WorldWideScience

Sample records for optimizing antiemetic therapy

  1. Optimizing antiemetic therapy in multiple-day and multiple cycles of chemotherapy

    DEFF Research Database (Denmark)

    Ellebaek, E.; Herrstedt, J.

    2008-01-01

    PURPOSE OF REVIEW: Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining...... problems in this field of antiemetic treatment. RECENT FINDINGS: Evidence-based guidelines recommend a combination of a 5-HT3-receptor antagonist and dexamethasone in the prophylaxis of nausea and vomiting in multiple-day cisplatin-based chemotherapy. In patients treated with multiple cycles...... of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated...

  2. Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. |

  3. A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients

    Science.gov (United States)

    Jeong, Yusook; Han, Hye Sook; Lee, Hyo Duk; Yang, Jiyoul; Jeong, Jiwon; Choi, Moon Ki; Kwon, Jihyun; Jeon, Hyun-Jung; Oh, Tae-Keun; Lee, Ki Hyeong; Kim, Seung Taik

    2016-01-01

    Purpose Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. Materials and Methods Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. Results Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). Conclusion We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone. PMID:26987397

  4. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

    Science.gov (United States)

    Idris, Mohammad

    2016-01-01

    The Transdermal Drug Delivery System (TDDS) is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP) is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra), Zanjabeel (Zingiber officinale), Podina (Mentha arvensis), and Sirka (Vinegar) were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics. PMID:27403377

  5. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

    Directory of Open Access Journals (Sweden)

    Mohd Nauman Saleem

    2016-01-01

    Full Text Available The Transdermal Drug Delivery System (TDDS is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra, Zanjabeel (Zingiber officinale, Podina (Mentha arvensis, and Sirka (Vinegar were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics.

  6. Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Imai, Saeko; Yamanoi, Koji; Abiko, Kaoru; Yoshioka, Yumiko; Yamaguchi, Ken; Hamanishi, Junzo; Baba, Tsukasa; Konishi, Ikuo

    2017-01-01

    Background The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). Material/Methods The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. Results In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. Conclusions Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well. PMID:28198358

  7. Antiemetic research: future directions

    DEFF Research Database (Denmark)

    Olver, Ian; Molassiotis, Alexander; Aapro, Matti

    2011-01-01

    the impact of nausea on work capacity. New antiemetic drugs may be targeted at different receptors, such as opioid, cannabinoid and peptide YY receptors. New research is needed into determining the extent of corticosteroid use. The emetic potential of a range of newer cytotoxics particularly when used...... and vomiting may combine algorithms based on observed prognostic factors relating to the patient and the anticancer therapy, the identification of the genes that code for receptors, and pharmacogenetic studies of the metabolism of drugs. Design issues for future trials include standardising the emetic stimulus...

  8. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--state of the art.

    Science.gov (United States)

    Grunberg, Steven M; Warr, David; Gralla, Richard J; Rapoport, Bernardo L; Hesketh, Paul J; Jordan, Karin; Espersen, Birgitte T

    2011-03-01

    Antiemetic drug development can follow the same logical path as antineoplastic drug development from appropriate preclinical models through Phase I, Phase II, and Phase III testing. However, due to the marked success of antiemetic therapy over the last 25 years, placebo antiemetic treatment against highly or moderately emetogenic chemotherapy is not acceptable. Promising antiemetic agents therefore rapidly reach Phase III testing, where they are substituted into or added to effective and accepted regimens. One challenge of antiemetic drug development is determining whether substitution is indeed acceptable or whether prior regimens must be maintained intact as a basis for further antiemetic drug development. An additional challenge is the classification of emetogenic level of new antineoplastic agents. Accurate reporting of emetogenicity of such antineoplastic agents in the absence of preventive antiemetic treatment may not be available. However, at the 2009 Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) Consensus Conference, an expert panel used best available data to establish rankings of emetogenicity. Oral chemotherapeutic agents are ranked separately from intravenous agents, recognizing intrinsic differences in emetogenicity as well as differing schedules of administration. Since oral chemotherapeutic agents are often administered in extended regimens, the distinction between acute and delayed emesis is less clear, and cumulative emesis must be considered. As control of vomiting has improved, attention has shifted to control of nausea, a related but distinct and equally important problem. Additional efforts will be necessary to understand mechanisms of nausea and to identify optimal remedies.

  9. Chemotherapy-induced nausea and vomiting. Easing patients' fear and discomfort with effective antiemetic regimens.

    Science.gov (United States)

    Bilgrami, S; Fallon, B G

    1993-10-01

    Patients receiving chemotherapy should be given optimal antiemetic therapy to maximize their comfort initially and to prevent development of delayed and anticipatory nausea and vomiting. Understanding the mechanisms of chemotherapy-induced nausea and vomiting allows the healthcare team to design drug regimens capable of avoiding these side effects. Prevention is important, because side effects can be debilitating and sometimes dose-limiting, and up to 10% of patients refuse chemotherapy altogether to avoid them. In general, combination antiemetic therapy is preferred over single-agent therapy for chemotherapeutic regimens that produce moderate to severe adverse effects.

  10. ANTIEMETICS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Amit Kumar* 1 and Anoop Kumar 2

    2013-01-01

    Full Text Available The act of emesis is controlled by the vomiting centre in the medulla, which integrates afferent input from the vestibular system, the chemoreceptor trigger zone (CTZ, the cortex and the gut. Nausea and vomiting induced by several cancer chemotherapy agents is often the most distressing side effect of treatment. The mechanism of action of antiemetic is related to blockage of various type of receptor located in various region of various organ of the body parts. Various drugs are classified under antiemetic like Ondansetron, Granisetron & Metochlopramide etc. A critical review of the studies of aprepitant (a new NK1 receptor antagonist and of palonosetron (a 5-HT3 receptor antagonist with a longer half-life presented in this article. Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly increase the control of acute emesis with respect to dexamethasone. Palonosetron showed superior or similar efficacy to Ondansetron and dolasetron in patients submitted to moderately emetogenic chemotherapy Certain side effects arise due to excessive use of antiemetic like twitching, flushing of skin, headaches, tiredness, indigestion etc.

  11. Antiemetics

    DEFF Research Database (Denmark)

    Herrstedt, Jørn

    2008-01-01

    Nausea and vomiting are two of the most severe problems for patients treated with chemotherapy. Until the late 1970s, nausea and vomiting induced by chemotherapy was an almost neglected research area. With the introduction of cisplatin, the cytotoxin with the highest emetic potential, research...

  12. Algorithms for optimizing drug therapy

    Directory of Open Access Journals (Sweden)

    Martin Lene

    2004-07-01

    Full Text Available Abstract Background Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. Methods One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface and JavaScript (program logic. Results Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs

  13. Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

    Science.gov (United States)

    Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

    2015-03-01

    The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV.

  14. Optimal therapy in Gaucher disease

    Directory of Open Access Journals (Sweden)

    Ozlem Goker-Alpan

    2010-07-01

    Full Text Available Ozlem Goker-AlpanLysosomal Diseases Research and Treatment Unit, Center for Clinical Trials, O&O Alpan LLC, Springfield, VA, USAAbstract: Gaucher disease (GD, the inherited deficiency of the lysosomal enzyme glucocerebrosidase, presents with a wide range of symptoms of varying severity, and primarily affects the skeletal, hematologic and nervous systems. To date, the standard of care has included enzyme replacement therapy with imiglucerase. Although imiglucerase is highly effective in reversing the visceral and hematologic manifestations, skeletal disease is slow to respond, pulmonary involvement is relatively resistant, and the CNS involvement is not impacted. Because of the recent manufacturing and processing problems, the research and development of alternative therapeutics has become more pressing. The divergent phenotypes and the heterogeneity involving different organ systems implicates the involvement of several pathological processes that include enzyme deficiency, substrate accumulation, protein misfolding, and macrophage activation, that differ in each patient with GD. Thus, the therapy should be tailored individually in order to target multiple pathways that interplay in GD.Keywords: glucocerebrosidase, enzyme replacement therapy, substrate reduction therapy, protein misfolding and chaperone therapy, macrophage

  15. Optimizing adherence to antiretroviral therapy.

    Science.gov (United States)

    Sahay, Seema; Reddy, K Srikanth; Dhayarkar, Sampada

    2011-12-01

    HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of 'universal access' and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients' health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested.

  16. Antiemetic prophylaxis with promethazine or ondansetron in major ...

    African Journals Online (AJOL)

    Studio G5

    PONV include age, gender, obesity, menstrual period, history of motion sickness ... antiemetic drugs forms the basis of the prevention and treatment of postoperative ... vomiting by a senior registrar blinded to the designated agent. Nausea and ...

  17. Stochastic optimal therapy for enhanced immune response.

    Science.gov (United States)

    Stengel, Robert F; Ghigliazza, Raffaele

    2004-10-01

    Therapeutic enhancement of humoral immune response to microbial attack is addressed as the stochastic optimal control of a dynamic system. Without therapy, the modeled immune response depends upon the initial concentration of pathogens in a simulated attack. Immune response can be augmented by agents that kill the pathogen directly, that stimulate the production of plasma cells or antibodies, or that enhance organ health. Using a generic mathematical model of immune response to the infection (i.e., of the dynamic state of the system), previous papers demonstrated optimal (open-loop) and neighboring-optimal (closed-loop) control solutions that defeat the pathogen and preserve organ health, given initial conditions that otherwise would be lethal [Optimal Contr. Appl. Methods 23 (2002) 91, Bioinformatics 18 (2002) 1227]. Therapies based on separate and combined application of the agents were derived by minimizing a quadratic cost function that weighted both system response and drug usage, providing implicit control over harmful side effects. Here, we focus on the effects that corrupted or incomplete measurements of the dynamic state may have on neighboring-optimal feedback control. Imperfect measurements degrade the precision of feedback adjustments to therapy; however, optimal state estimation allows the feedback strategy to be implemented with incomplete measurements and minimizes the expected effects of measurement error. Complete observability of the perturbed state for this four state example is provided by measurement of four of the six possible pairs of two variables, either set of three variables, or all four variables. The inclusion of state estimation extends the applicability of optimal control theory for developing new therapeutic protocols to enhance immune response.

  18. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  19. Survey of Implementation of Antiemetic Prescription Standards in Indian Oncology Practices and Its Adherence to the American Society of Clinical Oncology Antiemetic Clinical Guideline

    Directory of Open Access Journals (Sweden)

    Vijay Patil

    2017-08-01

    Full Text Available Purpose: Adherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned. Methods: This study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens. Results: Sixty-six (62.9% of 105 responded and 65 centers (98.5% were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8% than the highly emetogenic regimens (6.1%. The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%, lack of national guidelines (12 centers; 18.2%, and lack of administrative support (10 centers; 15.2%. Conclusion: Awareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice.

  20. Optimizing insulin pump therapy: a quality improvement project.

    Science.gov (United States)

    Meade, Lisa T; Rushton, Wanda E

    2013-01-01

    The purpose of the study was to assess insulin pump use and provide ongoing education. A quality improvement project using a pump assessment questionnaire was implemented at an endocrinology office in the southeastern United States. The questionnaire was designed to evaluate all aspects of insulin pump therapy, including pump operations, infusion set failure, management of acute complications, and usage of advanced device features. Eighty-nine patients (80% with type 1 diabetes and 20% with type 2 diabetes) completed the questionnaire at the endocrinology practice. A certified diabetes educator reviewed the questions with each patient, identifying deficiencies and training opportunities. The most common areas of deficiency identified after implementation of the assessment form included the following: expired or no basal insulin prescription in the event of pump failure or removal, no mupirocin (Bactroban®, GlaxoSmithKline, Research Triangle Park, North Carolina) prescription for suspected site infections, lack of insulin syringe if pump stopped working, failure to check urine ketones, no antiemetic prescription for sick day intervention, using manual bolus instead of bolus calculator, and lack of in-date glucagon kit. Use of a pump assessment questionnaire allows for focused discussion concerning patient behaviors related to pump operations, troubleshooting, and self-management. Incorporating use of a pump assessment questionnaire into routine practice may result in improved patient education and avoidance of adverse events specific to insulin pump therapy.

  1. An Evidence Practice Gap in Antiemetic Prescription with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Chepsy C-Philip

    2015-10-01

    Full Text Available Background: Chemotherapy induced nausea and vomiting is an added distress to patients burdened by the illness. In an effort to tackle the emetogenic potential of the agents, guidelines have been proposed to maintain uniformity in prescription and improvement in patient tolerance; but their utility and practice is not consistent. The aim of this clinical audit was to assess the antiemetic.practice and investigate the adherence to antiemetic clinical practice guidelineMethods: We performed an audit of the antiemetic practices in our tertiary referral centre. A.questionnaire based interview was completed at the outpatient visit to tabulate the dataResults: 99 (81.8% patients received chemotherapy of at least low emetogenic risk. 83 (84% patients received prophylaxis which was appropriate in 65% based on the our centre’s antiemetic regimen. This was however inappropriate in 76% of patients based on the international practice.parametersConclusions: Guidelines are not uniformly representative of all populations and modifications toguidelines based on local data are required to ensure success of such policies. There exist evidence-.practice gaps in antiemetic policies

  2. 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.

  3. Hollow silicon microneedle array based trans-epidermal antiemetic patch for efficient management of chemotherapy induced nausea and vomiting

    Science.gov (United States)

    Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit

    2015-12-01

    Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.

  4. Effect of formulation pH on transdermal penetration of antiemetics formulated in poloxamer lecithin organogel.

    Science.gov (United States)

    Woodall, Rachel; Arnold, John J; McKay, Doug; Asbill, C Scott

    2013-01-01

    The purpose of this study was to assess the impact of altering formulation pH on the transdermal penetration of several commonly used antiemetic, weakly basic drugs incorporated into poloxamer lecithin organogel vehicle. Poloxamer lecithin organogel formulations containing promethazine hydrochloride (25 mg/mL), metoclopramide hydrochloride (10 mg/mL), and ondansetron hydrochloride (8 mg/mL) were examined for both drug release and transdermal penetration across porcine skin in modified Franz diffusion cells for a period of 24 hours. For the transdermal studies, each antiemetic drug was formulated at a pH above and below their acid dissociation constant (pKa) in an attempt to assure that the drug would be primarily in their respective ionized or non-ionized states. In addition, drug content in skin was assessed at the end of the 24-hour experiment. Drug content analysis was determined via high-performance liquid chromatography. As a percent of total drug release from the poloxamer lecithin organogel vehicle, promethazine hydrochloride demonstrated the most transdermal drug penetration after 24 hours (30.2% +/- 20.2%), followed by ondansetron hydrochloride (2.7% +/- 1.1%) and metoclopramide hydrochloride (1.8% +/- 1.6%). Subsequently, the pH of the Pluronic F-127 gel was adjusted in order to ensure that each antiemetic drug would be primarily in its unionized state. The transdermal permeation of each antiemetic drug primarily in its unionized state increased over that observed with the drug primarily in its ionized state after 24 hours (promethazine: 1.6-fold increase; metoclopramide: 1.3-fold increase; ondansetron: 1.8-fold increase). A similar trend was noted in the amount of each drug found in the skin after 24 hours (promethazine: 1.2-fold increase; metoclopramide: 2.4-fold increase; ondansetron: 3.0-fold increase). These results suggest that proper optimization of drug ionization state may be a useful strategy for compounding pharmacists to increase the efficacy

  5. Gantry optimization of the Shanghai Advanced Proton Therapy facility

    Institute of Scientific and Technical Information of China (English)

    吴军; 杜涵文; 薛; 潘家珍; 杜月斐; 龙亚文

    2015-01-01

    A proton therapy system is a large medical device to treat tumors. Its gantry is of large structure and high precision. A new half-gantry was designed in the Shanghai Advanced Proton Therapy (SAPT) project. In this paper, the weight of gantry in design is reduced significantly by size and structure optimizations, to improve its cost-effectiveness, while guaranteeing the functions and precision. The processes of physics optimization, empirical design optimization, topological optimization and size optimization, together with factors of consid-eration, are described. The gantry weight is reduced by 30%, with the same precision.

  6. Risk-optimized proton therapy to minimize radiogenic second cancers

    DEFF Research Database (Denmark)

    Rechner, Laura A; Eley, John G; Howell, Rebecca M

    2015-01-01

    Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

  7. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents

    Directory of Open Access Journals (Sweden)

    Zbys Fedorowicz

    Full Text Available BACKGROUND: Vomiting is a common manifestation of acute gastroenteritis in children and adolescents. When untreated, it can be a hindrance to oral rehydration therapy, which is the cornerstone in the management of acute gastroenteritis. Evidence is needed concerning the safety and efficacy of antiemetic use for vomiting in acute gastroenteritis in children. OBJECTIVES: To assess the safety and effectiveness of antiemetics on gastroenteritis induced vomiting in children and adolescents. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conferences. The search was re-run and is up to date as on 20 July 2010. SELECTION CRITERIA: Randomized controlled trials comparing antiemetics with placebo or no treatment, in children and adolescents under the age of 18, for vomiting due to gastroenteritis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included seven trials involving 1,020 participants. Mean time to cessation of vomiting in one study was 0.34 days less with dimenhydrinate suppository compared to placebo (P value = 0.036. Pooled data from three studies comparing oral ondansetron with placebo showed: a reduction in the immediate hospital admission rate (RR 0.40, NNT 17, 95% CI 10 to 100 but no difference between the hospitalization rates at 72 hours after discharge from the Emergency Department (ED; a reduction in IV rehydration rates both during the ED stay (RR 0.41, NNT 5, 95% CI 4 to 8, and in follow-up to 72 hours after discharge from the ED stay (worst-best scenario for ondansetron RR 0.57, NNT 6, 95% CI 4 to 13 and an increase in the proportion of patients with cessation of vomiting (RR 1.34, NNT 5, 95% CI 3 to 7. No significant difference was noted in the revisit

  8. Bioavailability of the antiemetic metopimazine given as a microenema

    DEFF Research Database (Denmark)

    Herrstedt, J.; Jørgensen, M.; Angelo, H.R.

    1996-01-01

    The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite ...... were measured. The bioavailability of MPZ given orally and as enemas was 22.3 and 19.5% respectively. Partial avoidance of hepatic first pass metabolism was seen with the enemas, which in contrast to suppositories, seems to represent a reliable form of rectal administration....

  9. Two Effective Heuristics for Beam Angle Optimization in Radiation Therapy

    CERN Document Server

    Yarmand, Hamed

    2013-01-01

    In radiation therapy, mathematical methods have been used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to critical surrounding structures minimal. This optimization problem can be modeled using mixed integer programming (MIP) whose solution gives the optimal beam orientation as well as optimal beam intensity. The challenge, however, is the computation time for this large scale MIP. We propose and investigate two novel heuristic approaches to reduce the computation time considerably while attaining high-quality solutions. We introduce a family of heuristic cuts based on the concept of 'adjacent beams' and a beam elimination scheme based on the contribution of each beam to deliver the dose to the tumor in the ideal plan in which all potential beams can be used simultaneously. We show the effectiveness of these heuristics for intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) on a clinical liver case.

  10. Optimal combination of antiangiogenic therapy forhepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The success of sorafenib in prolonging survival of patientswith hepatocellular carcinoma (HCC) makes therapeuticinhibition of angiogenesis a component of treatmentfor HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination ofantiangiogenic agents with chemotherapy,radiotherapyor other targeted agents were evaluated. Nevertheless,the use of antiangiogenic therapy remains suboptimalregarding dosage, schedule and duration of therapy.The issue is further complicated by combinationantiangiogenesis to other cytotoxic or biologic agents.There is no way to determine which patients are mostlikely respond to a given form of antiangiogenic therapy.Activation of alternative pathways associated with diseaseprogression in patients undergoing antiangiogenictherapy has also been recognized. There is increasingimportance in identifying, validating and standardizingpotential response biomarkers for antiangiogenesistherapy for HCC patients. In this review, biomarkers forantiangiogenesis therapy including systemic, circulating,tissue and imaging ones are summarized. The strengthand deficit of circulating and imaging biomarkerswere further demonstrated by a series of studies inHCC patients receiving radiotherapy with or withoutthalidomide.

  11. The quest for optimal antimicrobial therapy

    NARCIS (Netherlands)

    Mol, Petrus Gerardus Maria

    2005-01-01

    Since the discovery of sulphonam ides and penicillin in the 1930's, and their widespread use in clinical practice during World War II a plethora of new antimicrobial agents have entered the market. Initial optim ism has faded that these new drugs would eliminate infectious diseases as killer disease

  12. The quest for optimal antimicrobial therapy

    NARCIS (Netherlands)

    Mol, Petrus Gerardus Maria

    2005-01-01

    Since the discovery of sulphonam ides and penicillin in the 1930's, and their widespread use in clinical practice during World War II a plethora of new antimicrobial agents have entered the market. Initial optim ism has faded that these new drugs would eliminate infectious diseases as killer

  13. [Stomach carcinoma. Optimizing therapy by neoadjuvant or adjuvant therapy?].

    Science.gov (United States)

    Rosen, H

    1999-01-01

    Despite the decreasing frequency of gastric cancer in most Western countries prognosis could not be improved by surgery alone in the past. Advanced tumor stage due to late diagnosis is one of the reasons for this observation. Contrary to breast and colorectal cancer, postoperative chemotherapy failed to improve prognosis in gastric cancer. Small number of patients in Western studies, insufficient surgical procedures and the high frequency of locoregional relapse may be attributed for this observation. Intraperitoneal, adjuvant chemotherapy showed a positive impact on survival in Asian studies only, but was also used successfully as a part of a multimodality approach in Western phase II trials. Since neoadjuvant therapy proved to create downstaging of tumor size in some patients with advanced gastric cancer some working groups tried to influence prognosis of potentially resectable tumors by preoperative chemotherapy, surgical resection and postoperative, adjuvant therapy in the recent past. However, the efficacy of this therapeutic approach has to be reconfirmed in a controlled, phase III fashion.

  14. Optimization approaches to volumetric modulated arc therapy planning

    Energy Technology Data Exchange (ETDEWEB)

    Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bortfeld, Thomas; Craft, David [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Alber, Markus [Department of Medical Physics and Department of Radiation Oncology, Aarhus University Hospital, Aarhus C DK-8000 (Denmark); Bangert, Mark [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg D-69120 (Germany); Bokrantz, Rasmus [RaySearch Laboratories, Stockholm SE-111 34 (Sweden); Chen, Danny [Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Li, Ruijiang; Xing, Lei [Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States); Men, Chunhua [Department of Research, Elekta, Maryland Heights, Missouri 63043 (United States); Nill, Simeon [Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London SM2 5NG (United Kingdom); Papp, Dávid [Department of Mathematics, North Carolina State University, Raleigh, North Carolina 27695 (United States); Romeijn, Edwin [H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Salari, Ehsan [Department of Industrial and Manufacturing Engineering, Wichita State University, Wichita, Kansas 67260 (United States)

    2015-03-15

    Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed.

  15. A validated micellar electrokinetic chromatography method for the quantitation of dexamethasone, ondansetron and aprepitant, antiemetic drugs, in organogel.

    Science.gov (United States)

    Bourdon, Florence; Lecoeur, Marie; Duhaut, Marion; Odou, Pascal; Vaccher, Claude; Foulon, Catherine

    2013-12-01

    A micellar electrokinetic chromatography (MEKC) method was developed for the determination of three anti-vomiting drugs (aprepitant, dexamethasone and ondansetron) in pharmaceutical formulations. The method was optimized using a central composite design (CCD). Four main factors (borate buffer concentration, pH, methanol content and sodium dodecyl sulfate concentration) were optimized in order to obtain best resolutions and peak efficiencies in a minimum runtime. The separation was performed in a fused-silica capillary. After optimization, the background electrolyte consisted of a borate buffer (62.5mM, pH 8.75) containing sodium dodecyl sulfate (77.5mM) and methanol (3.75%). Under these conditions, a complete separation of each antiemetic drug and its respective internal standards was achieved in 38min. The method was validated with trueness values from 94.9 to 107.2% and precision results (repeatability and intermediate precision) lower than 5.9%. MEKC-UV was the first method allowing the separation of aprepitant, dexamethasone and ondansetron and was suitable for the quantitation of these three antiemetic drugs in organogel formulations. The rapid sample preparation coupled with an automated separation technique make this method convenient for quality control of extemporaneous magistral ready-to-use formulation.

  16. Optimizing antimicrobial therapy in critically ill patients

    Directory of Open Access Journals (Sweden)

    Vitrat V

    2014-10-01

    Full Text Available Virginie Vitrat,1 Serge Hautefeuille,2 Cécile Janssen,1 David Bougon,2 Michel Sirodot,2 Leonardo Pagani1,3 1Antimicrobial Stewardship Program, Infectious Diseases Unit, 2Intensive Care Unit, Annecy-Genevois Hospital Center (CHANGE, Annecy, France; 3Infectious Diseases Unit, Bolzano Central Hospital, Bolzano, Italy Abstract: Critically ill patients with infection in the intensive care unit (ICU would certainly benefit from timely bacterial identification and effective antimicrobial treatment. Diagnostic techniques have clearly improved in the last years and allow earlier identification of bacterial strains in some cases, but these techniques are still quite expensive and not readily available in all institutions. Moreover, the ever increasing rates of resistance to antimicrobials, especially in Gram-negative pathogens, are threatening the outcome for such patients because of the lack of effective medical treatment; ICU physicians are therefore resorting to combination therapies to overcome resistance, with the direct consequence of promoting further resistance. A more appropriate use of available antimicrobials in the ICU should be pursued, and adjustments in doses and dosing through pharmacokinetics and pharmacodynamics have recently shown promising results in improving outcomes and reducing antimicrobial resistance. The aim of multidisciplinary antimicrobial stewardship programs is to improve antimicrobial prescription, and in this review we analyze the available experiences of such programs carried out in ICUs, with emphasis on results, challenges, and pitfalls. Any effective intervention aimed at improving antibiotic usage in ICUs must be brought about at the present time; otherwise, we will face the challenge of intractable infections in critically ill patients in the near future. Keywords: ICU, antimicrobial therapies, antimicrobial stewardship, pharmacokinetics, pharmacodynamics, antimicrobial resistance, early diagnosis

  17. Optimization of adaptive radiation therapy in cervical cancer: Solutions for photon and proton therapy

    NARCIS (Netherlands)

    van de Schoot, A.J.A.J.

    2016-01-01

    In cervical cancer radiation therapy, an adaptive strategy is required to compensate for interfraction anatomical variations in order to achieve adequate dose delivery. In this thesis, we have aimed at optimizing adaptive radiation therapy in cervical cancer to improve treatment efficiency and

  18. Optimization of adaptive radiation therapy in cervical cancer: Solutions for photon and proton therapy

    NARCIS (Netherlands)

    van de Schoot, A.J.A.J.

    2016-01-01

    In cervical cancer radiation therapy, an adaptive strategy is required to compensate for interfraction anatomical variations in order to achieve adequate dose delivery. In this thesis, we have aimed at optimizing adaptive radiation therapy in cervical cancer to improve treatment efficiency and reduc

  19. EUD-based biological optimization for carbon ion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748 (Germany)

    2015-11-15

    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

  20. [Combination effects of capsicum plaster at the Korean hand acupuncture points k-d2 with prophylactic antiemetic on postoperative nausea and vomiting after gynecologic laparoscopy].

    Science.gov (United States)

    Jung, Hyun Jung; Park, Sang Youn

    2013-04-01

    This study was done to evaluate the combination effects of capsicum plaster at the Korean hand acupuncture points K-D2 with prophylactic antiemetic on Postoperative Nausea and Vomiting (PONV). An experimental research design (a randomized, a double-blinded, and a placebo-control procedure) was used. The participants were female patients undergoing gynecologic laparoscopy; the control group (n=34) received intravenous prophylactic ramosetron 0.3mg, while the experimental group (n=34) had Korean Hand Therapy additionally. In the experimental group, capsicum plaster was applied at K-D2 of both 2nd and 4th fingers by means of Korean Hand Therapy for a period of 30 minutes before the induction of anesthesia and removed 8 hours after the laparoscopy. The occurrence of nausea, nausea intensity and need for rescue with antiemetic in the experimental group was significantly less than in the control group 2 hours after surgery. Results of the study show capsicum plaster at K-D2 is an effective method for reducing PONV in spite of the low occurrence of PONV because of the prophylactic antiemetic medication.

  1. Nausea and the quest for the perfect anti-emetic.

    Science.gov (United States)

    Andrews, Paul L R; Sanger, Gareth J

    2014-01-05

    The discovery of anti-emetic agents is reviewed to illustrate the large database (>129,000 papers in PubMed) available for potential data mining and to provide a background to the shift in interest to nausea from vomiting. Research on nausea extends to identification of biomarkers for diagnosis/clinical trials and to understanding why nausea is such a common dose-limiting toxicity of diverse therapeutic agents. The lessons learned for translation from animals to humans, from the discovery of the anti-vomiting effects of 5-HT3 and NK1 receptor antagonists, is discussed in terms of the similarities between the emetic pathways and their pharmacology, and also in terms of the limitations of rodent models of "nausea" (pica, conditioned taste aversion, conditioned gaping and disgust). The review focuses on the established view that anti-emetics are more efficacious against vomiting than nausea. In particular we examine studies of 5-HT3, NK1 and D2 receptor antagonists, gabapentin and various receptor agonists. The potential for targeting anti-nausea agents is then considered, by targeting mechanisms which correct delayed gastric emptying (prokinetics), the rise in plasma vasopressin (AVP) and/or act at central targets revealed by the growing knowledge of cortical regions activated/inhibited in subjects reporting nausea. Modulation of the projections from the brainstem to the cortical areas responsible for the genesis of the sensation of nausea provides the most likely approach to a target at which an anti-nausea drug could be targeted with the expectation that it would affect nausea from multiple causes.

  2. Optimization of growth hormone therapy in growth hormone deficient children

    NARCIS (Netherlands)

    S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1991-01-01

    textabstractIt is obvious that the results published so far as well as the present preliminary data do not answer many questions regarding the optimal therapeutic regimen in GH deficiency. In particular, long-term follow-up must be organized to evaluate efficacy and safety of GH therapy not only in

  3. Optimizing asparaginase therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin

    2013-03-01

    of crisantaspase given intravenously at 20,000 IU/m2 on alternate days when clinical allergy or silent inactivation is present. Based on the indications of different protocols, lack of cross-reactivity to the E. coli-derived products and taking into consideration regulatory factors and availability, crisantaspase may be considered a viable second-line therapy.

  4. Optimal Control of Drug Therapy in a Hepatitis B Model

    Directory of Open Access Journals (Sweden)

    Jonathan E. Forde

    2016-08-01

    Full Text Available Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

  5. Pacemaker optimization guided by echocardiography in cardiac resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Trifunović Danijela

    2009-01-01

    Full Text Available Introduction. Cardiac resynchronization therapy (CRT or biventricular pacing is a contemporary treatment in the management of advanced heart failure. Echocardiography plays an evolving and important role in patient selection for CRT, follow-up of acute and chronic CRT effects and optimization of device settings after biventricular pacemaker implantation. In this paper we illustrate usefulness of echocardiography for successful AV and VV timing optimization in patients with CRT. A review of up-to-date literature concerning rationale for AV and VV delay optimization, echocardiographic protocols and current recommendations for AV and VV optimization after CRT are also presented. Outline of Cases. The first case is of successful AV delay optimization guided by echocardiography in a patient with dilated cardiomyopathy treated with CRT is presented. Pulsed blood flow Doppler was used to detect mitral inflow while programming different duration of AV delay. The AV delay with optimal transmittal flow was established. The optimal mitral flow was the one with clearly defined E and A waves and maximal velocity time integral (VTI of the mitral flow. Improvement in clinical status and reverse left ventricle remodelling with improvement of ejection fraction was registered in our patient after a month. The second case presents a patient with heart failure caused by dilated cardiomyopathy; six months after CRT implantation the patient was still NYHA class III and with a significantly depressed left ventricular ejection fraction. Optimization of VV interval guided by echocardiography was undertaken measuring VTI of the left ventricular outflow tract (LVOT during programming of different VV intervals. The optimal VV interval was determined using a maximal LVOT VTI. A month after VV optimization our patient showed improvement in LV ejection fraction. Conclusion. Optimal management of patients treated with CRT integrate both clinical and echocardiographic follow

  6. The optimization of laser systems for photodynamic therapy of malignancies

    Science.gov (United States)

    Lim, Hyun S.; Lee, Sang Chan; Kim, Ju Ock

    2005-04-01

    In this paper, we optimized the PDT laser system to improve the therapy effects of malignancies. In order to optimizes, the variation of laser output and specific wavelength shift have to reduced. To improved the PDT therapy clincian require the diverse radiation mode which irradiate the tumor surface. Continuous wave mode that general application may causes tissue thermal damage not only to tumor tissue, but also to nomal tissue. Therefore, we suggested new technique for radiation method to improved PDT effects and prevented to the thermal effects for the tissue. In experimental we verified the stability of wavelength, laser output stability and proved the reduced thermal effects to the tissue using the pulse & burst radiation modes in vitro.

  7. Prioritized efficiency optimization for intensity modulated proton therapy

    Science.gov (United States)

    Müller, Birgit S.; Wilkens, Jan J.

    2016-12-01

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade-offs for a multicriteria optimization setting. Then, the planner can select the preferred compromise between treatment time and quality for each individual patient.

  8. Heuristic optimization of the scanning path of particle therapy beams.

    Science.gov (United States)

    Pardo, J; Donetti, M; Bourhaleb, F; Ansarinejad, A; Attili, A; Cirio, R; Garella, M A; Giordanengo, S; Givehchi, N; La Rosa, A; Marchetto, F; Monaco, V; Pecka, A; Peroni, C; Russo, G; Sacchi, R

    2009-06-01

    Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

  9. Heuristic optimization of the scanning path of particle therapy beams

    Energy Technology Data Exchange (ETDEWEB)

    Pardo, J.; Donetti, M.; Bourhaleb, F.; Ansarinejad, A.; Attili, A.; Cirio, R.; Garella, M. A.; Giordanengo, S.; Givehchi, N.; La Rosa, A.; Marchetto, F.; Monaco, V.; Pecka, A.; Peroni, C.; Russo, G.; Sacchi, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Fondazione CNAO, Via Caminadella 16, I-20123, Milano (Italy); Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Torino, Via P. Giuria 1, I-10125 Torino (Italy) and Dipartimento di Fisica Sperimentale, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy)

    2009-06-15

    Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

  10. Optimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy.

    Science.gov (United States)

    Vazquez-Grande, Gloria; Kumar, Anand

    2015-02-01

    There has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. This review explores the pathophysiology of sepsis in an attempt to produce a better understanding and define key determinants of antimicrobial therapy response in septic shock. Optimizing existing antimicrobials delivery can drive significant improvements in the outcome of sepsis and septic shock. Inappropriate antimicrobial selection and dosing or delays in the administration substantially increase mortality and morbidity in life-threatening infections. Definitive combination therapy (where a pathogen known to be susceptible to a given agent is additionally covered by another agent) remains controversial. Although some in vitro studies, animal models, and clinical studies of infection including endocarditis, gram-negative bacteremia, and neutropenic infections have supported combination therapy, the potential clinical benefit in other severe infections has been questioned. Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.

  11. FINITE ELEMENT ANALYSIS FOR OPTIMIZING ANTENNA FOR MICROWAVE COAGULATION THERAPY

    Directory of Open Access Journals (Sweden)

    MARWAHA S.

    2012-08-01

    Full Text Available Microwave coagulation therapy (MCT is emerging as an attractive modality for thermal therapy of soft tissues targeted in short periods of time, making it particularly suitable for ablation of hepatic and other tumors. In this field of microwave coagulation therapy, the use of minimally invasive antenna is recognized as a very promising technique for the treatment of small tumors because a very thin antenna can be easily inserted inside the body and precisely localized using the advanced 3D imaging techniques and surgical robots. The authors investigated the microwave coaxial antenna operating at 2.45 GHz by varying the slots size for the removal of liver tumor. The analysis was done using 2D finite element modeling. By several optimization steps the antenna is simulated and optimized by comparing the values of specific absorption rate (SAR, mesh statistics and temperature distributions in tissue generated by the antenna with the variations of dimensions of slot from 1 mm to 1.7 mm.

  12. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  13. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  14. Raltegravir with optimized background therapy for resistant HIV-1 infection

    DEFF Research Database (Denmark)

    Steigbigel, Roy T; Cooper, David A; Kumar, Princy N;

    2008-01-01

    for the length of follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups. CONCLUSIONS: In HIV-infected patients with limited treatment options, raltegravir plus......BACKGROUND: Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs. METHODS: We conducted two identical trials in different geographic regions to evaluate the safety and efficacy...... of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that has triple-class drug resistance in whom antiretroviral therapy had failed. Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio. RESULTS: In the combined studies...

  15. Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs.

    Science.gov (United States)

    Matok, Ilan; Clark, Shannon; Caritis, Steve; Miodovnik, Menachem; Umans, Jason G; Hankins, Gary; Mattison, Donald R; Koren, Gideon

    2014-12-01

    Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre-specified substudy of a randomized, placebo-controlled trial comparing the antiemetic effect of the doxylamine-vitamin B6 combination (Diclectin®) (n = 131) to placebo (n = 126) in women with nausea and vomiting of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5' phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With Diclectin® exhibiting a significant antiemetic effect in pregnancy, serum concentrations of pyridoxine were unmeasurable in almost all patients and those of pyridoxal were undetectable in half of patients. In contrast, PLP was measurable at sustained, stable steady-state levels in all patients. Our data suggest that there is a correlation between PLP levels and PUQE score of morning sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and hence they might be prodrugs of PLP, which may be the active antiemetic form of vitamin B6.

  16. Improving adherence with oral antiemetic agents in patients with breast cancer receiving chemotherapy.

    Science.gov (United States)

    Hendricks, Carolyn B

    2015-05-01

    In this small breast cancer-dedicated solo practice, a retrospective medical record review disclosed the following: significant rate of chemotherapy-related nausea and vomiting and discordance between patient-reported compliance with prescribed antiemetics and medical record documentation of compliance. As part of the curriculum for the American Society of Clinical Oncology (ASCO) Quality Training Program, a quality improvement project was developed to improve adherence to oral antiemetics in our patients with breast cancer receiving highly emetogenic chemotherapy. The following steps were undertaken in plan-do-study-act cycles to improve adherence: enhanced patient education at time of chemotherapy consent, implementation of standardized in-person or e-mail contact with our patients receiving chemotherapy, and improvement of our electronic health record documentation of adherence to oral antiemetics. A run chart was generated to analyze our data. After our interventions, the percentage of patients who took their antiemetics as prescribed rose from a baseline of 49% to 79%. Significant improvement in adherence to oral antiemetics among patients with breast cancer receiving chemotherapy was achieved and sustained in this small-practice setting using the framework provided by participation in the ASCO Quality Training Program. Copyright © 2015 by American Society of Clinical Oncology.

