroups, the recurrence rate is 20-50 per cent. There are some data to suggest either preoperative or postoperative radiation therapy as an adjuvant to potentially curative surgery can reduce the local operative failure rate. However, since radiation therapy has significant side effects, patient selection to maximize the therapeutic ratio is important. This report defines the criteria at the Massachusetts General Hospital for selection of patients with colorectal cancer for adjuvant radiation therapy, defines radiation therapy-surgery sequencing alternatives used, and describes techniques to reduce radiation side effects. Over a period of three and a half years, 196 patients received adjuvant radiation therapy: 51 patients received either moderate or low dose preoperative radiation therapy to rectal or rectosigmoid cancers, and 161 patients received postoperative radiation therapy to the pelvis or extrapelvic colonic tumor-lymph node beds. Some patients who received low-dose preoperative radiation therapy also received moderate-dose postoperative radiation therapy. We prefer moderate-dose postoperative radiation therapy as the approach most likely to decrease the local recurrence rate with minimal interference with surgical procedures and late small-bowel complications. Patients who received postoperative radiation therapy were those without distant metastases, whose primary tumor pathology revealed macroscopic or extensive microscopic transmural tumor penetration into extraperitoneal tissues. Careful case selection, multiple field techniques, the use of reperitonealization, omental flaps, and retroversion of the uterus into the pelvis were combined with postoperative small-bowel x-rays, bladder distention, and lateral portals to minimize radiation damage to normal structures

Models for synthetic biology.

Science.gov (United States)

Kaznessis, Yiannis N

2007-11-06

Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

[Non-pharmaceutical therapy of candidates for geriatric rehabilitation: Non-pharmaceutical therapy prescribed by SHI-accredited doctors after application for outpatient geriatric rehabilitative care].

Science.gov (United States)

Krupp, Sonja; Schnoor, Maike; Lohse, Kristina; Katalinic, Alexander; Willkomm, Martin

2015-06-01

The rejection of an application for ambulant geriatric rehabilitation (AGRV) is usually justified by the argument that non-pharmaceutical therapy prescribed by doctors accredited by social housing institutions (SHI) would suffice. The reality in healthcare during the 6 months following an application is unknown. In this study 203 patients who had made an application for AGRV in the second half of 2010 in Flensburg, Lübeck or Ratzeburg were interviewed by telephone. The survey revealed that 25.7% of the applications for AGRV had been rejected. The majority of these patients received no ambulant non-pharmaceutical therapy (e.g. physical therapy, physiotherapy, occupational therapy, speech therapy or psychological therapy), less than 20% received more than 12 therapy sessions and in most cases exclusively physiotherapy. The 141 successful AGRV applicants received additional ambulant therapies of a similar magnitude. The difference between the intensified interdisciplinary therapy offered in the AGRV and additionally and the offer to rejected applicants is substantial.

The utility and cost-effectiveness of serial complete blood count monitoring in patients receiving radiation therapy for localized prostate cancer

International Nuclear Information System (INIS)

Blank, Kenneth; Cascardi, Michelle; Kao, Gary D.

1997-01-01

Purpose/Objective: It has been a standard practice in our department to monitor weekly complete blood counts (CBC) in patients receiving pelvic radiation therapy for prostate cancer. The utility and cost-effectiveness of this practice has not been analyzed. Material and Methods: We analyzed 1572 separate CBCs performed on 110 consecutive outpatients treated at the Veterans Administration Medical Center, Philadelphia, PA from June 1994 to June 1996 for localized prostate cancer. 92 of these patients fulfilled the study inclusion criteria of blood counts on at least four different weeks of treatment, a baseline hemoglobin (pretreatment or week one of radiation therapy), and at least one CBC after week four. Complete data was subjected to chi-square statistical analysis of factors including age, field size, concomitant hormonal therapy and the presence of hypertension or diabetes. Results: The mean hemoglobin level at the beginning of treatment of was 13.2 grams/dl (gms) and mean change in hemoglobin from baseline to the last week of treatment was - 0.53 gms (range +2.0 to -3.5 gm). No patients required blood transfusion or erythropoeitin treatment, and only five patients experienced declines of >2.0 gms (-2.1, -2.3, -2.5, -2.9 and -3.5). Two of these patients sustained the hemoglobin declines concomitantly with congestive heart failure requiring intensive care unit admission (suggesting fluid overload). The hemoglobin level in the remaining patients has returned to normal without treatment by one month after the end of radiation. No significant differences were found between the group of patients that dropped more than 1.0 gm (n=34) and the group that did not (n = 58) in field size (p0.08), presence of diabetes (p= 0.48) or hypertension (p= 0.43), concurrent or prior hormone therapy (p= 0.37), or age (p=0.83). No consistent trends in white blood cell or platelet counts could be detected during radiation and no patients had white blood cells counts fall below 2000/mm