  17. Automatic CT simulation optimization for radiation therapy: A general strategy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hua, E-mail: huli@radonc.wustl.edu; Chen, Hsin-Chen; Tan, Jun; Gay, Hiram; Michalski, Jeff M.; Mutic, Sasa [Department of Radiation Oncology, Washington University, St. Louis, Missouri 63110 (United States); Yu, Lifeng [Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (United States); Anastasio, Mark A. [Department of Biomedical Engineering, Washington University, St. Louis, Missouri 63110 (United States); Low, Daniel A. [Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California 90095 (United States)

    2014-03-15

    Purpose: In radiation therapy, x-ray computed tomography (CT) simulation protocol specifications should be driven by the treatment planning requirements in lieu of duplicating diagnostic CT screening protocols. The purpose of this study was to develop a general strategy that allows for automatically, prospectively, and objectively determining the optimal patient-specific CT simulation protocols based on radiation-therapy goals, namely, maintenance of contouring quality and integrity while minimizing patient CT simulation dose. Methods: The authors proposed a general prediction strategy that provides automatic optimal CT simulation protocol selection as a function of patient size and treatment planning task. The optimal protocol is the one that delivers the minimum dose required to provide a CT simulation scan that yields accurate contours. Accurate treatment plans depend on accurate contours in order to conform the dose to actual tumor and normal organ positions. An image quality index, defined to characterize how simulation scan quality affects contour delineation, was developed and used to benchmark the contouring accuracy and treatment plan quality within the predication strategy. A clinical workflow was developed to select the optimal CT simulation protocols incorporating patient size, target delineation, and radiation dose efficiency. An experimental study using an anthropomorphic pelvis phantom with added-bolus layers was used to demonstrate how the proposed prediction strategy could be implemented and how the optimal CT simulation protocols could be selected for prostate cancer patients based on patient size and treatment planning task. Clinical IMRT prostate treatment plans for seven CT scans with varied image quality indices were separately optimized and compared to verify the trace of target and organ dosimetry coverage. Results: Based on the phantom study, the optimal image quality index for accurate manual prostate contouring was 4.4. The optimal tube

  18. [Optimization of modern conservative therapy of micropenis in hypogonadal men].

    Science.gov (United States)

    Petrovich, R Iu; Sokoll'shchik, M M; Tiuzikov, I A; Konstantinova, I V; Astakhova, M A

    2014-01-01

    The study was aimed to the optimization of conservative therapy of micropenis in hypogonadal men using combination of traction therapy and androgen replacment therapy (ART) with injections of prolonged testosterone undecanoate (Nebido) and to evaluatiom of the safety of ART in terms of the risk of prostate cancer against the background of combined treatment of micropenis by both methods within 12 months. The study included 16 men aged 22-62 years with micropenis and hypogonadism. 10 men were diagnosed with primary hypogonadism, 6 men were diagnosed with secondary hypogonadism without reserve gonadal function; therefore, all 16 patients were treated with testosterone undecanoate 1000 mg intramuscularly according to the scheme: the second injection 6 weeks after the first injection, then each injection once a 12 weeks, the course of 12 months. During the first 3 months of ART, hypogonadism in all men was eliminated, but only at 6 month of ART, the length of the penis in the flaccid state at maximum extension increased from 5.8±1.2 to 8.3±1.2 cm (ppenis - from 6.8±1.1 to 11.8±0.9 (ppenis in the flaccid state at maximum extension increased by 58% of the original length, and in a state of erection - by 114% (psize of the prostate in healthy men. Total blood PSA level increased from 0.72±0.03 to 1.4±0.05 ng/ml (p<0.05), but it was in the acceptable range of reference values for healthy men during whole period of ART in all patients. Start therapy with prolonged testosterone undecanoate for 6 months significantly increases the efficiency of traction therapy in men with hypogonadism and micropenis, but for maintenance of the effect, ART should be continued during all period of treatment.

  19. [Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

    Science.gov (United States)

    Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

    2016-05-01

    Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

  20. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.

    Science.gov (United States)

    Srivastava, Manish; Brito-Dellan, Norman; Davis, Mellar P; Leach, Marie; Lagman, Ruth

    2003-06-01

    Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed.

  1. Optimizing patient positioning for intensity modulated radiation therapy in hippocampal-sparing whole brain radiation therapy.

    Science.gov (United States)

    Siglin, Joshua; Champ, Colin E; Vakhnenko, Yelena; Witek, Matthew E; Peng, Cheng; Zaorsky, Nicholas G; Harrison, Amy S; Shi, Wenyin

    2014-01-01

    Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT. A variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose-volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans. Hippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm(3), 12.5 cm(3), and 1185.1 cm(3), respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans. Compared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar

  2. Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

    Science.gov (United States)

    Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

    2015-01-01

    To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

  3. Optimal antiviral switching to minimize resistance risk in HIV therapy.

    Directory of Open Access Journals (Sweden)

    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  4. Projections onto the Pareto surface in multicriteria radiation therapy optimization

    Energy Technology Data Exchange (ETDEWEB)

    Bokrantz, Rasmus, E-mail: bokrantz@kth.se, E-mail: rasmus.bokrantz@raysearchlabs.com [Optimization and Systems Theory, Department of Mathematics, KTH Royal Institute of Technology, Stockholm SE-100 44, Sweden and RaySearch Laboratories, Sveavägen 44, Stockholm SE-103 65 (Sweden); Miettinen, Kaisa [Optimization and Systems Theory, Department of Mathematics, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden and University of Jyvaskyla, Department of Mathematical Information Technology, FI-400 14 University of Jyvaskyla (Finland)

    2015-10-15

    Purpose: To eliminate or reduce the error to Pareto optimality that arises in Pareto surface navigation when the Pareto surface is approximated by a small number of plans. Methods: The authors propose to project the navigated plan onto the Pareto surface as a postprocessing step to the navigation. The projection attempts to find a Pareto optimal plan that is at least as good as or better than the initial navigated plan with respect to all objective functions. An augmented form of projection is also suggested where dose–volume histogram constraints are used to prevent that the projection causes a violation of some clinical goal. The projections were evaluated with respect to planning for intensity modulated radiation therapy delivered by step-and-shoot and sliding window and spot-scanned intensity modulated proton therapy. Retrospective plans were generated for a prostate and a head and neck case. Results: The projections led to improved dose conformity and better sparing of organs at risk (OARs) for all three delivery techniques and both patient cases. The mean dose to OARs decreased by 3.1 Gy on average for the unconstrained form of the projection and by 2.0 Gy on average when dose–volume histogram constraints were used. No consistent improvements in target homogeneity were observed. Conclusions: There are situations when Pareto navigation leaves room for improvement in OAR sparing and dose conformity, for example, if the approximation of the Pareto surface is coarse or the problem formulation has too permissive constraints. A projection onto the Pareto surface can identify an inaccurate Pareto surface representation and, if necessary, improve the quality of the navigated plan.

  5. Optimizing nutrition therapy to enhance mobility in critically ill patients.

    Science.gov (United States)

    Cherry-Bukowiec, Jill R

    2013-01-01

    Critically ill patients are at high risk of malnutrition and lean body mass loss. Screening for malnutrition and performing detailed assessment of energy needs should be routine for patients admitted to intensive care units. Providing adequate calorie and protein provisions can attenuate muscle loss in many at-risk patients. Enteral nutrition is associated with decreased risks of morbidity and infections and is therefore preferred to parenteral nutrition in hemodynamically stable patients with favorable anatomy. Judicious use of steroids and paralytics in combination with adequate glucose control may decrease the risk of developing critical illness polyneuromyopathy. There is growing evidence for the potential immune-enhancing benefits of many micronutrients and vitamins in the critically ill, but more research is needed to determine which nutrients are most effective in which disease processes and what dosing regimens are safe and effective. Elderly, obese, and very young patients pose unique challenges for nutrition therapy and early mobility programs. Pairing early mobility programs with optimal nutrition therapy can help reduce morbidity, limit muscle loss, and speed recovery in intensive care unit patients.

  6. Optimized Photodynamic Therapy with Multifunctional Cobalt Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kyong-Hoon Choi

    2017-06-01

    Full Text Available Photodynamic therapy (PDT has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and determine the influence of light parameters on the photosensitizing agent. In particular, much more knowledge concerning the importance of fluence and exposure time is required to gain a better understanding of the photodynamic efficacy. In the present study, we synthesized novel folic acid-(FA and hematoporphyrin (HP-conjugated multifunctional magnetic nanoparticles (CoFe2O4-HPs-FAs, which were characterized as effective anticancer reagents for PDT, and evaluated the influence of incubation time and light exposure time on the photodynamic anticancer activities of CoFe2O4-HPs-FAs in prostate cancer cells (PC-3 cells. The results indicated that the same fluence at different exposure times resulted in changes in the anticancer activities on PC-3 cells as well as in reactive oxygen species formation. In addition, an increase of the fluence showed an improvement for cell photo-inactivation. Therefore, we have established optimized conditions for new multifunctional magnetic nanoparticles with direct application for improving PDT for cancer patients.

  7. Optimizing global liver function in radiation therapy treatment planning

    Science.gov (United States)

    Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

    2016-09-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and

  8. Optimizing global liver function in radiation therapy treatment planning

    Science.gov (United States)

    Wu, Victor W; Epelman, Marina A; Wang, Hesheng; Romeijn, H Edwin; Feng, Mary; Cao, Yue; Haken, Randall K Ten; Matuszak, Martha M

    2017-01-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (ℓEUD) (conventional ‘ℓEUD model’), the so-called perfusion-weighted ℓEUD (fEUD) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting ℓEUD, fEUD, and GLF plans delivering the same target ℓEUD are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6%(7.5%) more liver function than the fEUD (ℓEUD) plan does in 2D cases, and up to 4.5%(5.6%) in 3D cases. The GLF and fEUD plans worsen in ℓEUD of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than ℓEUD model optimization does, the GLF model directly optimizes a more clinically

  9. Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms.

    Science.gov (United States)

    Yang, Jie; Zhang, Pengcheng; Zhang, Liyuan; Shu, Huazhong; Li, Baosheng; Gui, Zhiguo

    2017-01-01

    In inverse treatment planning of intensity-modulated radiation therapy (IMRT), the objective function is typically the sum of the weighted sub-scores, where the weights indicate the importance of the sub-scores. To obtain a high-quality treatment plan, the planner manually adjusts the objective weights using a trial-and-error procedure until an acceptable plan is reached. In this work, a new particle swarm optimization (PSO) method which can adjust the weighting factors automatically was investigated to overcome the requirement of manual adjustment, thereby reducing the workload of the human planner and contributing to the development of a fully automated planning process. The proposed optimization method consists of three steps. (i) First, a swarm of weighting factors (i.e., particles) is initialized randomly in the search space, where each particle corresponds to a global objective function. (ii) Then, a plan optimization solver is employed to obtain the optimal solution for each particle, and the values of the evaluation functions used to determine the particle's location and the population global location for the PSO are calculated based on these results. (iii) Next, the weighting factors are updated based on the particle's location and the population global location. Step (ii) is performed alternately with step (iii) until the termination condition is reached. In this method, the evaluation function is a combination of several key points on the dose volume histograms. Furthermore, a perturbation strategy - the crossover and mutation operator hybrid approach - is employed to enhance the population diversity, and two arguments are applied to the evaluation function to improve the flexibility of the algorithm. In this study, the proposed method was used to develop IMRT treatment plans involving five unequally spaced 6MV photon beams for 10 prostate cancer cases. The proposed optimization algorithm yielded high-quality plans for all of the cases, without human

  10. Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study.

    Science.gov (United States)

    Resor, Charles D; Nathan, Ashwin; Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Cutlip, Donald E; Gabriel Steg, P; Hsieh, Wen-Hua; Mauri, Laura

    2016-10-04

    Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. The DAPT (Dual Antiplatelet Therapy) Study, a double-blind trial, randomly assigned 11 648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use in patients with an American College of Cardiology/American Heart Association class I indication for each medication. Per protocol, all patients were treated with 75 to 325 mg aspirin daily. End points included myocardial infarction, major adverse cardiovascular and cerebrovascular events, and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate or severe bleeding events. Of 11 643 randomly assigned patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced myocardial infarction in comparison with placebo in both groups (on OMT 2.1% versus 3.3%, hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48-0.86; P=0.003; off OMT 2.2% versus 5.2%, HR, 0.41; CI, 0.29-0.58; Ptherapy reduced the rate of myocardial infarction regardless of OMT status and had consistent effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding. URL: http://clinicaltrials.gov. Unique identifier: NCT00977938. © 2016 American Heart Association, Inc.

  11. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

    Directory of Open Access Journals (Sweden)

    Milic S

    2015-08-01

    Full Text Available Sandra Milic,1 Ivana Mikolasevic,1,2 Irena Krznaric-Zrnic,1 Marija Stanic,3 Goran Poropat,1 Davor Stimac,1 Vera Vlahovic-Palcevski,4 Lidija Orlic2 1Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia; 2Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia; 3Department of Hematology, UHC Rijeka, Rijeka, Croatia; 4Department for Clinical Pharmacology, University of Rijeka Medical School, UHC Rijeka, Rijeka, Croatia Abstract: Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD. NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only

  12. Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy (DAPT) Study

    Science.gov (United States)

    Resor, Charles D; Nathan, Ashwin; Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Cutlip, Donald E; Steg, P. Gabriel; Hsieh, Wen-Hua; Mauri, Laura

    2017-01-01

    Background Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. Methods The Dual Antiplatelet Therapy Study, a double-blind trial, randomized 11,648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, beta blocker and angiotensin converting enzyme inhibitor/angiotensin receptor blocker use in patients with an ACC/AHA class I indication for each medication. Per protocol, all patients were treated with aspirin 75–325 mg daily. Endpoints included myocardial infarction (MI), major adverse cardiovascular and cerebrovascular events (MACCE) and GUSTO moderate or severe bleeding events. Results Of 11,643 randomized patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced MI compared with placebo in both groups (on OMT 2.1% vs 3.3%, HR 0.64, CI 0.48–0.86, p=0.003; off OMT 2.2% vs 5.2%, HR 0.41, CI 0.29–0.58, p OMT (HR 0.82, CI 0.66–1.02, p=0.077) and 4.5% vs 7.0% among those off OMT (HR 0.63, CI 0.49–0.82, pOMT were 2.2% vs 1.0% (HR 2.13, CI 1.43–3.17, pOMT were 2.8% vs 2.2% (HR 1.30, CI 0.88–1.92, p=0.189; interaction p=0.073). Overall, patients on OMT had lower rates of MI (2.7% vs 3.7%, p=0.003), MACCE (4.6% vs 5.7%, p=0.007) and bleeding (1.6% vs 2.5%, pOMT. Rates of stent thrombosis (0.8% vs 1.0%, p=0.171) and death (1.6% vs 1.9%, p=0.155) did not differ. Conclusions Continued thienopyridine therapy reduced the rate of MI regardless of OMT status and had consistent effects on reduction in MACCE and increased bleeding. Trial Registration https://clinicaltrials.gov, #NCT00977938 PMID:27576774

  13. Advanced cardiac imaging in heart failure : from subclinical myocardial dysfunction to therapy optimization

    NARCIS (Netherlands)

    Auger, Dominique

    2014-01-01

    Advanced echocardiographic techniques permit assessment of left ventricular dyssynchrony in overt heart failure patients and provide important prognostic data. These techniques may guide patients’ selection for cardiac resynchronization therapy and device optimization. Global left ventricular longit

  14. Optimizing proton therapy at the LBL medical accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, J.

    1992-03-01

    This Grant has marked the beginning of a multi-year study process expected to lead to design and construction of at least one, possibly several hospital-based proton therapy facilities in the United States.

  15. Optimizing proton therapy at the LBL medical accelerator. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, J.

    1992-03-01

    This Grant has marked the beginning of a multi-year study process expected to lead to design and construction of at least one, possibly several hospital-based proton therapy facilities in the United States.

  16. The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in Stage I seminoma of the testis: a randomized pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Khoo, V.S.; Rainford, K.; Horwich, A.; Dearnaley, D.P. [Royal Marsden NHS Trust, Sutton (United Kingdom)

    1997-12-31

    The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients randomized to dog-let RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized tiral of field sizes (TE10). (Author).

  17. Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics

    Directory of Open Access Journals (Sweden)

    Ilija Nenadić

    2017-07-01

    Full Text Available With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9,000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH assay accompanied by ALK inhibitor therapy (Crizotinib. The therapy success ranges between a full therapy failure and the complete remission of the tumor (i.e., healing, but the biomedical and systemic reasons for this range remain unknown so far. It appears that the variety of different ALK mutations and variants contributes to the discrepancy in therapy results. Although the major known fusion partner for ALK in NSCLC is the Echinoderm microtubule-associated protein-like 4 (EML4, of which a minimum of 15 variants have been described, an additional 20 further ALK fusion variants with other genes are known, of which three have already been found in NSCLC. We hypothesize that the wide variety of known (and unknown ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH and therapy (Crizotinib only partly applicable in ALK-related NSCLC treatment. In cell culture, differing sensitivity to Crizotinib has been shown for some fusion variants, but it is as yet unknown which of them are really biologically active in cancer patients, and how the respective variants affect the response to Crizotinib treatment. Moreover, it has been demonstrated that translocated ALK genes can

  18. A modular approach to intensity-modulated arc therapy optimization with noncoplanar trajectories

    Science.gov (United States)

    Papp, Dávid; Bortfeld, Thomas; Unkelbach, Jan

    2015-07-01

    Utilizing noncoplanar beam angles in volumetric modulated arc therapy (VMAT) has the potential to combine the benefits of arc therapy, such as short treatment times, with the benefits of noncoplanar intensity modulated radiotherapy (IMRT) plans, such as improved organ sparing. Recently, vendors introduced treatment machines that allow for simultaneous couch and gantry motion during beam delivery to make noncoplanar VMAT treatments possible. Our aim is to provide a reliable optimization method for noncoplanar isocentric arc therapy plan optimization. The proposed solution is modular in the sense that it can incorporate different existing beam angle selection and coplanar arc therapy optimization methods. Treatment planning is performed in three steps. First, a number of promising noncoplanar beam directions are selected using an iterative beam selection heuristic; these beams serve as anchor points of the arc therapy trajectory. In the second step, continuous gantry/couch angle trajectories are optimized using a simple combinatorial optimization model to define a beam trajectory that efficiently visits each of the anchor points. Treatment time is controlled by limiting the time the beam needs to trace the prescribed trajectory. In the third and final step, an optimal arc therapy plan is found along the prescribed beam trajectory. In principle any existing arc therapy optimization method could be incorporated into this step; for this work we use a sliding window VMAT algorithm. The approach is demonstrated using two particularly challenging cases. The first one is a lung SBRT patient whose planning goals could not be satisfied with fewer than nine noncoplanar IMRT fields when the patient was treated in the clinic. The second one is a brain tumor patient, where the target volume overlaps with the optic nerves and the chiasm and it is directly adjacent to the brainstem. Both cases illustrate that the large number of angles utilized by isocentric noncoplanar VMAT plans

  19. Optimizing anti-TNF therapy in inflammatory bowel disease

    NARCIS (Netherlands)

    Brandse, J.F.

    2015-01-01

    Anti-TNF, zoals infliximab en adalimumab, zijn effectief voor de behandeling van chronische ontstekingsziekten van de darm (IBD): de ziekte van Crohn en colitis ulcerosa. Deze middelen zijn echter kostbaar en niet alle patiënten hebben baat bij de therapie. Dit proefschrift beschrijft hoe de mate va

  20. Optimizing Antiretroviral Therapy in Children and Adolescents with HIV Infection

    NARCIS (Netherlands)

    N.Y. Rakhmanina (Natella)

    2010-01-01

    textabstractHIV infection became a newly recognized disease in the mid 1980s. High morbidity and mortality associated with it prompted the urgent development of new therapeutic agents and combination therapies. Throughout the next 20 years the hopes for cure have risen and fallen, and the vaccine re

  1. Optimizing Cognitive-Behavioral Therapy for Childhood Psychiatric Disorders

    Science.gov (United States)

    Piacentini, John

    2008-01-01

    Reports that expand the understanding of the treatment of childhood obsessive-compulsive disorder by using exposure-based cognitive-behavioral therapy in the age group of 5 to 8-year-olds are presented. A model for collecting the common core elements of evidence-based psychosocial treatments for childhood disorders is also presented.

  2. Optimizing Antiretroviral Therapy in Children and Adolescents with HIV Infection

    NARCIS (Netherlands)

    N.Y. Rakhmanina (Natella)

    2010-01-01

    textabstractHIV infection became a newly recognized disease in the mid 1980s. High morbidity and mortality associated with it prompted the urgent development of new therapeutic agents and combination therapies. Throughout the next 20 years the hopes for cure have risen and fallen, and the vaccine

  3. Optimizing anti-TNF therapy in inflammatory bowel disease

    NARCIS (Netherlands)

    Brandse, J.F.

    2015-01-01

    Anti-TNF, zoals infliximab en adalimumab, zijn effectief voor de behandeling van chronische ontstekingsziekten van de darm (IBD): de ziekte van Crohn en colitis ulcerosa. Deze middelen zijn echter kostbaar en niet alle patiënten hebben baat bij de therapie. Dit proefschrift beschrijft hoe de mate va

  4. Optimization of mirror therapy to excite ipsilateral primary motor cortex.

    Science.gov (United States)

    Hadoush, Hikmat; Mano, Hirofumi; Sunagawa, Toru; Nakanishi, Kazuyoshi; Ochi, Mitsu

    2013-01-01

    Mirror illusion therapy (mirror therapy) is based on the experimental substrate of a visual illusion of active hand movement to excite ipsilateral primary motor cortex (iM1). We tested whether iM1 excitability could be modulated by enabling or disabling vision of the active hand during mirror therapy. Motor cortical activations of healthy right-handed participants were identified by magnetoencephalography. Participants performed voluntary index finger extension of their dominant and non-dominant hands, separately, while viewing mirror reflection images of their active hand superimposed upon their hidden inactive hand. This was performed either with vision of the active hand (uncovered viewing condition) or without vision of the active hand (covered viewing condition). In the covered viewing condition, the iM1could be excited in all participants (n = 10) and this excitation did not differ whether the active hand was the dominant or non-dominant hand. However, in the uncovered viewing condition, dominant and non-dominant hands were able to excite iM1 only in some participants (n = 4 and n = 7, respectively). Moreover, the participants' responses to the illusion validation questionnaire revealed that the covered viewing condition could cause clearer visual illusion for the active hand than the uncovered viewing condition. Disabling vision of the active hand during mirror therapy was more effective to excite iM1 responses by creating more immersive visual illusion of the active hand.

  5. Optimized cardiac resynchronization therapy in patients with congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    NIU Hong-xia; HUA Wei; ZHANG Shu; SUN Xin; CHEN Ke-ping; WANG Fang-zheng; CHEN Xin

    2007-01-01

    @@ Heart failure was a major and increasing public health problem, with an almost "epidemic increase in the number of patients.1 Despite recent advances in pharmacotherapy, the prognosis remains poor. Cardiac resynchronization therapy (CRT), by pacing right and left ventricles, has been proved to improve symptoms and reduce mortality for heart failure patients with cardiac dyssynchrony.

  6. Antiemetics With Concomitant Sedative Use in Civil Aviation Pilot Fatalities: From 2000 to 2006

    Science.gov (United States)

    2007-10-01

    detected in liver. Case 10 A 37-year-old male pilot impacted terrain while at- tempting to land and died during the accident. Both seda - tives and...to have taken two different seda - tives and one antiemetic prior to his fl ight. Olanzapine was detected in the pilot’s blood and urine. Fluoxetine...140 mg/dL in blood, 170 mg/dL in urine, 107 mg/hg in skeletal muscle, and 134 mg/hg in brain. This seda - tive compound was taken while the victim was

  7. Brachytherapy optimal planning with application to intravascular radiation therapy

    DEFF Research Database (Denmark)

    Sadegh, Payman; Mourtada, Firas A.; Taylor, Russell H.;

    1999-01-01

    . Dose rate calculations are based on the sosimetry formulation of the American Association of Physicists in Medicine, Task Group 43. We apply the technique to optimal planning for intravascular brachytherapy of intimal hyperplasia using ultrasound data and 192Ir seeds. The planning includes...

  8. OPTIMIZATION OF ACUTE AND RECURRENT STREPTOCOCCOSIS THERAPY AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    E.A. Krasnova

    2006-01-01

    Full Text Available The researchers examined 56 children aged between 3 and 12 years old, suffering from acute tonsillitis caused by group A β-hemolytic streptococcus. After the antibacterial therapy of 10 days long all the children were divided into 2 groups. The first group comprised 30 children, who received the medication of the bacterial lysate (imudon, solvay pharma, Germany. The length of the medication intake was 14 days. The children of the second group (26 children underwent one-time injection of bycillin. The research findings showed that application of the bacterial lysate drastically increased the efficiency of therapy and improved the contents of pharynx microflora within the decubation of acute tonsillitis caused by group a hemolytic streptococcus.Key words: acute tonsillitis, group A β-hemolytic streptococcus, treatment.

  9. Optimization of therapy in outpatients with chronic lumbago

    Directory of Open Access Journals (Sweden)

    A. A. Averchenkova

    2014-01-01

    Full Text Available Lumbago is one of the most common lower back pain syndromes in medical practice, which is benign in the vast majority of cases and caused by spinal osteochondrosis, injury, and muscle strain or spasm. The primary task of examining a patient with lumbago is to be certain that the pain is musculoskeletal and unassociated with a potentially dangerous spinal disease requiring emergency special therapy.Objective: to analyze the efficiency of treatment in outpatients with chronic lumbago.Patients and methods. One hundred and four patients followed up by us in the Smolensk Kinesitherapy Center were examined. A study group comprised 84 patients (34 men and 50 women; mean age 44.2±1.29 years with dorsalgia (pain duration ≥3 months; mean 7.6±6.83 years;a control group included 20 persons (10 men and  10 women; mean age 31.9±1.88 years without pain in the back. Neurological examination and magnetic resonance imaging revealed nonspecific lower back pain in 67 (79.8% patients and radiculopathy in 17 (20.2%. Combination treatment including pharmacotherapy and kinesitherapy was proposed in all the patients.Results. 2.5–3 months after the initiation of therapy, pain regressed completely in 29 (34.5% patients and was considerably alleviated in 27 (32.1%. Quality of life after therapy improved in the majority of patients. The patients in whom therapy was ineffective (n = 26; 31% did not attend kinesitherapy classes and were cautious towards physical rehabilitation.Discussion. The findings indicated the high efficiency of a comprehensive approach to treating chronic lumbago, which is largely associated with rational psychotherapy, early patient activation, and adaptive behavior training.

  10. Real-Time Dosimetry and Optimization of Prostate Photodynamic Therapy

    Science.gov (United States)

    2006-09-01

    bound on dose is provided for every voxel. The goal is to find the vector x of source strengths that satisfies the in- equality constraints of...current estimate x of the unknown optimal result xopt. Rays are directed from x perpendicularly toward each violated hyperplane, and a resultant vector ...Analisi Matematica , Dipartimento di Matem- atica dell ’Universita’ di Bologna, Volune speciale: Ciclo di conferenze in ricordo di Gianfranco Cimmino, Marzo

  11. Eliminating Postoperative Nausea and Vomiting in Outpatient Surgery with Multimodal Strategies including Low Doses of Nonsedating, Off-Patent Antiemetics: Is “Zero Tolerance“ Achievable?

    Directory of Open Access Journals (Sweden)

    Susan J. Skledar

    2007-01-01

    Full Text Available For ondansetron, dexamethasone, and droperidol (when used for prophylaxis, each is estimated to reduce risk of postoperative nausea and/or vomiting (PONV by approximately 25%. Current consensus guidelines denote that patients with 0–1 risk factors still have a 10–20% risk of encountering PONV, but do not yet advocate routine prophylaxis for all patients with 10–20% risk. In ambulatory surgery, however, multimodal prophylaxis has gained favor, and our previously published experience with routine prophylaxis has yielded PONV rates below 10%. We now propose a “zero-tolerance” antiemetic algorithm for outpatients that involves routine prophylaxis by first avoiding volatile agents and opioids to the extent possible, using locoregional anesthesia, multimodal analgesia, and low doses of three nonsedating off-patent antiemetics. Routine oral administration (immediately on arrival to the ambulatory surgery suite of perphenazine 8 mg (antidopaminergic or cyclizine 50 mg (antihistamine, is followed by dexamethasone 4 mg i.v. after anesthesia induction (dexamethasone is avoided in diabetic patients. At the end of surgery, ondansetron (4 mg i.v., now off-patent is added. Rescue therapy consists of avoiding unnecessary repeat doses of drugs acting by the same mechanism: haloperidol 2 mg i.v. (antidopaminergic is prescribed for patients pretreated with cyclizine or promethazine 6.25 mg i.v. (antihistamine for patients having been pretreated with perphenazine. If available, a consultation for therapeutic acupuncture procedure is ordered. Our approach toward “zero tolerance” of PONV emphasizes liberal identification of and prophylaxis against common risks.

  12. Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics

    Directory of Open Access Journals (Sweden)

    May MB

    2016-05-01

    Full Text Available Megan Brafford May,1 Ashley E Glode2 1Department of Pharmacy, Baptist Health Lexington, Lexington, KY, USA; 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Abstract: Chemotherapy-induced nausea and vomiting (CINV is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC. The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine. Keywords: dronabinol, cannabinoids, antiemetic, chemotherapy-induced nausea and vomiting

  13. Antiemetic efficacy of capsicum plaster on acupuncture points in patients undergoing thyroid operation.

    Science.gov (United States)

    Koo, Min Seok; Kim, Kyo Sang; Lee, Hee-Jong; Jeong, Ji Seon; Lee, Jung-Won

    2013-12-01

    Postoperative nausea and vomiting (PONV) occurs in up to 63-84% of patients after thyroid surgery. This study aims to assess the effects of using a capsicum plaster to reduce PONV after thyroid surgery at either the Chinese acupuncture point (acupoint) Pericardium 6 (P6) or Korean hand acupuncture point K-D2. One-hundred eighty-four patients who underwent thyroid surgery were randomized in four groups (n = 46 each): control group = inactive tape at P6 acupoints and on both shoulders as a nonacupoint; P6 group = capsicum plaster at P6 points and inactive tape on both shoulders; K-D2 group = capsicum plaster at K-D2 acupoints and inactive tape on both shoulders; Sham group = capsicum plaster on both shoulders and inactive tape at P6 acupoints. The capsicum plaster was applied before the induction of anesthesia and removed at 8 hr after surgery. The incidence and severity of nausea and vomiting and the need for rescue antiemetics were decreased in the patients in the P6 and K-D2 groups compared to the patients in the control and sham groups (P plaster at the P6 and K-D2 acupoint was a promising antiemetic method for the patients undergoing thyroid surgery.

  14. The role of optimism in the process of schema-focused cognitive therapy of personality problems.

    Science.gov (United States)

    Hoffart, Asle; Sexton, Harold

    2002-06-01

    The aim of this study was to examine the determinants and effects of optimism in the process of schema-focused cognitive therapy of personality problems. The sample consisted of 35 patients with panic disorder and/or agoraphobia and DSM-IV Cluster C personality traits who participated in an 11-week residential program with one symptom-focused and one personality-focused phase. This study examines the role played by optimism during the individual sessions of the second phase, using a time series approach. Decreased patient's belief in his/her primary Early Maladaptive Schema and increased patient-experienced empathy from the therapist in a session predicted increased patient-rated optimism before the subsequent session. Increased patient-rated optimism in turn predicted decreased schema belief and distress and increased insight, empathy, and therapist-rated optimism. The slope of optimism across sessions was related to change in most of the overall outcome measures. There appears to be a positive feedback in the process of schema-focused cognitive therapy between decreased schema belief and increased optimism. In addition, optimism appears to mediate the effects of schema belief and therapist empathy on overall improvement, and to serve as an antecedent to decreased distress and to increased empathy, insight, and therapist's optimism.

  15. Optimal lipid modification: the rationale for combination therapy

    Directory of Open Access Journals (Sweden)

    James M Backes

    2005-12-01

    Full Text Available James M Backes1, Cheryl A Gibson2, Patricia A Howard31Department of Pharmacy Practice, Lipid, Atherosclerosis, Metabolic and LDL Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 3Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, KS, USABackground: An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence.Objective: To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations. Method: Literature was obtained from MEDLINE (1966 – June 2005 and references from selected articles.Results: A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising.Conclusion: Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.Keywords: combination therapy, coronary heart disease, hypercholesterolemia, lipid-lowering, low-density lipoprotein, statins

  16. SU-E-T-295: Simultaneous Beam Sampling and Aperture Shape Optimization for Station Parameter Optimized Radiation Therapy (SPORT)

    Energy Technology Data Exchange (ETDEWEB)

    Zarepisheh, M; Li, R; Xing, L [Stanford UniversitySchool of Medicine, Stanford, CA (United States); Ye, Y [Stanford Univ, Management Science and Engineering, Stanford, Ca (United States); Boyd, S [Stanford University, Electrical Engineering, Stanford, CA (United States)

    2014-06-01

    Purpose: Station Parameter Optimized Radiation Therapy (SPORT) was recently proposed to fully utilize the technical capability of emerging digital LINACs, in which the station parameters of a delivery system, (such as aperture shape and weight, couch position/angle, gantry/collimator angle) are optimized altogether. SPORT promises to deliver unprecedented radiation dose distributions efficiently, yet there does not exist any optimization algorithm to implement it. The purpose of this work is to propose an optimization algorithm to simultaneously optimize the beam sampling and aperture shapes. Methods: We build a mathematical model whose variables are beam angles (including non-coplanar and/or even nonisocentric beams) and aperture shapes. To solve the resulting large scale optimization problem, we devise an exact, convergent and fast optimization algorithm by integrating three advanced optimization techniques named column generation, gradient method, and pattern search. Column generation is used to find a good set of aperture shapes as an initial solution by adding apertures sequentially. Then we apply the gradient method to iteratively improve the current solution by reshaping the aperture shapes and updating the beam angles toward the gradient. Algorithm continues by pattern search method to explore the part of the search space that cannot be reached by the gradient method. Results: The proposed technique is applied to a series of patient cases and significantly improves the plan quality. In a head-and-neck case, for example, the left parotid gland mean-dose, brainstem max-dose, spinal cord max-dose, and mandible mean-dose are reduced by 10%, 7%, 24% and 12% respectively, compared to the conventional VMAT plan while maintaining the same PTV coverage. Conclusion: Combined use of column generation, gradient search and pattern search algorithms provide an effective way to optimize simultaneously the large collection of station parameters and significantly improves

  17. Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

    Directory of Open Access Journals (Sweden)

    Sarah J. Tennant

    2015-12-01

    Full Text Available Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.

  18. OPTIMIZATION OF PALLIATIVE EXTERNAL BEAM RADIATION THERAPY FOR BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    Yu. V. Gumenetskaya

    2014-08-01

    Full Text Available Purpose: To improve the efficacy of palliative radiation therapy for patients with bladder cancer (BC.Materials and Methods: In the years 1990−2010, 90 patients with BC were treated with palliative external beam radiation therapy (EBRT using three regimens: conventional fractionation in group 1 (n = 37, hypofractionation in group 2 (n = 22 and accelerated dynamic fractionation in group 3 (n = 31.Results: The immediate efficacy of EBRT was evaluated taking into account rapid relief of local symptoms of disease. In group 1, a clinically significant response (hematuria relief was achieved in 63,0 % cases, in group 2 — in 62,5 %, in group 3 — in 91,7 % cases. The 10-year follow-up showed that in group 1, the median survival was 21,8 ± 3,3 months; in groups 2 and 3, the median survival was 27,0 ± 7,8 and 32,6 ± 9,8 months, respectively. In group 2, an increase in the rate of acute radiation reactions was noted, whereas in group 3, palliative EBRT did not produce higher rates and severity of acute radiation reactions and complications.Conclusion: Accelerated dynamic fractionation was found to shorten treatment times and to improve outcomes and quality of life for incurable patients with BC.

  19. OPTIMIZATION OF PALLIATIVE EXTERNAL BEAM RADIATION THERAPY FOR BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    Yu. V. Gumenetskaya

    2012-01-01

    Full Text Available Purpose: To improve the efficacy of palliative radiation therapy for patients with bladder cancer (BC.Materials and Methods: In the years 1990−2010, 90 patients with BC were treated with palliative external beam radiation therapy (EBRT using three regimens: conventional fractionation in group 1 (n = 37, hypofractionation in group 2 (n = 22 and accelerated dynamic fractionation in group 3 (n = 31.Results: The immediate efficacy of EBRT was evaluated taking into account rapid relief of local symptoms of disease. In group 1, a clinically significant response (hematuria relief was achieved in 63,0 % cases, in group 2 — in 62,5 %, in group 3 — in 91,7 % cases. The 10-year follow-up showed that in group 1, the median survival was 21,8 ± 3,3 months; in groups 2 and 3, the median survival was 27,0 ± 7,8 and 32,6 ± 9,8 months, respectively. In group 2, an increase in the rate of acute radiation reactions was noted, whereas in group 3, palliative EBRT did not produce higher rates and severity of acute radiation reactions and complications.Conclusion: Accelerated dynamic fractionation was found to shorten treatment times and to improve outcomes and quality of life for incurable patients with BC.

  20. Optimization of combined radiation therapy of the cervix cancer

    Directory of Open Access Journals (Sweden)

    Vladimir Philippenko

    2010-04-01

    Full Text Available Use of a new combination of known medical products - inhibitorsenzyme of cyclooxigenase-2 (diclofenac, ketoprofen with smalldoses cytostatics (methotrexate, 5-fluorouracil as“nonconventional” radiosensibilizators for optimization of combinedradial treatment of cervical cancer is offered. One hundred andtwenty patients with cervix cancer were involved into research(average age - 52.5±3.3, mainly II stage of process (50.8±4.6%,morphologically - nonkeratinizing squamous cell carcinoma(65.0±4.4%. Frequency of full regress of a tumor in the basicgroups has reached in 77.5±6.6% (1-basic group and 82.5±6.0% (2-basic group in comparison with a control group 70.0±7.2%(р<0.05. By results of the cytological research in cells thepathomorphosis of IV degree was recorded in 1-basic group - 60.0%(superficial smears and 57.5% (a puncture biopsy, in 2-basic group- 85.0% (superficial smears and 82.5% (a puncture biopsy incomparison with the control - 55.0% (superficial smears and apuncture biopsy, р<0.05.

  1. Major depression in 1998: are we providing optimal therapy?

    Science.gov (United States)

    Angst, J

    1999-01-01

    Depression is a common illness associated with long duration of episodes, high rates of chronicity, relapse and recurrence, psychosocial and physical impairment, and high suicide rate. A lifetime prevalence of approximately 17% has been widely reported, and the likelihood of recurrence is more than 50%. A conceptual shift has occurred in our understanding of depression. It is now seen as a chronic medical disorder that produces as much functional limitation and morbidity as chronic diseases such as hypertension and diabetes. Predictors of chronicity include long duration of index episode, relationship difficulties, low family income, admitting research center, and inpatient hospitalization. Risk factors for recurrence include lack of self-confidence, neuroticism, previous hospital admission, loss events, and age. The aim of treatment is to induce a stable, fully asymptomatic state with full restoration of psychosocial function and to establish a long-term state of wellness. Despite effective pharmacotherapy, depressed patients are often underdiagnosed and undertreated by both psychiatrists and primary care physicians. The psychosocial and physical impairment, comorbidity, and high suicide rate associated with chronic, recurrent depression require optimal treatment strategies. The future of antidepressant treatment should focus on remission or getting the patient well and drugs that will induce and maintain long-term recovery.