Gift Giving and Receiving in Child-Centered Play Therapy: An Ethical Response

Science.gov (United States)

Blanco, Pedro J.; Sheely-Moore, Angela I.

2012-01-01

Child-centered play therapists are often confronted with the challenge of receiving gifts from clients. This article highlights recommended strategies when faced with gift receiving, exemplified by actual ethical dilemmas encountered by child-centered play therapists. Ethical and therapeutic considerations of therapist gift giving to child clients…

Bio-heat transfer model of electroconvulsive therapy: Effect of biological properties on induced temperature variation.

Science.gov (United States)

de Oliveira, Marilia M; Wen, Paul; Ahfock, Tony

2016-08-01

A realistic human head model consisting of six tissue layers was modelled to investigate the behavior of temperature profile and magnitude when applying electroconvulsive therapy stimulation and different biological properties. The thermo-electrical model was constructed with the use of bio-heat transfer equation and Laplace equation. Three different electrode montages were analyzed as well as the influence of blood perfusion, metabolic heat and electric and thermal conductivity in the scalp. Also, the effect of including the fat layer was investigated. The results showed that temperature increase is inversely proportional to electrical and thermal conductivity increase. Furthermore, the inclusion of blood perfusion slightly drops the peak temperature. Finally, the inclusion of fat is highly recommended in order to acquire more realistic results from the thermo-electrical models.

An official American Thoracic Society workshop report: stem cells and cell therapies in lung biology and diseases.

Science.gov (United States)

Weiss, Daniel J; Chambers, Daniel; Giangreco, Adam; Keating, Armand; Kotton, Darrell; Lelkes, Peter I; Wagner, Darcy E; Prockop, Darwin J

2015-04-01

The University of Vermont College of Medicine and the Vermont Lung Center, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, European Respiratory Society, International Society for Cell Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," held July 29 to August 1, 2013 at the University of Vermont. The conference objectives were to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are all rapidly expanding areas of study that both provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, discuss and debate current controversies, and identify future research directions and opportunities for both basic and translational research in cell-based therapies for lung diseases. This conference was a follow-up to four previous biennial conferences held at the University of Vermont in 2005, 2007, 2009, and 2011. Each of those conferences, also sponsored by the National Institutes of Health, American Thoracic Society, and Respiratory Disease Foundations, has been important in helping guide research and funding priorities. The major conference recommendations are summarized at the end of the report and highlight both the significant progress and major challenges in these rapidly progressing fields.

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

Science.gov (United States)

He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination

Antiprotons get biological

CERN Multimedia

2003-01-01

After its final run in September, the first results of the Antiproton Cell Experiment (ACE) look very promising. It was the first experiment to take data on the biological effects of antiproton beams to evaluate the potential of antiprotons in radiation therapy.

Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients

NARCIS (Netherlands)

Sonis, Stephen T.; Hashemi, Sepehr; Epstein, Joel B.; Nair, Raj G.; Raber-Durlacher, Judith E.

2016-01-01

Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our

Biological dosimetry of irradiation accidents

International Nuclear Information System (INIS)

Durand, V.; Chambrette, V.; Le Roy, A.; Paillole, N.; Sorokine, I.; Voisin, P.

1994-01-01

The biological dosimetry in radiation protection allows to evaluate the received dose by a potentially irradiated person from biological markers such chromosomal abnormalities. The technologies of Hybridization In Situ by Fluorescence (F.I.S.H) allow the detection of steady chromosomal aberrations of translocation type

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

Energy Technology Data Exchange (ETDEWEB)

Bakeine, G.J. [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste (Italy)], E-mail: jamesbakeine1@yahoo.com; Di Salvo, M. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bertolotti, A.; Nano, R. [Department of Animal Biology University of Pavia, Piazza Botta, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C. [Department of Surgery University of Pavia, Piazza Botta, Pavia (Italy); Marchetti, A. [Scientific Research Office, Fondazione San Matteo University Policlinic, Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy)

2009-07-15

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

International Nuclear Information System (INIS)

Bakeine, G.J.; Di Salvo, M.; Bortolussi, S.; Stella, S.; Bruschi, P.; Bertolotti, A.; Nano, R.; Clerici, A.; Ferrari, C.; Zonta, C.; Marchetti, A.; Altieri, S.

2009-01-01

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Biological detector and method

Science.gov (United States)

Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F

2013-02-26

A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

Biological effect of OK-432 (picibanil) and possible application to dendritic cell therapy.

Science.gov (United States)

Ryoma, Yoshiki; Moriya, Yoichiro; Okamoto, Masato; Kanaya, Isao; Saito, Motoo; Sato, Mitsunobu

2004-01-01

OK-432 (Picibanil), a streptococcal preparation with potent biological response modifying activities, was approved in Japan as an anticancer agent in 1975. In the ensuing 30 years, since then, a significant amount of data, including clinical as well as experimental studies, has been accumulated. OK-432 has been reported to induce various cytokines, activate immunological cells and thus augment anticancer immunity. Recently, the interrelation between innate immunity and adaptive immunity has become clear and it was reported that OK-432 acts, at least in part, via Toll-like receptor (TLR) 4-MD2 signaling pathway. In addition, dendritic cells (DCs) are considered to play a pivotal role in immunological response and it is reported that OK-432 induced maturation of DCs both in vitro and in vivo. These results suggest that OK-432 is a useful adjuvant in DC-based anticancer immunotherapy. Clinical studies of DC therapy with OK-432 are under way.

Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

Science.gov (United States)

Teixeira, Marcus Zulian

2016-11-01

Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

Science.gov (United States)

Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

2010-07-01

The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

Science.gov (United States)

Chien, A Jo; Chambers, Julia; Mcauley, Fiona; Kaplan, Tessa; Letourneau, Joseph; Hwang, Jimmy; Kim, Mi-Ok; Melisko, Michelle E; Rugo, Hope S; Esserman, Laura J; Rosen, Mitchell P

2017-08-01

To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

CMV infection in a cohort of HIV-exposed infants born to mothers receiving antiretroviral therapy during pregnancy and breastfeeding.

Science.gov (United States)

Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswel; Sagno, Jean-Baptiste; Scarcella, Paola; Mancinelli, Sandro; Buonomo, Ersilia; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Giuliano, Marina

2017-02-01

Antiretroviral therapy has been shown to reduce rates of congenital CMV infection. Little information is available on the possible impact of antiretroviral therapy on postnatal breastfeeding-associated CMV infection acquisition. A cohort of 89 HIV-infected mothers and their children was studied. Women received antiretroviral therapy from week 25 of gestation until 6 months postpartum or indefinitely if meeting the criteria for treatment. All women were evaluated for CMV IgG presence and CMV DNA in breast milk. Children were tested for CMV infection by either the presence of IgM or the presence of CMV DNA in plasma at 1, 6 and 12 months and by the presence of IgG at 24 months. All mothers had high titers of CMV DNA in breast milk (5.7 log at Month 1 and 5.1 log at Month 6). Cumulative CMV infection rates were 60.3 % at Month 6, 69 % at Month 12 and 96.4 % at Month 24. There was a significant negative correlation between the duration of antiretroviral treatment during pregnancy and levels of CMV DNA in breast milk at Month 1 (P = 0.033). There was a trend for a correlation between high titers of CMV DNA in breast milk at 6 months and CMV infection at 6 months (P = 0.069). In this cohort, more than 95 % of the children had acquired CMV infection by 2 years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2 years was certainly relevant in determining CMV infection acquisition.

The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

CERN Document Server

Mairani, A; Kraemer, M; Sommerer, F; Parodi, K; Scholz, M; Cerutti, F; Ferrari, A; Fasso, A

2010-01-01

Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fur Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed C-12 ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-d...

Effectiveness of cognitive behavioral therapy for depression in patients receiving disability benefits: a systematic review and individual patient data meta-analysis.