  2. Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

    Science.gov (United States)

    Sengbusch, Evan R.

    Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing

  3. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies

    Directory of Open Access Journals (Sweden)

    Chiorean EG

    2015-07-01

    this deadly disease. Keywords: pancreatic cancer, immunotherapies, signaling pathway inhibitors, targeted therapies

  4. Optimal control of combined therapy in a single strain HIV-1 model

    Directory of Open Access Journals (Sweden)

    Winston Garira

    2005-05-01

    Full Text Available Highly active antiretroviral therapy (HAART is administered to symptomatic human immunodeficiency virus (HIV infected individuals to improve their health. Various administration schemes are used to improve patients' lives and at the same time suppressing development of drug resistance, reduce evolution of new viral strains, minimize serious side effects, improve patient adherence and also reduce the costs of drugs. We deduce an optimal drug administration scheme useful in improving patients' health especially in poor resourced settings. In this paper we use the Pontryagin's Maximum Principle to derive optimal drug dosages based on a mathematical dynamical model. We use methods of optimal control to determine optimal controls analytically, and then use the Runge-Kutta scheme of order four to numerically simulate different therapy effects. We simulate the different effects of a drug regimen composed of a protease inhibitor and a nucleoside reverse transcriptase inhibitor. Our results indicate that for highly toxic drugs, small dosage sizes and allowing drug holidays make a profound impact in both improving the quality of life and reducing economic costs of therapy. The results show that for drugs with less toxicity, continuous therapy is beneficial.

  5. Local hypothermia and optimal temperature for stroke therapy in rats

    Institute of Scientific and Technical Information of China (English)

    WU Hao; JIANG Li-dan; Karsten H.Wrede; JI Xun-ming; ZHAO Xi-qing; TIAN Xin; GAO Yu-fei; LING Feng

    2009-01-01

    Background Local hypothermia induced by intravascular infusion of cold saline solution effectively reduces brain damage in stroke. We further determined the optimal temperature of local hypothermia in our study. Methods Seventy-eight adult male Sprague Dawley rats (260-300 g) were randomly divided into 3 groups: group A, ischemia/reperfusion without cold saline infusion (n=-26) (control group); group B, infusion with 20℃ saline before reperfusion (n=26); group C: infusion with 10~C saline before reperfusion (n=26). In each group, we chose 15 rats for monitoring physical indexes and the temperature of the brain (cortex and striatum) and body (anus), measurement of brain infarction volume, assessment of neurological deficits and the survival rate of reperfusion at 48 hours. Another 8 rats from each group was chosen for examining brain edema, another 3 from each group for histological observation by electron microscopy (EM) and light microscopy (LM) at 48 hours after reperfusion. Results There was no significant difference among the 3 groups for physical indexes during the examination (F(2,45)=0.577, P=0.568; F(2, 45)= 0.42, P=0.78 for blood pressure and blood gas analysis, respectively). The brain temperature was significantly reduced in the group C compared to the other groups (F(2, 45)=37.074, P=0.000; F(2, 45)=32.983, P=0.000, for cortex and striatum temperature respectively), while the difference in rectal temperature between group A and B or C after reperfusion was not significant (F(2, 45)= 0.17115, P=0.637). And the brain infarct volume was significantly reduced in group C (from 40%±10% in group A, 26%±8% in group B, to 12%±6% in group C, F<(2,45)=43.465, P=0.000) with the neurological deficits improving in group C (X2=27.626, P=0.000). The survival rate at 48 hours after 10℃ and 20℃ saline reperfusion was increased by 132.5% and 150%, respectively, as compared to the control group (X2=10.489, P=0.005). The extent of the brain edema showed no

  6. Optimal therapy for adults with Langerhans cell histiocytosis bone lesions.

    Directory of Open Access Journals (Sweden)

    Maria A Cantu

    Full Text Available BACKGROUND: There is little data on treatment of Langerhans cell histiocytosis (LCH in adults. Available data is on small numbers of patients with short follow-up times and no comparison of results from different treatment regimens. We analyzed the responses of adult LCH patients with bone lesions to three primary chemotherapy treatments to define the optimal one. METHODS AND FINDINGS: Fifty-eight adult patients with bone lesions, either as a solitary site or as a component of multisystem disease, were analyzed for disease location and response to surgery, curettage, steroids, radiation, vinblastine/prednisone, 2-Chlorodeoxyadenosine (2-CdA, or cytosine arabinoside (ARA-C. The mean age of patients was 32 years, with equal gender distribution. Twenty-nine patients had 1 lesion; 16, 2 lesions; 5, 3 lesions; and 8 had 4 or more. Most bone lesions were in the skull, spine, or jaw. Chemotherapy, surgery, curettage, or radiation, but not steroids alone, achieved improvement or resolution of lesions in a majority of patients. Comparison of the three chemotherapy regimens revealed 84% of patients treated with vinblastine/prednisone either did not respond or relapsed within a year, whereas 59% of patients treated with 2-CdA and 21% treated with ARA-C failed. Toxicity was worse with the vinblastine/prednisone group as 75% had grade 3-4 neuropathy. Grade 3-4 cytopenias occurred in 37% of the 2-CdA -treated patients and 20% of the ARA-C-treated patients. The major limitation of this study is it is retrospective and not a clinical trial. CONCLUSIONS: ARA-C is an effective and minimally toxic treatment for LCH bone lesions in adults. In contrast, vinblastine/prednisone results in poor overall responses and excessive toxicity.

  7. Open- and closed-loop multiobjective optimal strategies for HIV therapy using NSGA-II.

    Science.gov (United States)

    Heris, S Mostapha Kalami; Khaloozadeh, Hamid

    2011-06-01

    In this paper, multiobjective open- and closed-loop optimal treatment strategies for HIV/AIDS are presented. It is assumed that highly active antiretroviral therapy is available for treatment of HIV infection. Amount of drug usage and the quality of treatment are defined as two objectives of a biobjective optimization problem, and Nondominated Sorting Genetic Algorithm II is used to solve this problem. Open- and closed-loop control strategies are used to produce optimal control inputs, and the Pareto frontiers obtained from these two strategies are compared. Pareto frontier, resulted from the optimization process, suggests a set of treatment strategies, which all are optimal from a perspective, and can be used in different medical and economic conditions. Robustness of closed-loop system in the presence of measurement noises is analyzed, assuming various levels of noise.

  8. Dynamics of hepatitis C under optimal therapy and sampling based analysis

    Science.gov (United States)

    Pachpute, Gaurav; Chakrabarty, Siddhartha P.

    2013-08-01

    We examine two models for hepatitis C viral (HCV) dynamics, one for monotherapy with interferon (IFN) and the other for combination therapy with IFN and ribavirin. Optimal therapy for both the models is determined using the steepest gradient method, by defining an objective functional which minimizes infected hepatocyte levels, virion population and side-effects of the drug(s). The optimal therapies for both the models show an initial period of high efficacy, followed by a gradual decline. The period of high efficacy coincides with a significant decrease in the viral load, whereas the efficacy drops after hepatocyte levels are restored. We use the Latin hypercube sampling technique to randomly generate a large number of patient scenarios and study the dynamics of each set under the optimal therapy already determined. Results show an increase in the percentage of responders (indicated by drop in viral load below detection levels) in case of combination therapy (72%) as compared to monotherapy (57%). Statistical tests performed to study correlations between sample parameters and time required for the viral load to fall below detection level, show a strong monotonic correlation with the death rate of infected hepatocytes, identifying it to be an important factor in deciding individual drug regimens.

  9. How to optimize current therapy of HCV genotype 1 infection with boceprevir.

    Science.gov (United States)

    Bourlière, Marc; Adhoute, Xavier; Wendt, Astrid; Ansaldi, Christelle; Oules, Valérie; Castellani, Paul

    2014-02-01

    Treatment with first generation protease inhibitors (PIs) is a milestone in the history of HCV therapy. Triple therapy with boceprevir (BOC) improves sustained virological response (SVR) by 30% in treatment naïve genotype 1 patients and by 50-60% in relapsers, 40-45% in partial responders and 25% in null responders compared with the Pegylated Interferon (PEG-IFN) and ribavirin regimen. To optimize BOC treatment, screening and access to treatment must be improved in genotype 1 patients. To select the ideal candidate for immediate treatment with triple therapy, an individual risk/benefit ratio must be assessed. Recent data have shown that patients with compensated cirrhosis and more advanced disease may also benefit from this regimen. Moreover, in HCV patients with extrahepatic manifestations, patients with HCV recurrence after liver transplantation and HIV-HCV co-infected patients, immediate treatment with triple therapy should be discussed. There is growing evidence that triple therapy with BOC is cost-effective in genotype 1 patients. Finally, the treatment design of BOC must be optimized in relation to baseline characteristics, so that optimal stopping rules can be followed, Drug-drug interactions (DDIs) can be prevented and AEs can be accurately prevented and managed. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Paul J. Hesketh

    2015-01-01

    Full Text Available Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA, netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.

  11. Effect of refrigeration of the antiemetic Cerenia (maropitant) on pain on injection.

    Science.gov (United States)

    Narishetty, Sunil Thomas; Galvan, Betsy; Coscarelli, Eileen; Aleo, Michelle; Fleck, Tim; Humphrey, William; McCall, Robert B

    2009-01-01

    Injection pain has been associated with veterinary use of the antiemetic maropitant (Cerenia, Pfizer Animal Health). Cerenia is formulated using sulphobutylether-beta-cyclodextrin to bind maropitant and mitigate injection pain. The objective of this study was to determine whether the temperature of Cerenia alters binding between maropitant and sulphobutylether-beta-cyclodextrin and affects injection pain. Binding decreased as temperature increased, and Cerenia-elicited injection pain increased at warmer drug temperatures. These data suggest that the amount of free unbound maropitant increases with temperature and that injection pain increases with temperature in a similar fashion. Clinically, these studies suggest that injection of refrigerated Cerenia may significantly reduce or eliminate pain associated with SC injection of Cerenia.

  12. Cardiac resynchronization therapy: Dire need for targeted left ventricular lead placement and optimal device programming

    Institute of Scientific and Technical Information of China (English)

    Sokratis; Pastromas; Antonis; S; Manolis

    2014-01-01

    Cardiac resynchronization therapy(CRT) effected via biventricular pacing has been established as prime therapy for heart failure patients of New York Heart Association functional class Ⅱ, Ⅲ and ambulatory Ⅳ, reduced left ventricular(LV) function, and a widened QRS complex. CRT has been shown to improve symptoms, LV function, hospitalization rates, and survival. In order to maximize the benefit from CRT and reduce the number of non-responders, consideration should be given to target the optimal site for LV lead implantation away from myocardial scar and close to the latest LV site activation; and also to appropriately program the device paying particular attention to optimal atrioventricular and interventricular intervals. We herein review current data related to both optimal LV lead placement and device programming and their effects on CRT clinical outcomes.

  13. Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance.

    Science.gov (United States)

    Molina-Infante, Javier; Gisbert, Javier P

    2014-08-14

    The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high-dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates.

  14. Comparing the Antiemetic Effects of Ondansetron and Metoclopramide in Patients with Minor Head Trauma

    Directory of Open Access Journals (Sweden)

    Majid Zamani

    2014-09-01

    Full Text Available Introduction: Nausea and vomiting are the most common complications after minor head trauma that increases the risk of intracranial pressure rising. Therefore, the present study was aimed to compare the antiemetic effects of metoclopramide and ondansetron in the treatment of post-traumatic nausea and vomiting. Methods: The study was a controlled, randomized, double blind clinical trial, which was conducted in the first 6 months of 2014 in emergency department Al-Zahra and Kashani Hospitals in Isfahan, Iran. The patients with minor head trauma associated with nausea and vomiting were randomly divided into 2 groups: treatment with metoclopramide (10mg/2ml, slow injection and treatment with ondansetron (4mg/2ml, slow injection. The comparison between the 2 groups was done regarding antiemetic efficacy and side effects using SPSS 21 statistical software. Results: 120 patients with minor head trauma were distributed and studied into two groups of 60 patients (mean age 35.6±14.1 years; 50.0% male. Administration of both ondansetron and metoclopramide significantly reduced the severity of nausea (P<0.001. Changes in the severity of nausea in both groups before and after the treatment revealed that nausea had been decreased significantly in both groups (P < 0.001. The incidence of fatigue (p=0.44, headache (p=0.58 and dystonia (p=0.06 had no significant difference in the two groups but the incidence of drowsiness and anxiety in the metoclopramide group was significantly higher (P < 0.001. Conclusion: The present study indicated that the treatment effectiveness of ondansetron and metoclopramide are similar. However, incidence of drowsiness and anxiety in the metoclopramide was considerably higher. Since these complications can have adverse effects on the treatment of patients with brain injury, it is suggested that it may be better to use ondansetron in these patients.

  15. Resource Utilization for Chemotherapy-Induced Nausea and Vomiting Events in Patients with Solid Tumors Treated with Antiemetic Regimens

    Science.gov (United States)

    Schwartzberg, Lee; Harrow, Brooke; Lal, Lincy S.; Radtchenko, Janna; Lyman, Gary H.

    2015-01-01

    Background Chemotherapy-induced nausea and vomiting (CINV) can lead to increased emergency department visits and hospitalizations, which may contribute to increased cost of care. Antiemetic agents, such as neurokinin-1 (NK1) receptor antagonists and 5-hydroxytryptamine (5-HT3) receptor antagonists, are prescribed for patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). The current guidelines recommend a 3-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone with HEC regimens and certain MEC regimens. Objective To compare the incidence of CINV and CINV-related resource utilization among patients who receive guideline-adherent HEC and MEC regimens and patients who receive non–guideline-adherent regimens. Methods In this retrospective, claims-based study, Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) Research Edition database was used to identify 8089 patients with solid tumors receiving therapy with anthracycline plus cyclophosphamide (AC), cisplatin, or carboplatin from June 2013 to December 2013. The patients were stratified according to the use of an NK1 receptor antagonist regimen. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify CINV events associated with hospital, emergency department, and outpatient office visits among patients in the NK1 receptor antagonist group and the non-NK1 receptor antagonist group. Results A total of 1059 patients were included in the analysis, of whom 51% (N = 536) used an NK1 receptor antagonist–based regimen and 49% (N = 523) used non-NK1 receptor antagonist therapy. A higher percentage of patients receiving AC (73%) than cisplatin (56%) or carboplatin (23%) received an NK1 receptor antagonist. The incidence rates of total CINV events and CINV-related emergency department visits were lower in the group receiving an NK1 receptor

  16. Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy

    Science.gov (United States)

    Bedford, J. L.; Webb, S.

    2007-01-01

    Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

  17. Optimizing proton pump inhibitor therapy for treatment of nonvariceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Worden, Jarett C; Hanna, Kirollos S

    2017-02-01

    The pharmacology, rationale, and dosing optimization strategies of proton pump inhibitors (PPIs) for the treatment of upper gastrointestinal bleeding (UGIB) are discussed. In combination with endoscopic therapy, PPIs are the treatment of choice for UGIB. While the advent of PPIs has improved patient outcomes, controversy still exists over optimal PPI therapy for UGIB. Pharmacologic treatment in combination with endoscopic therapy has demonstrated improved outcomes in patients with nonvariceal UGIB. PPIs are the treatment of choice for suppressing gastric acid and preventing rebleeding, though a mortality benefit from these agents has not been strongly established. Although the current guidelines recommend an i.v. bolus injection followed by continuous infusion of a high-dose PPI, intermittent PPI therapy has been found to be safe and effective while significantly reducing cost, even in patients with high-risk stigmata after endoscopy. Oral PPIs may be effective in patients who can tolerate oral therapy but require further evaluation in patients with higher-risk stigmata. Regardless of stigmata, after 72 hours of i.v. therapy, patients with UGIB may be safely transitioned to oral PPIs if hemodynamically stable and able to tolerate oral medication. As the risk of rebleeding significantly decreases after the first three days, continuation of high-dose therapy beyond 72 hours is not necessary in hemodynamically stable patients. Current guidelines recommend that PPIs be given as an i.v. bolus injection followed by a continuous infusion, but intermittent i.v. dosing and oral PPI therapy have been found to be effective in treating patients with UGIB and associated with reductions in cost. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  18. Optimization of anti-TNF therapy in patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Strik, A S; Bots, S J A; D'Haens, G; Löwenberg, M

    2016-01-01

    After the introduction of anti-tumor necrosis factor (anti-TNF) agents, the clinical outcome of patients with Inflammatory Bowel Disease (IBD) has improved significantly. However, use of anti-TNF therapy is complicated by loss of response. In order to maintain remission, adequate serum levels are required. Hence, therapeutic drug monitoring (TDM) is important in order to optimize serum drug levels, especially in patients with loss of response to these agents. Optimization of anti-TNF therapy by applying TDM enables clinicians to regain response to TNF blockers in a significant proportion of patients. It is important to use anti-TNF agents in their most optimal way, since these therapeutic agents are expensive and the medical options after failing anti-TNF therapy are limited. Here, we will discuss how to optimize treatment with anti-TNF agents in IBD patients in order to improve treatment efficacy, prevent anti-drug antibody formation, reduce side effects, discontinue unnecessary treatment and manage costs.

  19. Nonlinear system identification for prostate cancer and optimality of intermittent androgen suppression therapy.

    Science.gov (United States)

    Suzuki, Taiji; Aihara, Kazuyuki

    2013-09-01

    These days prostate cancer is one of the most common types of malignant neoplasm in men. Androgen ablation therapy (hormone therapy) has been shown to be effective for advanced prostate cancer. However, continuous hormone therapy often causes recurrence. This results from the progression of androgen-dependent cancer cells to androgen-independent cancer cells during the continuous hormone therapy. One possible method to prevent the progression to the androgen-independent state is intermittent androgen suppression (IAS) therapy, which ceases dosing intermittently. In this paper, we propose two methods to estimate the dynamics of prostate cancer, and investigate the IAS therapy from the viewpoint of optimality. The two methods that we propose for dynamics estimation are a variational Bayesian method for a piecewise affine (PWA) system and a Gaussian process regression method. We apply the proposed methods to real clinical data and compare their predictive performances. Then, using the estimated dynamics of prostate cancer, we observe how prostate cancer behaves for various dosing schedules. It can be seen that the conventional IAS therapy is a way of imposing high cost for dosing while keeping the prostate cancer in a safe state. We would like to dedicate this paper to the memory of Professor Luigi M. Ricciardi.

  20. Direct leaf trajectory optimization for volumetric modulated arc therapy planning with sliding window delivery

    CERN Document Server

    Papp, Dávid

    2013-01-01

    We propose a novel optimization model for volumetric modulated arc therapy (VMAT) planning that directly optimizes deliverable leaf trajectories in the treatment plan optimization problem, and eliminates the need for a separate arc-sequencing step. In this model, a 360-degree arc is divided into a given number of arc segments in which the leaves move unidirectionally. This facilitates an algorithm that determines the optimal piecewise linear leaf trajectories for each arc segment, which are deliverable in a given treatment time. Multi-leaf collimator (MLC) constraints, including maximum leaf speed and interdigitation, are accounted for explicitly. The algorithm is customized to allow for VMAT delivery using constant gantry speed and dose rate, however, the algorithm generalizes to variable gantry speed if beneficial. We demonstrate the method for three different tumor sites: a head-and-neck case, a prostate case, and a paraspinal case. For that purpose, we first obtain a reference plan for intensity modulated...

  1. [How I treat...Recommendations for controlling and optimizing a pharmacological therapy].

    Science.gov (United States)

    Scheen, A J

    2014-11-01

    Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In case of not reaching the predefined objectives, the causes of failure should first be screened (for instance, exclusion of poor patient compliance), and the treatment should be then optimized: dose adjustment, add-on of another drug (if possible synergistic combination) and/or shift to a more effective pharmacological therapy. In some cases, therapeutic monitoring may be useful or even mandatory in order to better adjust drug dosing and thus guarantee both efficacy and safety.

  2. Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy.

    Science.gov (United States)

    Byrne, Thomas J; Rakela, Jorge

    2016-06-24

    Hepatocellular carcinoma (HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation (LT) is considered the most feasible pathway to cure. Resection - even with favorable survival - is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, loco-regional therapy (LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT (and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

  3. Weighted optimization of irradiance for photodynamic therapy of port wine stains

    Science.gov (United States)

    He, Linhuan; Zhou, Ya; Hu, Xiaoming

    2016-10-01

    Planning of irradiance distribution (PID) is one of the foremost factors for on-demand treatment of port wine stains (PWS) with photodynamic therapy (PDT). A weighted optimization method for PID was proposed according to the grading of PWS with a three dimensional digital illumination instrument. Firstly, the point clouds of lesions were filtered to remove the error or redundant points, the triangulation was carried out and the lesion was divided into small triangular patches. Secondly, the parameters such as area, normal vector and orthocenter for optimization of each triangular patch were calculated, and the weighted coefficients were determined by the erythema indexes and areas of patches. Then, the optimization initial point was calculated based on the normal vectors and orthocenters to optimize the light direction. In the end, the irradiation can be optimized according to cosine values of irradiance angles and weighted coefficients. Comparing the irradiance distribution before and after optimization, the proposed weighted optimization method can make the irradiance distribution match better with the characteristics of lesions, and has the potential to improve the therapeutic efficacy.

  4. Optimization of irradiance for photodynamic therapy of port-wine stain

    Science.gov (United States)

    Zhang, Feng-juan; Hu, Xiao-ming; Zhou, Ya; Li, Qin

    2015-04-01

    Controllable and effective irradiation of lesions is among the key factors that affect the potency of photodynamic therapy (PDT). An optimization method for the irradiance distribution of treatment was proposed which can be used to improve the efficacy of PDT and allow more lesions to receive the desired irradiance level in a single therapy session. With the proposed digital illumination binocular treatment system, the preferred surface normal vectors, irradiation angles, as well as area and weight coefficients of lesions can be achieved and used as characteristic parameters to optimize the irradiation direction. Two port-wine stain phantom experiments were performed. The comparison of the illumination area between preoptimization and postoptimization showed that the proposed method can effectively guide the light source control, improve the distribution of light dose, and increase the effective treatment area.

  5. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice.

    Science.gov (United States)

    Lee, Ho Sup; Min, Chang-Ki

    2016-09-01

    Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control. Many clinical trials have reported increased progression-free and overall survival rates after consolidation and maintenance therapy. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation and is a valuable option in clinical trial settings. However, the decision to use consolidation and/or maintenance therapy needs to be guided by the individual patient situation in actual clinical practice. This review analyzes the currently available evidence from several reported clinical trials to determine the optimal consolidation and maintenance therapy in clinical practice.

  6. Beam neutron energy optimization for boron neutron capture therapy using Monte Carlo method

    OpenAIRE

    Ali Pazirandeh; Elham Shekarian

    2006-01-01

     In last two decades the optimal neutron energy for the treatment of deep seated tumors in boron neutron capture therapy in view of neutron physics and chemical compounds of boron carrier has been under thorough study. Although neutron absorption cross section of boron is high (3836b), the treatment of deep seated tumors such as gliobelastoma multiform (GBM) requires beam of neutrons of higher energy that can penetrate deeply into the brain and thermalize in the proximity of the tumor. Dosage...

  7. Optimal control oriented to therapy for a free-boundary tumor growth model.

    Science.gov (United States)

    Calzada, M Carmen; Fernández-Cara, Enrique; Marín, Mercedes

    2013-05-21

    This paper is devoted to present and solve some optimal control problems, oriented to therapy, for a particular model of tumor growth. In the considered systems, the state is given by one or several functions that provide information on the cell population and also the tumor shape evolution and the control is a time dependent function associated to the therapy strategy (in practice, a cytotoxic drug). We first present and analyze the model (based on PDEs) and the related optimal control problems. The solutions are expected to provide the best therapy strategies for a given set of constraints (here, the cost or objective function is a measure of the number of cells at a given final time T). We also recall some mathematical techniques for solving the related optimization problems and we illustrate the behavior of the methods and the validity of the models with several numerical experiments. In view of the results, we are able to design appropriate strategies that, at least to some extent, are confirmed by real data. Finally, we present some conclusions and indications on future work. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Effect of antiemetic drugs on decrease in gastric emptying in experimental model of motion sickness in rats

    Institute of Scientific and Technical Information of China (English)

    YKGUPTA; GeetaCHAUDHARY

    2003-01-01

    AIM:To study the effect of pretreatment with different antiemetic drugs on the motion sickness-induced inhibition in gastric emptying.METHODS:The rats were rotated for a period of 45 min at the rate of 30 rotations per min.RESULTS:Rotating the rats caused a significant decrease in gastric emptying as cvompared to the non-rotated group.Pretreatment with scopolamine(5 mg/kg,ip)did not reverse the delay in gastric emptying,while it per se caused inhibition of gastric emptying in the non-rotated group.Similarly other drugs mepyramine,cisapride,and granisetron did not have any effect on delay in gastric emptying caused by rotation.However beta blocker propranolol could partially but significantly reverse the decrease in gastric emptying.CONCLUSION:The present study demonstrated the potential use of propranolol as adjuvant with conventional antiemetics for motion sickness to combat associated secondary symptoms.

  9. Evaluating risks, costs, and benefits of new and emerging therapies to optimize outcomes in multiple sclerosis.

    Science.gov (United States)

    Bandari, Daniel S; Sternaman, Debora; Chan, Theodore; Prostko, Chris R; Sapir, Tamar

    2012-01-01

    Multiple sclerosis (MS) is a complex, chronic, and often disablingneurological disease. Despite the recent incorporation of new treatmentapproaches early in the disease course, care providers still face difficultdecisions as to which therapy will lead to optimal outcomes and whento initiate or escalate therapies. Such decisions require proper assessmentof relative risks, costs, and benefits of new and emerging therapies, as wellas addressing challenges with adherence to achieve optimal managementand outcomes.At the 24th Annual Meeting Expo of the Academy of Managed CarePharmacy (AMCP), held in San Francisco on April 18, 2012, a 4-hour activitytitled "Analyzing and Applying the Evidence to Improve Cost-Benefit andRisk-Benefit Outcomes in Multiple Sclerosis" was conducted in associationwith AMCP's Continuing Professional Education Partner Program (CPEPP).The practicum, led by the primary authors of this supplement, featureddidactic presentations, a roundtable session, and an expert panel discussiondetailing research evidence, ideas, and discussion topics central to MSand its applications to managed care. To review (a) recent advances in MS management, (b) strategiesto optimize the use of disease-modifying therapies for MS, (c) costs ofcurrent MS therapies, (d) strategies to promote adherence and complianceto disease-modifying therapies, and (e) potential strategies for managedcare organizations to improve care of their MS patient populations and optimizeclinical and economic outcomes. Advances in magnetic resonance imaging and newer therapieshave allowed earlier diagnosis and reduction of relapses, reduction in progressionof disability, and reduction in total cost of care in the long term.Yet, even with the incorporation of new disease-modifying therapies intothe treatment armamentarium of MS, challenges remain for patients, providers,caregivers, and managed care organizations as they have to makeinformed decisions based on the properties, risks, costs, and benefits

  10. Drug Cocktail Optimization in Chemotherapy of Cancer

    Science.gov (United States)

    Preissner, Saskia; Dunkel, Mathias; Hoffmann, Michael F.; Preissner, Sarah C.; Genov, Nikolai; Rong, Wen Wei; Preissner, Robert; Seeger, Karlheinz

    2012-01-01

    Background In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. Objective The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. Data sources and methods Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. Results We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy. PMID:23236419

  11. Drug cocktail optimization in chemotherapy of cancer.

    Directory of Open Access Journals (Sweden)

    Saskia Preissner

    Full Text Available BACKGROUND: In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP. Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. OBJECTIVE: The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. DATA SOURCES AND METHODS: Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. RESULTS: We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.

  12. Systems Pharmacology Approaches for Optimization of Antiangiogenic Therapies: Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Satish eSharan

    2015-02-01

    Full Text Available Targeted therapies have become an important therapeutic paradigm for multiple malignancies. The rapid development of resistance to these therapies impedes the successful management of advanced cancer. Due to the redundancy in angiogenic signaling, alternative proangiogenic factors are activated upon treatment with anti-VEGF agents. Higher doses of the agents lead to greater stimulation of compensatory proangiogenic pathways that limit the therapeutic efficacy of VEGF-targeted drugs and produce escape mechanisms for tumor. Evidence suggests that dose intensity and schedules affect the dynamics of the development of this resistance. Thus, an optimal dosing regimen is crucial to maximizing the therapeutic benefit of antiangiogenic agents and limiting treatment resistance. A systems pharmacology approach using multiscale computational modeling can facilitate a mechanistic understanding of these dynamics of angiogenic biomarkers and their impacts on tumor reduction and resistance. Herein, we discuss a systems pharmacology approach integrating the biology of VEGF-targeted therapy resistance, including circulating biomarkers, and pharmacodynamics to enable the optimization of antiangiogenic therapy for therapeutic gains.

  13. The Anti-Emetic Properties of 1-Sulpiride in a Ground-Based Model of Space Motion Sickness

    Science.gov (United States)

    Miller, Joseph D.; Brizzee, Kenneth R.

    1987-01-01

    L-sulpiride, at a dose of 4 mg/kg, essentially abolished motion- induced emesis in a group of 6 squirrel monkeys undergoing horizontal rotation at 25 rpm, a terrestrial model of space motion sickness (SMS). Extrapyramidal side effects were not observed. In the absence of the drug, the usual emetic response returned. In comparison while typical neuroleptics were also strongly anti-emetic, they produced a considerable degree of rigidity and akinesia.

  14. A nested partitions framework for beam angle optimization in intensity-modulated radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    D' Souza, Warren D; Nazareth, Daryl P [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Zhang, Hao H; Shi Leyuan [Department of Industrial and Systems Engineering, University of Wisconsin, Madison, WI (United States); Meyer, Robert R [Computer Sciences Department, University of Wisconsin, Madison, WI (United States)], E-mail: dsouzaw@ohsu.edu

    2008-06-21

    Coupling beam angle optimization with dose optimization in intensity-modulated radiation therapy (IMRT) increases the size and complexity of an already large-scale combinatorial optimization problem. We have developed a novel algorithm, nested partitions (NP), that is capable of finding suitable beam angle sets by guiding the dose optimization process. NP is a metaheuristic that is flexible enough to guide the search of a heuristic or deterministic dose optimization algorithm. The NP method adaptively samples from the entire feasible region, or search space, and coordinates the sampling effort with a systematic partitioning of the feasible region at successive iterations, concentrating the search in promising subsets. We used a 'warm-start' approach by initiating NP with beam angle samples derived from an integer programming (IP) model. In this study, we describe our implementation of the NP framework with a commercial optimization algorithm. We compared the NP framework with equi-spaced beam angle selection, the IP method, greedy heuristic and random sampling heuristic methods. The results of the NP approach were evaluated using two clinical cases (head and neck and whole pelvis) involving the primary tumor and nodal volumes. Our results show that NP produces better quality solutions than the alternative considered methods.

  15. A nested partitions framework for beam angle optimization in intensity-modulated radiation therapy

    Science.gov (United States)

    D'Souza, Warren D.; Zhang, Hao H.; Nazareth, Daryl P.; Shi, Leyuan; Meyer, Robert R.

    2008-06-01

    Coupling beam angle optimization with dose optimization in intensity-modulated radiation therapy (IMRT) increases the size and complexity of an already large-scale combinatorial optimization problem. We have developed a novel algorithm, nested partitions (NP), that is capable of finding suitable beam angle sets by guiding the dose optimization process. NP is a metaheuristic that is flexible enough to guide the search of a heuristic or deterministic dose optimization algorithm. The NP method adaptively samples from the entire feasible region, or search space, and coordinates the sampling effort with a systematic partitioning of the feasible region at successive iterations, concentrating the search in promising subsets. We used a 'warm-start' approach by initiating NP with beam angle samples derived from an integer programming (IP) model. In this study, we describe our implementation of the NP framework with a commercial optimization algorithm. We compared the NP framework with equi-spaced beam angle selection, the IP method, greedy heuristic and random sampling heuristic methods. The results of the NP approach were evaluated using two clinical cases (head and neck and whole pelvis) involving the primary tumor and nodal volumes. Our results show that NP produces better quality solutions than the alternative considered methods.

  16. Optimization of Radiation Therapy Fractionation Schedules in the Presence of Tumor Repopulation

    CERN Document Server

    Bortfeld, Thomas; Tsitsiklis, John N; Unkelbach, Jan

    2013-01-01

    We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily motivated by accelerated tumor repopulation towards the end of radiation treatment, which is believed to play a role in treatment failure for some tumor sites. A dynamic programming framework is developed to determine an optimal fractionation scheme based on a model of cell kill due to radiation and tumor growth in between treatment days. We find that faster tumor growth suggests shorter overall treatment duration. In addition, the presence of accelerated repopulation suggests larger dose fractions later in the treatment to compensate for the increased tumor proliferation. We prove that the optimal dose fractions are increasing over time. Numerical simulations indicate potential for improvement in treatment effectiveness.

  17. The Optimal Drug Therapy National Symposium 2001: a call for action.

    Science.gov (United States)

    MacLeod, S

    2001-01-01

    There is widespread concern internationally and within Canada about the rapid escalation in pharmaceutical costs. Although there is reason to believe that the quality of prescribing has improved in recent years, with heightened emphasis on evidence-based therapeutic decision-making, there is enormous pressure to prescribe in almost every clinical situation. Busy clinicians need improved tools to aid therapeutic decision-making. Access to timely information about drug efficacy and safety is essential. Most importantly, there is a need for a new partnership model that may blend the interests of patients, professionals, payors and manufacturers to better define disease state management approaches that will lead to an optimal return on the investment in pharmaceutical care. The new model will depend on high standards of research to show what does and does not work to secure the most effective pharmacotherapy. It will also require renewed efforts in education for patients and caregivers, and progress on that front will, in turn, rely on the most effective use of expanded capacity in information technology. One early impact will be seen in the reduction of medication errors. The framework for therapeutic decision-making must evolve in keeping with the revolution in human biology. With improved understanding of human genomics and proteomics, prescribers are better able to consider highly individualized and targeted drug therapies while actively concentrating on risk minimization. The Optimal Drug Therapy National Symposium 2001 has created a consensus among stakeholders and pointed the way to improvements in drug therapy that may be achieved through enhanced research, educa- tion, public involvement and professional support. Unequivocal commitment to the laudable goal of optimal drug therapy is now required from all sides.

  18. Antiemetic role of thalidomide in a rat model of cisplatin-induced emesis.

    Science.gov (United States)

    Han, Zheng-xiang; Xu, Jie; Wang, Hong-mei; Ma, Jan; Sun, Xuan; Du, Xiu-ping

    2014-09-01

    The efficacy of thalidomide to attenuate cisplatin-induced emesis was evaluated in a rat model. Four groups were utilized: control group (peritoneal injection and gastric lavage with normal saline), cisplatin group (peritoneal injection of cisplatin at 10 mg/kg and gastric lavage with normal saline), thalidomide group (cisplatin as above and gastric lavage with thalidomide at 10 mg/kg), and granisetron group (positive control for antiemetic effects; cisplatin given as above and gastric lavage done with granisetron at 0.5 mg/kg). The cisplatin-induced kaolin consumption (pica behavior) was used as a model of emesis in patients. The animals' kaolin and food intakes were measured. Further, medulla and gastric tissues were obtained 5 and 33 h after peritoneal injections to quantify the levels of Substance P and Neurokinin-1 receptor (NK-1R). The cisplatin-induced kaolin consumption was significantly (p thalidomide 72 h after the injection. The levels of Substance P in the medulla and gastric tissue were increased 5 h after the injection in both cisplatin and thalidomide groups, however, returned faster to normal levels in the thalidomide group (p thalidomide, and granisetron group were significantly increased at both 5 and 33 h (p thalidomide attenuates animal equivalent of cisplatin-induced emesis, and this beneficial effect is associated with decreased levels of Substance P levels in the medulla and gastric tissue.

  19. Value of mink vomit model in study of anti-emetic drugs

    Institute of Scientific and Technical Information of China (English)

    Fang Zhang; Lei Wang; Zhi-Hong Yang; Zhan-Tao Liu; Wang Yue

    2006-01-01

    AIM: To establish a new, reliable vomit model of minks.METHODS: Adult male minks were randomly divided into 8 groups (n=6): cisplatin (7.5 mg/kg)intraperitoneal injection (ip) group, copper sulfate (40mg/kg) intragastric injection (ig) group, apomorphine (1.6 mg/kg) subcutaneous injection (sc) group, and 18Gy whole-body X-irradiation group, ondansetron injection group (2 mg/kg ip) 30 min later followed by cisplatin (7.5 mg/kg) ip, normal saline (NS) ip injection control group, metoclopramide injection group (4 mg/kg ip) 30min later followed by apomorphine (1.6 mg/kg) sc, NS ig control group. The frequency of retching and vomiting was calculated. After behavioral experiment, distribution of 5-HT in the ileum was detected by immunohistologic method.RESULTS: Cisplatin, apomorphine, copper sulfate and X-irradiation administered to minks evoked a profound emetic response in the animals. However, retching and vomiting were significantly inhibited by pretreatment with ondansetron and metoclopramide in cisplatin and copper sulfate groups (P=0.018). Immunohistologic result showed that 5-HT released from enterochromaffin cells (EC cells) was involved in vomiting mechanism.CONCLUSION: Mink vomit model has a great value in studying the vomiting mechanism and screening new antiemetic drugs.

  20. Balancing efficacy with cost: antiemetic control in the pediatric stem cell transplant (SCT) population.

    Science.gov (United States)

    Parsons, S K; Hoorntje, L E; Levine, K J; Mayer, D K; Eichelberger, W J; Guinan, E C

    2000-03-01

    We studied the practice patterns regarding intravenous (i.v.) ondansetron in children receiving stem cell transplants (SCT) at The Children's Hospital, Boston to identify cost efficiencies. The pharmacy provided information on material and preparation costs on 36 patients who received i.v. ondansetron during 41 SCT in 1995. We examined the effects of frequency, duration, and route of administration on costs. There were 498 days of ondansetron administration costing $49,083 (95$). Tremendous variation existed in frequency and duration with one third receiving i.v. ondansetron once daily, despite published evidence of equivalence of once a day and divided dosing. A switch to once daily i.v. dosing for all patients would have resulted in >/=28% savings. The median duration of use was 11 days (range 1-48); placing a cap for 7-10 days based on the length of SCT conditioning regimens, would produce savings of 48-60% over current use. By shifting administration route from i.v. to oral, a savings of 67% over current use, without a cap on duration, would be realized. Identifying areas for cost savings can be achieved after thorough analysis of all the component costs. We demonstrated that significant cost reductions could be realized by simple changes in prescribing practices without jeopardizing efficacy. These savings are achieved by standardizing dosing interval, route of administration and duration of treatment without altering daily dosage or access to an effective antiemetic. Bone Marrow Transplantation (2000) 25, 553-557.