Directory of Open Access Journals (Sweden)

Shanil Ebrahim

Full Text Available To systematically summarize the randomized trial evidence regarding the relative effectiveness of cognitive behavioural therapy (CBT in patients with depression in receipt of disability benefits in comparison to those not receiving disability benefits.All relevant RCTs from a database of randomized controlled and comparative studies examining the effects of psychotherapy for adult depression (http://www.evidencebasedpsychotherapies.org, electronic databases (MEDLINE, EMBASE, PSYCINFO, AMED, CINAHL and CENTRAL to June 2011, and bibliographies of all relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTION: Adult patients with major depression, randomly assigned to CBT versus minimal/no treatment or care-as-usual.Three teams of reviewers, independently and in duplicate, completed title and abstract screening, full text review and data extraction. We performed an individual patient data meta-analysis to summarize data.Of 92 eligible trials, 70 provided author contact information; of these 56 (80% were successfully contacted to establish if they captured receipt of benefits as a baseline characteristic; 8 recorded benefit status, and 3 enrolled some patients in receipt of benefits, of which 2 provided individual patient data. Including both patients receiving and not receiving disability benefits, 2 trials (227 patients suggested a possible reduction in depression with CBT, as measured by the Beck Depression Inventory, mean difference [MD] (95% confidence interval [CI] = -2.61 (-5.28, 0.07, p = 0.06; minimally important difference of 5. The effect appeared larger, though not significantly, in those in receipt of benefits (34 patients versus not receiving benefits (193 patients; MD (95% CI = -4.46 (-12.21, 3.30, p = 0.26.Our data does not support the hypothesis that CBT has smaller effects in depressed patients receiving disability benefits versus other patients. Given that the confidence interval is wide, a

Determination of production biology of Cladocera in a reservoir receiving hyperthermal effluents from a nuclear production reactor

International Nuclear Information System (INIS)

Vigerstad, T.J.

1980-01-01

The effects on zooplankton of residence in a cooling reservoir receiving hyperthermal effluents directly from a nuclear-production-reactor were examined. The design of the study was to compare rates of cladoceran population production at two stations in the winter and summer of 1976 on Par Pond, the cooling reservoir located on the Savannah River Plant, Aiken, SC. One station was located in an area of the reservoir directly receiving hyperthermal effluent (Station MAS), and the second was located about 4 km away in an area where surface temperatures were normal for reservoirs in the general geographical region (Station CAS). The statistical properties of the Edmondson egg ratio model (Edmondson, 1960) were examined to determine if it would be a suitable method for calculating cladoceran production rates for comparison between stations. Based on an examination of the variance associated with standing stock and fecundity measurements and other consideratios, the use of the egg ratio model was abandoned. Instead, a non-parametric comparison between stations of standing stock and fecundity data for Bosmina longirostris, taken for the egg ratio model, were used to observe potential hyperthermal effluent effects. There was a statistically higher incidence of deformed eggs in the Bosmina population at Station MAS in the summer. Bosmina standing stock underwent two large oscillations in the winter and three large oscillations in the summer at Station MAS compared with two in the winter and one in the summer at Station CAS. These results are consistent with almost all other Par Pond studies which have found the two stations to be essentially similar in species composition but with some statistically significant differences in various aspects of the biology of the species

Patterns of Care Among Patients Receiving Radiation Therapy for Bone Metastases at a Large Academic Institution

Energy Technology Data Exchange (ETDEWEB)

Ellsworth, Susannah G. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Alcorn, Sara R., E-mail: salcorn2@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K.; McNutt, Todd R.; DeWeese, Theodore L. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Smith, Thomas J. [Department of Medical Oncology and Harry J. Duffey Family Program in Palliative Care, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2014-08-01

Purpose: This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. Methods and Materials: Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. Results: We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patients (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. Conclusions: These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival.

Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin.

Science.gov (United States)

Chen, Chih-Yen; Tsai, Chang-Youh; Lee, Pui-Ching; Lee, Shou-Dong

2013-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated. Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study). Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group. Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors).

Science.gov (United States)

Reinwald, M; Silva, J T; Mueller, N J; Fortún, J; Garzoni, C; de Fijter, J W; Fernández-Ruiz, M; Grossi, P; Aguado, J M

2018-06-01

The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the

Mathematical modeling of biological processes

CERN Document Server

Friedman, Avner

2014-01-01

This book on mathematical modeling of biological processes includes a wide selection of biological topics that demonstrate the power of mathematics and computational codes in setting up biological processes with a rigorous and predictive framework. Topics include: enzyme dynamics, spread of disease, harvesting bacteria, competition among live species, neuronal oscillations, transport of neurofilaments in axon, cancer and cancer therapy, and granulomas. Complete with a description of the biological background and biological question that requires the use of mathematics, this book is developed for graduate students and advanced undergraduate students with only basic knowledge of ordinary differential equations and partial differential equations; background in biology is not required. Students will gain knowledge on how to program with MATLAB without previous programming experience and how to use codes in order to test biological hypothesis.

Dysphagia management: an analysis of patient outcomes using VitalStim therapy compared to traditional swallow therapy.

Science.gov (United States)

Kiger, Mary; Brown, Catherine S; Watkins, Lynn

2006-10-01

This study compares the outcomes using VitalStim therapy to outcomes using traditional swallowing therapy for deglutition disorders. Twenty-two patients had an initial and a followup videofluoroscopic swallowing study or fiberoptic endoscopic evaluation of swallowing and were divided into an experimental group that received VitalStim treatments and a control group that received traditional swallowing therapy. Outcomes were analyzed for changes in oral and pharyngeal phase dysphagia severity, dietary consistency restrictions, and progression from nonoral to oral intake. Results of chi(2) analysis showed no statistically significant difference in outcomes between the experimental and control groups.

Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

Science.gov (United States)

Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

2002-06-13

Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.

The effectiveness of RECIST on survival in patients with NSCLC receiving chemotherapy with or without target agents as first-line treatment.

Science.gov (United States)

Zhou, Ting; Zheng, Lie; Hu, Zhihuang; Zhang, Yang; Fang, Wenfeng; Zhao, Yuanyuan; Ge, Jieying; Zhao, Hongyun; Zhang, Li

2015-01-08

We analyzed the correlation between survival and antitumor effect evaluated by RECIST in advanced NSCLC patients with chemotherapy plus target therapy or not as first-line treatment, to examine the applicability of RECIST in this population. The patients were screened from 4 clinical trials (12621, 12006, FASTACT-I, and FASTACT-II), and those who received chemotherapy plus target therapy or chemotherapy alone were eligible. Among the 59 enrolled patients, 29 received combination therapy, while the other 30 received chemotherapy only. In the combination therapy group, patients with PR or SD had longer overall survival (OS) than those with PD (P chemotherapy alone group, compared with PD patients, either PR or SD group had no significant overall survival benefit (P = 0.690 and P = 0.528, respectively). In summary, for advanced NSCLC patients receiving chemotherapy plus target therapy as first-line treatment and evaluated by RECIST criteria, SD has the same overall survival benefit as PR, suggesting that antitumor effective evaluation by RECIST criteria cannot be translated to overall survival benefit especially for this kind of patients. Therefore, developing a more comprehensive evaluation method to perfect RECIST criteria is thus warranted for patients received target therapy in NSCLC.

Sudden Gains in Cognitive Therapy and Interpersonal Therapy for Social Anxiety Disorder

Science.gov (United States)

Bohn, Christiane; Aderka, Idan M.; Schreiber, Franziska; Stangier, Ulrich; Hofmann, Stefan G.

2013-01-01

Objective: The present study examined the effects of sudden gains on treatment outcome in a randomized controlled trial including individual cognitive therapy (CT) and interpersonal therapy (IPT) for social anxiety disorder (SAD). Method: Participants were 67 individuals with SAD who received 16 treatment sessions. Symptom severity at each session…

Inflammatory bowel disease: adherence to immunomodulators in a biological therapy era.

Science.gov (United States)