  1. Optimal planning strategy among various arc arrangements for prostate stereotactic body radiotherapy with volumetric modulated arc therapy technique

    Directory of Open Access Journals (Sweden)

    Kang Sang Won

    2017-03-01

    Full Text Available The aim of this study was to determine the optimal strategy among various arc arrangements in prostate plans of stereotactic body radiotherapy with volumetric modulated arc therapy (SBRT-VMAT.

  2. Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

    Science.gov (United States)

    Unkelbach, Jan; Chan, Timothy C Y; Bortfeld, Thomas

    2007-05-21

    Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches--although conceptually different--yield very similar results on a qualitative level.

  3. Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program.

    Science.gov (United States)

    Lange, Karin; Ziegler, Ralph; Neu, Andreas; Reinehr, Thomas; Daab, Iris; Walz, Marion; Maraun, Michael; Schnell, Oliver; Kulzer, Bernhard; Reichel, Andreas; Heinemann, Lutz; Parkin, Christopher G; Haak, Thomas

    2015-03-01

    Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles. Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient-physician communication and supports patients' diabetes self-management skills. We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy.

  4. Determination of the optimal atrioventricular and interventricular delays in cardiac resynchronization therapy

    Institute of Scientific and Technical Information of China (English)

    Hongxia NIU; Wei HUA; Shu ZHANG; Fangzheng WANG; Keping CHEN; Xin CHEN

    2005-01-01

    In order to provide the maximum benefit of cardiac resynchronization therapy (CRT), we tried to use an echocardiography method to optimize the atrioventricular and interventricular delay. Methods The study included 6 patients who underwent implantation of biventricular pacemakers for drug-resistant heart failure. Two-dimensional echocardiography and tissue Doppler imaging were carried out before and after the pacemaker implantation. The optimal AV delay was defined as the AV delay resulting in maximum timevelocity integral (TVI) of transmitral filling flow, the longest left ventricular filling time (LVFT) and the minimum mitral regurgitation(MR). The optimal VV delay was defined as the VV delay producing the maximum LV synchrony and the largest aortic TVI. Results CRT was successfully performed in all patients. After pacemaker implantation, an acute improvement in left ventricular ejection fraction (LVEF) was observed from 26.5% to 35%. Meanwhile, the QRS duration decreased from 170ms to 150ms. The optimal AV delay was programmed at 130, 120, 120, 120, 150 and 110ms respectively with heart rate corrected, LVFT significantly lengthened and TVI of MR decreased (non-optimal vs optimal AV delay: LVFT: 469ms vs 523ms; TVI of MR: 16.43cm vs 13.06cm, P<0.05). The optimal VV delay was programmed at 4, 4, 4, 8, 12 and 8ms with LV preactivation respectively. Programming the optimal VV delay increased the aortic TVI from 17.33cm up to 21.42cm (P<0.05). In the septal and lateral wall, peak systolic velocities improved from2.70cm/s to 3.02cm/s (P>0.05) and froml.31cm/s to 2.50cm/s (P<0.05) respectively. The septal-to-lateral delay in peak velocity improved from 56.4ms to 13.3ms after CRT (P<0.01). Conclusions Optimization of AV and VV delays may further enhance the efficacy of CRT. However, there was interindividual variability of optimal values, warranting individual patient examination.

  5. Optimal systemic therapy for early breast cancer in women: a clinical practice guideline.

    Science.gov (United States)

    Eisen, A; Fletcher, G G; Gandhi, S; Mates, M; Freedman, O C; Dent, S F; Trudeau, M E

    2015-03-01

    The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was "What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?" A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint. Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine

  6. Regulating Near-Infrared Photodynamic Properties of Semiconducting Polymer Nanotheranostics for Optimized Cancer Therapy.

    Science.gov (United States)

    Zhu, Houjuan; Fang, Yuan; Miao, Qingqing; Qi, Xiaoying; Ding, Dan; Chen, Peng; Pu, Kanyi

    2017-09-26

    Development of optical nanotheranostics for the capability of photodynamic therapy (PDT) provides opportunities for advanced cancer therapy. However, most nanotheranostic systems fail to regulate their generation levels of reactive oxygen species (ROS) according to the disease microenvironment, which can potentially limit their therapeutic selectivity and increase the risk of damage to normal tissues. We herein report the development of hybrid semiconducting polymer nanoparticles (SPNs) with self-regulated near-infrared (NIR) photodynamic properties for optimized cancer therapy. The SPNs comprise a binary component nanostructure: a NIR-absorbing semiconducting polymer acts as the NIR fluorescent PDT agent, while nanoceria serves as the smart intraparticle regular to decrease and increase ROS generation at physiologically neutral and pathologically acidic environments, respectively. As compared with nondoped SPNs, the NIR fluorescence imaging ability of nanoceria-doped SPNs is similar due to the optically inactive nature of nanoceria; however, the self-regulated photodynamic properties of nanoceria-doped SPN not only result in dramatically reduced nonspecific damage to normal tissue under NIR laser irradiation but also lead to significantly enhanced photodynamic efficacy for cancer therapy in a murine mouse model. This study thus provides a simple yet effective hybrid approach to modulate the phototherapeutic performance of organic photosensitizers.

  7. Clinico-psychological analysis of systematic (vestibular and nonsystematic (psychogenic vertigo, therapy optimization

    Directory of Open Access Journals (Sweden)

    Elena Mikhailovna Illarionova

    2011-01-01

    Full Text Available Objective: to study the clinical and psychoemotional characteristics in patients with systematic and nonsystematic vertigo and to optimize therapy. Patients and methods. The clinical features were analyzed in 25 patients with systematic vertigo and 25 patients with psychogenic vertigo. Their psychoemotional sphere was studied using the Beck depression inventory, the Spielberger-hanin personality- and situation-related anxiety inventory, and the vestibular inventory. Results. There were statistically significant clinical differences and a higher degree of anxiety-depressive disorders in the patients with psychogenic vertigo. Drug therapy in combination with stabilometric platform exercises based on the biological feedback principle was stated to be effective in patients with different types of vertigo, in those with psychogenic dizziness in particular.

  8. Optimization of insulin pump therapy based on high order run-to-run control scheme.

    Science.gov (United States)

    Tuo, Jianyong; Sun, Huiling; Shen, Dong; Wang, Hui; Wang, Youqing

    2015-07-01

    Continuous subcutaneous insulin infusion (CSII) pump is widely considered a convenience and promising way for type 1 diabetes mellitus (T1DM) subjects, who need exogenous insulin infusion. In the standard insulin pump therapy, there are two modes for insulin infusion: basal and bolus insulin. The basal-bolus therapy should be individualized and optimized in order to keep one subject's blood glucose (BG) level within the normal range; however, the optimization procedure is troublesome and it perturb the patients a lot. Therefore, an automatic adjustment method is needed to reduce the burden of the patients, and run-to-run (R2R) control algorithm can be used to handle this significant task. In this study, two kinds of high order R2R control methods are presented to adjust the basal and bolus insulin simultaneously. For clarity, a second order R2R control algorithm is first derived and studied. Furthermore, considering the differences between weekdays and weekends, a seventh order R2R control algorithm is also proposed and tested. In order to simulate real situation, the proposed method has been tested with uncertainties on measurement noise, drifts, meal size, meal time and snack. The proposed method can converge even when there are ±60 min random variations in meal timing or ±50% random variations in meal size. According to the robustness analysis, one can see that the proposed high order R2R has excellent robustness and could be a promising candidate to optimize insulin pump therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. CANCER IMMUNOLOGY AND IMMUNOTHERAPY – UNDERSTANDING AND ADAPTATION THE CURRENT EVIDENCE TO OPTIMIZE PATIENT THERAPY OUTCOMES.

    Directory of Open Access Journals (Sweden)

    Orlin Savov

    2015-11-01

    Full Text Available The aim of this publication includes the try to act as intermediary to the readers, which should be able to understand: - The description of the cancer immunotherapy mechanisms in the context of current therapy decisions for the treatment of cancer - The including criteria for those patients with cancer who could be appropriate candidates for immunotherapy - And to optimize patient outcomes by using best practices to manage the adverse events associated with immunotherapy treatment More than 15 promising immunotherapy approaches being tested in clinical trials with appropriate patients and colleagues for enrollment and peer-to-peer education purposes, respectively.

  10. Optimizing Salmonella enterica serovar Typhimurium for bacteria-mediated tumor therapy.

    Science.gov (United States)

    Felgner, Sebastian; Kocijancic, Dino; Frahm, Michael; Curtiss, Roy; Erhardt, Marc; Weiss, Siegfried

    2016-01-01

    Bacteria-mediated tumor therapy using Salmonella enterica serovar Typhimurium is a therapeutic option with great potential. Numerous studies explored the potential of Salmonella Typhimurium for therapeutic applications, however reconciling safety with vectorial efficacy remains a major issue. Recently we have described a conditionally attenuated Salmonella vector that is based on genetic lipopolysaccharide modification. This vector combines strong attenuation with appropriate anti-tumor properties by targeting various cancerous tissues in vivo. Therefore, it was promoted as an anti-tumor agent. In this addendum, we summarize these findings and demonstrate additional optimization steps that may further improve the therapeutic efficacy of our vector strain.

  11. Acquiring the optimal time for hyperbaric therapy in the rat model of CFA induced arthritis.

    Science.gov (United States)

    Koo, Sung Tae; Lee, Chang-Hyung; Shin, Yong Il; Ko, Hyun Yoon; Lee, Da Gyo; Jeong, Han-Sol

    2014-01-01

    We previously published an article about the pressure effect using a rheumatoid animal model. Hyperbaric therapy appears to be beneficial in treating rheumatoid arthritis (RA) by reducing the inflammatory process in an animal model. In this sense, acquiring the optimal pressure-treatment time parameter for RA is important and no optimal hyperbaric therapy time has been suggested up to now. The purpose of our study was to acquire the optimal time for hyperbaric therapy in the RA rat model. Controlled animal study. Following injection of complete Freund's adjuvant (CFA) into one side of the knee joint, 32 rats were randomly assigned to 3 different time groups (1, 3, 5 hours a day) under 1.5 atmospheres absolute (ATA) hyperbaric chamber for 12 days. The pain levels were assessed daily for 2 weeks by weight bearing force (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. The reduction of WBF was high at 2 days after injection and then it was spontaneously increased up to 14 days in all 3 groups. There were significant differences of WBF between 5 hours and control during the third through twelfth days, between 3 hours and control during the third through fifth and tenth through twelfth days, and between 3 hours and 5 hours during the third through seventh days (P CFA injection in all groups compared to the initial findings, however, the 3 hour group showed a smaller MMP-9/MMP-2 ratio than the control group. Although enough samples were used for the study to support our hypothesis, more samples will be needed to raise the validity and reliability. The effect of hyperbaric treatment appears to be dependent upon the elevated therapy time under 1.5 ATA pressure for a short period of time; however, the long-term effects were similar in all pressure groups. Further study will be needed to acquire the optimal pressure-treatment parameter relationship in various conditions for

  12. Multi-criteria optimization methods in radiation therapy planning: a review of technologies and directions

    CERN Document Server

    Craft, David

    2013-01-01

    We review the field of multi-criteria optimization for radiation therapy treatment planning. Special attention is given to the technique known as Pareto surface navigation, which allows physicians and treatment planners to interactively navigate through treatment planning options to get an understanding of the tradeoffs (dose to the target versus over-dosing of important nearby organs) involved in each patient's plan. We also describe goal programming and prioritized optimization, two other methods designed to handle multiple conflicting objectives. Issues related to nonconvexities, both in terms of dosimetric goals and the fact that the mapping from controllable hardware parameters to patient doses is usually nonconvex, are discussed at length since nonconvexities have a large impact on practical solution techniques for Pareto surface construction and navigation. A general planning strategy is recommended which handles the issue of nonconvexity by first finding an ideal Pareto surface with radiation delivere...

  13. Optimal Neutron Source and Beam Shaping Assembly for Boron Neutron Capture Therapy

    CERN Document Server

    Vujic, J L; Greenspan, E; Guess, S; Karni, Y; Kastenber, W E; Kim, L; Leung, K N; Regev, D; Verbeke, J M; Waldron, W L; Zhu, Y

    2003-01-01

    There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly.

  14. Ultra-fast treatment plan optimization for volumetric modulated arc therapy (VMAT)

    CERN Document Server

    Men, Chunhua; Jia, Xun; Jiang, Steve B

    2010-01-01

    Purpose: To develop a novel aperture-based algorithm for volumetric modulated arc therapy (VMAT) treatment plan optimization with high quality and high efficiency. Methods: The VMAT optimization problem is formulated as a large-scale convex programming problem solved by a column generation approach. We consider a cost function consisting two terms, the first which enforces a desired dose distribution while the second guarantees a smooth dose rate variation between successive gantry angles. At each iteration of the column generation method, a subproblem is first solved to generate one more deliverable MLC aperture which potentially decreases the cost function most effectively. A subsequent master problem is then solved to determine the dose rate at all currently generated apertures by minimizing the cost function. The iteration of such an algorithm yields a set of deliverable apertures, as well as dose rates, at all gantry angles. Results: The algorithm was preliminarily tested on five prostate and five head-a...

  15. Optimization of parodontium tissue irradiation method for fluorescent diagnostic (FD) and photodynamic therapy (PDT)

    Science.gov (United States)

    Sinyaeva, Maria L.; Mamedov, Ad. A.; Lervkin, V. V.; Kharnas, Sergey S.; Volkova, Anna I.; Loschenov, Victor B.; Berezin, Anatoly N.; Kiselev, Gennady L.

    2004-06-01

    During the last several years research activities have been conducted to study PDT availability in stomatology for pathogenic microflora suppression, which presence causes different kinds of oral cavity inflammatory disease. Studies indicate that PDT can be alternative to traditional antibiotic therapy. We carried out research in order to determine the optimal method of tooth irradiation to provide necessary therapeutic radiation dose for affected parodontium tissue in case of inflammatory disease. These data can be used for fiber-optic catheter positioning for further influence on oral cavity nidus of inflammation during PDT and PD. 20 teeth ex vivo were examined. Teeth were irradiated with diode laser (680 nm). In different teeth regions laser radiation intensity was measured by LESA-01-Biospec spectrometer. Optimal radiation method for PDT and PD was found.

  16. Optimal Neutron Source & Beam Shaping Assembly for Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    J. Vujic; E. Greenspan; W.E. Kastenber; Y. Karni; D. Regev; J.M. Verbeke, K.N. Leung; D. Chivers; S. Guess; L. Kim; W. Waldron; Y. Zhu

    2003-04-30

    There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly.

  17. Collimator angle influence on dose distribution optimization for vertebral metastases using volumetric modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mancosu, Pietro; Cozzi, Luca; Fogliata, Antonella; Lattuada, Paola; Reggiori, Giacomo; Cantone, Marie Claire; Navarria, Pierina; Scorsetti, Marta [Department of Radiation Oncology, IRCCS Istituto Clinico Humanitas, Milano (Rozzano) 20089 (Italy); Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona 6504 (Switzerland); Department of Radiation Oncology, IRCCS Istituto Clinico Humanitas, Milano (Rozzano) 20089 (Italy); Department of Physics, Universita Degli Studi di Milano, Milano 20133 (Italy); Department of Radiation Oncology, IRCCS Istituto Clinico Humanitas, Milano (Rozzano) 20089 (Italy)

    2010-08-15

    Purpose: The cylindrical symmetry of vertebrae favors the use of volumetric modulated arc therapy in generating a dose ''hole'' on the center of the vertebrae limiting the dose to the spinal cord. The authors have evaluated if collimator angle is a significant parameter for dose distribution optimization in vertebral metastases. Methods: Three patients with one-three vertebrae involved were considered. Twenty-one differently optimized plans (nine single-arc and 12 double-arc plans) were performed, testing various collimator angle positions. Clinical target volume was defined as the whole vertebrae, excluding the spinal cord canal. The planning target volume (PTV) was defined as CTV+5 mm. Dose prescription was 5x4 Gy{sup 2} with normalization to PTV mean dose. The dose at 1 cm{sup 3} of spinal cord was limited to 11.5Gy. Results: The best plans in terms of target coverage and spinal cord sparing were achieved by two arcs and Arc1-80 deg. and Arc2-280 deg. collimator angles for all the cases considered (i.e., leaf travel parallel to the spinal cord primary orientation). If one arc is used, only 80 deg. reached the objectives. Conclusions: This study demonstrated the role of collimation rotation for the vertebrae metastasis irradiation, with the leaf travel parallel to the spinal cord primary orientation to be better than other solutions. Thus, optimal choice of collimator angle increases the optimization freedom to shape a desired dose distribution.

  18. Optimal marker-strategy clinical trial design to detect predictive markers for targeted therapy.

    Science.gov (United States)

    Zang, Yong; Liu, Suyu; Yuan, Ying

    2016-07-01

    In developing targeted therapy, the marker-strategy design (MSD) provides an important approach to evaluate the predictive marker effect. This design first randomizes patients into non-marker-based or marker-based strategies. Patients allocated to the non-marker-based strategy are then further randomized to receive either the standard or targeted treatments, while patients allocated to the marker-based strategy receive treatments based on their marker statuses. Little research has been done on the statistical properties of the MSD, which has led to some widespread misconceptions and placed clinical researchers at high risk of using inefficient designs. In this article, we show that the commonly used between-strategy comparison has low power to detect the predictive effect and is valid only under a restrictive condition that the randomization ratio within the non-marker-based strategy matches the marker prevalence. We propose a Wald test that is generally valid and also uniformly more powerful than the between-strategy comparison. Based on that, we derive an optimal MSD that maximizes the power to detect the predictive marker effect by choosing the optimal randomization ratios between the two strategies and treatments. Our numerical study shows that using the proposed optimal designs can substantially improve the power of the MSD to detect the predictive marker effect. We use a lung cancer trial to illustrate the proposed optimal designs.

  19. On-line re-optimization of prostate IMRT plans for adaptive radiation therapy.

    Science.gov (United States)

    Wu, Q Jackie; Thongphiew, Danthai; Wang, Zhiheng; Mathayomchan, Boonyanit; Chankong, Vira; Yoo, Sua; Lee, W Robert; Yin, Fang-Fang

    2008-02-01

    For intermediate and high risk prostate cancer, both the prostate gland and seminal vesicles are included in the clinical target volume. Internal motion patterns of these two organs vary, presenting a challenge for adaptive treatment. Adaptive techniques such as isocenter repositioning and soft tissue alignment are effective when tumor volumes only exhibit translational shift, while direct re-optimization of the intensity-modulated radiation therapy (IMRT) plan maybe more desirable when extreme deformation or differential positioning changes of the organs occur. Currently, direct re-optimization of the IMRT plan using beamlet (or fluence map) has not been reported. In this study, we report a novel on-line re-optimization technique that can accomplish plan adjustment on-line. Deformable image registration is used to provide position variation information on each voxel along the three dimensions. The original planned dose distribution is used as the 'goal' dose distribution for adaptation and to ensure planning quality. Fluence maps are re-optimized via linear programming, and a plan solution can be achieved within 2 min. The feasibility of this technique is demonstrated with a clinical case with large deformation. Such on-line ART process can be highly valuable with hypo-fractionated prostate IMRT treatment.

  20. On-line re-optimization of prostate IMRT plans for adaptive radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Q Jackie [Department of Radiation Oncology, Duke University Medical Center Durham, NC (United States); Thongphiew, Danthai [Department of Radiation Oncology, Duke University Medical Center Durham, NC (United States); Wang, Zhiheng [Department of Radiation Oncology, Duke University Medical Center Durham, NC (United States); Mathayomchan, Boonyanit [Department of Electrical Engineering and Computer Science, Case Western Reserve University Cleveland, OH (United States); Chankong, Vira [Department of Electrical Engineering and Computer Science, Case Western Reserve University Cleveland, OH (United States); Yoo, Sua [Department of Radiation Oncology, Duke University Medical Center Durham, NC (United States); Lee, W Robert [Department of Radiation Oncology, Duke University Medical Center Durham, NC (United States); Yin, Fang-Fang [Department of Radiation Oncology, Duke University Medical Center Durham, NC (United States)

    2008-02-07

    For intermediate and high risk prostate cancer, both the prostate gland and seminal vesicles are included in the clinical target volume. Internal motion patterns of these two organs vary, presenting a challenge for adaptive treatment. Adaptive techniques such as isocenter repositioning and soft tissue alignment are effective when tumor volumes only exhibit translational shift, while direct re-optimization of the intensity-modulated radiation therapy (IMRT) plan maybe more desirable when extreme deformation or differential positioning changes of the organs occur. Currently, direct re-optimization of the IMRT plan using beamlet (or fluence map) has not been reported. In this study, we report a novel on-line re-optimization technique that can accomplish plan adjustment on-line. Deformable image registration is used to provide position variation information on each voxel along the three dimensions. The original planned dose distribution is used as the 'goal' dose distribution for adaptation and to ensure planning quality. Fluence maps are re-optimized via linear programming, and a plan solution can be achieved within 2 min. The feasibility of this technique is demonstrated with a clinical case with large deformation. Such on-line ART process can be highly valuable with hypo-fractionated prostate IMRT treatment.

  1. On-line re-optimization of prostate IMRT plans for adaptive radiation therapy

    Science.gov (United States)

    Wu, Q. Jackie; Thongphiew, Danthai; Wang, Zhiheng; Mathayomchan, Boonyanit; Chankong, Vira; Yoo, Sua; Lee, W. Robert; Yin, Fang-Fang

    2008-02-01

    For intermediate and high risk prostate cancer, both the prostate gland and seminal vesicles are included in the clinical target volume. Internal motion patterns of these two organs vary, presenting a challenge for adaptive treatment. Adaptive techniques such as isocenter repositioning and soft tissue alignment are effective when tumor volumes only exhibit translational shift, while direct re-optimization of the intensity-modulated radiation therapy (IMRT) plan maybe more desirable when extreme deformation or differential positioning changes of the organs occur. Currently, direct re-optimization of the IMRT plan using beamlet (or fluence map) has not been reported. In this study, we report a novel on-line re-optimization technique that can accomplish plan adjustment on-line. Deformable image registration is used to provide position variation information on each voxel along the three dimensions. The original planned dose distribution is used as the 'goal' dose distribution for adaptation and to ensure planning quality. Fluence maps are re-optimized via linear programming, and a plan solution can be achieved within 2 min. The feasibility of this technique is demonstrated with a clinical case with large deformation. Such on-line ART process can be highly valuable with hypo-fractionated prostate IMRT treatment. Abstract and preliminary data presented at 49th AAPM Annual Meeting, Minneapolis, MN, USA, July 2007.

  2. Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy.

    Science.gov (United States)

    Boccia, Ralph; Cooper, William; O'Boyle, Erin

    2015-02-01

    A phase 3 trial in patients with cancer who received chemotherapy has shown that subcutaneous (SC) APF530, a sustained-delivery formulation of granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV). To investigate the sustainability of APF530 antiemetic responses during multiple chemotherapy cycles. 1,395 patients receiving moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg, respectively) or palonosetron 0.25 mg intravenously before cycle 1 of chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1 continued their APF530 dose. Between-group response rates were compared using the Fisher exact test. Complete response (CR; no emesis, no rescue medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4 cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase. Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses showed no significant differences. With HEC, APF530 500 mg provided sustained CRs through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in 57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%. Nausea prevention was nearly as effective as emesis prevention. Chemotherapy emetogenicity was classified according to Hesketh criteria during the time of this study. However, subsequent post hoc analyses indicate that reclassification according to newer ASCO emetogenicity guidelines did not alter the original study noninferiority conclusions. CR rates with APF530 during the acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. ©2015 Frontline Medical Communications.

  3. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    Science.gov (United States)

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [

  4. Efficiency gains for spinal radiosurgery using multicriteria optimization intensity modulated radiation therapy guided volumetric modulated arc therapy planning.

    Science.gov (United States)

    Chen, Huixiao; Winey, Brian A; Daartz, Juliane; Oh, Kevin S; Shin, John H; Gierga, David P

    2015-01-01

    To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively (P < .05). The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced

  5. Optimal simulations of ultrasonic fields produced by large thermal therapy arrays using the angular spectrum approach.

    Science.gov (United States)

    Zeng, Xiaozheng; McGough, Robert J

    2009-05-01

    The angular spectrum approach is evaluated for the simulation of focused ultrasound fields produced by large thermal therapy arrays. For an input pressure or normal particle velocity distribution in a plane, the angular spectrum approach rapidly computes the output pressure field in a three dimensional volume. To determine the optimal combination of simulation parameters for angular spectrum calculations, the effect of the size, location, and the numerical accuracy of the input plane on the computed output pressure is evaluated. Simulation results demonstrate that angular spectrum calculations performed with an input pressure plane are more accurate than calculations with an input velocity plane. Results also indicate that when the input pressure plane is slightly larger than the array aperture and is located approximately one wavelength from the array, angular spectrum simulations have very small numerical errors for two dimensional planar arrays. Furthermore, the root mean squared error from angular spectrum simulations asymptotically approaches a nonzero lower limit as the error in the input plane decreases. Overall, the angular spectrum approach is an accurate and robust method for thermal therapy simulations of large ultrasound phased arrays when the input pressure plane is computed with the fast nearfield method and an optimal combination of input parameters.

  6. Development of an optimization concept for arc-modulated cone beam therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ulrich, Silke; Nill, Simeon; Oelfke, Uwe [Department of Medical Physics in Radiation Therapy, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2007-07-21

    In this paper, we propose an optimization concept for a rotation therapy technique which is referred to as arc-modulated cone beam therapy (AMCBT). The aim is a reduction of the treatment time while achieving a treatment plan quality equal to or better than that of IMRT. Therefore, the complete dose is delivered in one single gantry rotation and the beam is modulated by a multileaf collimator. The degrees of freedom are the field shapes and weights for a predefined number of beam directions. In the new optimization loop, the beam weights are determined by a gradient algorithm and the field shapes by a tabu search algorithm. We present treatment plans for AMCBT for two clinical cases. In comparison to step-and-shoot IMRT treatment plans, it was possible by AMCBT to achieve dose distributions with a better dose conformity to the target and a lower mean dose for the most relevant organ at risk. Furthermore, the number of applied monitor units was reduced for AMCBT in comparison to IMRT treatment plans.

  7. THE EFFICIENCY OF PHYSICAL THERAPY IN OPTIMIZING THE RESPIRATORY FUNCTION FOR ASTHMATIC CHILDREN

    Directory of Open Access Journals (Sweden)

    Rata Marinela

    2013-12-01

    Full Text Available The purpose of this paper is to highlight the role of physical therapy in the field of respiratory pathology in children, mainly in bronchial asthma. By the hypothesis we want to prove that the intervention through physical therapy applied based on structured programs according to the needs of the subject and implemented by a specific methodology is able to optimize the functionality of asthmatic children. Material. The subjects of the study were three in number, aged 4-6 years, diagnosed with infantile asthma around the age of three years old. The experimental methods were selected based on objective clinical and functional assessment and intervention methods were chosen according with specific objectives, exemplifying respiratory exercises, games with objects and equipment, respiratory flow modulation techniques. Sessions were conducted three times a week totaling an amount of 36 sessions over three months. We obtained favorable results for all evaluated parameters, which were also influenced by the severity and number of occurrences of crises, the precocity of diagnosis and the moment when the treatment program started, the consistency of treatment sessions, the conditions of their entire activity and permanent collaboration between physician, physical therapist and parents. In conclusion, the experiment confirms the effectiveness of respiratory physiotherapy to optimize functionality in asthmatic children. Performing breathing exercises significantly reduces the occurrence of wheezing and improves effort capacity.

  8. Whether noninvasive optimization of AV and VV delays improves the response to cardiac resynchronization therapy.

    Science.gov (United States)

    Urbanek, Bożena; Chudzik, Michał; Klimczak, Artur; Rosiak, Marcin; Lewek, Joanna; Wranicz, Jerzy Krzysztof

    2013-01-01

    Device optimization is not routinely performed in patients who underwent cardiac resynchronization therapy (CRT) device implantation. Noninvasive optimization of CRT devices by measurement of cardiac output (CO) can be used as a simple method to assess ventricular systolic performance. The aim of this study was to assess whether optimization of atrioventricular (AV) and interventricular (VV) delay can improve hemodynamic response to CRT and whether this optimization should be performed for each patient individually. Twenty patients with advanced heart failure New York Heart Association (NYHA) class III/IV, left ventricular ejection fraction ≤ 35% and left bundle branch block (QRS ≥ 120 ms) in sinus rhythm were evaluated from 24 h to 48 h after implantation of a CRT device by means of impedance cardiography (ICG). CO was first measured at each patient's intrinsic rhythm. Patients then underwent adjustments of AV and VV delay from 80 ms to 140 ms and from -60 ms to +60 ms, respectively in 20 ms increment steps and CO at each setting was measured by ICG. Both AV and VV delays were programmed according to the greatest improvement in CO compared to intrinsic rhythm. There was a statistically signifi cant increase in CO measured at the intrinsic rhythm compared to different AV delay by mean of 21% (3.8 ± 1.0 vs. 4.6 ± 0.1 L/min, p AV/VV delays with left ventricle-preexcitation or simultaneous biventricular pacing caused additional increased CO from intrinsic rhythm by mean of 32.6% (3.8 ± 1.0 vs. 5.04 ± ± 1.0 L/min, p AV/VV setting delays also resulted in improved hemodynamic responses compared to VV factory setting delay. Both AV and VV delay optimization should be performed in clinical practice. Optimal AV delay improved outcome. However, combination of optimized AV/VV delays provided the best hemodynamic response. Optimized AV/VV delays with left ventricle-preexcitation or simultaneous biventricular pacing increased hemodynamic output compared to intrinsic

  9. Laboratory evaluations to optimize outcomes of antioxidant nutrition therapy in diabetes management

    Directory of Open Access Journals (Sweden)

    Ezekiel Uba Nwose

    2009-01-01

    Full Text Available Medical nutrition therapy (MNT guidelines acknowledge the need to identify deficiencies of antioxidant vitamins. However, the guidelines contain that such identification is difficult. Thus, there is evidence that available clinical laboratory tests for antioxidant vitamins C and E are not in perspective in clinical practice. Coenzyme-Q 10 and glutathione tests are also available in research laboratories. These indices are invaluable tools for discrete recommendation and monitoring of antioxidant nutrition therapies. This commentary addresses biomarker insight to what the MNT guidelines consider difficult. The importance and limits of the various dietary antioxidants is overviewed. It puts in perspective how clinical laboratory monitoring of vitamins C and E levels can be used to optimize the outcomes of dietary evaluations for diabetes management. Insight to how to interpret the laboratory results is presented. The importance of this commentary is hinged on the premise that the outcome of dietary therapy can be counter-productive when laboratory evaluation or limitations of the antioxidant nutrients are undermined. (Nwose EU.

  10. Laboratory evaluations to optimize outcomes of antioxidant nutrition therapy in diabetes management

    Directory of Open Access Journals (Sweden)

    Ezekiel Uba Nwose

    2009-08-01

    Full Text Available Medical nutrition therapy (MNT guidelines acknowledge the need to identify deficiencies of antioxidant vitamins. However, the guidelines contain that such identification is difficult. Thus, there is evidence that available clinical laboratory tests for antioxidant vitamins C and E are not in perspective in clinical practice. Coenzyme-Q10 and glutathione tests are also available in research laboratories. These indices are invaluable tools for discrete recommendation and monitoring of antioxidant nutrition therapies. This commentary addresses biomarker insight to what the MNT guidelines consider difficult. The importance and limits of the various dietary antioxidants is overviewed. It puts in perspective how clinical laboratory monitoring of vitamins C and E levels can be used to optimize the outcomes of dietary evaluations for diabetes management. Insight to how to interpret the laboratory results is presented. The importance of this commentary is hinged on the premise that the outcome of dietary therapy can be counter-productive when laboratory evaluation or limitations of the antioxidant nutrients are undermined.

  11. Spectromicroscopy of boron for the optimization of boron neutron capture therapy (BNCT) for cancer

    Science.gov (United States)

    Gilbert, B.; Redondo, J.; Baudat, P.-A.; Lorusso, G. F.; Andres, R.; Van Meir, E. G.; Brunet, J.-F.; Hamou, M.-F.; Suda, T.; Mercanti, Delio; Ciotti, M. Teresa; Droubay, T. C.; Tonner, B. P.; Perfetti, P.; Margaritondo, M.; DeStasio, Gelsomina

    1998-10-01

    We used synchrotron spectromicroscopy to study the microscopic distribution of boron in rat brain tumour and healthy tissue in the field of boron neutron capture therapy (BNCT). The success of this experimental cancer therapy depends on the preferential uptake of ? in tumour cells after injection of a boron compound (in our case ?, or BSH). With the Mephisto (microscope à emission de photoélectrons par illumination synchrotronique de type onduleur) spectromicroscope, high-magnification imaging and chemical analysis was performed on brain tissue sections from a rat carrying an implanted brain tumour and the results were compared with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) detection of boron in bulk tissue. Boron was found to have been taken up more favourably by regions of tumour rather than healthy tissue, but the resulting boron distribution in the tumour was inhomogeneous. The results demonstrate that Mephisto can perform microchemical analysis of tissue sections, detect and localize the presence of boron with submicron spatial resolution. The application of this technique to boron in brain tissue can therefore be used to evaluate the current efforts to optimize BNC therapy.

  12. Spectromicroscopy of boron for the optimization of boron neutron capture therapy (BNCT) for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, B.; Redondo, J.; Baudat, P-A. [Institut de Physique Appliquee, Ecole Polytechnique Federale, Lausanne (Switzerland)] [and others

    1998-10-07

    We used synchrotron spectromicroscopy to study the microscopic distribution of boron in rat brain tumour and healthy tissue in the field of boron neutron capture therapy (BNCT). The success of this experimental cancer therapy depends on the preferential uptake of {sup 10}B in tumour cells after injection of a boron compound (in our case B{sub 12}H{sub 11}SH, or BSH). With the Mephisto (microscope a emission de photoelectrons par illumination synchrotronique de type onduleur) spectromicroscope, high-magnification imaging and chemical analysis was performed on brain tissue sections from a rat carrying an implanted brain tumour and the results were compared with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) detection of boron in bulk tissue. Boron was found to have been taken up more favourably by regions of tumour rather than healthy tissue, but the resulting boron distribution in the tumour was inhomogeneous. The results demonstrate that Mephisto can perform microchemical analysis of tissue sections, detect and localize the presence of boron with submicron spatial resolution. The application of this technique to boron in brain tissue can therefore be used to evaluate the current efforts to optimize BNC therapy. (author)

  13. The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease.

    Science.gov (United States)

    Chen, Shi-Jian; Liu, Wei; Huang, Bao-Tao; Tsauo, Jia-Yu; Pu, Xiao-Bo; Peng, Yong; Chen, Mao; Huang, De-Jia

    2017-02-01

    To analyze the current usage of optimal medical therapy (OMT), influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease (CAD) patients with different subgroups. A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Out of 3176 patients, only 39.8% (n = 1265) were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% (n = 217) of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (HR: 0.65, 95% CI: 0.45-0.95; P = 0.025). Sub-group analyses indicate that male acute coronary syndrome (ACS) patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. OMT was associated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.

  14. Optimized noninvasive monitoring of thermal changes on digital B-mode renal sonography during revascularization therapy.

    Science.gov (United States)

    Abolhassani, Mohammad D; Tavakoli, Vahid; Sahba, Nima

    2009-11-01

    Noninvasive real-time thermal change monitoring of human internal organs can play a critical role in diagnosis and treatment of many disorders, including reperfusion of renal arteries during anticoagulation therapy. This article focuses on tissue temperature detection using ultrasound velocity changes in different structures and their related speckle shift from their primary locations on high-quality B-mode digital sonography. We evaluated different speckle-tracking techniques and optimized them using appropriate motion estimation methods to determine the best algorithm and parameters. Performing thermal detection methods on simulated phantoms showed a good correlation between speckle shifts and the ground truth temperature. For the simulated images, average thermal error was 0.5 degrees C with an SD of 0.5 degrees C, where lower errors can be obtained in noiseless (motionless) data. The proposed technique was evaluated on real in vivo cases during surgical occlusion and reopening of the renal segmental artery and showed the potential of the algorithm for observation of internal organ changes using only digital ultrasound systems for diagnosis and therapy. The adaptive Rood pattern search proved to be the best block-matching technique, whereas the multiresolution Horn-Schunck technique was the best gradient optical flow method. The extracted thermal change during in vivo revascularization therapy is promising. In addition, we present an evaluation of several block-matching and optical flow motion estimation techniques.

  15. Range optimization for mono- and bi-energetic proton modulated arc therapy with pencil beam scanning

    Science.gov (United States)

    Sanchez-Parcerisa, Daniel; Kirk, Maura; Fager, Marcus; Burgdorf, Brendan; Stowe, Malorie; Solberg, Tim; Carabe, Alejandro

    2016-11-01

    The development of rotational proton therapy plans based on a pencil-beam-scanning (PBS) system has been limited, among several other factors, by the energy-switching time between layers, a system-dependent parameter that ranges between a fraction of a second and several seconds. We are investigating mono- and bi-energetic rotational proton modulated arc therapy (PMAT) solutions that would not be affected by long energy switching times. In this context, a systematic selection of the optimal proton energy for each arc is vital. We present a treatment planning comparison of four different range selection methods, analyzing the dosimetric outcomes of the resulting treatment plans created with the ranges obtained. Given the patient geometry and arc definition (gantry and couch trajectories, snout elevation) our in-house treatment planning system (TPS) FoCa was used to find the maximum, medial and minimum water-equivalent thicknesses (WETs) of the target viewed from all possible field orientations. Optimal ranges were subsequently determined using four methods: (1) by dividing the max/min WET interval into equal steps, (2) by taking the average target midpoints from each field, (3) by taking the average WET of all voxels from all field orientations, and (4) by minimizing the fraction of the target which cannot be reached from any of the available angles. After the range (for mono-energetic plans) or ranges (for bi-energetic plans) were selected, the commercial clinical TPS in use in our institution (Varian Eclipse™) was used to produce the PMAT plans using multifield optimization. Linear energy transfer (LET) distributions of all plans were also calculated using FoCa and compared among the different methods. Mono- and bi-energetic PMAT plans, composed of a single 180° arc, were created for two patient geometries: a C-shaped target located in the mediastinal area of a thoracic tissue-equivalent phantom and a small brain tumor located directly above the brainstem. All

  16. Formulation, Optimization, and Characterization of Repaglinide Loaded Nanocrystal for Diabetes Therapy

    Directory of Open Access Journals (Sweden)

    Gajanan Shinde

    2015-01-01

    Full Text Available The aim of the present investigation was to formulate and characterize nanocrystal formulation of Repaglinide for diabetes therapy. Formulation was done by high pressure homogenization. HPH pressure and cycles range were screened by preliminary batches (T1 and T2. 5, 8, and 10 cycles and 500 to 1500 bar pressure range had kept for further investigation. Taguchi design was used to optimize type of polymer, % polymer concentration, number of cycles, and HPH pressure for nanocrystal formulation. Formulations were characterized for particle size, zeta potential, and in vitro drug release. Optimized formulation (NC 3 showed particle size of 187 nm, zeta potential of −29.4 mv, and % drug release of 80.58% and it was used for further study. Data analysis proved significant effects of factors on responses. Polydispersity index (PDI Analysis of optimized formulation were found to be 0.248. SEM showed nanocrystal aggregation of drug, may be due to water removal process. DSC showed slight change in crystallinity, may be due to the presence of PEG 4000. Stability study was carried out for 3 months. It indicated no significant change in particle size and zeta potential. However, further studies in higher animals and human being need to be performed before this formulation can be commercially exploited.