Campos, Sara; Portela, Francisco; Sousa, Paula; Sofia, Carlos

2016-11-01

Combination therapy, with anti-tumor necrosis factor-α agents and immunomodulators, is the most effective option to induce and maintain remission in inflammatory bowel disease (IBD). Infliximab, with its administration features, determines particular conditions of adherence; the same is not possible with thiopurines. Nevertheless, research on adherence to these treatments is scarce. Nonadherence worsens the prognosis of IBD. (a) Assess adherence to immunomodulators and (b) determine therapeutic nonadherence predictors. We included all IBD outpatients consecutively evaluated over a 6-month period in our center. Participants completed a study-specific questionnaire on IBD, IBD therapeutic adherence (Morisky Medication Adherence Scale-8-item), Therapeutics Complexity questionnaire, Beliefs about Medication questionnaire, and Hospital Anxiety and Depression Scale. A total of 112 patients under azathioprine were considered; 49.1% were also under anti-tumor necrosis factor-α. Self-assessed questionnaire showed that 70.5% were adherent to immunosuppression. Similar adherence was found with and without infliximab (68.4%-monotherapy vs. 72.7%-combination therapy; P=0.61). Nonintentional nonadherence was documented in 57.6%; 42.4% reported voluntary nonadherence. Nonadherence was higher in male patients [odds ratio (OR): 3.79; 95% confidence interval (CI): 1.2-11.95; P=0.023], younger patients (OR: 0.93; 95% CI: 0.87-0.98; P=0.01), nonsmokers (OR: 4.90; 95% CI: 1.22-19.73; P=0.025), and those who had depression (OR: 2.22; 95% CI: 1.36-3.62; P=0.001). Most of the IBD patients believed in the necessity of maintaining immunosuppression (86.7%), but 36.6% reported concerns about drugs. Nonadherence to thiopurines plays a significant role in IBD. Nonetheless, it does not increase with association with biological agents. Involuntary nonadherence is higher. Male sex, younger age, nonsmoker, and presence of depression were independent predictors of nonadherence to immunomodulators

A systematic review of orofacial pain in patients receiving cancer therapy

NARCIS (Netherlands)

Epstein, Joel B.; Hong, Catherine; Logan, Richard M.; Barasch, Andrei; Gordon, Sharon M.; Oberlee-Edwards, Lorree; McGuire, Deborah; Napenas, Joel J.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

We present the findings of a structured systematic review of the literature assessing orofacial pain induced by malignant disease and/or its therapy (excluding mucositis). This evaluation of the literature published after the 1989 NIH Development Consensus conference on the oral complications of

Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

Science.gov (United States)

Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

1989-11-30

The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Eley, John G., E-mail: jeley@som.umaryland.edu [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Friedrich, Thomas [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Homann, Kenneth L.; Howell, Rebecca M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Scholz, Michael; Durante, Marco [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Newhauser, Wayne D. [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, Louisiana (United States); Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana (United States)

2016-05-01

Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.

Comparing Relaxation Programs for Breast Cancer Patients Receiving Radiotherapy

Science.gov (United States)

In this study, women with breast cancer who have had surgery and are scheduled to undergo radiation therapy will be randomly assigned to one of two different stretching and relaxation programs or to a control group that will receive usual care.

Prevalence of patients receiving renal replacement therapy in El Salvador in 2014.

Science.gov (United States)

García-Trabanino, Ramón; Trujillo, Zulma; Colorado, Ana Verónica; Magaña Mercado, Salvador; Henríquez, Carlos Atilio

El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. To determine the RRT prevalence in El Salvador and some basic characteristics. The association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. National RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years, 67.5% male. By modality: peritoneal dialysis (PD) 289 pmp, haemodialysis (HD) 233 pmp, with functioning kidney transplantation 74 pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five percent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. Despite the increase in RRT services, the prevalence is lower than the Latin American average (660 pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands). Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective

International Nuclear Information System (INIS)

Raben, David; Helfrich, Barb; Bunn, Paul A.

2004-01-01

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small-cell lung cancers (NSCLCs). This presents an opportune target for new treatment strategies designed to selectively interfere with the cancer cell growth cycle. Recent investigations into the biology of the EGFR and its downstream signaling pathways have reminded us of the complexity of cancer cell communications from the cytoplasm to the nucleus. Multiple pathways are activated with stimulation of the autocrine and paracrine EGFR loop, from the ras-raf-MEK activation of ERK 1/2 to the P13K-Akt pathway, each playing an important role in cancer cell survival, invasion, and angiogenesis. Preclinical studies have demonstrated that molecules targeting the EGFR, either through extracellular blockade or intracellular interference with the EGFR-associated tyrosine kinase, reversibly or irreversibly, inhibit cancer cell growth. Potent antitumor effects have been observed in human tumor xenograft models. Preclinical studies have also demonstrated cooperative effects when anti-EGFR agents are combined with radiation or chemotherapy. Many of these agents have now entered into advanced human clinical trials with modest dose-related toxicity despite chronic administration. Encouraging response rates with single-agent targeted therapy have been reported in heavily pretreated patients with advanced NSCLC. In addition, agents targeting the angiogenic pathway, which plays a key role in the regulation of angiogenesis, may play an important role in enhancing the efficacy of anti-EGFR agents. This article will focus on the biology, rationale, and preclinical studies with targeted anti-EGFR and antiangiogenic therapies for the management of NSCLC

Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis.