  17. Beam neutron energy optimization for boron neutron capture therapy using Monte Carlo method

    Directory of Open Access Journals (Sweden)

    Ali Pazirandeh

    2006-06-01

    Full Text Available  In last two decades the optimal neutron energy for the treatment of deep seated tumors in boron neutron capture therapy in view of neutron physics and chemical compounds of boron carrier has been under thorough study. Although neutron absorption cross section of boron is high (3836b, the treatment of deep seated tumors such as gliobelastoma multiform (GBM requires beam of neutrons of higher energy that can penetrate deeply into the brain and thermalize in the proximity of the tumor. Dosage from recoil proton associated with fast neutrons however poses some constraints on maximum neutron energy that can be used in the treatment. For this reason neutrons in the epithermal energy range of 10eV-10keV are generally to be the most appropriate. The simulation carried out by Monte Carlo methods using MCBNCT and MCNP4C codes along with the cross section library in 290 groups extracted from ENDF/B6 main library. The optimal neutron energy for deep seated tumors depends on the size and depth of tumor. Our estimated optimized energy for the tumor of 5cm wide and 1-2cm thick stands at 5cm depth is in the range of 3-5keV

  18. Optimal duration of dual antiplatelet therapy following percutaneous coronary intervention: protocol for an umbrella review

    Science.gov (United States)

    Kelly, Shannon E; Bai, Zemin; Liu, Wenfei; Skidmore, Becky; Boucher, Michel; So, Derek Y F; Wells, George A

    2017-01-01

    Introduction Although dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting, the optimal duration is unknown. Recent evidence indicates there may be benefits in extending the duration beyond 12 months but such decisions may increase the risk of bleeding. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review assessing the optimal duration of DAPT. Methods and analysis We will perform a comprehensive search of the published and grey literature for systematic reviews involving randomised controlled trials (RCTs) assessing the optimal duration of DAPT following PCI with stenting. The intervention of interest is extended DAPT (beyond 12 months) compared with short-term DAPT (6–12 months). Studies will be selected for inclusion by two reviewers, and the quality will be assessed. The primary outcomes of interest are all-cause mortality and cardiovascular mortality. Secondary outcomes will be bleeding (major, minor and gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Outcomes will be assessed while on DAPT and after withdrawal of DAPT. Data will be summarised with respect to the number of included RCTs, number of participants, effect estimates and heterogeneity. Data will be reported separately based on patient demographics, procedural parameters (eg, stent types, lesion complexity and concurrent disease) and clinical presentation (eg, acute coronary syndromes, infarct type). Ethics and dissemination Our umbrella review aims to provide a comprehensive overview of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration and reimbursement of DAPT following PCI with stenting

  19. Proton energy optimization and reduction for intensity-modulated proton therapy

    Science.gov (United States)

    Cao, Wenhua; Lim, Gino; Liao, Li; Li, Yupeng; Jiang, Shengpeng; Li, Xiaoqiang; Li, Heng; Suzuki, Kazumichi; Zhu, X. Ronald; Gomez, Daniel; Zhang, Xiaodong

    2014-10-01

    Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To ‘scan’ the target volume, the proton beam is controlled by varying its energy to penetrate the patient’s body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20 m s-1, changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%-18.9% for the prostate cancer cases, 11.0% for the lung cancer cases and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed.

  20. Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Tayarani-Najaran, Z; Talasaz-Firoozi, E; Nasiri, R; Jalali, N; Hassanzadeh, Mk

    2013-01-01

    This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ(2) test, relative risk, and Student's t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p essential oils were used. M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective.

  1. 化疗止吐药物的研究进展%The Progress of Chemotherapy Antiemetic Drugs

    Institute of Scientific and Technical Information of China (English)

    陈露露; 王亚芹; 欧阳冬生

    2014-01-01

    Nausea and vomiting are the most frequent adverse reactions of chemotherapeutic agents. Severe vomiting may affect the efficacy of drugs by affecting the compliance of patients. The common chemotherapy antiemetic drugs include dopamine blockers, 5-HT3 receptor antagonists, NK-1 receptor antagonists and hormones. Meanwhile, Chinese herbal medi-cine play an important role in preventing vomiting caused by chemotherapy. In this essay, we reviewed the pharmacological mechanisms and security of the common antiemetics so as to provide a guidance for their clinical applications.%恶心、呕吐是肿瘤化疗药物最常见的不良反应。严重呕吐会影响患者的依从性,进而影响药物的疗效。常见的止吐药物包括多巴胺阻断剂、5-HT3受体阻断剂、NK-1受体阻断剂和激素类。中草药在防治化疗呕吐中也具有重要地位。本文对止吐药的药理作用机制和安全性研究进展进行了综述,以期为化疗止吐药物的临床使用提供参考。

  2. Explicit and convex optimization of plan quality measures in intensity-modulated radiation therapy treatment planning

    CERN Document Server

    Engberg, Lovisa; Forsgren, Anders; Hårdemark, Björn

    2016-01-01

    Given the widespread agreement that doses-at-volume play important roles in quality assessment of radiation therapy treatment plans, planning objectives that correlate well with explicit dose-at-volume optimization are likely to correlate well with plan quality. In this study, planning objectives are formulated to explicitly either minimize or maximize convex approximations of dose-at-volume, namely, mean-tail-doses. This is in contrast to the conventionally used planning objectives, which are used to maximize clinical goal fulfilment by relating to deviations from dose-at-volume thresholds. Advantages of the proposed planning objectives are investigated through juxtaposition with conventional objectives in a computational study of two patient cases, each with three doses-at-volume to be minimized subject to PTV coverage. With proposed planning objectives, this is translated into minimizing three mean-tail-doses. Comparison with conventional objectives is carried out in the dose-at-volume domain and in the no...

  3. Quantum dot nanoparticle for optimization of breast cancer diagnostics and therapy in a clinical setting.

    Science.gov (United States)

    Radenkovic, Dina; Kobayashi, Hisataka; Remsey-Semmelweis, Ernö; Seifalian, Alexander M

    2016-08-01

    Breast cancer is the most common cancer in the world. Sentinel lymph node (SLN) biopsy is used for staging of axillary lymph nodes. Organic dyes and radiocolloid are currently used for SLN mapping, but expose patients to ionizing radiation, are unstable during surgery and cause local tissue damage. Quantum dots (QD) could be used for SLN mapping without the need for biopsy. Surgical resection of the primary tumor is the optimal treatment for early-diagnosed breast cancer, but due to difficulties in defining tumor margins, cancer cells often remain leading to reoccurrences. Functionalized QD could be used for image-guided tumor resection to allow visualization of cancer cells. Near Infrared QD are photostable and have improved deep tissue penetration. Slow elimination of QD raises concerns of potential accumulation. Nevertheless, promising findings with cadmium-free QD in recent in vivo studies and first in-human trial suggest huge potential for cancer diagnostic and therapy.

  4. The Use of Optimism in Narrative Therapy with Sexual Abuse Survivors

    Directory of Open Access Journals (Sweden)

    Z. Seda Sahin

    2009-12-01

    Full Text Available Examining the victim’s causal attributions and attribution style associated with sexual abuse may add to the understanding of how survivors make meaning of such experiences and create the related narratives. Through the use of optimism in narrative therapy, the survivor is encouraged to deconstruct the dominant story of being a victim and making new, personal meanings in order to broaden the possibility for other plot-lines and preferred stories with the problems related to sexual abuse being attributed to external, unstable and specific factors. By using the questions that the authors of this paper propose, the therapist can help to deconstruct their dominant stories and create a more optimistic subjugated story.

  5. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II {approx} IV or WHO tumor type B2 {approx} C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; {rho} = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; {rho} = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; {rho} = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; {rho} = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated.

  6. Effects of Anti-Helicobacter pylori Treatment as Part of Antiemetic Cancer Chemotherapy%抗幽门螺杆菌治疗在肿瘤化疗止吐中的作用研究

    Institute of Scientific and Technical Information of China (English)

    朴瑛; 刘兆喆; 丁震宇; 徐龙; 郭放; 孙庆庆; 谢晓冬

    2012-01-01

    Objective: This work aims to assess the effects of anti-Helicobacter pylori (anti-H. pylori) therapy combined with antiemetic drugs on chemotherapy-induced gastrointestinal toxicity. Methods: Out of the 176 patients who were enrolled in the research from January 2010 to January 2011, 86 were infected by H. pylori. Infected patients were randomly divided into Groups A and B. Patients in Group A (n= 43) received anti-H. pylori therapy combined with antiemetic drugs (20 mg omeprazole, 500 mg clarithromycin, and 500 mg tinidazole, twice a day, plus 5 mg tropisetron, for four weeks) Patients in Group B (n=43) only received antiemetic drugs (5 mg tropisetron for four weeks). No statistical significance was observed between Groups A and B for gender, age, and clinical manifestations. Clinical symptoms were observed and evaluated based on the gastrointestinal reaction indexing standards of the World Health Organization. The H. pylori eradication rate was assessed by 4C-urea breath test. Results: The vomiting severity was higher in the patients who were infected by H. pylori and subsequently underwent chemotherapy compared with the non-infected patients. Significant differences were observed between grades Ⅲ and Ⅳ vomiting (x2=21.92, P<0.001), as well as between grades I and Ⅱvomiting (x2=9.73, PO.01). The degree of nausea and vomiting was reduced in the patients who underwent anti-H. pylori therapy combined with antiemetic drugs, compared with those who only received antiemetic drugs. The total efficiency of the treatment was significantly higher in group A than in group B (x2=4.46, P<0.05). Conclusion: Anti-H. pylori treatment combined with antiemetic drugs may effectively reduce and relieve chemotherapy-induced gastrointestinal toxicity for patients infected with H. pylori.%目的:评估抗幽门螺杆菌(Helicobacter pylori,HP)治疗及联合常规止吐药物对肿瘤患者化疗所致胃肠道不良反应的疗效.方法:2010年1月至2011年1

  7. Optimization of immunoglobulin substitution therapy by a stochastic immune response model.

    Directory of Open Access Journals (Sweden)

    Marc Thilo Figge

    Full Text Available BACKGROUND: The immune system is a complex adaptive system of cells and molecules that are interwoven in a highly organized communication network. Primary immune deficiencies are disorders in which essential parts of the immune system are absent or do not function according to plan. X-linked agammaglobulinemia is a B-lymphocyte maturation disorder in which the production of immunoglobulin is prohibited by a genetic defect. Patients have to be put on life-long immunoglobulin substitution therapy in order to prevent recurrent and persistent opportunistic infections. METHODOLOGY: We formulate an immune response model in terms of stochastic differential equations and perform a systematic analysis of empirical therapy protocols that differ in the treatment frequency. The model accounts for the immunoglobulin reduction by natural degradation and by antigenic consumption, as well as for the periodic immunoglobulin replenishment that gives rise to an inhomogeneous distribution of immunoglobulin specificities in the shape space. Results are obtained from computer simulations and from analytical calculations within the framework of the Fokker-Planck formalism, which enables us to derive closed expressions for undetermined model parameters such as the infection clearance rate. CONCLUSIONS: We find that the critical value of the clearance rate, below which a chronic infection develops, is strongly dependent on the strength of fluctuations in the administered immunoglobulin dose per treatment and is an increasing function of the treatment frequency. The comparative analysis of therapy protocols with regard to the treatment frequency yields quantitative predictions of therapeutic relevance, where the choice of the optimal treatment frequency reveals a conflict of competing interests: In order to diminish immunomodulatory effects and to make good economic sense, therapeutic immunoglobulin levels should be kept close to physiological levels, implying high

  8. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael; Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Weber, Randal S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kies, Merrill S. [Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lewin, Jan S. [Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Palmer, Matthew B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-07-15

    Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

  9. GPU-based ultra-fast direct aperture optimization for online adaptive radiation therapy

    CERN Document Server

    Men, Chunhua; Jiang, Steve B

    2010-01-01

    Online adaptive radiation therapy (ART) has great promise to significantly reduce normal tissue toxicity and/or improve tumor control through real-time treatment adaptations based on the current patient anatomy. However, the major technical obstacle for clinical realization of online ART, namely the inability to achieve real-time efficiency in treatment re-planning, has yet to be solved. To overcome this challenge, this paper presents our work on the implementation of an intensity modulated radiation therapy (IMRT) direct aperture optimization (DAO) algorithm on graphics processing unit (GPU) based on our previous work on CPU. We formulate the DAO problem as a large-scale convex programming problem, and use an exact method called column generation approach to deal with its extremely large dimensionality on GPU. Five 9-field prostate and five 5-field head-and-neck IMRT clinical cases with 5\\times5 mm2 beamlet size and 2.5\\times2.5\\times2.5 mm3 voxel size were used to evaluate our algorithm on GPU. It takes onl...

  10. Adjuvant Systemic Therapy in Older Breast Cancer Women: Can We Optimize the Level of Care?

    Directory of Open Access Journals (Sweden)

    Anna Rachelle Mislang

    2015-07-01

    Full Text Available Defining optimal adjuvant treatment for older women with breast cancer is challenged by the lack of level-1 clinical evidence and the heterogeneity of the older population. Nevertheless, recommendations based on reviews of available evidence mainly from retrospective subgroup analyses and extrapolation of study results from younger patients, and expert opinions, may be useful to guide treatment decisions in fit patients. But how can we properly define a “fit” older patient? In clinical practice, age by itself and clinical impression generally drive treatment decision, although the appropriateness of this judgment is under-documented. Such an approach risks overtreatment or, more frequently, undertreatment. A geriatric assessment can be valuable in oncology practice to address this issue. In this review article, we will focus only on systemic treatment and will discuss “standard” adjuvant systemic treatment strategies for fit older breast cancer patients and the role of “personalized” systemic therapy in unfit patients. The concepts conveyed in this review cannot be extrapolated to locoregional therapy.

  11. Optimization of the geometry and composition of a neutron system for treatment by Boron Neutron Capture Therapy

    OpenAIRE

    2015-01-01

    Background: In the field of the treatment by Boron Neutron Capture Therapy (BNCT), an optimized neutron system was proposed. This study (simulation) was conducted to optimize the geometry and composition of neutron system and increase the epithermal neutron flux for the treatment of deep tumors is performed. Materials and Methods: A neutron system for BNCT was proposed. The system included 252Cf neutron source, neutron moderator/reflector arrangement, filter and concrete. To capture fast ...

  12. Including robustness in multi-criteria optimization for intensity-modulated proton therapy

    CERN Document Server

    Chen, Wei; Trofimov, Alexei; Madden, Thomas; Kooy, Hanne; Bortfeld, Thomas; Craft, David

    2011-01-01

    We present a method to include robustness into a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios. The optimization method is based on a linear...

  13. Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

    Science.gov (United States)

    Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

    2013-06-01

    In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less

  14. OPTIMAL REGIMENS OF THE BASAL-BOLUS INSULIN THERAPY IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    G. A. Galkina

    2015-01-01

    Full Text Available This study was aimed to determine peculiarities in regimens of the pump insulin therapy and to reveal the optimal basal-to-bolus insulin ratio that are necessary for achieving optimal glycemic control in adoles-cents with type 1 diabetes mellitus (T1DM.  82 adolescents at the age of 14–18 with T1DM, using continuous subcutaneous insulin infusion (CSII from 5 months to 7.5 years were monitored with continuous glucose monitoring (CGM system «Guar-dian Real Time» or CGM system, built in MiniMed Paradigm Revel System 722 (Medtronic Minimed, USA. Assessing the quality of glycaemic control was based on the level of glycated haemoglobin (HbA1c. The results of CGM were reviewed and average for 3 days performances: total daily dose of insulin, dose of basal and bolus insulin, basal-to-bolus insulin ratio, carbohydrate content of the meal, expressed in BE, carbohydrate ratio, insulin sensitivity factor were determined. The patients were subdivided into 2 groups: group 1 – adolescents with the optimal/suboptimal glycemic control (n = 55, 2 – adolescents with long-standing poorly controlled T1DM (n = 27. Average total daily dose of basal insulin (U in a day, U per kg in a day in adolescents group 1 was significantly higher, com-pared with patients in group 2 (р = 0.043; р = 0.038 respectively. Patients in group 2 received more car-bohydrates with a meal intake and had higher doses of average total daily bolus insulin. The average ba-sal-to-bolus ratio from group 1 patients was 51/49%, compared with group 2 patients – 45/55% (р = 0.026.  An important condition for achieving optimal glycemic control is a high level of compliance and skills of adolescents. Optimal well-balanced basal-to-bolus insulin ratio in adolescents with T1DM on CSII, which can provide improvements in blood glucose management and reducing the risk of complications of the disease, is 51/49%. 

  15. Optimization of extracranial stereotactic radiation therapy of small lung lesions using accurate dose calculation algorithms

    Directory of Open Access Journals (Sweden)

    Polednik Martin

    2006-11-01

    Full Text Available Abstract Background The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. Methods A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. Results The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. Conclusion The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction.

  16. Does imiquimod pretreatment optimize 308-nm excimer laser (UVB) therapy in psoriasis patients?

    Science.gov (United States)

    Tacastacas, Joselin D; Oyetakin-White, Patricia; Soler, David C; Young, Andrew; Groft, Sarah; Honda, Kord; Cooper, Kevin D; McCormick, Thomas S

    2017-07-01

    Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques. Eucerin(®) Original Moisturizing Lotion (topical vehicle) or Aldara(®) (imiquimod 5% topical cream) were applied for 5 days once daily to a maximum contiguous area of 25 cm(2) (5 cm × 5 cm area). Patients were provided with sachets containing 12.5 mg of imiquimod each and were instructed to apply imiquimod (I) to two psoriasis plaques (5 sachets of imiquimod allotted to each plaque). A PHAROS excimer Laser EX-308 (Ra Medical Systems, Inc. Carlsbad, CA, USA) with an output of monochromatic 308-nm light and pulse width of 20-50 ns was used for all patients. Punch biopsies of psoriatic lesions (6 mm) were taken at 4 and 48 h after final application of topical treatment with or without excimer laser treatment. Real-time quantitative RT-PCR was performed according to manufacturer's instructions and Inmunohistochemistry was used as described before. Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses. The observation that psoriasis involvement was

  17. A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy

    Science.gov (United States)

    Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

    2017-01-01

    Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

  18. Reduced Need for Rescue Antiemetics and Improved Capacity to Eat in Patients Receiving Acupuncture Compared to Patients Receiving Sham Acupuncture or Standard Care during Radiotherapy

    Science.gov (United States)

    Steineck, Gunnar; Börjeson, Sussanne

    2017-01-01

    Objective. To evaluate if consumption of emesis-related care and eating capacity differed between patients receiving verum acupuncture, sham acupuncture, or standard care only during radiotherapy. Methods. Patients were randomized to verum (n = 100) or sham (n = 100) acupuncture (telescopic blunt sham needle) (median 12 sessions) and registered daily their consumption of antiemetics and eating capacity. A standard care group (n = 62) received standard care only and delivered these data once. Results. More patients in the verum (n = 73 of 89 patients still undergoing radiotherapy; 82%, Relative Risk (RR) 1.23, 95% Confidence Interval (CI) 1.01–1.50) and the sham acupuncture group (n = 79 of 95; 83%, RR 1.24, CI 1.03–1.52) did not need any antiemetic medications, as compared to the standard care group (n = 42 out of 63; 67%) after receiving 27 Gray dose of radiotherapy. More patients in the verum (n = 50 of 89; 56%, RR 1.78, CI 1.31–2.42) and the sham acupuncture group (n = 58 of 94 answering patients; 62%, RR 1.83, CI 1.20–2.80) were capable of eating as usual, compared to the standard care group (n = 20 of 63; 39%). Conclusion. Patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture. PMID:28270851

  19. Optimization of dual-energy CT acquisitions for proton therapy using projection-based decomposition.

    Science.gov (United States)

    Vilches-Freixas, Gloria; Létang, Jean Michel; Ducros, Nicolas; Rit, Simon

    2017-09-01

    Dual-energy computed tomography (DECT) has been presented as a valid alternative to single-energy CT to reduce the uncertainty of the conversion of patient CT numbers to proton stopping power ratio (SPR) of tissues relative to water. The aim of this work was to optimize DECT acquisition protocols from simulations of X-ray images for the treatment planning of proton therapy using a projection-based dual-energy decomposition algorithm. We have investigated the effect of various voltages and tin filtration combinations on the SPR map accuracy and precision, and the influence of the dose allocation between the low-energy (LE) and the high-energy (HE) acquisitions. For all spectra combinations, virtual CT projections of the Gammex phantom were simulated with a realistic energy-integrating detector response model. Two situations were simulated: an ideal case without noise (infinite dose) and a realistic situation with Poisson noise corresponding to a 20 mGy total central dose. To determine the optimal dose balance, the proportion of LE-dose with respect to the total dose was varied from 10% to 90% while keeping the central dose constant, for four dual-energy spectra. SPR images were derived using a two-step projection-based decomposition approach. The ranges of 70 MeV, 90 MeV, and 100 MeV proton beams onto the adult female (AF) reference computational phantom of the ICRP were analytically determined from the reconstructed SPR maps. The energy separation between the incident spectra had a strong impact on the SPR precision. Maximizing the incident energy gap reduced image noise. However, the energy gap was not a good metric to evaluate the accuracy of the SPR. In terms of SPR accuracy, a large variability of the optimal spectra was observed when studying each phantom material separately. The SPR accuracy was almost flat in the 30-70% LE-dose range, while the precision showed a minimum slightly shifted in favor of lower LE-dose. Photon noise in the SPR images (20 mGy dose

  20. OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

  1. 'Ins' and 'outs' of triple therapy: Optimal antiplatelet therapy in patients on chronic oral anticoagulation who need coronary stenting.

    Science.gov (United States)

    Dewilde, W; Verheugt, F W A; Breet, N; Koolen, J J; Ten Berg, J M

    2010-09-01

    Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.).

  2. Optimal beam design on intensity-modulated radiation therapy with simultaneous integrated boost in nasopharyngeal cancer.

    Science.gov (United States)

    Cheng, Mei-Chun; Hu, Yu-Wen; Liu, Ching-Sheng; Lee, Jeun-Shenn; Huang, Pin-I; Yen, Sang-Hue; Lee, Yuh-Lin; Hsieh, Chun-Mei; Shiau, Cheng-Ying

    2014-01-01

    This study aims to determine the optimal beam design among various combinations of field numbers and beam trajectories for intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique for the treatment of nasopharyngeal cancer (NPC). We used 10 fields with gantry angles of 155°, 130°, 75°, 25°, 0° L, 0° R, 335°, 285°, 230°, and 205° denoted as F10. To decrease doses in the spinal cord, the F10 technique was designed by featuring 2 pairs of split-opposed beam fields at 155° to 335° and 205° to 25°, as well as one pair of manually split beam fields at 0°. The F10 technique was compared with 4 other common field arrangements: F7E, 7 fields with 50° equally spaced gantry angles; F7, the basis of F10 with 155°, 130°, 75°, 0°, 285°, 230°, and 205°; F9E, 9 fields with 40° equally spaced gantry angles; and FP, 7 posterior fields with 180°, 150°, 120°, 90°, 270°, 240°, and 210°. For each individual case of 10 patients, the customized constraints derived after optimization with the standard F10 technique were applied to 4 other field arrangements. The 4 new optimized plans of each individual case were normalized to achieve the same coverage of planning target volume (PTV)63Gy as that of the standard F10 technique. The F10 field arrangement exhibited the best coverage in PTV70Gy and the least mean dose in the trachea-esophagus region. Furthermore, the F10 field arrangement demonstrated the highest level of conformity in the low-dose region and the least monitor unit. The F10 field arrangement performed more outstandingly than the other field arrangements in PTV70Gy coverage and spared the central organ. This arrangement also exhibited the highest conformity and delivery efficiency. The F10 technique is recommended as the standard beam geometry for the SIB-IMRT of NPC. Copyright © 2014 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  3. Optimal beam design on intensity-modulated radiation therapy with simultaneous integrated boost in nasopharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Mei-Chun [Division of Radiation Oncology, Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China); Hu, Yu-Wen; Liu, Ching-Sheng [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lee, Jeun-Shenn [Division of Radiation Oncology, Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Huang, Pin-I; Yen, Sang-Hue; Lee, Yuh-Lin; Hsieh, Chun-Mei [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Shiau, Cheng-Ying, E-mail: cyshiau@vghtpe.gov.tw [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China)

    2014-10-01

    This study aims to determine the optimal beam design among various combinations of field numbers and beam trajectories for intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique for the treatment of nasopharyngeal cancer (NPC). We used 10 fields with gantry angles of 155°, 130°, 75°, 25°, 0° L, 0° R, 335°, 285°, 230°, and 205° denoted as F10. To decrease doses in the spinal cord, the F10 technique was designed by featuring 2 pairs of split-opposed beam fields at 155° to 335° and 205° to 25°, as well as one pair of manually split beam fields at 0°. The F10 technique was compared with 4 other common field arrangements: F7E, 7 fields with 50° equally spaced gantry angles; F7, the basis of F10 with 155°, 130°, 75°, 0°, 285°, 230°, and 205°; F9E, 9 fields with 40° equally spaced gantry angles; and FP, 7 posterior fields with 180°, 150°, 120°, 90°, 270°, 240°, and 210°. For each individual case of 10 patients, the customized constraints derived after optimization with the standard F10 technique were applied to 4 other field arrangements. The 4 new optimized plans of each individual case were normalized to achieve the same coverage of planning target volume (PTV){sub 63} {sub Gy} as that of the standard F10 technique. The F10 field arrangement exhibited the best coverage in PTV{sub 70} {sub Gy} and the least mean dose in the trachea-esophagus region. Furthermore, the F10 field arrangement demonstrated the highest level of conformity in the low-dose region and the least monitor unit. The F10 field arrangement performed more outstandingly than the other field arrangements in PTV{sub 70} {sub Gy} coverage and spared the central organ. This arrangement also exhibited the highest conformity and delivery efficiency. The F10 technique is recommended as the standard beam geometry for the SIB-IMRT of NPC.

  4. Optimal Duration of Imatinib Mesylate Therapy in Metastatic Gastrointestinal Stromal Tumours

    Directory of Open Access Journals (Sweden)

    Ruth Gauden

    2011-04-01

    Full Text Available While current literature provides evidence that imatinib mesylate has significant activity in patients with advanced and metastatic gastrointestinal stromal tumour (GIST, and highlights the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers, specific recommendations concerning the optimal duration of therapy remain controversial. This case presents the favourable outcome of a patient who originally presented almost 9 years ago with widespread, bulky, metastatic GIST involving the abdomen and pelvis. A sustained, complete response was achieved with imatinib and prompted an interruption in treatment 7 years after initial presentation. The disease reoccurred extensively within 9 months of treatment interruption, but once again rapidly completely responded to the recommencement of imatinib, with that response being now maintained for over 9 months. This report suggests that dramatic and durable responses to imatinib can be achieved in individual cases despite the lack of specific guidelines in the literature with respect to defining how long treatment with imatinib should be continued in the absence of evidence of tumour progression.

  5. Ten years of "Optimal Therapy in Advanced Ovarian Cancer. Update" meeting.

    Science.gov (United States)

    Poveda, A

    2008-01-01

    The International Symposium on Advanced Ovarian Cancer: Optimal Therapy was founded by Dr. Andrés Poveda and Prof. Jan B. Vermorken, and each edition has been directed by them. The 6th edition was held on March 2, 2007. This symposium is organized every other year by GEICO (Grupo Español de Investigación de Cáncer de Ovario/Spanish Ovarian Cancer Research Group), under the auspices of the Spanish Society of Medical Oncology (SEOM), the Gynecologic Cancer Intergroup (GCIG), and the European Society of Medical Oncology (ESMO) Educational Committee for its Medical Oncology Recertification Approval (ESMO/MORA) Program. One hundred and fifty people attended the symposium's 1st edition, held in 1996. Since then, the interest in this meeting has increased. Last year, almost three hundred people coming not only from Spain but also from Europe, North and Latin America, Asia, and Australia were present in the symposium. This is a great challenge for us. Some important international cooperative groups from Europe, America, and Australia collaborate with this symposium, such as GOG, NCIC, EORTC, AGO, Scottish Group, ICON, GINECO, NSGO, ANZGOG, and others.

  6. Acceptance and Commitment Therapy and Selective Optimization with Compensation for Institutionalized Older People with Chronic Pain.

    Science.gov (United States)

    Alonso-Fernández, Miriam; López-López, Almudena; Losada, Andres; González, José Luis; Wetherell, Julie Loebach

    2016-02-01

    Recent studies support the efficacy of Acceptance and Commitment Therapy (ACT) with people with chronic pain. In addition, Selective Optimization with Compensation strategies (SOC) can help the elderly with chronic pain to accept their chronic condition and increase functional autonomy. Our aim was to analyze the efficacy of an ACT treatment program combined with training in SOC strategies for elderly people with chronic pain living in nursing homes. 101 participants (mean age = 82.26; SD = 10.00; 78.6% female) were randomized to the intervention condition (ACT-SOC) or to a minimal support group (MS). Complete data are available for 53 participants (ACT-SOC: n = 27; MS: n = 26). Assessments of functional performance, pain intensity, pain acceptance, SOC strategies, emotional well being and catastrophizing beliefs were done preintervention and postintervention. Significant time by intervention changes (P = 0.05) were found in acceptance, pain related anxiety, compensation strategies, and pain interference in walking ability. Simple effects changes were found in acceptance (P = 0.01), selection strategies (P = 0.05), catastrophizing beliefs (P = 0.03), depressive symptoms (P = 0.05), pain anxiety (P = 0.01) and pain interference in mood and walking ability (P = 0.03) in the ACT-SOC group. No significant changes were found in the MS group. These results suggest that an ACT intervention combined with training in SOC strategies could help older people with pain to improve their emotional well being and their functional capability.

  7. Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients

    DEFF Research Database (Denmark)

    Ghotbi, Adam Ali; Sander, Mikael; Køber, Lars

    2015-01-01

    by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL. RESULTS: DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac......BACKGROUND: The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL). METHODS: Twelve CRT...... patients with non-ischemic heart failure (NYHA class II-III) were enrolled in a randomized, double-blind, crossover trial, in which the basal pacing rate was set at DDD-60 and DDD-80 for 3 months (DDD-R for 2 patients). At baseline, 3 months and 6 months, we assessed sympathetic nerve activity...

  8. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Kara Bradford; David Q Shih

    2011-01-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor a; 6-TGN administration; desensitization trials; and split dosing of 6-MP.

  9. Physical therapy adjuvants to promote optimization of walking recovery after stroke.

    Science.gov (United States)

    Bowden, Mark G; Embry, Aaron E; Gregory, Chris M

    2011-01-01

    Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s) to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s) will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1) walking specific motor control; (2) dynamic balance; (3) cardiorespiratory fitness and (4) muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance.

  10. Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

    Directory of Open Access Journals (Sweden)

    Mark G. Bowden

    2011-01-01

    Full Text Available Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1 walking specific motor control; (2 dynamic balance; (3 cardiorespiratory fitness and (4 muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance.

  11. Choosing optimal wavelength for photodynamic therapy of port wine stains by mathematic simulation

    Science.gov (United States)

    Wang, Ying; Gu, Ying; Zuo, Zhaohui; Huang, Naiyan

    2011-09-01

    Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine stains (PWS). However, how these wavelengths result in different PDT outcomes has not been clearly illuminated. This study is designed to analyze which wavelengths would be the most advantageous for use in PDT for PWS. The singlet oxygen yield in PDT-treated PWS skin under different wavelengths at the same photosensitizer dosage was simulated and the following three situations were simulated and compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation at clinical dosage (100 mW/cm2, 40 min); 2. PDT efficiency of different wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency of different wavelengths for PWS, in which only deeply located ectatic vessels remained. The results showed that singlet oxygen yield is the highest at 510 nm, it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This result is identical to the state in clinic. According to this theoretical study, the optimal wavelength for PDT in the treatment of PWS should near the absorption peaks of photosensitizer and where absorption from native chromophores (haemoglobin and melanin) is diminished.

  12. Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andreozzi, Jacqueline M., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org; Glaser, Adam K. [Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755 (United States); Zhang, Rongxiao [Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755 (United States); Gladstone, David J.; Williams, Benjamin B.; Jarvis, Lesley A., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org [Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766 (United States); Pogue, Brian W. [Thayer School of Engineering and Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755 (United States)

    2016-02-15

    Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R{sup 2} = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial

  13. Acute beneficial hemodynamic effects of a novel 3D-echocardiographic optimization protocol in cardiac resynchronization therapy.

    Directory of Open Access Journals (Sweden)

    Carolin Sonne

    Full Text Available BACKGROUND: Post-implantation therapies to optimize cardiac resynchronization therapy (CRT focus on adjustments of the atrio-ventricular (AV delay and ventricular-to-ventricular (VV interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE and three-dimensional echocardiography (3DE for individualized optimization of device based AV delays and VV intervals compared to empiric programming. METHODS: 25 recipients of CRT (male: 56%, mean age: 67 years were included in this study. Ejection fraction (EF, the primary outcome parameter, and left ventricular (LV dimensions were evaluated by 3DE before CRT (baseline, after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI, calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation, and the VV interval with the lowest SDI was programmed (individualized optimization. RESULTS: EF increased from baseline 23±7% to 30±8 (p<0.001 after AV delay optimization and to 32±8% (p<0.05 after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001. Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001. CONCLUSIONS: Compared with empiric programming of biventricular pacemakers

  14. Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

    Science.gov (United States)

    Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Giulio Favalli, Ennio; Becciolini, Andrea; Benucci, Maurizio; Gobbi, Francesca Li; Guiducci, Serena; Foti, Rosario; Mosca, Marta; Goletti, Delia

    2017-03-22

    , second-line biologic therapy may be reasonably optimized in patients with RA, SpA, and PsA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  16. EFFECTS OF RELIGIOUS VERSUS STANDARD COGNITIVE-BEHAVIORAL THERAPY ON OPTIMISM IN PERSONS WITH MAJOR DEPRESSION AND CHRONIC MEDICAL ILLNESS.

    Science.gov (United States)

    Koenig, Harold G; Pearce, Michelle J; Nelson, Bruce; Daher, Noha

    2015-11-01

    We compared the effectiveness of religiously integrated cognitive behavioral therapy (RCBT) versus standard CBT (SCBT) on increasing optimism in persons with major depressive disorder (MDD) and chronic medical illness. Participants aged 18-85 were randomized to either RCBT (n = 65) or SCBT (n = 67) to receive ten 50-min sessions remotely (94% by telephone) over 12 weeks. Optimism was assessed at baseline, 12 and 24 weeks by the Life Orientation Test-Revised. Religiosity was assessed at baseline using a 29-item scale composed of religious importance, individual religious practices, intrinsic religiosity, and daily spiritual experiences. Mixed effects growth curve models were used to compare the effects of treatment group on trajectory of change in optimism. In the intention-to-treat analysis, both RCBT and SCBT increased optimism over time, although there was no significant difference between treatment groups (B = -0.75, SE = 0.57, t = -1.33, P = .185). Analyses in the highly religious and in the per protocol analysis indicated similar results. Higher baseline religiosity predicted an increase in optimism over time (B = 0.07, SE = 0.02, t = 4.12, P depressive symptoms over time (B = -0.61, SE = 0.10, t = -6.30, P < .0001), both independent of treatment group. RCBT and SCBT are equally effective in increasing optimism in persons with MDD and chronic medical illness. While baseline religiosity does not moderate this effect, religiosity predicts increases in optimism over time independent of treatment group. © 2015 Wiley Periodicals, Inc.

  17. Determination and production of an optimal neutron energy spectrum for boron neutron capture therapy

    Science.gov (United States)

    Bleuel, Darren Leo

    An accelerator-based neutron irradiation facility employing an electrostatic quadrupole (ESQ) accelerator for Boron Neutron Capture Therapy (BNCT) has been proposed at Lawrence Berkeley National Laboratory. In this dissertation, the properties of an ideal neutron beam for delivering a maximized dose to a glioblastoma multiforme tumor in a reasonable time while minimizing the dose to healthy tissue is examined. A variety of materials, beam shaping assemblies, and neutron sources were considered to deliver a neutron spectrum as close to the calculated idealized spectrum as possible. Several optimization studies were performed to determine the best proton energy and moderator material to maximize the efficacy of an accelerator-based BNCT facility utilizing the 7Li(p,n)7Be reaction as a neutron source. A new, faster method of performing such an optimization was developed, known as the "Ubertally" method, in which data from a single Monte Carlo simulation is reweighted to produce results for any neutron spatial, energy and angular source distribution. Results were confirmed experimentally at Lawrence Berkeley National Laboratory's 88″ cyclotron. Thermal fluxes in this experiment were found to be approximately 30% lower than expected, but the depth-dose profile was confirmed to within 8% maximum deviation. A final beam shaping assembly is then recommended. Utilizing a material known as Fluental as a moderating material, deep-seated tumor doses 50% higher than that delivered by clinical trials at the Brookhaven Medical Research Reactor (BMRR) are predicted. The final recommended design should contain a 37 cm thickness of Fluental(TM) moderator, a 1--2 cm gamma shield, an Al2O3 reflector, a V-shaped aluminum-backed or copper-backed source with heavy water cooling, and a 13 cm lithiated polyethylene delimiter. This design would be operated at 2.4 MeV proton energy at 20 mA to conduct treatments in less than an hour and a half. However, this design may be easily altered

  18. A feedback constraint optimization method for intensity-modulated radiation therapy of nasopharyngeal carcinoma

    Science.gov (United States)

    LI, YONGWU; SUN, XIAONAN; WANG, QI; ZHOU, QINXUAN; GU, BENXING; SHI, GUOZHI; JIANG, DONGLIANG

    2015-01-01

    Intensity-modulated radiation therapy (IMRT) is able to achieve good target conformance with a limited dose to organs at risk (OARs); however, IMRT increases the irradiation volume and monitor units (MUs) required. The present study aimed to evaluate the use of an IMRT plan with fewer segments and MUs, while maintaining quality in the treatment of nasopharyngeal carcinoma. In the present study, two types of IMRT plan were therefore compared: The direct machine parameter optimization (DMPO)-RT method and the feedback constraint DMPO-RT (fc_DMPO-RT) method, which utilizes compensative feedback constraint in DMPO-RT and maintains optimization. Plans for 23 patients were developed with identical dose prescriptions. Each plan involved synchronous delivery to various targets, with identical OAR constraints, by means of 7 coplanar fields. The average dose, maximum dose, dose-volume histograms of targets and the OAR, MUs of the plan, the number of segments, delivery time and accuracy were subsequently compared. The fc_DMPO-RT exhibited superior dose distribution in terms of the average, maximum and minimum doses to the gross tumor volume compared with that of DMPO-RT (t=62.7, 20.5 and 22.0, respectively; P<0.05). The fc_DMPO-RT also resulted in a smaller maximum dose to the spinal cord (t=7.3; P<0.05), as well as fewer MUs, fewer segments and decreased treatment times than that of the DMPO-RT (t=6.2, 393.4 and 244.3, respectively; P<0.05). The fc_DMPO-RT maintained plan quality with fewer segments and MUs, and the treatment time was significantly reduced, thereby resulting in reduced radiation leakage and an enhanced curative effect. Therefore, introducing feedback constraint into DMPO may result in improved IMRT planning. In nasopharyngeal carcinoma specifically, feedback constraint resulted in the improved protection of OARs in proximity of targets (such as the brainstem and parotid) due to sharp dose distribution and reduced MUs. PMID:26622793

  19. Treatment planning of intensity modulated composite particle therapy with dose and linear energy transfer optimization

    Science.gov (United States)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Noda, Koji; Kamada, Tadashi

    2017-06-01

    The biological effect of charged-particle beams depends on both dose and particle spectrum. As one of the physical quantities describing the particle spectrum of charged-particle beams, we considered the linear energy transfer (LET) throughout this study. We investigated a new therapeutic technique using two or more ion species in one treatment session, which we call an intensity modulated composite particle therapy (IMPACT), for optimizing the physical dose and dose-averaged LET distributions in a patient as its proof of principle. Protons and helium, carbon, and oxygen ions were considered as ion species for IMPACT. For three cubic targets of 4  ×  4  ×  4, 8  ×  8  ×  8, and 12  ×  12  ×  12 cm3, defined at the center of the water phantom of 20  ×  20  ×  20 cm3, we made IMPACT plans of two composite fields with opposing and orthogonal geometries. The prescribed dose to the target was fixed at 1 Gy, while the prescribed LET to the target was varied from 1 keV µm-1 to 120 keV µm-1 to investigate the range of LET valid for prescription. The minimum and maximum prescribed LETs, (L T_min, L T_max), by the opposing-field geometry, were (3 keV µm-1, 115 keV µm-1), (2 keV µm-1, 84 keV µm-1),and (2 keV µm-1, 66 keV µm-1), while those by the orthogonal-field geometry were (8 keV µm-1, 98 keV µm-1), (7 keV µm-1, 72 keV µm-1), and (8 keV µm-1, 57 keV µm-1) for the three targets, respectively. To show the proof of principle of IMPACT in a clinical situation, we made IMPACT plans for a prostate case. In accordance with the prescriptions, the LETs in prostate, planning target volume (PTV), and rectum could be adjusted at 80 keV µm-1, at 50 keV µm-1, and below 30 keV µm-1, respectively, while keeping the dose to the PTV at 2 Gy uniformly. IMPACT enables the optimization of the dose and the LET distributions in a patient, which will maximize the

  20. Predictors and Outcomes of Routine Versus Optimal Medical Therapy in Stable Coronary Heart Disease.

    Science.gov (United States)

    Chun, Soohun; Qiu, Feng; Austin, Peter C; Ko, Dennis T; Mamdani, Muhammad; Wijeysundera, Duminda N; Czarnecki, Andrew; Bennell, Maria C; Wijeysundera, Harindra C

    2015-09-01

    Although randomized studies have shown optimal medical therapy (OMT) to be as efficacious as revascularization in stable coronary heart disease (CHD), the application of OMT in routine practice is suboptimal. We sought to understand the predictors of receiving OMT in stable CHD and its impact on clinical outcomes. All patients with stable CHD based on coronary angiography from October 2008 to September 2011 were identified in Ontario, Canada. OMT was defined as concurrent use of β blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and statin. Aspirin use was not part of the OMT definition because of database limitations. Multivariable hierarchical logistic models identified predictors of OMT in the 12 months after angiography. Cox proportional hazard models with time-varying covariates for OMT and revascularization status examined differences in death and nonfatal myocardial infarction (MI). In these models, patients transitioned among 4 mutually exclusive treatment groups: no OMT and no revascularization, no OMT and revascularization, OMT and no revascularization, OMT and revascularization. Our cohort had 20,663 patients. Over a mean period of 2.5 years, 8.7% had died. Only 61% received OMT within 12 months. The strongest predictor of receiving OMT at 12 months was OMT before the angiogram (odds ratio 14.40, 95% confidence interval [CI] 13.17 to 15.75, p OMT and nonrevascularized patients, patients on OMT and revascularized had the greatest reduction in mortality (hazard ratio 0.52, 95% CI 0.45 to 0.60, p OMT in stable CHD. Patients who received both OMT and revascularization achieved the greatest reduction in mortality and nonfatal MI. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Gamma evaluation combined with isocenter optimal matching in intensity modulated radiation therapy quality assurance

    Science.gov (United States)

    Bak, Jino; Choi, Jin Hwa; Park, Suk Won; Park, Kwangwoo; Park, Sungho

    2015-12-01

    Two-dimensional (2D) dose comparisons are widely performed by using a gamma evaluation with patient-specific intensity modulated radiation therapy quality assurance (IMRT QA) or dose delivery quality assurance (DQA). In this way, a pass/fail determination is made for a particular treatment plan. When gamma evaluation results are close to the failure criterion, the pass/fail decision may change applying a small shift to the center of the 2D dose distribution. In this study, we quantitatively evaluated the meaning of such a small relative shift in a 2D dose distribution comparison. In addition, we propose the use of a small shift for a pass/fail criterion in gamma analysis, where the concept of isocenter optimal matching (IOM) is applied to IMRT QA of 20 patients. Gamma evaluations were performed to compare two dose distributions, one with and the other without IOM. In-house software was developed in C++ in order to find IOM values including both translational and rotational shifts. Upon gamma evaluation failure, further investigation was initiated using IOM. In this way, three groups were categorized: group 1 for `pass' on gamma evaluation, group 21 for `fail' on the gamma evaluation and `pass' on the gamma the evaluation with IOM, and group 22 for `fail' on the both gamma evaluations and the IOM calculation. IOM results revealed that some failures could be considered as a `pass'. In group 21, 88.98% (fail) of the averaged gamma pass rate changed to 90.45% (pass) when IOM was applied. On average, a ratio of γ ≥ 1 was reduced by 11.06% in 20 patients. We propose that gamma evaluations that do not pass with a rate of 85% to 90% may be augmented with IOM to reveal a potential pass result.

  2. Optimal Dosing for Targeted Therapies in Oncology: Drug Development Cases Leading by Example.

    Science.gov (United States)

    Sachs, Jeffrey R; Mayawala, Kapil; Gadamsetty, Satvik; Kang, Soonmo Peter; de Alwis, Dinesh P

    2016-03-15

    One of the key objectives of oncology first-in-human trials has often been to establish the maximum tolerated dose (MTD). However, targeted therapies might not exhibit dose-limiting toxicities (DLT) at doses significantly higher than sufficiently active doses, and there is frequently a limited ability to objectively quantify adverse events. Thus, while MTD-based determination of recommended phase II dose may have yielded appropriate dosing for some cytotoxics, targeted therapeutics (including monoclonal antibodies and/or immunotherapies) sometimes need alternative or complementary strategies to help identify dose ranges for a randomized dose-ranging study. One complementary strategy is to define a biologically efficacious dose (BED) using an "effect marker." An effect marker could be a target engagement, pharmacodynamic, or disease progression marker (change in tumor size for solid tumors or bone marrow blast count for some hematologic tumors). Although the concept of BED has been discussed extensively, we review specific examples in which the approach influenced oncology clinical development. Data extracted from the literature and the examples support improving dose selection strategies to benefit patients, providers, and the biopharmaceutical industry. Although the examples illustrate key contributions of effect markers in dose selection, no one-size-fits-all approach to dosing can be justified. Higher-than-optimal dosing can increase toxicity in later trials (and in clinical use), which can have a negative impact on efficacy (via lower adherence or direct sequelae of toxicities). Proper dose selection in oncology should follow a multifactorial decision process leading to a randomized, dose-ranging study instead of a single phase II dose. ©2015 American Association for Cancer Research.

  3. HybridArc: A novel radiation therapy technique combining optimized dynamic arcs and intensity modulation

    Energy Technology Data Exchange (ETDEWEB)

    Robar, James L., E-mail: james.robar@cdha.nshealth.ca [Department of Radiation Oncology, Dalhousie University, Halifax (Canada); Department of Physics and Atmospheric Science, Dalhousie University, Halifax (Canada); Thomas, Christopher [Department of Radiation Oncology, Dalhousie University, Halifax (Canada)

    2012-01-01

    This investigation focuses on possible dosimetric and efficiency advantages of HybridArc-a novel treatment planning approach combining optimized dynamic arcs with intensity-modulated radiation therapy (IMRT) beams. Application of this technique to two disparate sites, complex cranial tumors, and prostate was examined. HybridArc plans were compared with either dynamic conformal arc (DCA) or IMRT plans to determine whether HybridArc offers a synergy through combination of these 2 techniques. Plans were compared with regard to target volume dose conformity, target volume dose homogeneity, sparing of proximal organs at risk, normal tissue sparing, and monitor unit (MU) efficiency. For cranial cases, HybridArc produced significantly improved dose conformity compared with both DCA and IMRT but did not improve sparing of the brainstem or optic chiasm. For prostate cases, conformity was improved compared with DCA but not IMRT. Compared with IMRT, the dose homogeneity in the planning target volume was improved, and the maximum doses received by the bladder and rectum were reduced. Both arc-based techniques distribute peripheral dose over larger volumes of normal tissue compared with IMRT, whereas HybridArc involved slightly greater volumes of normal tissues compared with DCA. Compared with IMRT, cranial cases required 38% more MUs, whereas for prostate cases, MUs were reduced by 7%. For cranial cases, HybridArc improves dose conformity to the target. For prostate cases, dose conformity and homogeneity are improved compared with DCA and IMRT, respectively. Compared with IMRT, whether required MUs increase or decrease with HybridArc was site-dependent.

  4. Optimize and refine therapeutic index in radiation therapy: Overview of a century.

    Science.gov (United States)

    Chargari, Cyrus; Magne, Nicolas; Guy, Jean-Baptiste; Rancoule, Chloé; Levy, Antonin; Goodman, Karyn A; Deutsch, Eric

    2016-04-01

    In 1936, Holthusen theorized the probability of achieving tumor control and of developing normal tissue complications after radiotherapy as a function of radiation dose. This concept was formalized and further developed in 1975. Several concepts for improving the therapeutic gain had been anticipated, including the possibility of modulating the tumor/normal tissue differential response. Eight decades later, it is possible to review and analyze progress achieved in the knowledge of radiation-induced toxicity. The clinical developments using new technologies and biological modulators of radiation response have corroborated a posteriori this model, however, many questions remain unanswered. A few randomized trials have validated the benefit of modern irradiation techniques for improving the therapeutic index; but the level I evidence of a survival improvement is still lacking. In the field of bio-modulation, large meta-analyses have shown that concurrent chemotherapy improves local control in many cancer types. Clinical investigations using molecularly targeted therapies have been rather disappointing, with only one exception: head and neck squamous cell carcinoma. Numerous recent biological findings question the possibility to target tumor tissue without impacting normal tissue response. Moreover, the abscopal and bystander effects suggest that normal tissue irradiation should not be perceived only as a source of toxicity, but may also result in downstream therapeutic effects. This paper reexamines the multiple efforts made to modulate the tumor versus normal tissue differential response, which have translated into incremental therapeutic gain and highlights the ongoing effort to better understand the optimal integration of radiation biology, chemotherapeutic, novel drugs and novel technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Optimism

    Science.gov (United States)

    Carver, Charles S.; Scheier, Michael F.; Segerstrom, Suzanne C.

    2010-01-01

    Optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. Higher levels of optimism have been related prospectively to better subjective well-being in times of adversity or difficulty (i.e., controlling for previous well-being). Consistent with such findings, optimism has been linked to higher levels of engagement coping and lower levels of avoidance, or disengagement, coping. There is evidence that optimism is associated with taking proactive steps to protect one's health, whereas pessimism is associated with health-damaging behaviors. Consistent with such findings, optimism is also related to indicators of better physical health. The energetic, task-focused approach that optimists take to goals also relates to benefits in the socioeconomic world. Some evidence suggests that optimism relates to more persistence in educational efforts and to higher later income. Optimists also appear to fare better than pessimists in relationships. Although there are instances in which optimism fails to convey an advantage, and instances in which it may convey a disadvantage, those instances are relatively rare. In sum, the behavioral patterns of optimists appear to provide models of living for others to learn from. PMID:20170998

  6. Optimized treatment parameters to account for interfractional variability in scanned ion beam therapy of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Brevet, Romain

    2015-02-04

    Scanned ion beam therapy of lung tumors is severely limited in its clinical applicability by intrafractional organ motion, interference effects between beam and tumor motion (interplay) as well as interfractional anatomic changes. To compensate for dose deterioration by intrafractional motion, motion mitigation techniques, such as gating have been developed. The latter confines the irradiation to a predetermined breathing state, usually the stable end-exhale phase. However, optimization of the treatment parameters is needed to further improve target dose coverage and normal tissue sparing. The aim of the study presented in this dissertation was to determine treatment planning parameters that permit to recover good target coverage and homogeneity during a full course of lung tumor treatments. For 9 lung tumor patients from MD Anderson Cancer Center (MDACC), a total of 70 weekly time-resolved computed tomography (4DCT) datasets were available, which depict the evolution of the patient anatomy over the several fractions of the treatment. Using the GSI in-house treatment planning system (TPS) TRiP4D, 4D simulations were performed on each weekly 4DCT for each patient using gating and optimization of a single treatment plan based on a planning CT acquired prior to treatment. It was found that using a large beam spot size, a short gating window (GW), additional margins and multiple fields permitted to obtain the best results, yielding an average target coverage (V95) of 96.5%. Two motion mitigation techniques, one approximating the rescanning process (multiple irradiations of the target with a fraction of the planned dose) and one combining the latter and gating, were then compared to gating. Both did neither show an improvement in target dose coverage nor in normal tissue sparing. Finally, the total dose delivered to each patient in a simulation of a fractioned treatment was calculated and clinical requirements in terms of target coverage and normal tissue sparing were

  7. Optimization

    CERN Document Server

    Pearce, Charles

    2009-01-01

    Focuses on mathematical structure, and on real-world applications. This book includes developments in several optimization-related topics such as decision theory, linear programming, turnpike theory, duality theory, convex analysis, and queuing theory.

  8. Optimal matching of 3D film-measured and planned doses for intensity-modulated radiation therapy quality assurance.

    Science.gov (United States)

    Shin, Dongho; Yoon, Myonggeun; Park, Sung Yong; Park, Dong Hyun; Lee, Se Byeong; Kim, Dae Yong; Cho, Kwan Ho

    2007-01-01

    Intensity-modulated radiation therapy (IMRT) is one of the most complex applications of radiotherapy that requires patient-specific quality assurance (QA). Here, we describe a novel method of 3-dimensional (3D) dose-verification using 12 acrylic slabs in a 3D phantom (30 x 30 x 12 cm(3)) with extended dose rate (EDR2) films, which is both faster than conventionally used methods, and clinically useful. With custom-written software modules written in Microsoft Excel Visual Basic Application, the measured and planned dose distributions for the axial, coronal, and sagittal planes were superimposed by matching their origins, and the point doses were compared at all matched positions. Then, an optimization algorithm was used to correct the detected setup errors. The results show that this optimization method significantly reduces the average maximum dose difference by 7.73% and the number of points showing dose differences of more than 5% by 8.82% relative to the dose differences without an optimization. Our results indicate that the dose difference was significantly decreased with optimization and this optimization method is statistically reliable and effective. The results of 3D optimization are discussed in terms of various patient-specific QA data obtained from statistical analyses.

  9. Dosimetric comparison of RapidPlan and manually optimized plans in volumetric modulated arc therapy for prostate cancer.

    Science.gov (United States)

    Kubo, Kazuki; Monzen, Hajime; Ishii, Kentaro; Tamura, Mikoto; Kawamorita, Ryu; Sumida, Iori; Mizuno, Hirokazu; Nishimura, Yasumasa

    2017-07-10

    This study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer. We used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D95%, and D2% to planning target volume (PTV), mean dose, V50Gy, V70Gy, V75Gy, and V78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity. RP and CMO values for PTV D95%, PTV D2%, HI, and CN were significantly similar (pplans (pplans (pplans created by a single optimization were clinically acceptable in VMAT for patient with prostate cancer. Our simple model could reduce optimization time, independently of planner's skill and knowledge. Copyright © 2017. Published by Elsevier Ltd.

  10. SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liao, L [Proton Therapy Center, UT MD Anderson Cancer Center, Houston, TX (United States); Department of Industrial Engineering, University of Houston, Houston, TX (United States); Yu, J; Zhu, X; Li, H; Zhang, X [Proton Therapy Center, UT MD Anderson Cancer Center, Houston, TX (United States); Li, Y [Proton Therapy Center, UT MD Anderson Cancer Center, Houston, TX (United States); Varian Medical Systems, Houston, TX (United States); Lim, G [Department of Industrial Engineering, University of Houston, Houston, TX (United States)

    2015-06-15

    Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used to evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.

  11. Optimization of an ex vivo wound healing model in the adult human skin: Functional evaluation using photodynamic therapy.

    Science.gov (United States)

    Mendoza-Garcia, Jenifer; Sebastian, Anil; Alonso-Rasgado, Teresa; Bayat, Ardeshir

    2015-09-01

    Limited utility of in vitro tests and animal models of human repair, create a demand for alternative models of cutaneous healing capable of functional testing. The adult human skin Wound Healing Organ Culture (WHOC) provides a useful model, to study repair and enable evaluation of therapies such as the photodynamic therapy (PDT). Thus, the aim here was to identify the optimal WHOC model and to evaluate the role of PDT in repair. Wound geometry, system of support, and growth media, cellular and matrix biomarkers were investigated in WHOC models. Subsequently, cellular activity, extracellular matrix remodeling, and oxidative stress plus gene and protein levels of makers of wound repair measured the effect of PDT on the optimized WHOC. WHOCs embedded in collagen and supplemented DMEM were better organized showing stratified epidermis and compact dermis with developing neo-epidermis. Post-PDT, the advancing reepithelialization tongue was 3.5 folds longer, and was highly proliferative with CK-14 plus p16 increased (p < 0.05) compared to controls. The neo-epidermis was fully differentiated forming neo-collagen. Proliferating nuclear antigen, p16, COLI, COLIII, MMP3, MMP19, and α-SMA were significantly more expressed (p < 0.05) in dermis surrounding the healing wound. In conclusion, an optimal model of WHOC treated with PDT shows increased reepithelialization and extracellular matrix reconstruction and remodeling, supporting evidence toward development of an optimal ex vivo wound healing model.

  12. Optimal Finite Cancer Treatment Duration by Using Mixed Vaccine Therapy and Chemotherapy: State Dependent Riccati Equation Control

    Directory of Open Access Journals (Sweden)

    Ali Ghaffari

    2014-01-01

    Full Text Available The main objective of this paper is to propose an optimal finite duration treatment method for cancer. A mathematical model is proposed to show the interactions between healthy and cancerous cells in the human body. To extend the existing models, the effect of vaccine therapy and chemotherapy are also added to the model. The equilibrium points and the related local stability are derived and discussed. It is shown that the dynamics of the cancer model must be changed and modified for finite treatment duration. Therefore, the vaccine therapy is used to change the parameters of the system and the chemotherapy is applied for pushing the system to the domain of attraction of the healthy state. For optimal chemotherapy, an optimal control is used based on state dependent Riccati equation (SDRE. It is shown that, in spite of eliminating the treatment, the system approaches the healthy state conditions. The results show that the development of optimal vaccine-chemotherapy protocols for removing tumor cells would be an appropriate strategy in cancer treatment. Also, the present study states that a proper treatment method not only reduces the population of the cancer cells but also changes the dynamics of the cancer.

  13. EVALUATION OF CISPLATIN-INDUCED PICA BEHAVIOUR IN RATS BY MEASURING FAECAL CARMINE-DYE EXCRETION: AN IMPROVED EXPERIMENTAL MODEL TO SCREEN SAMPLES WITH ANTI-EMETIC PROPERTIES

    Directory of Open Access Journals (Sweden)

    Rajesh S.

    2012-02-01

    Full Text Available The objective of the present study is to evaluate the Cisplatin-induced pica behaviour in rats by measuring faecal carmine dye excretion and to evaluate the anti-emetic effect of drugs on Cisplatin-induced pica behaviour in rats. Thirty-two rats were divided into 4 groups of 8 animals each. Rats from group I and II received DM water (10ml/kg p.o. Rats from group III and IV received Himalaya Anti-emetic Tablets (HAT 250 mg/kg p.o. and ondansetron 4mg/kg p.o, respectively. After one hour of the assigned treatment, all the animals except in group I were injected with Cisplatin 3mg/kg i.p. Rats in group I were injected with saline (1ml/kg i.p.. All the animals were fed with normal as well as kaolin pellets (impregnated with carmine dye. The faeces of each rat was collected after 72 hrs of drug administration and analysed for the carmine content.Cisplatin injection (3mg/kg caused a significant increase in kaolin consumption, which was indicated by increased carmine dye excretion in faeces compared to control. Pre-treatment with HAT and ondansetron significantly suppressed kaolin consumption induced by Cisplatin. The present findings showed that the exact kaolin consumption can be quantified by measuring the faecal excretion of carmine, which was added in kaolin pellets and this can be a sensitive model to study the anti-emetic potential of drugs, overcoming the inherent disadvantages of measuring direct kaolin intake. Pre-treatment with ondansetron and HAT significantly decreased kaolin consumption in rats-induced by Cisplatin injection, which was further shown by decrease in faecal excretion of carmine, indicating anti-emetic potential of tested drugs.

  14. Real-time fast inverse dose optimization for image guided adaptive radiation therapy-Enhancements to fast inverse dose optimization (FIDO)

    Science.gov (United States)

    Goldman, S. P.; Turnbull, D.; Johnson, C.; Chen, J. Z.; Battista, J. J.

    2009-05-01

    A fast, accurate and stable optimization algorithm is very important for inverse planning of intensity-modulated radiation therapy (IMRT), and for implementing dose-adaptive radiotherapy in the future. Conventional numerical search algorithms with positive beam weight constraints generally require numerous iterations and may produce suboptimal dose results due to trapping in local minima regions of the objective function landscape. A direct solution of the inverse problem using conventional quadratic objective functions without positive beam constraints is more efficient but it will result in unrealistic negative beam weights. We review here a direct solution of the inverse problem that is efficient and does not yield unphysical negative beam weights. In fast inverse dose optimization (FIDO) method the objective function for the optimization of a large number of beamlets is reformulated such that the optimization problem is reducible to a linear set of equations. The optimal set of intensities is then found through a matrix inversion, and negative beamlet intensities are avoided without the need for externally imposed ad hoc conditions. In its original version [S. P. Goldman, J. Z. Chen, and J. J. Battista, in Proceedings of the XIVth International Conference on the Use of Computers in Radiation Therapy, 2004, pp. 112-115; S. P. Goldman, J. Z. Chen, and J. J. Battista, Med. Phys. 32, 3007 (2005)], FIDO was tested on single two-dimensional computed tomography (CT) slices with sharp KERMA beams without scatter, in order to establish a proof of concept which demonstrated that FIDO could be a viable method for the optimization of cancer treatment plans. In this paper we introduce the latest advancements in FIDO that now include not only its application to three-dimensional volumes irradiated by beams with full scatter but include as well a complete implementation of clinical dose-volume constraints including maximum and minimum dose as well as equivalent uniform dose

  15. Collimator optimization for small animal radiation therapy at a micro-CT

    Energy Technology Data Exchange (ETDEWEB)

    Felix, Manuela C. [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Glatting, Gerhard [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Giordano, Frank A.; Wenz, Frederik; Fleckenstein, Jens [Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Brockmann, Marc A. [Heidelberg Univ., Mannheim (Germany). Dept. of Neuroradiology; University Medical Center Mainz (Germany). Dept. of Neuroradiology

    2017-05-01

    In radiation therapy of small animals treatment depths range from a few millimetres to several centimetres. In order to spare surrounding organs at risk steep dose gradients are necessary. To minimize the treatment time, and therefore the strain to the animals, a high dose rate is required. A description how these parameters can be optimized through an appropriate choice of collimators with different source surface distances (SSD) as well as different materials and geometries is presented. An industrial micro-CT unit (Y.Fox, YXLON GmbH, Hamburg, Germany) was converted into a precision irradiator for small animals. Different collimators of either stainless steel (Fe) with cylindrical bores (SSD = 42 mm) or tungsten (W) with conical bores (SSD = 14 mm) were evaluated. The dosimetry of very small radiation fields presents a challenge and was performed with GafChromic EBT3 films (Ashland, Vayne, KY, USA) in a water phantom. The films were calibrated with an ionization chamber in the uncollimated field. Treatments were performed via a rotation of the objects with a fixed radiation source. As expected, the shorter SSD of the W-collimators resulted in a (4.5 ± 1.6)-fold increase of the dose rates compared to the corresponding Fe-collimators. The ratios of the dose rates at 1 mm and 10 mm depth in the water phantom was (2.6 ± 0.2) for the Fe- and (4.5 ± 0.1) for the W-collimators. For rotational treatments in a cylindrical plastic phantom maximum dose rates of up to 1.2 Gy/min for Fe- and 5.1 Gy/min for W-collimators were measured. Choosing the smallest possible SSD leads to a high dose rate and a high surface dose, which is of advantage for the treatment of superficial target volumes. For larger SSD the dose rate is lower and the depth dose curve is shallower. This leads to a reduction of the surface dose and is best suited for treatments of deeper seated target volumes. Divergent collimator bores have, due to the reduced scatter within the collimators, a steeper

  16. Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug

    Directory of Open Access Journals (Sweden)

    T Singhal

    2015-01-01

    Full Text Available Background: In the end of 2009, a large number of patients with cancer undergoing chemotherapy at the day care unit of a private hospital in Mumbai, India developed Burkholderia cepacia complex (BCC blood stream infection (BSI. Objective: The objectives were to identify the source of the outbreak and terminate the outbreak as rapidly as possible. Materials and Methods: All infection control protocols and processes were reviewed. Intensive training was started for all nursing staff involved in patient care. Cultures were sent from the environment (surfaces, water, air, intravenous fluids, disinfectants and antiseptics and opened/unopened medication. Results: A total of 13 patients with cancer with tunneled catheters were affected with BCC BSI. The isolates were of similar antimicrobial sensitivity. No significant breach of infection control protocols could be identified. Cultures from the prepared intravenous medication bags grew BCC. Subsequently, culture from unused vials of the antiemetic granisetron grew BCC, whereas those from the unopened IV fluid bag and chemotherapy medication were negative. On review, it was discovered that the outbreak started when a new brand of granisetron was introduced. The result was communicated to the manufacturer and the brand was withdrawn. There were no further cases. Conclusions: This outbreak was thus linked to intrinsic contamination of medication vials. We acknowledge a delay in identifying the source as we were concentrating more on human errors in medication preparation and less on intrinsic contamination. We recommend that in an event of an outbreak, unopened vials be cultured at the outset.

  17. Optimization of beam angles for intensity modulated radiation therapy treatment planning using genetic algorithm on a distributed computing platform.

    Science.gov (United States)

    Nazareth, Daryl P; Brunner, Stephen; Jones, Matthew D; Malhotra, Harish K; Bakhtiari, Mohammad

    2009-07-01

    Planning intensity modulated radiation therapy (IMRT) treatment involves selection of several angle parameters as well as specification of structures and constraints employed in the optimization process. Including these parameters in the combinatorial search space vastly increases the computational burden, and therefore the parameter selection is normally performed manually by a clinician, based on clinical experience. We have investigated the use of a genetic algorithm (GA) and distributed-computing platform to optimize the gantry angle parameters and provide insight into additional structures, which may be necessary, in the dose optimization process to produce optimal IMRT treatment plans. For an IMRT prostate patient, we produced the first generation of 40 samples, each of five gantry angles, by selecting from a uniform random distribution, subject to certain adjacency and opposition constraints. Dose optimization was performed by distributing the 40-plan workload over several machines running a commercial treatment planning system. A score was assigned to each resulting plan, based on how well it satisfied clinically-relevant constraints. The second generation of 40 samples was produced by combining the highest-scoring samples using techniques of crossover and mutation. The process was repeated until the sixth generation, and the results compared with a clinical (equally-spaced) gantry angle configuration. In the sixth generation, 34 of the 40 GA samples achieved better scores than the clinical plan, with the best plan showing an improvement of 84%. Moreover, the resulting configuration of beam angles tended to cluster toward the patient's sides, indicating where the inclusion of additional structures in the dose optimization process may avoid dose hot spots. Additional parameter selection in IMRT leads to a large-scale computational problem. We have demonstrated that the GA combined with a distributed-computing platform can be applied to optimize gantry angle

  18. Guaranteed epsilon-optimal treatment plans with the minimum number of beams for stereotactic body radiation therapy.

    Science.gov (United States)

    Yarmand, Hamed; Winey, Brian; Craft, David

    2013-09-07

    Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam's-eye-view) known as 'apertures'. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan as the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined maximum deviation from the ideal plan is guaranteed). Since the treatment plan optimization is inherently a multi-criteria-optimization problem, the planner can navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing epsilon-optimality. We use mixed integer programming (MIP) for optimization. To reduce the computation time for the resultant MIP, we use two heuristics: a beam elimination scheme and a family of heuristic cuts, known as 'neighbor cuts', based on the concept of 'adjacent beams'. We show the effectiveness of the proposed technique on two clinical cases, a liver and a lung case. Based on our technique we propose an algorithm for fast generation of epsilon-optimal plans.

  19. Optimal control for mathematical models of cancer therapies an application of geometric methods

    CERN Document Server

    Schättler, Heinz

    2015-01-01

    This book presents applications of geometric optimal control to real life biomedical problems with an emphasis on cancer treatments. A number of mathematical models for both classical and novel cancer treatments are presented as optimal control problems with the goal of constructing optimal protocols. The power of geometric methods is illustrated with fully worked out complete global solutions to these mathematically challenging problems. Elaborate constructions of optimal controls and corresponding system responses provide great examples of applications of the tools of geometric optimal control and the outcomes aid the design of simpler, practically realizable suboptimal protocols. The book blends mathematical rigor with practically important topics in an easily readable tutorial style. Graduate students and researchers in science and engineering, particularly biomathematics and more mathematical aspects of biomedical engineering, would find this book particularly useful.

  20. Formulation development and evaluation of medicated chewing gum of anti-emetic drug

    Directory of Open Access Journals (Sweden)

    Mansi Paradkar

    2016-03-01

    Full Text Available Context: Medicated chewing gum (MCG of Domperidone Maleate (DM was developed by direct compression method with the goal to achieve quick onset of action and to improve patient compliance. Objective: Formulation development of MCG of DM and optimization of the formulation by screening of different excipients. Material and methods: MCG containing DM was prepared by screening different concentrations of sweeteners, flavouring agents, softening agents, lubricants and anti-adherents by changing one variable at a time. Performance evaluation was carried out by evaluating size, shape, thickness, taste, scanning electron microscopy, texture analysis, in vivo drug release study, ex vivo buccal permeation study and by studying statistical analysis for quality. Results and discussion: The statistical analysis showed significant improvement in organoleptic properties such as chewable mass, product taste, product consistency, product softness, total flavour lasting time and pharmaceutical properties like micromeritic properties after incorporation of appropriate excipients in an optimum amount in final optimized MCG formulation. In vivo drug release study showed 97% DM release whereas ex vivo buccal permeation study through goat buccal mucosa exhibited 11.27% DM permeation within 15 min indicating its potential for increasing bioavailability by decreasing time of onset. The optimized formulation showed good surface properties and the peak load required for drug release was found to be acceptable for crumbling action. Conclusion: The developed formulation of medicated chewing gum can be a better alternative to mouth dissolving and conventional tablet formulation. It may be proved as a promising approach to improve the bioavailability as well as to improve patient compliance.

  1. From analytic inversion to contemporary IMRT optimization: radiation therapy planning revisited from a mathematical perspective.

    Science.gov (United States)

    Censor, Yair; Unkelbach, Jan

    2012-04-01

    In this paper we look at the development of radiation therapy treatment planning from a mathematical point of view. Historically, planning for Intensity-Modulated Radiation Therapy (IMRT) has been considered as an inverse problem. We discuss first the two fundamental approaches that have been investigated to solve this inverse problem: Continuous analytic inversion techniques on one hand, and fully-discretized algebraic methods on the other hand. In the second part of the paper, we review another fundamental question which has been subject to debate from the beginning of IMRT until the present day: The rotation therapy approach versus fixed angle IMRT. This builds a bridge from historic work on IMRT planning to contemporary research in the context of Intensity-Modulated Arc Therapy (IMAT).

  2. Mathematical optimization of the combination of radiation and differentiation therapies of cancer

    Directory of Open Access Journals (Sweden)

    Jeff W.N. Bachman

    2013-03-01

    Full Text Available Cancer stem cells (CSC are considered to be a major driver of cancer progression and successful therapies must control CSCs. However, CSC are often less sensitive to treatment and they might survive radiation and/or chemotherapies. In this paper we combine radiation treatment with differentiation therapy. During differentiation therapy, a differentiation promoting agent is supplied (e.g. TGF-beta such that CSCs differentiate and become more radiosensitive. Then radiation can be used to control them. We consider three types of cancer: head and neck cancer, brain cancers (primary tumors and metastatic brain cancers, and breast cancer; and we use mathematical modelling to show that combination therapy of the above type can have a large beneficial effect for the patient; increasing treatment success and reducing side effects.

  3. Optimizing physical therapy for ankylosing spondylitis: a case study in a young football player

    OpenAIRE

    Tric?s-Moreno, Jos? Miguel; Lucha-L?pez, Mar?a Orosia; Lucha-L?pez, Ana Carmen; Salavera-Bord?s, Carlos; Vidal-Peracho, Concepci?n

    2016-01-01

    [Purpose] Ankylosing spondylitis is prevalent in men. Modern and expert consensus documents include physical therapy among the strategies for the treatment of ankylosing spondylitis. This study aimed to describe the physical therapy approach in an athlete with ankylosing spondylitis. [Subject and Methods] The patient, refractory to treatment with anti-inflammatory medication, showed pelvic and lumbar pain and joint, muscle, and functional disorders, which were treated with orthopedic joint mo...

  4. Investigation of photodynamic therapy optimization for port wine stain using modulation of photosensitizer administration methods.

    Science.gov (United States)

    Wang, Ying; Zuo, Zhaohui; Liao, Xiaohua; Gu, Ying; Qiu, Haixia; Zeng, Jing

    2013-12-01

    To raise photosensitizer concentration level during the photodynamic therapy process, two new methods of photosensitizer administration were investigated. The first method involves the slow intravenous injection of photosensitizer throughout the first 15 min of irradiation, and the second method involves 30 min fomentation before photosensitizer injection and irradiation. The fluorescence spectra of port wine stain skin were monitored and the therapeutic effect correlated index was calculated with a previously published spectral algorithm. Thirty cases were divided into group A (slow injection of photosensitizer during the first 15 min), group B (fomentation), and group C (control group, traditional injection method), with 10 cases in each group. To analyze the effect of these two new methods, the change of therapeutic effect correlated index values of two photodynamic therapy sessions for each patient were calculated, and the photodynamic therapy outcome was compared. The results showed that the change of therapeutic effect correlated index in group A was slightly more remarkable than that in the control group. The change of therapeutic effect correlated index in group B was similar to that in the control group. Slow injection of photosensitizer during photodynamic therapy has a potential to increase photosensitizer concentration level during photodynamic therapy. However, fomentation before photodynamic therapy has no such potential. There is a need for new methods to be attempted.

  5. Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs.

    Science.gov (United States)

    Abou-El-Enein, Mohamed; Römhild, Andy; Kaiser, Daniel; Beier, Carola; Bauer, Gerhard; Volk, Hans-Dieter; Reinke, Petra

    2013-03-01

    Advanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities. The "Clean-Room Technology Assessment Technique" (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system. CTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost. CTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  6. Neuroleptic Malignant syndrome (NMS): a rare presentation induced by an antiemetic - case report.

    Science.gov (United States)

    Kashyap, Gursharan Lal; Patel, Ashok G

    2011-09-01

    Neuroleptic Malignant Syndrome is one of the life threatening complications of antipsychotic psychotropic medication. We here report a case of a 39 years old male who has had a diagnosis of paranoid schizophrenia since the age of 18. He had been on antipsychotic therapy since then. He was stable on a combination of antipsychotics. He had mild hyper-salivation for a long time but was not very concerned about it. He requested and was prescribed Hyoscine Hydrobromide 300 mcg BD for hyper-salivation. There was no other medication change. After 5 days of starting Kwells, the patient presented with Neuroleptic Malignant syndrome. One has to watch for NMS while starting Hyoscine Hydrbromide for someone on antispychotics.

  7. [Mass spectrometry analysis of blood plasma lipidome as method of disease diagnostics, evuation of effectiveness and optimization of drug therapy].

    Science.gov (United States)

    Lokhov, P G; Maslov, D L; Balashova, E E; Trifonova, O P; Medvedeva, N V; Torkhovskaya, T I; Ipatova, O M; Archakov, A I; Malyshev, P P; Kukharchuk, V V; Shestakova, E A; Shestakova, M V; Dedov, I I

    2015-01-01

    A new method for the analysis of blood lipid based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. The versatility and quickness of the method significantly simplify its wide use. This method is applicable for diagnostics of atherosclerosis, diabetes, cancer and other diseases. Detalization of plasma lipid composition at the molecular level by means of mass spectrometry allows to assess the effectiveness of therapy and to optimize the drug treatment of cardiovascular diseases by phospholipid preparations.

  8. Predicting Optimal Outcomes in Cognitive Therapy or Interpersonal Psychotherapy for Depressed Individuals Using the Personalized Advantage Index Approach.