Science.gov (United States)

Garber, Caren; Plotnikova, Natalia; Au, Shiu-chung; Sorensen, Eric P; Gottlieb, Alice

2015-08-01

Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly

Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

Science.gov (United States)

Shibuya, Takashi; Honma, Masaru; Iinuma, Shin; Iwasaki, Takeshi; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

2018-06-01

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible. © 2018 Japanese Dermatological Association.

Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression : A longitudinal pilot study

NARCIS (Netherlands)

Tendolkar, Indira; van Beek, Marleen; van Oostrom, Iris; Mulder, Marlies; Janzing, Joost; Voshaar, Richard Oude; van Eijndhoven, Philip

2013-01-01

Electroconvulsive therapy (ECT) is the most potent biological therapy in depression. Animal studies suggest that ECT acts via neuroplasticity effects on limbic structures involved in the pathophysiology of depression but in vivo evidence at the human system level is scarce. Therefore, the aim of the

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

Energy Technology Data Exchange (ETDEWEB)

Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Lukka, Himu [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada); Corbett, Tom [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Briones-Urbina, Rosario [Department of Medicine, Women' s College Hospital, University of Toronto, Toronto (Canada); Vieth, Reinhold [Departments of Nutritional Sciences and Laboratory Medicine and Pathology, Mount Sinai Hospital, University of Toronto, Toronto (Canada); Ehrlich, Lisa [Department of Radiology, Sunnybrook Health Sciences Center, University of Toronto (Canada); Kiss, Alex [Department of Health Policy, Management, and Evaluation, Sunnybrook Health Sciences Center, University of Toronto, Toronto (Canada); Danjoux, Cyril, E-mail: Cyril.danjoux@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada)

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.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Defining the optimal biological monotherapy in rheumatoid arthritis

DEFF Research Database (Denmark)

Tarp, Simon; Furst, Daniel E; Dossing, Anna

2017-01-01

Objectives To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. Methods We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomi...... treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.......Objectives To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. Methods We searched MEDLINE, EMBASE, CENTRAL, and other sources...... for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct...

99mTc-HYNIC-Annexin A5 in Oncology: Evaluating Efficacy of Anti-Cancer Therapies

International Nuclear Information System (INIS)

Schaper, Frédéric L.W.V.J.; Reutelingsperger, Chris P.

2013-01-01

Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT). Structural changes, if present, become apparent 1–2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99m Tc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1–4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients

Integrative radiation systems biology

International Nuclear Information System (INIS)

Unger, Kristian

2014-01-01

Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology

An Official American Thoracic Society Workshop Report 2015. Stem Cells and Cell Therapies in Lung Biology and Diseases.

Science.gov (United States)

Wagner, Darcy E; Cardoso, Wellington V; Gilpin, Sarah E; Majka, Susan; Ott, Harald; Randell, Scott H; Thébaud, Bernard; Waddell, Thomas; Weiss, Daniel J

2016-08-01

The University of Vermont College of Medicine, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, Cystic Fibrosis Foundation, European Respiratory Society, International Society for Cellular Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," held July 27 to 30, 2015, at the University of Vermont. The conference objectives were to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are all rapidly expanding areas of study that both provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, discuss and debate current controversies, and identify future research directions and opportunities for both basic and translational research in cell-based therapies for lung diseases. This 10th anniversary conference was a follow up to five previous biennial conferences held at the University of Vermont in 2005, 2007, 2009, 2011, and 2013. Each of those conferences, also sponsored by the National Institutes of Health, American Thoracic Society, and respiratory disease foundations, has been important in helping guide research and funding priorities. The major conference recommendations are summarized at the end of the report and highlight both the significant progress and major challenges in these rapidly progressing fields.

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Directory of Open Access Journals (Sweden)

Marcella Goetz MORO

Full Text Available Abstract The consumption of low-dose aspirin (LDA to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib and a non-selective COX-2 inhibitor (ibuprofen nonsteroidal anti-inflammatory drug (NSAID in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p 0.05. These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

Synthetic biology platform technologies for antimicrobial applications.

Science.gov (United States)

Braff, Dana; Shis, David; Collins, James J

2016-10-01

The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.