    Directory of Open Access Journals (Sweden)

    Marcus J H Huibers

    Full Text Available Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works best for the depressed individual. In this paper, we aim to replicate a recently developed treatment selection method, using data from an RCT comparing the effects of cognitive therapy (CT and interpersonal psychotherapy (IPT.134 depressed patients completed the pre- and post-treatment BDI-II assessment. First, we identified baseline predictors and moderators. Second, individual treatment recommendations were generated by combining the identified predictors and moderators in an algorithm that produces the Personalized Advantage Index (PAI, a measure of the predicted advantage in one therapy compared to the other, using standard regression analyses and the leave-one-out cross-validation approach.We found five predictors (gender, employment status, anxiety, personality disorder and quality of life and six moderators (somatic complaints, cognitive problems, paranoid symptoms, interpersonal self-sacrificing, attributional style and number of life events of treatment outcome. The mean average PAI value was 8.9 BDI points, and 63% of the sample was predicted to have a clinically meaningful advantage in one of the therapies. Those who were randomized to their predicted optimal treatment (either CT or IPT had an observed mean end-BDI of 11.8, while those who received their predicted non-optimal treatment had an end-BDI of 17.8 (effect size for the difference = 0.51.Depressed patients who were randomized to their predicted optimal treatment fared much better than those randomized to their predicted non-optimal treatment. The PAI provides a great opportunity for formal decision-making to improve individual patient outcomes in depression. Although the utility of the PAI

  9. Predicting Optimal Outcomes in Cognitive Therapy or Interpersonal Psychotherapy for Depressed Individuals Using the Personalized Advantage Index Approach

    Science.gov (United States)

    Huibers, Marcus J. H.; Cohen, Zachary D.; Lemmens, Lotte H. J. M.; Arntz, Arnoud; Peeters, Frenk P. M. L.; Cuijpers, Pim; DeRubeis, Robert J.

    2015-01-01

    Introduction Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works best for the depressed individual. In this paper, we aim to replicate a recently developed treatment selection method, using data from an RCT comparing the effects of cognitive therapy (CT) and interpersonal psychotherapy (IPT). Methods 134 depressed patients completed the pre- and post-treatment BDI-II assessment. First, we identified baseline predictors and moderators. Second, individual treatment recommendations were generated by combining the identified predictors and moderators in an algorithm that produces the Personalized Advantage Index (PAI), a measure of the predicted advantage in one therapy compared to the other, using standard regression analyses and the leave-one-out cross-validation approach. Results We found five predictors (gender, employment status, anxiety, personality disorder and quality of life) and six moderators (somatic complaints, cognitive problems, paranoid symptoms, interpersonal self-sacrificing, attributional style and number of life events) of treatment outcome. The mean average PAI value was 8.9 BDI points, and 63% of the sample was predicted to have a clinically meaningful advantage in one of the therapies. Those who were randomized to their predicted optimal treatment (either CT or IPT) had an observed mean end-BDI of 11.8, while those who received their predicted non-optimal treatment had an end-BDI of 17.8 (effect size for the difference = 0.51). Discussion Depressed patients who were randomized to their predicted optimal treatment fared much better than those randomized to their predicted non-optimal treatment. The PAI provides a great opportunity for formal decision-making to improve individual patient outcomes in depression. Although

  10. Optimal management of children on antiretroviral therapy (ART) in primary care: a quality improvement project

    National Research Council Canada - National Science Library

    van Deventer, Claire; Golden, Lauren; du Plessis, Erica; Lion-Cachet, Carien

    2017-01-01

    .... The referral pattern is true for paediatric patients as well. With the added complexity of managing children, there was a concern in the research district that children were not being optimally managed at PHC level. Method...

  11. Optimization of an accelerator-based epithermal neutron source for neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kononov, O.E.; Kononov, V.N.; Bokhovko, M.V.; Korobeynikov, V.V.; Soloviev, A.N.; Chu, W.T.

    2004-02-20

    A modeling investigation was performed to choose moderator material and size for creating optimal epithermal neutron beams for BNCT based on a proton accelerator and the 7Li(p,n)7Be reaction as a neutrons source. An optimal configuration is suggested for the beam shaping assembly made from polytetrafluoroethylene and magnesium fluorine. Results of calculation were experimentally tested and are in good agreement with measurements.

  12. Effect of intensiti modulated radiation therapy according to equivalent uniform dose optimization method on patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    Yu-Fu Zhou; Qian Sun; Ya-Jun Zhang; Geng-Ming Wang; Bin He; Tao Qi; An Zhou

    2016-01-01

    Objective:To analyze the effect of the intensity modulated radiation therapy according to equivalent uniform dose optimization method on patients with lung cancer.Methods:A total of 82 cases of non-small cell lung cancer were divided into observation group and control group according to the random number table method. Patients in the control group received conventional radiotherapy while observation group received intensity modulated radiotherapy based on equivalent uniform dose optimization method. The treatment effects, survival times, blood vessel-related factors, blood coagulation function and the levels of inflammatory factors and so on were compared between the two groups of patients.Results:The effective rate of the observation group after treatment was higher than that of the control group. Progression free survival and median overall survival times were longer than those of patients in the control group (P<0.05). The serum VEGF and HIF-αα levels as well as D-D, TT, PT, APTT and FIB levels were lower in observation group patients after treatment than those in the control group(P<0.05). At the same time point, serum TNF-αα, CRP and PCT levels in the observation group after treatment were lower than those in the control group (P<0.05). Serum M2-PK, CA125, CEA and SCC values of patients in the observation group after treatment were all significantly lower than those in the control group (P< 0.05).Conclusions:Intensity modulated radiation therapy based on equivalent uniform dose optimized method can improve the treatment effect, prolong the survival time, optimize micro inflammatory environment and inhibit tumor biological behavior at the same time.

  13. Explicit optimization of plan quality measures in intensity-modulated radiation therapy treatment planning.

    Science.gov (United States)

    Engberg, Lovisa; Forsgren, Anders; Eriksson, Kjell; Hårdemark, Björn

    2017-06-01

    To formulate convex planning objectives of treatment plan multicriteria optimization with explicit relationships to the dose-volume histogram (DVH) statistics used in plan quality evaluation. Conventional planning objectives are designed to minimize the violation of DVH statistics thresholds using penalty functions. Although successful in guiding the DVH curve towards these thresholds, conventional planning objectives offer limited control of the individual points on the DVH curve (doses-at-volume) used to evaluate plan quality. In this study, we abandon the usual penalty-function framework and propose planning objectives that more closely relate to DVH statistics. The proposed planning objectives are based on mean-tail-dose, resulting in convex optimization. We also demonstrate how to adapt a standard optimization method to the proposed formulation in order to obtain a substantial reduction in computational cost. We investigated the potential of the proposed planning objectives as tools for optimizing DVH statistics through juxtaposition with the conventional planning objectives on two patient cases. Sets of treatment plans with differently balanced planning objectives were generated using either the proposed or the conventional approach. Dominance in the sense of better distributed doses-at-volume was observed in plans optimized within the proposed framework. The initial computational study indicates that the DVH statistics are better optimized and more efficiently balanced using the proposed planning objectives than using the conventional approach. © 2017 American Association of Physicists in Medicine.

  14. Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

    Energy Technology Data Exchange (ETDEWEB)

    Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.; Sterpin, E. [Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels B-1200 (Belgium); Janssens, G. [Ion Beam Applications S.A., Louvain-la-Neuve 1348 (Belgium)

    2015-04-15

    above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.

  15. Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

    Directory of Open Access Journals (Sweden)

    Tojo Katsuyoshi

    2008-05-01

    Full Text Available Abstract Background The large clinical trials proved that Basal-Bolus (BB insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy. Methods In PROBE (Prospective, Randomized, Open, Blinded-Endpoint design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range age: 64.5(56.8~71.0years with secondary failure of sulfonylurea (SU were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group, and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups. Results After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3 → 7.4(6.9~8.7%, p Conclusion Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure. Trial registration Current Controlled Trials number, NCT00348231

  16. Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine.

    Science.gov (United States)

    Verbeken, Gilbert; Pirnay, Jean-Paul; De Vos, Daniel; Jennes, Serge; Zizi, Martin; Lavigne, Rob; Casteels, Minne; Huys, Isabelle

    2012-06-01

    For practitioners at hospitals seeking to use natural (not genetically modified, as appearing in nature) bacteriophages for treatment of antibiotic-resistant bacterial infections (bacteriophage therapy), Europe's current regulatory framework for medicinal products hinders more than it facilitates. Although many experts consider bacteriophage therapy to be a promising complementary (or alternative) treatment to antibiotic therapy, no bacteriophage-specific framework for documentation exists to date. Decades worth of historical clinical data on bacteriophage therapy (from Eastern Europe, particularly Poland, and the former Soviet republics, particularly Georgia and Russia, as well as from today's 27 EU member states and the US) have not been taken into account by European regulators because these data have not been validated under current Western regulatory standards. Consequently, applicants carrying out standard clinical trials on bacteriophages in Europe are obliged to initiate clinical work from scratch. This paper argues for a reduced documentation threshold for Phase 1 clinical trials of bacteriophages and maintains that bacteriophages should not be categorized as classical medicinal products for at least two reasons: (1) such a categorization is scientifically inappropriate for this specific therapy and (2) such a categorization limits the marketing authorization process to industry, the only stakeholder with sufficient financial resources to prepare a complete dossier for the competent authorities. This paper reflects on the current regulatory framework for medicines in Europe and assesses possible regulatory pathways for the (re-)introduction of bacteriophage therapy in a way that maintains its effectiveness and safety as well as its inherent characteristics of sustainability and in situ self-amplification and limitation.

  17. Optimization of Radiation Therapy Techniques for Prostate Cancer With Prostate-Rectum Spacers: A Systematic Review

    Energy Technology Data Exchange (ETDEWEB)

    Mok, Gary [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Department of Radiation Oncology, Centre Intégré de Cancérologie de Laval, Centre de Santé et de Services Sociaux de Laval, Laval, Québec (Canada); Department of Radiology, Radiation Oncology, and Nuclear Medicine, Centre Hospitalier Universitaire de Montréal, Montréal, Québec (Canada); Benz, Eileen [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Vallee, Jean-Paul [Department of Radiology, Geneva University Hospital, Geneva (Switzerland); Miralbell, Raymond [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Zilli, Thomas, E-mail: Thomas.Zilli@hcuge.ch [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland)

    2014-10-01

    Dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity. A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity. This systematic review focuses on the published data regarding the different types of commercially available prostate-rectum spacers. Dosimetric results and preliminary clinical data using prostate-rectum spacers in patients with localized prostate cancer treated by curative radiation therapy are compared and discussed.

  18. Mesenchymal Stem Cells for Regenerative Therapy: Optimization of Cell Preparation Protocols

    Directory of Open Access Journals (Sweden)

    Chiho Ikebe

    2014-01-01

    Full Text Available Administration of bone marrow-derived mesenchymal stem cells (MSCs is an innovative approach for the treatment of a range of diseases that are not curable by current therapies including heart failure. A number of clinical trials have been completed and many others are ongoing; more than 2,000 patients worldwide have been administered with culture-expanded allogeneic or autologous MSCs for the treatment of various diseases, showing feasibility and safety (and some efficacy of this approach. However, protocols for isolation and expansion of donor MSCs vary widely between these trials, which could affect the efficacy of the therapy. It is therefore important to develop international standards of MSC production, which should be evidence-based, regulatory authority-compliant, of good medical practice grade, cost-effective, and clinically practical, so that this innovative approach becomes an established widely adopted treatment. This review article summarizes protocols to isolate and expand bone marrow-derived MSCs in 47 recent clinical trials of MSC-based therapy, which were published after 2007 onwards and provided sufficient methodological information. Identified issues and possible solutions associated with the MSC production methods, including materials and protocols for isolation and expansion, are discussed with reference to relevant experimental evidence with aim of future clinical success of MSC-based therapy.

  19. Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies.

    Science.gov (United States)

    McCusker, Catherine D; Gardiner, David M

    2014-06-01

    Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the 'old' existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this positional information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the positional information in grafted cell populations, and to promote the communication of positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying positional information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.

  20. Optimizing Planning and Delivery of High-Precision Robotic Radiotherapy and Intensity-Modulated Proton Therapy

    NARCIS (Netherlands)

    S. van de Water (Steven)

    2015-01-01

    markdownabstract__Abstract__ High-precision robotic radiotherapy and intensity-modulated proton therapy (IMPT) are two relatively new radiotherapy techniques that particularly aim at a highly localized delivery of a curative dose to the tumor, while achieving excellent sparing of the surrounding

  1. Optimization of delivery strategies for cardiac cell therapy in ischemic heart disease

    NARCIS (Netherlands)

    van der Spoel, T.I.G.

    2012-01-01

    Cardiac cell therapy has been proposed as an alternative treatment option for patients after acute myocardial infarction (MI). Irrespective of the chosen regenerative strategy, it is essential to deliver sufficient number of cells to the infarcted myocardium to become effective which is important si

  2. The Canadian Optimal Therapy of COPD Trial: Design, Organization and Patient Recruitment

    Directory of Open Access Journals (Sweden)

    Shawn D Aaron

    2004-01-01

    Full Text Available BACKGROUND: There are no published studies that have assessed whether adding long-acting beta 2-agonist bronchodilators and/or inhaled steroids to chronic therapy with tiotropium would provide additional clinical benefit to patients with moderate to severe chronic obstructive pulmonary disease (COPD.

  3. Optimizing Planning and Delivery of High-Precision Robotic Radiotherapy and Intensity-Modulated Proton Therapy

    NARCIS (Netherlands)

    S. van de Water (Steven)

    2015-01-01

    markdownabstract__Abstract__ High-precision robotic radiotherapy and intensity-modulated proton therapy (IMPT) are two relatively new radiotherapy techniques that particularly aim at a highly localized delivery of a curative dose to the tumor, while achieving excellent sparing of the surrounding he

  4. Effect of number density on optimal design of gold nanoshells for plasmonic photothermal therapy.

    Science.gov (United States)

    Sikdar, Debabrata; Rukhlenko, Ivan D; Cheng, Wenlong; Premaratne, Malin

    2013-01-01

    Despite much research efforts being devoted to the design optimization of metallic nanoshells, no account is taken of the fact that the number of the nanoshells that can be delivered to a given cancerous site vary with their size. In this paper, we study the effect of the nanoshell number density on the absorption and scattering properties of a gold-nanoshell ensemble exposed to a broadband near-infrared radiation, and optimize the nanoshells' dimensions for efficient cancer treatment by analyzing a wide range of human tissues. We first consider the general situation in which the number of the delivered nanoshells decreases with their mean radius R as ∝ R(-β), and demonstrate that the optimal design of nanoshells required to treat cancer most efficiently depends critically on β. In the case of β = 2, the maximal energy absorbed (scattered) by the ensemble is achieved for the same dimensions that maximize the absorption (scattering) efficiency of a single nanoshell. We thoroughly study this special case by the example of gold nanoshells with silica core. To ensure that minimal thermal injury is caused to the healthy tissue surrounding a cancerous site, we estimate the optimal dimensions that minimize scattering by the nanoshells for a desired value of the absorption efficiency. The comparison of gold nanoshells with different cores shows that hollow nanoshells exhibiting relatively low absorption efficiency are less harmful to the healthy tissue and, hence, are preferred over the strongly absorbing nanoshells. For each of the cases analyzed, we provide approximate analytical expressions for the optimal nanoshell dimensions, which may be used as design guidelines by experimentalists, in order to optimize the synthesis of gold nanoshells for treating different types of human cancer at their various growth stages.

  5. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  6. SU-E-T-589: Optimization of Patient Head Angle Position to Spare Hippocampus During the Brain Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, G; Kang, Y [Radiation Oncology, Seoul St. Mary’s Hospital, Seoul (Korea, Republic of); Kang, S; Kim, T; Kim, D; Suh, T [The Catholic University of Korea, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: Hippocampus is one of the important organs which controls emotions, behaviors, movements the memorizing and learning ability. In the conventional head & neck therapy position, it is difficult to perform the hippocampal-sparing brain radiation therapy. The purpose of this study is to investigate optimal head angle which can save the hippocampal-sparing and organ at risk (OAR) in conformal radiation therapy (CRT), Intensity modulation radiation therapy (IMRT) and helical tomotherapy (HT). Methods: Three types of radiation treatment plans, CRT, IMRT and Tomotherapy plans, were performed for 10 brain tumor patients. The image fusion between CT and MRI data were used in the contour due to the limited delineation of the target and OAR in the CT scan. The optimal condition plan was determined by comparing the dosimetric performance of the each plan with the use of various parameters which include three different techniques (CRT, IMRT, HT) and 4 angle (0, 15, 30, 40 degree). The each treatment plans of three different techniques were compared with the following parameters: conformity index (CI), homogeneity index (HI), target coverage, dose in the OARs, monitor units (MU), beam on time and the normal tissue complication probability (NTCP). Results: HI, CI and target coverage was most excellent in head angle 30 degree among all angle. When compared by modality, target coverage and CI showed good results in IMRT and TOMO than compared to the CRT. HI at the head angle 0 degrees is 1.137±0.17 (CRT), 1.085±0.09 (IMRT) and 1.077±0.06 (HT). HI at the head angle 30 degrees is 1.056±0.08 (CRT), 1.020±0.05 (IMRT) and 1.022±0.07 (HT). Conclusion: The results of our study show that when head angle tilted at 30 degree, target coverage, HI, CI were improved, and the dose delivered to OAR was reduced compared with conventional supine position in brain radiation therapy. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid

  7. An optimized clarithromycin-free 14-day triple therapy for Helicobacter pylori eradication achieves high cure rates in Uruguay.

    Science.gov (United States)

    Dacoll, Cristina; Sánchez-Delgado, Jordi; Balter, Henia; Pazos, Ximena; Di Pace, María; Sandoya, Gabriela; Cohen, Henry; Calvet, Xavier

    Strong acid inhibition increases cure rates with triple therapy and 14-day are more effective than 7-day treatments. The combination of amoxicillin plus metronidazole at full doses has been shown to overcome metronidazole resistance and to achieve good eradication rates even in patients harboring resistant strains. No previous studies have been reported in Latin-America with this optimized triple-therapy scheme. The aim of the present study was to assess the eradication rate and tolerance of a new first-line treatment regimen associating strong acid inhibition, amoxicillin and metronidazole. Patients from the Clínica de Gastroenterología of the Hospital de Clínicas (Montevideo, Uruguay) were included. Hp status was mainly assessed by at least one of the following: histologyor urea breath test (UBT). A 14-day treatment was prescribed comprising esomeprazole 40mg twice a day plus amoxicillin 1g and metronidazole 500mg, both three times a day. H. pylori cure was assessed by UBT. Forty-one patients were enrolled. Mean age was 53.3±13 years and 17.1% of patients were male. Main indications for treatment were: functional dyspepsia (27.5%), gastritis (45%), gastric or duodenal erosions (20%), gastric ulcer (5%) and intestinal metaplasia (2.5%). H. pylori eradication was achieved in 33 of the 37 patients who returned for follow-up. Eradication rates were 80.5% (95% CI: 68.4-92.6) by intention-to-treat (ITT) analysis and 89.2% (95% CI; 79.2-99.2) per protocol (PP). No major side effects were reported; 26 patients (65.8%) complained of mild side effects (nausea, diarrhea and headache). Cure rates of this triple therapy including esomeprazole, amoxicillin and metronidazole were 81% per ITT and the treatment was well tolerated. These optimal results with a simple clarithromycin-free triple therapy are better than described for standard triple therapy but there is still room for improvement to reach the desired target of 90% per ITT. Copyright © 2017 Elsevier España, S

  8. Optimizing Collimator Margins for Isotoxically Dose-Escalated Conformal Radiation Therapy of Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Oxford Cancer Centre, Oxford University Hospitals, Oxford (United Kingdom); Panettieri, Vanessa [William Buckland Radiotherapy Centre, Alfred Hospital, Commercial Road, Melbourne (Australia); Panakis, Niki; Bates, Nicholas [Oxford Cancer Centre, Oxford University Hospitals, Oxford (United Kingdom); Lester, Jason F. [Velindre Cancer Centre, Velindre Road, Whitchurch, Cardiff (United Kingdom); Jain, Pooja [Clatterbridge Cancer Centre, Clatterbridge Road, Wirral (United Kingdom); Landau, David B. [Department of Radiotherapy, Guy' s and St. Thomas' NHS Foundation Trust, London (United Kingdom); Nahum, Alan E.; Mayles, W. Philip M. [Clatterbridge Cancer Centre, Clatterbridge Road, Wirral (United Kingdom); Fenwick, John D. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Oxford Cancer Centre, Oxford University Hospitals, Oxford (United Kingdom)

    2014-04-01

    Purpose: Isotoxic dose escalation schedules such as IDEAL-CRT [isotoxic dose escalation and acceleration in lung cancer chemoradiation therapy] (ISRCTN12155469) individualize doses prescribed to lung tumors, generating a fixed modeled risk of radiation pneumonitis. Because the beam penumbra is broadened in lung, the choice of collimator margin is an important element of the optimization of isotoxic conformal radiation therapy for lung cancer. Methods and Materials: Twelve patients with stage I-III non-small cell lung cancer (NSCLC) were replanned retrospectively using a range of collimator margins. For each plan, the prescribed dose was calculated according to the IDEAL-CRT isotoxic prescription method, and the absolute dose (D{sub 99}) delivered to 99% of the planning target volume (PTV) was determined. Results: Reducing the multileaf collimator margin from the widely used 7 mm to a value of 2 mm produced gains of 2.1 to 15.6 Gy in absolute PTV D{sub 99}, with a mean gain ± 1 standard error of the mean of 6.2 ± 1.1 Gy (2-sided P<.001). Conclusions: For NSCLC patients treated with conformal radiation therapy and an isotoxic dose prescription, absolute doses in the PTV may be increased by using smaller collimator margins, reductions in relative coverage being offset by increases in prescribed dose.

  9. Optimal structure of particles-based superparamagnetic microrobots: application to MRI guided targeted drug therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mellal, Lyès [INSA Centre Val de Loire, Université d’Orléans, PRISME EA 4229 (France); Belharet, Karim [Hautes Études d’Ingénieur campus Centre, PRISME EA 4229 (France); Folio, David; Ferreira, Antoine, E-mail: antoine.ferreira@insa-cvl.fr, E-mail: antoine.ferreira@ensi-bourges.fr [INSA Centre Val de Loire, Université d’Orléans, PRISME EA 4229 (France)

    2015-02-15

    This paper presents an optimal design strategy for therapeutic magnetic micro carriers (TMMC) guided in real time by a magnetic resonance imaging (MRI) system. As aggregates of TMMCs must be formed to carry the most amount of drug and magnetic actuation capability, different clustering agglomerations could be arranged. Nevertheless, its difficult to predict the hydrodynamic behavior of any arbitrary-shaped object due to the nonlinear hydrodynamic effects. Indeed, the drag effect is related not only to the properties of the bolus but also to its interaction with the fluid viscosity, the free-stream velocity and the container geometry. In this work, we propose a mathematical framework to optimize the TMMC aggregates to improve the steering efficiency in experimental endovascular conditions. The proposed analysis is carried out on various sizes and geometries of microcarrier: spherical, ellipsoid-like, and chain-like of microsphere structures. We analyze the magnetophoretic behavior of such designs to exhibit the optimal configuration. Based on the optimal design of the boluses, experimental investigations were carried out in mm-sized fluidic artery phantoms to demonstrate the steerability of the magnetic bolus using a proof-of-concept setup. The experiments demonstrate the steerability of the magnetic bolus under different velocity, shear-stress, and trajectory constraints with a laminar viscous fluidic environment. Preliminary experiments with a MRI system confirm the feasibility of the steering of these TMMCs in hepatic artery microchannel phantom.

  10. Inverse planning in the age of digital LINACs: station parameter optimized radiation therapy (SPORT)

    Science.gov (United States)

    Xing, Lei; Li, Ruijiang

    2014-03-01

    The last few years have seen a number of technical and clinical advances which give rise to a need for innovations in dose optimization and delivery strategies. Technically, a new generation of digital linac has become available which offers features such as programmable motion between station parameters and high dose-rate Flattening Filter Free (FFF) beams. Current inverse planning methods are designed for traditional machines and cannot accommodate these features of new generation linacs without compromising either dose conformality and/or delivery efficiency. Furthermore, SBRT is becoming increasingly important, which elevates the need for more efficient delivery, improved dose distribution. Here we will give an overview of our recent work in SPORT designed to harness the digital linacs and highlight the essential components of SPORT. We will summarize the pros and cons of traditional beamlet-based optimization (BBO) and direct aperture optimization (DAO) and introduce a new type of algorithm, compressed sensing (CS)-based inverse planning, that is capable of automatically removing the redundant segments during optimization and providing a plan with high deliverability in the presence of a large number of station control points (potentially non-coplanar, non-isocentric, and even multi-isocenters). We show that CS-approach takes the interplay between planning and delivery into account and allows us to balance the dose optimality and delivery efficiency in a controlled way and, providing a viable framework to address various unmet demands of the new generation linacs. A few specific implementation strategies of SPORT in the forms of fixed-gantry and rotational arc delivery are also presented.

  11. Hemodynamic device-based optimization in cardiac resynchronization therapy: concordance with systematic echocardiographic assessment of AV and VV intervals

    Directory of Open Access Journals (Sweden)

    Oliveira MM

    2015-08-01

    Full Text Available Mário M Oliveira, Luisa M Branco, Ana Galrinho, Nogueira da Silva, Pedro S Cunha, Bruno Valente, Joana Feliciano, Ricardo Pimenta, Ana Sofia Delgado, Rui Cruz Ferreira Santa Marta Hospital, Lisbon, Portugal Background: Inappropriate settings of atrioventricular (AV and ventriculo-ventricular (VV intervals can be one of the factors impacting response to cardiac resynchronization therapy (CRT. Optimal concordance of AV and VV intervals between echocardiographic-based assessment and a device-based automatic programming with a hemodynamic sensor was investigated, together with left ventricle (LV reverse remodeling after 6 months of regular automatic device-based optimization.Methods: We evaluated blindly 30 systematic echocardiographic examinations during 6 months in 17 patients (12 men, 64±10 years, in sinus rhythm and New York Heart Association class III; 76% with non-ischemic dilated cardiomyopathy, LV ejection fraction [LVEF] <35%, QRS 130 milliseconds and LV dyssynchrony implanted with the SonRtip lead and a cardioverter-defibrillator device. Dyssynchrony (AV, VV, or intraventricular was evaluated by an experienced operator blinded to the device programming, using conventional echocardiography, tissue synchronization imaging, tissue Doppler imaging, radial strain, and 3D echocardiography.Results: Either no AV or VV dyssynchrony (n=11; 36.7% or a slight septal or lateral delay (n=13; 43.3% was found in most echocardiography examinations (80%. AV or VV dyssynchrony requiring further optimization was identified in one-fifth of the examinations (20%. At 6 months, 76.5% patients were responders with LV reverse remodeling, of which 69% were super-responders (LVEF >40%. A statistically significant increase in LVEF was observed between baseline and 6 months post implant (P<0.01. One patient died from non-cardiac causes.Conclusion: Concordance between echocardiographic methods and device-based hemodynamic sensor optimization was found in most

  12. Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies

    Directory of Open Access Journals (Sweden)

    Catherine D. McCusker

    2014-06-01

    Full Text Available Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this positional information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the positional information in grafted cell populations, and to promote the communication of positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying positional information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.

  13. Optimizing physical therapy for ankylosing spondylitis: a case study in a young football player.

    Science.gov (United States)

    Tricás-Moreno, José Miguel; Lucha-López, María Orosia; Lucha-López, Ana Carmen; Salavera-Bordás, Carlos; Vidal-Peracho, Concepción

    2016-04-01

    [Purpose] Ankylosing spondylitis is prevalent in men. Modern and expert consensus documents include physical therapy among the strategies for the treatment of ankylosing spondylitis. This study aimed to describe the physical therapy approach in an athlete with ankylosing spondylitis. [Subject and Methods] The patient, refractory to treatment with anti-inflammatory medication, showed pelvic and lumbar pain and joint, muscle, and functional disorders, which were treated with orthopedic joint mobilization, dry needling, exercise, and whole-body hyperthermia. [Results] After the treatment, pain relief, normal joint mobility, improved muscle function, and return to activities of daily living and competitive sporting activities were recorded. [Conclusion] The literature provides evidence for the use of joint mobilization techniques; however, no previous studies have used the same techniques and methods. There is no previous evidence for the use of dry needling in this pathology. Exercise therapy has a higher level of evidence, and guidelines with scientific support were followed. This research confirms the effectiveness of hyperthermia for arthritis. The early stage of ankylosing spondylitis, and the young age, good overall condition, and cooperative attitude of the patient led to positive outcomes. In conclusion, a favorable response that promoted the remission of the disease was observed.

  14. A systematic approach to determine optimal composition of gel used in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yuan-Jen [Department of Management Information Systems, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Institute of Biomedical Engineering and Material Science, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Hsieh, Bor-Tsung, E-mail: bthsieh@ctust.edu.tw [Department of Biomedical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China)

    2011-10-01

    The design of experiment was used to find the optimal composition of N-isopropyl acrylamide (NIPAM) gel. Optical computed tomography was used to scan the polymer gel dosimeter, which was irradiated from 0 to 20 Gy. The study was conducted following a statistical method using a two-level fractional factorial plan involving four variables (gelatin-5% and 6%, NIPAM-3% and 5%, Bis-2.5% and 3%, and THPC-5 and 10 mM). We produced three batches of gels of the same composition to replicate the experiments. Based on the statistical analysis, a regression model was built. The optimal gel composition for the dose range 0-15 Gy with linearity up to 1.000 is as follows: gelatin (5.67%), NIPAM (5%), Bis (2.56%), and THPC (10 mM). The dose response of the NIPAM polymer gel attains stability about 24 h after irradiation and remains stable up to 3 months.

  15. Intra-operative radiation therapy optimization using the Monte Carlo method

    Energy Technology Data Exchange (ETDEWEB)

    Rosetti, M. [ENEA, Bologna (Italy); Benassi, M.; Bufacchi, A.; D' Andrea, M. [Ist. Regina Elena, Rome (Italy); Bruzzaniti, V. [ENEA, S. Maria di Galeria (Rome) (Italy)

    2001-07-01

    The problem addressed with reference to the treatment head optimization has been the choice of the proper design of the head of a new 12 MeV linear accelerator in order to have the required dose uniformity on the target volume while keeping the dose rate sufficiently high and the photon production and the beam impact with the head walls within acceptable limits. The second part of the optimization work, concerning the TPS, is based on the rationale that the TPSs generally used in radiotherapy use semi-empirical algorithms whose accuracy can be inadequate particularly when irregular surfaces and/or inhomogeneities, such as air cavities or bone, are present. The Monte Carlo method, on the contrary, is capable of accurately calculating the dose distribution under almost all circumstances. Furthermore it offers the advantage of allowing to start the simulation of the radiation transport in the patient from the beam data obtained with the transport through the specific treatment head used. Therefore the Monte Carlo simulations, which at present are not yet widely used for routine treatment planning due to the required computing time, can be employed as a benchmark and as an optimization tool for conventional TPSs. (orig.)

  16. Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization.

    Science.gov (United States)

    Maher, Dermot P; Chen, Lucy; Mao, Jianren

    2017-02-01

    Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes. Increased duration of relief from neuropathic pain is associated with (1) higher total infused doses of ketamine; (2) prolonged infusion durations, although the rate of infusion does not appear to be a factor; and (3) coadministration of adjunct medications such as midazolam and/or clonidine that mitigate some of the unpleasant psychomimetic side effects. However, there are few studies designed to optimize ketamine infusion protocols by defining what an effective infusion protocol entails with regard to a respective neuropathic pain condition. Therefore, despite common clinical practice, the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence. The objectives of this topical review are to (1) analyze the available clinical evidence related to ketamine infusion protocols and (2) call for clinical studies to identify optimal ketamine infusion protocols tailored for individual neuropathic pain conditions. The Oxford Center for Evidence-Based Medicine classification for levels of evidence was used to stratify the grades of clinical recommendation for each infusion variable studied.

  17. Influence of the atrio-ventricular delay optimization on the intra left ventricular delay in cardiac resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Nienaber Christoph A

    2006-01-01

    Full Text Available Abstract Background Cardiac Resynchronization Therapy (CRT leads to a reduction of left-ventricular dyssynchrony and an acute and sustained hemodynamic improvement in patients with chronic heart failure. Furthermore, an optimized AV-delay leads to an improved myocardial performance in pacemaker patients. The focus of this study is to investigate the acute effect of an optimized AV-delay on parameters of dyssynchrony in CRT patients. Method 11 chronic heart failure patients with CRT who were on stable medication were included in this study. The optimal AV-delay was defined according to the method of Ismer (mitral inflow and trans-oesophageal lead. Dyssynchrony was assessed echocardiographically at three different settings: AVDOPT; AVDOPT-50 ms and AVDOPT+50 ms. Echocardiographic assessment included 2D- and M-mode echo for the assessment of volumes and hemodynamic parameters (CI, SV and LVEF and tissue Doppler echo (strain, strain rate, Tissue Synchronisation Imaging (TSI and myocardial velocities in the basal segments Results The AVDOPT in the VDD mode (atrially triggered was 105.5 ± 38.1 ms and the AVDOPT in the DDD mode (atrially paced was 186.9 ± 52.9 ms. Intra-individually, the highest LVEF was measured at AVDOPT. The LVEF at AVDOPT was significantly higher than in the AVDOPT-50setting (p = 0.03. However, none of the parameters of dyssynchrony changed significantly in the three settings. Conclusion An optimized AV delay in CRT patients acutely leads to an improved systolic left ventricular ejection fraction without improving dyssynchrony.

  18. Comparison of the Prophylactic Antiemetic Efficacy of Aprepitant Plus Palonosetron Versus Aprepitant Plus Ramosetron in Patients at High Risk for Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy: A Prospective Randomized-controlled Trial.

    Science.gov (United States)

    Choi, Eun Kyung; Kim, Dong Gyeong; Jeon, Younghoon

    2016-10-01

    We compared the antiemetic efficacy of aprepitant plus palonosetron versus aprepitant plus ramosetron in patients after laparoscopic cholecystectomy. A total of 88, nonsmoking, female patients undergoing laparoscopic cholecystectomy were randomly allocated to 2 groups of 44 each who received palonosetron 0.075 mg (aprepitant plus palonosetron group) and ramosetron 0.3 mg (aprepitant plus ramosetron group) after induction of anesthesia. All patients received aprepitant 80 mg 2 hours before surgery. The incidence of postoperative nausea and vomiting (PONV), use of rescue antiemetic, pain severity, and any side effects were assessed for 24 hours after surgery. The incidence of PONV and use of rescue antiemetic were less in aprepitant plus palonosetron group than in aprepitant plus ramosetron group for 24 hours after surgery (Pplus palonosetron significantly prevents PONV, compared with aprepitant plus ramosetron in patients at high risk for PONV after laparoscopic cholecystectomy.

  19. The main factors influencing canine demodicosis treatment outcome and determination of optimal therapy.

    Science.gov (United States)

    Arsenović, Milica; Pezo, Lato; Vasić, Nebojša; Ćirić, Rodoljub; Stefanović, Milan

    2015-07-01

    The main idea of this research was to evaluate the efficacy of canine demodicosis conventional treatments using mathematical analyses. All available papers published between 1980 and 2014 were used in this study. One hundred six clinical trials enrolling 3414 cases of generalized demodicosis in dogs are studied. Dogs entered in the analysis were only the ones in which the disease occurred naturally, excluding the studies in which transplantation of Demodex canis mites was done from other animals. In conventional acaricide treatments, sorted according to active substances (moxidectin, amitraz, doramectin, ivermectin, and milbemycin oxime), the way of application (spot-on, dips, orally, or subcutaneous), concentration, and interval of application were used as input parameters in mathematical modeling. Data of interest were the treatment outcome, the number of dogs that went into remission, the number of animals not responding to treatment microscopically, the average duration of therapy, the follow-up period, the number of patients with disease recurrence, the number of adverse effects, and the number of animals with side effects. Dogs lost to follow-up or when the treatment was discontinued, due to various reasons not in connection with the therapy protocol, were not considered. Statistical and mathematical analyses were applied for prediction of the drugs' effectiveness. Developed mathematical models showed satisfactorily r (2), higher than 0.87. Good evidence for recommending the use of milbemycin oxime PO (0.5 mg/kg, daily) and moxidectin spot-on (Advocate®, Bayer) weekly is found. A bit less effective therapies were based on ivermectin PO (0.5 mg/kg, daily), moxidectin PO (0.35 mg/kg, daily), and amitraz dips (0.05 % solution, weekly), respectively. It is important to keep in mind that Advocate® is recommended by the manufacturer for use in milder cases.

  20. Optimization of photon beam energies in gold nanoparticle enhanced arc radiation therapy using Monte Carlo methods.

    Science.gov (United States)

    Koger, B; Kirkby, C

    2016-12-02

    As a recent area of development in radiation therapy, gold nanoparticle (GNP) enhanced radiation therapy has shown potential to increase tumour dose while maintaining acceptable levels of healthy tissue toxicity. In this study, the effect of varying photon beam energy in GNP enhanced arc radiation therapy (GEART) is quantified through the introduction of a dose scoring metric, and GEART is compared to a conventional radiotherapy treatment. The PENELOPE Monte Carlo code was used to model several simple phantoms consisting of a spherical tumour containing GNPs (concentration: 15 mg Au g(-1) tumour, 0.8 mg Au g(-1) normal tissue) in a cylinder of tissue. Several monoenergetic photon beams, with energies ranging from 20 keV to 6 MeV, as well as 100, 200, and 300 kVp spectral beams, were used to irradiate the tumour in a 360° arc treatment. A dose metric was then used to compare tumour and tissue doses from GEART treatments to a similar treatment from a 6 MV spectrum. This was also performed on a simulated brain tumour using patient computed tomography data. GEART treatments showed potential over the 6 MV treatment for many of the simulated geometries, delivering up to 88% higher mean dose to the tumour for a constant tissue dose, with the effect greatest near a source energy of 50 keV. This effect is also seen with the inclusion of bone in a brain treatment, with a 14% increase in mean tumour dose over 6 MV, while still maintaining acceptable levels of dose to the bone and brain.

  1. Opportunities in multimodal neuroimaging for optimizing thrombolytic therapy for ischemic stroke

    Directory of Open Access Journals (Sweden)

    M. M. Odinak

    2016-01-01

    Full Text Available The main purpose of examination of patients before thrombolytic therapy for ischemic stroke (IS is to timely identify contraindications to the use of recombinant tissue plasminogen activator.Objective: to estimate opportunities and benefits in applying multimodal magnetic resonance imaging (MRI to improve clinical outcomes in acute stroke, among other processes, by enhancing the efficiency and safety of thrombolytic therapy.Patients and methods. The clinical experience of the S.M. Kirov Military Medical Academy in using multimodal MRI of the brain since 2004 was analyzed in patients with stroke.Results. Comprehensive assessment of the results of perfusion-weighted MRI of the brain and those of transcranial Doppler ultrasound identified five clinically significant variants of perfusion changes in IS: normal perfusion; postischemic hyperemia; persistent hypoperfusion; acute pathological hyperperfusion, and unrecovered perfusion. With an irreversible tissue damage volume of >60 cm3 on day 1 of stroke, as evidenced by diffusion-weighted MRI, the odd ratio for cerebral edema in the acutest period of the disease is 39.4% (95% CI 2.57–2436; p<0.05. The risk of hemorrhagic transformation increases with a measured diffusion coefficient in the area of the nucleus of developing nonlacunar infarct <35×10-5 mm2/sec within the first 24 hours after disease onset (p<0.005.Conclusion. The data of local clinical practice and the results of international clinical trials show that multimodal MRI of the brain is a reliable tool for the detailed evaluation of the expected efficiency and safety of thrombolytic therapy for IS. When persistent hypoperfusion is detected, the determination of perfusion-diffusion mismatch is of no informative value in deciding on whether thrombolytic therapy can be performed. Estimating the volume of pathological changes on diffusion-weighted images and the measured diffusion coefficient in the area of the nucleus of

  2. Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer.

    Science.gov (United States)

    Shaikh, Talha; Meyer, Joshua E; Horwitz, Eric M

    2017-07-01

    Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Optimizing Single Agent Panitumumab Therapy in Pre-Treated Advanced Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Giampietro Gasparini

    2014-09-01

    Full Text Available PURPOSE: To improve the selection of advanced colorectal cancer patients to panitumumab by optimizing the assessment of RAS (KRAS-NRAS mutations. EXPERIMENTAL DESIGN: Using a centralized pyrosequencing RAS assay, we analyzed the tumors of 94 patients, wild-type for KRAS mutations (codons 12 to 13 by Sanger sequencing (SS, treated with panitumumab. RESULTS: By SS analysis, 94 (62% of 152 patients were wild-type and their objective response rate to panitumumab was 17%. We first optimized the KRAS test, by performing an accurate tissue-dissection step followed by pyrosequencing, a more sensitive method, and found further mutations in 12 (12.8% cases. Secondly, tumors were subjected to RAS extension analysis (KRAS, exons 3 to 4; NRAS exons 2 to 4 by pyrosequencing that allowed to identify several rare mutations: KRAS codon 61, 5.3%; codon 146, 5.3%; NRAS, 9.5%. Overall, RAS mutation rate was 32.9%. All patients with additional RAS mutations had progressive or stable disease, except 3 patients with mutations at codon 61 of KRAS or NRAS who experienced partial (2 cases or complete response. By excluding from the analysis 11 cases with mutations at codons 61, no patient was responsive to treatment (P = .021. RAS wild-type versus RAS mutated cases had a significantly better time to progression (P = .044, that resulted improved (p = .004 by excluding codon 61 mutations. CONCLUSION: This study shows that by optimizing the RAS test it is possible to significantly improve the identification of patients who do not gain benefit of panitumumab. Prospective studies are warranted to determine the clinical significance of rare mutations.

  4. [Optimization of aerosol therapy in otorhinolaryngology: stability and granulometry of dexamethasone-gomenol-framycetin solution].

    Science.gov (United States)

    Bellanger, A; Becquemin, M H; Feldman, D; Bertholon, J F; Tankere, F

    2001-02-01

    Nebulization of solutions associating gomenol, dexamethasone and framycetin is very widespread in otorhinolaryngology (particularly for the treatment of actue laryngitis and post-traumatic laryngitis and rhinitis and for the tracheotomy care). A rigorous clinical evaluation is however lacking. The aim of this work was to evaluate use of such solutions in comparison with the recommendations issuing from the National Session in April 1997 on good practices for aerosol therapeutics. Stability and granulometry were studied in order to optimize processing. A new formulation and new technical methods of administration are proposed in relation to the results of this study and the national recommendations.

  5. Simultaneous delivery time and aperture shape optimization for the volumetric-modulated arc therapy (VMAT) treatment planning problem

    Science.gov (United States)

    Mahnam, Mehdi; Gendreau, Michel; Lahrichi, Nadia; Rousseau, Louis-Martin

    2017-07-01

    In this paper, we propose a novel heuristic algorithm for the volumetric-modulated arc therapy treatment planning problem, optimizing the trade-off between delivery time and treatment quality. We present a new mixed integer programming model in which the multi-leaf collimator leaf positions, gantry speed, and dose rate are determined simultaneously. Our heuristic is based on column generation; the aperture configuration is modeled in the columns and the dose distribution and time restriction in the rows. To reduce the number of voxels and increase the efficiency of the master model, we aggregate similar voxels using a clustering technique. The efficiency of the algorithm and the treatment quality are evaluated on a benchmark clinical prostate cancer case. The computational results show that a high-quality treatment is achievable using a four-thread CPU. Finally, we analyze the effects of the various parameters and two leaf-motion strategies.

  6. Optimization of the Epithermal Neutron Beam for Boron Neutron Capture Therapy at the Brookhaven Medical Research Reactor

    Science.gov (United States)

    Hu, Jih-Perng; Rorer, David C.; Reciniello, Richard N.; Holden, Norman E.

    2003-06-01

    Clinical trials of Boron Neutron Capture Therapy for patients with malignant brain tumor had been carried out for half a decade, using an epithermal neutron beam at the Brookhaven Medical Reactor. The decision to permanently close this reactor in 2000 cut short the efforts to implement a new conceptual design to optimize this beam in preparation for use with possible new protocols. Details of the conceptual design to produce a higher intensity, more forward-directed neutron beam with less contamination from gamma rays, fast and thermal neutrons are presented here for their potential applicability to other reactor facilities. Monte Carlo calculations were used to predict the flux and absorbed dose produced by the proposed design. The results were benchmarked by the dose rate and flux measurements taken at the facility then in use.

  7. Optimization of the epithermal neutron beam for Boron Neutron Capture Therapy at the Brookhaven Medical Research Reactor.

    Science.gov (United States)

    Hu, Jih-Perng; Reciniello, Richard N; Holden, Norman E

    2004-05-01

    The use of epithermal neutron beam in clinical trials of Boron Neutron Capture Therapy for patients with malignant brain tumors had been carried out for half a decade at the Brookhaven's Medical Reactor. The decision to permanently close this reactor in 2000 cut short the efforts to implement a new conceptual design to optimize this beam in preparation for use with possible new BNCT protocols. Details of the conceptual design to produce a highly intensified and focused neutron beam with less gamma and neutron contamination in tissues are presented here for their potential applicability to other reactor facilities. Neutron-photon coupled Monte Carlo calculations were used to predict the flux, current, heating, and absorbed dose produced by the proposed design. The results were benchmarked by the dose rate and flux measurements taken at the facility then in use.

  8. Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials

    Directory of Open Access Journals (Sweden)

    Fischer A

    2009-12-01

    Full Text Available Abstract In the treatment of pulmonary diseases the inhalation of aerosols plays a key role - it is the preferred route of drug delivery in asthma, chronic obstructive pulmonary disease (COPD and cystic fibrosis. But, in contrast to oral and intravenous administration drug delivery to the lungs is controlled by additional parameters. Beside its pharmacology the active agent is furthermore determined by its aerosol characteristics as particle diameter, particle density, hygroscopicity and electrical charge. The patient related factors like age and stage of pulmonary disease will be additionally affected by the individual breathing pattern and morphometry of the lower airways. A number of these parameters with essential impact on the pulmonary drug deposition can be influenced by the performance of the inhalation system. Therefore, the optimization of nebulisation technology was a major part of aerosol science in the last decade. At this time the control of inspiration volume and air flow as well as the administration of a defined aerosol bolus was in the main focus. Up to date a more efficient and a more targeted pulmonary drug deposition - e.g., in the alveoli - will be provided by novel devices which also allow shorter treatment times and a better reproducibility of the administered lung doses. By such means of precise dosing and drug targeting the efficacy of inhalation therapy can be upgraded, e.g., the continuous inhalation of budesonide in asthma. From a patients' perspective an optimized inhalation manoeuvre means less side effects, e.g., in cystic fibrosis therapy the reduced oropharyngeal tobramycin exposure causes fewer bronchial irritations. Respecting to shorter treatment times also, this result in an improved quality of life and compliance. For clinical trials the scaling down of dose variability in combination with enhanced pulmonary deposition reduces the number of patients to be included and the requirement of pharmaceutical

  9. Nutrigenomics of Neuradaptogen Amino-Acid-Therapy and Neurometabolic Optimizers: Overcoming carbohydrate bingeing and overeating through neurometabolic mechanisms

    Directory of Open Access Journals (Sweden)

    Eric R. Braverman

    2011-09-01

    Full Text Available Despite progress that has been made in the treatment of obesity, the epidemic continues to rise worldwide. While pharmacological treatment of obesity may be effective, medications may have significant side effects and can be potentially fatal. This review will provide significant evidence to substantiate the existence of Reward Deficiency Syndrome in Obesity and the role of catecholaminergic pathways in aberrant substance seeking behavior, in particular cravings for carbohydrates. The genetic basis for generalized craving behavior will be established. Evidence to support the augmentation of precursor amino acid therapy and enkephalinase, MOA and COMT inhibition leading to enhanced levels of neurotransmitters: serotonin, enkephalins, GABA and dopamine/norepinephrine as well increasing insulin sensitivity (affecting dopamineFunctional Foods in Health and Disease: 9:310-378neuronal synthesis regulation through the use of certain neurometabolic optimizers will also be provided. This review article cites many published studies to support a conceptual paradigm shift towards the use of this proposed nutrigenomic formula. The analysis and research preceding this formulation is outlined. This formulation has a generalized anti-craving effect and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and prevention of relapse. This is the first time that components of this formula have been combined, at the dosage levels indicated with the goal of promoting successful and sustainable body recomposition. We are encouraging other laboratories to further evaluate Neuroadtagen Amino-Acid Therapy (NAAT/Nurometabolic optimizers as a putative anti-obesity complex in larger controlled blinded studies and await interpretation of must these needed studies.

  10. How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

    Science.gov (United States)

    Ward, Mark G; Irving, Peter M; Sparrow, Miles P

    2015-10-28

    In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

  11. Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.

    Science.gov (United States)

    Zhang, Bo; Shi, Wei; Jiang, Ting; Wang, Lanting; Mei, Heng; Lu, Heng; Hu, Yu; Pang, Zhiqing

    2016-09-20

    Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.

  12. Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy

    Science.gov (United States)

    Jiang, Ting; Wang, Lanting; Mei, Heng; Lu, Heng; Hu, Yu; Pang, Zhiqing

    2016-01-01

    Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment. PMID:27566585

  13. Guaranteed epsilon-optimal treatment plans with minimum number of beams for stereotactic body radiation therapy

    CERN Document Server

    Yarmand, Hamed

    2013-01-01

    Stereotactic body radiotherapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam's-eye-view) known as "apertures". Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan since the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used simultaneously, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined m...

  14. SU-E-T-358: Empirical Beam Angle Optimization for Lung Cancer Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Doozan, B [Florida Atlantic University (United States); Pella, S [South Florida Radiation Oncology, Boca Raton, FL (United States)

    2015-06-15

    Purpose: Creating an improved BAO can decrease the amount of time a dosimetrist spends on making a treatment plan, improve the treatment quality and enhance the tools an inexperienced dosimetrist can use to develop planning techniques. Methods: Using empirical data created by experienced dosimetrists from 69 patients treated for lung cancer, the most frequently used gantry angles were applied to four different regions in each lung to gather an optimal set of fields that could be used to treat future lung cancer patients. This method, given the moniker FAU BAO, is compared in 7 plans created with the Eclipse BAO choosing 5 fields and 9 fields. Results: The results show that the conformality index improved by 30% or 3% when using the 5 and 9 fields. The conformation number was better by 12% from the 5 fields and 9% from the 9 fields. The organs at risk (OAR) were overall more protected to produce fewer nonstochastic effects from the radiation treatment with the FAU BAO. Conclusion: Empirical methods for beam angle optimization is a viable method for IMRT treatment planning techniques.

  15. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  16. Oral targeted therapies: managing drug interactions, enhancing adherence and optimizing medication safety in lymphoma patients.

    Science.gov (United States)

    Liewer, Susanne; Huddleston, Ashley N

    2015-04-01

    The advent of newer, targeted oral chemotherapy medications such as small molecule kinase inhibitors, ibrutinib and idelalisib, has created additional options for the treatment of lymphoma. The targeted nature of these agents offers many patient-identified advantages over older, intravenously administered chemotherapy regimens such as ease of self-administration and an increased sense of independence. However, newer oral agents also present unique challenges not previously experienced with older therapies that may affect safety, efficacy and patient adherence. In this article, we review oral agents for the treatment of lymphoma, how to evaluate and manage drug-drug and drug-food interactions with concomitant oral medications, and issues with patient adherence as well as methods to determine adherence for oral chemotherapy.

  17. Optimal medical therapy and percutaneous coronary intervention for stable angina: why patients should 'be taking' and 'keep taking' the tablets.

    Science.gov (United States)

    Mohee, K; Wheatcroft, S B

    2014-08-01

    Cardioprotective drug regimens improve outcomes in patients with stable coronary artery disease. Revascularization is recommended for the persistence of symptoms despite optimal medical therapy (OMT) or in patients likely to derive prognostic benefit. Our objective is to comment on recent evidence that initiation of OMT is suboptimal in patients undergoing percutaneous coronary intervention (PCI) but conversely adherence to medication may be higher in patients treated with PCI. Large randomized controlled trials demonstrate that the risk of death or myocardial infarction is similar in patients treated by OMT alone and those treated with PCI and OMT. Despite the recommendations of international practice guidelines, OMT remains underutilized in recent analyses of patients referred for PCI. Notwithstanding the underutilization of proven therapies, a recent study suggests that adherence to medication is significantly higher in patients treated with PCI than in those treated with OMT alone. We discuss the potential factors that may contribute to underprescription of OMT and predict adherence in patients undergoing PCI. Contemporary studies continue to demonstrate underutilization of OMT in patients referred for PCI but increased medication adherence in patients treated by PCI. We argue for increased recognition of OMT as the definitive treatment for stable angina, so that we can be sure those patients who require PCI 'are taking' and 'keep taking' the tablets. © 2014 John Wiley & Sons Ltd.

  18. Optimizing the modified microdosimetric kinetic model input parameters for proton and 4He ion beam therapy application

    Science.gov (United States)

    Mairani, A.; Magro, G.; Tessonnier, T.; Böhlen, T. T.; Molinelli, S.; Ferrari, A.; Parodi, K.; Debus, J.; Haberer, T.

    2017-06-01

    Models able to predict relative biological effectiveness (RBE) values are necessary for an accurate determination of the biological effect with proton and 4He ion beams. This is particularly important when including RBE calculations in treatment planning studies comparing biologically optimized proton and 4He ion beam plans. In this work, we have tailored the predictions of the modified microdosimetric kinetic model (MKM), which is clinically applied for carbon ion beam therapy in Japan, to reproduce RBE with proton and 4He ion beams. We have tuned the input parameters of the MKM, i.e. the domain and nucleus radii, reproducing an experimental database of initial RBE data for proton and He ion beams. The modified MKM, with the best fit parameters obtained, has been used to reproduce in vitro cell survival data in clinically-relevant scenarios. A satisfactory agreement has been found for the studied cell lines, A549 and RENCA, with the mean absolute survival variation between the data and predictions within 2% and 5% for proton and 4He ion beams, respectively. Moreover, a sensitivity study has been performed varying the domain and nucleus radii and the quadratic parameter of the photon response curve. The promising agreement found in this work for the studied clinical-like scenarios supports the usage of the modified MKM for treatment planning studies in proton and 4He ion beam therapy.

  19. Development of allogeneic NK cell adoptive transfer therapy in metastatic melanoma patients: in vitro preclinical optimization studies.

    Directory of Open Access Journals (Sweden)

    Michal J Besser

    Full Text Available Natural killer (NK cells have long been considered as potential agents for adoptive cell therapy for solid cancer patients. Until today most studies utilized autologous NK cells and yielded disappointing results. Here we analyze various modular strategies to employ allogeneic NK cells for adoptive cell transfer, including donor-recipient HLA-C mismatching, selective activation and induction of melanoma-recognizing lysis receptors, and co-administration of antibodies to elicit antibody-dependent cell cytotoxicity (ADCC. We show that NK cell activation and induction of the relevant lysis receptors, as well as co-administration of antibodies yield substantial anti-cancer effects, which are functionally superior to HLA-C mismatching. Combination of the various strategies yielded improved effects. In addition, we developed various clinically-compatible ex vivo expansion protocols that were optimized according to fold expansion, purity and expression of lysis receptors. The main advantages of employing allogeneic NK cells are accessibility, the ability to use a single donor for many patients, combination with various strategies associated with the mechanism of action, e.g. antibodies and specific activation, as well as donor selection according to HLA or CD16 genotypes. This study rationalizes a clinical trial that combines adoptive transfer of highly potent allogeneic NK cells and antibody therapy.

  20. Optimal duration of therapy in the recovery period of vestibular diseases

    Directory of Open Access Journals (Sweden)

    M. V. Zamergrad

    2014-01-01

    Full Text Available Dizziness is a common symptom in neurological and general medical practice. In most cases it is caused by diseases of the central or peripheral vestibular system. The most common vestibular system diseases include benign paroxysmal postural vertigo, dizziness, Meniere's disease, vestibular neuronitis, and cerebrovascular diseases. One of the main treatments for the diseases accompanied by dizziness is vestibular rehabilitation that is a complex of exercises, the goal of which is to stimulate vestibular compensation. Adequate vestibular compensation allows a patient to get rid of dizziness and unsteadiness even though vestibular system injury is irreversible. Some medications are able to enhance the efficiency of vestibular rehabilitation. At the same time, the optimal duration of treatment for the most common vestibular disorders has not beenadequately explored. The paper gives the results of an observational program, whose purpose was to determine the optimal duration of vestibular rehabilitation in combination with the use of tanakan in patients with non-progressive unilateral peripheral vestibular disorder.Patients and methods. Data on 46 patients aged 19 to 70 years who underwent vestibular rehabilitation and took tanakan for vertigo caused by vestibular neuronitis (n = 44, labyrinthitis (n =1, or Ramsay Hunt syndrome (n = 1 were analyzed. All the patients were examined four times. The symptoms were recorded and the histories of disease were considered. The degree of vestibular disorders, including vertigo, was assessed when collecting complaints. The symptoms of vertigo were objectivized using its vertigo rating scale and five-point subjective rating scale for vertigo. All the patients underwent standard somatic and neurological examinations and videonystagmography. During the first visit after diagnosis, vestibular exercises were chosen for the patients and tanakan was used in a dose of 40 mg thrice daily to accelerate

  1. Seneca Valley Virus 3Cpro Substrate Optimization Yields Efficient Substrates for Use in Peptide-Prodrug Therapy.

    Directory of Open Access Journals (Sweden)

    Linde A Miles

    Full Text Available The oncolytic picornavirus Seneca Valley Virus (SVV-001 demonstrates anti-tumor activity in models of small cell lung cancer (SCLC, but may ultimately need to be combined with cytotoxic therapies to improve responses observed in patients. Combining SVV-001 virotherapy with a peptide prodrug activated by the viral protease 3Cpro is a novel strategy that may increase the therapeutic potential of SVV-001. Using recombinant SVV-001 3Cpro, we measured cleavage kinetics of predicted SVV-001 3Cpro substrates. An efficient substrate, L/VP4 (kcat/KM = 1932 ± 183 M(-1s(-1, was further optimized by a P2' N→P substitution yielding L/VP4.1 (kcat/KM = 17446 ± 2203 M(-1s(-1. We also determined essential substrate amino acids by sequential N-terminal deletion and substitution of amino acids found in other picornavirus genera. A peptide corresponding to the L/VP4.1 substrate was selectively cleaved by SVV-001 3Cpro in vitro and was stable in human plasma. These data define an optimized peptide substrate for SVV-001 3Cpro, with direct implications for anti-cancer therapeutic development.

  2. Seneca Valley Virus 3Cpro Substrate Optimization Yields Efficient Substrates for Use in Peptide-Prodrug Therapy.

    Science.gov (United States)

    Miles, Linde A; Brennen, W Nathaniel; Rudin, Charles M; Poirier, John T

    2015-01-01

    The oncolytic picornavirus Seneca Valley Virus (SVV-001) demonstrates anti-tumor activity in models of small cell lung cancer (SCLC), but may ultimately need to be combined with cytotoxic therapies to improve responses observed in patients. Combining SVV-001 virotherapy with a peptide prodrug activated by the viral protease 3Cpro is a novel strategy that may increase the therapeutic potential of SVV-001. Using recombinant SVV-001 3Cpro, we measured cleavage kinetics of predicted SVV-001 3Cpro substrates. An efficient substrate, L/VP4 (kcat/KM = 1932 ± 183 M(-1)s(-1)), was further optimized by a P2' N→P substitution yielding L/VP4.1 (kcat/KM = 17446 ± 2203 M(-1)s(-1)). We also determined essential substrate amino acids by sequential N-terminal deletion and substitution of amino acids found in other picornavirus genera. A peptide corresponding to the L/VP4.1 substrate was selectively cleaved by SVV-001 3Cpro in vitro and was stable in human plasma. These data define an optimized peptide substrate for SVV-001 3Cpro, with direct implications for anti-cancer therapeutic development.

  3. Seneca Valley Virus 3Cpro Substrate Optimization Yields Efficient Substrates for Use in Peptide-Prodrug Therapy

    Science.gov (United States)

    Miles, Linde A.; Brennen, W. Nathaniel; Rudin, Charles M.; Poirier, John T.

    2015-01-01

    The oncolytic picornavirus Seneca Valley Virus (SVV-001) demonstrates anti-tumor activity in models of small cell lung cancer (SCLC), but may ultimately need to be combined with cytotoxic therapies to improve responses observed in patients. Combining SVV-001 virotherapy with a peptide prodrug activated by the viral protease 3Cpro is a novel strategy that may increase the therapeutic potential of SVV-001. Using recombinant SVV-001 3Cpro, we measured cleavage kinetics of predicted SVV-001 3Cpro substrates. An efficient substrate, L/VP4 (kcat/KM = 1932 ± 183 M-1s-1), was further optimized by a P2’ N→P substitution yielding L/VP4.1 (kcat/KM = 17446 ± 2203 M-1s-1). We also determined essential substrate amino acids by sequential N-terminal deletion and substitution of amino acids found in other picornavirus genera. A peptide corresponding to the L/VP4.1 substrate was selectively cleaved by SVV-001 3Cpro in vitro and was stable in human plasma. These data define an optimized peptide substrate for SVV-001 3Cpro, with direct implications for anti-cancer therapeutic development. PMID:26069962

  4. Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background

    Directory of Open Access Journals (Sweden)

    Marzia Rigolli

    2011-01-01

    Full Text Available Background. Neurohormonal systems play an important role in chronic heart failure (CHF. Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (=.003 and =.002, respectively but not of LV ejection fraction (LVEF; β1AR389 GlyGly was related to improvement of LVEF (=.02 and LV end-systolic volume (=.01. The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (<.05 for all. Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.

  5. The clinical potential of high energy, intensity and energy modulated electron beams optimized by simulated annealing for conformal radiation therapy

    Science.gov (United States)

    Salter, Bill Jean, Jr.

    Purpose. The advent of new, so called IVth Generation, external beam radiation therapy treatment machines (e.g. Scanditronix' MM50 Racetrack Microtron) has raised the question of how the capabilities of these new machines might be exploited to produce extremely conformal dose distributions. Such machines possess the ability to produce electron energies as high as 50 MeV and, due to their scanned beam delivery of electron treatments, to modulate intensity and even energy, within a broad field. Materials and methods. Two patients with 'challenging' tumor geometries were selected from the patient archives of the Cancer Therapy and Research Center (CTRC), in San Antonio Texas. The treatment scheme that was tested allowed for twelve, energy and intensity modulated beams, equi-spaced about the patient-only intensity was modulated for the photon treatment. The elementary beams, incident from any of the twelve allowed directions, were assumed parallel, and the elementary electron beams were modeled by elementary beam data. The optimal arrangement of elementary beam energies and/or intensities was optimized by Szu-Hartley Fast Simulated Annealing Optimization. Optimized treatment plans were determined for each patient using both the high energy, intensity and energy modulated electron (HIEME) modality, and the 6 MV photon modality. The 'quality' of rival plans were scored using three different, popular objective functions which included Root Mean Square (RMS), Maximize Dose Subject to Dose and Volume Limitations (MDVL - Morrill et. al.), and Probability of Uncomplicated Tumor Control (PUTC) methods. The scores of the two optimized treatments (i.e. HIEME and intensity modulated photons) were compared to the score of the conventional plan with which the patient was actually treated. Results. The first patient evaluated presented a deeply located target volume, partially surrounding the spinal cord. A healthy right kidney was immediately adjacent to the tumor volume, separated

  6. Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally.

    Science.gov (United States)

    Kyriacou, Andreas; Pabari, Punam A; Mayet, Jamil; Peters, Nicholas S; Davies, D Wyn; Lim, P Boon; Lefroy, David; Hughes, Alun D; Kanagaratnam, Prapa; Francis, Darrel P; Whinnett, Zachary I

    2014-02-01

    The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing ("cardiac resynchronization therapy", CRT) are unknown. Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p=0.001, and aortic VTI by 11(SEM 3)%, p=0.002, but also increased MVO2 by 11(SEM 5)%, p=0.04. AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p=0.035 and aortic VTI by 4(SEM 1)%, p=0.017. MVO2 trended further up by 7(SEM 5)%, p=0.22. Mechanoenergetics at AV-40 were no different from LBBB. The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly >1 (p=0.02). Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect - which may therefore not be mainly "resynchronization". © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2015-05-15

    Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

  8. Optimization of an on-board imaging system for extremely rapid radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cherry Kemmerling, Erica M.; Wu, Meng, E-mail: mengwu@stanford.edu; Yang, He; Fahrig, Rebecca [Department of Radiology, Stanford University, Stanford, California 94305 (United States); Maxim, Peter G.; Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California 94305 and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California 94305 (United States)

    2015-11-15

    Purpose: Next-generation extremely rapid radiation therapy systems could mitigate the need for motion management, improve patient comfort during the treatment, and increase patient throughput for cost effectiveness. Such systems require an on-board imaging system that is competitively priced, fast, and of sufficiently high quality to allow good registration between the image taken on the day of treatment and the image taken the day of treatment planning. In this study, three different detectors for a custom on-board CT system were investigated to select the best design for integration with an extremely rapid radiation therapy system. Methods: Three different CT detectors are proposed: low-resolution (all 4 × 4 mm pixels), medium-resolution (a combination of 4 × 4 mm pixels and 2 × 2 mm pixels), and high-resolution (all 1 × 1 mm pixels). An in-house program was used to generate projection images of a numerical anthropomorphic phantom and to reconstruct the projections into CT datasets, henceforth called “realistic” images. Scatter was calculated using a separate Monte Carlo simulation, and the model included an antiscatter grid and bowtie filter. Diagnostic-quality images of the phantom were generated to represent the patient scan at the time of treatment planning. Commercial deformable registration software was used to register the diagnostic-quality scan to images produced by the various on-board detector configurations. The deformation fields were compared against a “gold standard” deformation field generated by registering initial and deformed images of the numerical phantoms that were used to make the diagnostic and treatment-day images. Registrations of on-board imaging system data were judged by the amount their deformation fields differed from the corresponding gold standard deformation fields—the smaller the difference, the better the system. To evaluate the registrations, the pointwise distance between gold standard and realistic registration

  9. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway.

    Science.gov (United States)

    Zitvogel, Laurence; Kepp, Oliver; Senovilla, Laura; Menger, Laurie; Chaput, Nathalie; Kroemer, Guido

    2010-06-15

    In response to some chemotherapeutic agents such as anthracyclines and oxaliplatin, cancer cells undergo immunogenic apoptosis, meaning that their corpses are engulfed by dendritic cells and that tumor cell antigens are presented to tumor-specific CD8(+) T cells, which then control residual tumor cells. One of the peculiarities of immunogenic apoptosis is the early cell surface exposure of calreticulin (CRT), a protein that usually resides in the lumen of the endoplasmic reticulum (ER). When elicited by anthracyclines or oxaliplatin, the CRT exposure pathway is activated by pre-apoptotic ER stress and the phosphorylation of the eukaryotic translation initiation factor eIF2alpha by the kinase PERK, followed by caspase-8-mediated proteolysis of the ER-sessile protein BAP31, activation of the pro-apoptotic proteins Bax and Bak, anterograde transport of CRT from the ER to the Golgi apparatus and exocytosis of CRT-containing vesicles, finally resulting in CRT translocation onto the plasma membrane surface. Interruption of this complex pathway abolishes CRT exposure, annihilates the immunogenicity of apoptosis, and reduces the immune response elicited by anticancer chemotherapies. We speculate that human cancers that are incapable of activating the CRT exposure pathway are refractory to the immune-mediated component of anticancer therapies.

  10. Pattern of electroconvulsive therapy use in Spain: Proposals for an optimal practice and equitable access.

    Science.gov (United States)

    Sanz-Fuentenebro, Javier; Vera, Ignacio; Verdura, Ernesto; Urretavizcaya, Mikel; Martínez-Amorós, Erika; Soria, Virginia; Bernardo, Miquel

    The main aims of our study were to estimate the current rates and pattern of electroconvulsive therapy (ECT) use in Spain, as well as exploring the causes that may be limiting its use in our country. A cross-sectional survey was conducted covering every psychiatric unit in Spain as of 31 December 2012. More than half (54.9%) of the psychiatric units applied ECT at a rate of 0.66 patients per 10,000 inhabitants. There are wide variations with regard to ECT application rates between the different autonomous communities (0.00-1.39) and provinces (0.00-3.90). ECT was prescribed to a mean of 25.5 patients per hospital that used the technique and 4.5 in referral centre (P=.000), but wide differences were reported in the number of patients who were prescribed ECT from hospital to hospital. Although the percentage of psychiatric units applying ECT in our country is among the highest in the world, the ECT application rate in Spain is among the lowest within western countries. Large differences in ECT use have been reported across the various autonomous communities, provinces and hospitals. Thus, health planning strategies need to be implemented, as well as promoting training in ECT among health professionals, if these differences in ECT use are to be reduced. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Margarita Gutova

    2017-03-01

    Full Text Available Despite improved survival for children with newly diagnosed neuroblastoma (NB, recurrent disease is a significant problem, with treatment options limited by anti-tumor efficacy, patient drug tolerance, and cumulative toxicity. We previously demonstrated that neural stem cells (NSCs expressing a modified rabbit carboxylesterase (rCE can distribute to metastatic NB tumor foci in multiple organs in mice and convert the prodrug irinotecan (CPT-11 to the 1,000-fold more toxic topoisomerase-1 inhibitor SN-38, resulting in significant therapeutic efficacy. We sought to extend these studies by using a clinically relevant NSC line expressing a modified human CE (hCE1m6-NSCs to establish proof of concept and identify an intravenous dose and treatment schedule that gave maximal efficacy. Human-derived NB cell lines were significantly more sensitive to treatment with hCE1m6-NSCs and irinotecan as compared with drug alone. This was supported by pharmacokinetic studies in subcutaneous NB mouse models demonstrating tumor-specific conversion of irinotecan to SN-38. Furthermore, NB-bearing mice that received repeat treatment with intravenous hCE1m6-NSCs and irinotecan showed significantly lower tumor burden (1.4-fold, p = 0.0093 and increased long-term survival compared with mice treated with drug alone. These studies support the continued development of NSC-mediated gene therapy for improved clinical outcome in NB patients.

  12. Optimal administration routes for adipose-derived stem cells therapy in ischaemic flaps.

    Science.gov (United States)

    Lee, Dong Won; Jeon, Yeo Reum; Cho, Eul Je; Kang, Jong Hwa; Lew, Dae Hyun

    2014-08-01

    Improvement of flap survival represents an ongoing challenge in reconstructive surgery. The angiogenic potential of adipose-derived stem cells (ASCs) offers a promising approach to improve the viability of random pattern flaps. Recently, to maximize the therapeutic effects of ASCs, increasing focus is being placed on how to deliver the stem cells to target lesions. The purpose of the present study was to compare the effectiveness of different administration routes of ASCs to improve the viability of the random pattern skin flap. ASCs labelled with PKH26 were applied via four methods to the cranially-based random pattern skin flaps of rats: (a) intravenous injection; (b) subcutaneous injection; (c) application with collagen sponge seeding; and (d) application with fibrin glue seeding. ASCs led to a significant increase in flap viability in the subcutaneous injection group and the collagen sponge group. Cutaneous blood flow was increased in the intravenous injection, subcutaneous injection and collagen sponge groups. Capillary density in the intravenous injection group and collagen sponge group was significantly greater than in the control group (no treatment). PKH26-positive cells via the collagen sponge were distributed more densely within the flap than in other groups. This study demonstrated that the collagen sponge method delivered ASCs most effectively within the flap and increased flap vascularity. The clinical therapeutic effects of ASCs can therefore be maximized when the optimal delivery route is chosen.

  13. Experiments to optimize enzyme substitution therapy in pancreatic duct-ligated pigs.

    Science.gov (United States)

    Kammlott, E; Karthoff, J; Stemme, K; Gregory, P; Kamphues, J

    2005-01-01

    Ligation of the pancreatic duct in pigs leads to severe maldigestion and malabsorption of crude nutrients. Supplementation with 24 capsules of Creon (Solvay Pharmaceuticals GmbH, Hannover, Germany) per meal led to an increased digestibility of crude nutrients. With regard to optimization of the treatment of EPI no essential improvements can be achieved by adding omeprazol or lecithin to the diet. In pancreatic duct-ligated pigs the isolated addition of omeprazol led to an increase of the pre-caecal digestibility of crude fat and organic matter. With additional enzyme substitution, the application of omeprazol did not result in an improved fat digestibility. Isolated addition of lecithin to the diet resulted in a reduced total digestibility of crude fat. Offering the diet twice a day and using a higher frequency of enzyme applications (four or six instead of only two applications) had no effects on the digestibilty of crude fat or organic matter. According to the observations in pancreatic duct-ligated pigs, the addition of missing enzymes to the diet led to the best treatment results in EPI. Administration of omeprazol or a higher feeding frequency as well as the application of enzymes in small proportion of the whole meal or dosages given consecutively over the day showed no advantages. Furthermore, the present study suggests that the addition of lecithin cannot be recommended in EPI, when given diets with butter as the predominant fat source as in human dietetics.

  14. An optimized triple modality reporter for quantitative in vivo tumor imaging and therapy evaluation.

    Science.gov (United States)

    Levin, Rachel A; Felsen, Csilla N; Yang, Jin; Lin, John Y; Whitney, Michael A; Nguyen, Quyen T; Tsien, Roger Y

    2014-01-01

    We present an optimized triple modality reporter construct combining a far-red fluorescent protein (E2-Crimson), enhanced firefly luciferase enzyme (Luc2), and truncated wild type herpes simplex virus I thymidine kinase (wttk) that allows for sensitive, long-term tracking of tumor growth in vivo by fluorescence, bioluminescence, and positron emission tomography. Two human cancer cell lines (MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer) were successfully transduced to express this triple modality reporter. Fluorescence and bioluminescence imaging of the triple modality reporter were used to accurately quantify the therapeutic responses of MDA-MB-231 tumors to the chemotherapeutic agent monomethyl auristatin E in vivo in athymic nude mice. Positive correlation was observed between the fluorescence and bioluminescence signals, and these signals were also positively correlated with the ex vivo tumor weights. This is the first reported use of both fluorescence and bioluminescence signals from a multi-modality reporter construct to measure drug efficacy in vivo.

  15. An optimized triple modality reporter for quantitative in vivo tumor imaging and therapy evaluation.

    Directory of Open Access Journals (Sweden)

    Rachel A Levin

    Full Text Available We present an optimized triple modality reporter construct combining a far-red fluorescent protein (E2-Crimson, enhanced firefly luciferase enzyme (Luc2, and truncated wild type herpes simplex virus I thymidine kinase (wttk that allows for sensitive, long-term tracking of tumor growth in vivo by fluorescence, bioluminescence, and positron emission tomography. Two human cancer cell lines (MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer were successfully transduced to express this triple modality reporter. Fluorescence and bioluminescence imaging of the triple modality reporter were used to accurately quantify the therapeutic responses of MDA-MB-231 tumors to the chemotherapeutic agent monomethyl auristatin E in vivo in athymic nude mice. Positive correlation was observed between the fluorescence and bioluminescence signals, and these signals were also positively correlated with the ex vivo tumor weights. This is the first reported use of both fluorescence and bioluminescence signals from a multi-modality reporter construct to measure drug efficacy in vivo.

  16. Energy Optimization And Calculation Of Dose Absorption Enhancement Factor In Photon Activation Therapy

    Directory of Open Access Journals (Sweden)

    Hassan Ranjbar

    2010-06-01

    Full Text Available Introduction: Secondary radiation such as photoelectrons, Auger electrons and characteristic radiations cause a local boost in dose for a tumor when irradiated with an external X-ray beam after being loaded with elements capable of activating the tumor, e.g.; I and Gd. Materials and Methods:  In this investigation, the MCNPX code was used for simulation and calculation of dose enhancement factor for a tumor loaded with activating elements. The designed model comprised the X-ray source, phantom (target tissue and loaded tumor with activating agent, detector, interactions modeling and results. The source was defined as monochromatic and plane surface situated at 50 cm (z = 50. Phantom geometry was a 10 × 10 × 10 cm3 cube centered at (0, 0, 0 with a 2.2 × 2.2 × 2.2 cm3 cubic tumor with a center located at 3 cm depth inside the phantom Results: Dose enhancement factor and optimum energy in radiotherapy are evaluated using the photon activation therapy method. Result show that the dose enhancement factor increases with activating concentration in the tumor. The maximum dose enhancement factor for iodine in the tumor occurs for photons in the energy range of 50-60 keV. Dose uniformity is less for lower energy photons within the activated region inside the tumor. Results indicate that the dose enhancement factor varies linearly with the activating concentration agent. Discussion and Conclusion: In this study, the obtained results point out a considerable enhancement in dose in the presence of activating agents in the tumor regions.

  17. Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam activated radiation therapy.

    Science.gov (United States)

    Engels, Elette; Corde, Stéphanie; McKinnon, Sally; Incerti, Sébastien; Konstantinov, Konstantin; Rosenfeld, Anatoly; Tehei, Moeava; Lerch, Michael; Guatelli, Susanna

    2016-12-01

    Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue sparing with spatially fractionated kilovoltage X-ray microbeams through the dose volume effect. Experimental measurements with Ta2O5 nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. Ta2O5 NPs were observed to form shells around cell nuclei which may be the reason for their efficiency in MRT. In this article, our experimental observation of NP shell formation is the basis of a Geant4 radiation transport study to characterise dose enhancement by Ta2O5 NPs in MRT. Our study showed that NP shells enhance the physical dose depending microbeam energy and their location relative to a single microbeam. For monochromatic microbeam energies below ∼70keV, NP shells show highly localised dose enhancement due to the short range of associated secondary electrons. Low microbeam energies indicate better targeted treatment by allowing higher microbeam doses to be administered to tumours and better exploit the spatial fractionation related selectivity observed with MRT. For microbeam energies above ∼100keV, NP shells extend the physical dose enhancement due to longer-range secondary electrons. Again, with NPs selectively internalised, the local effectiveness of MRT is expected to increase in the tumour. Dose enhancement produced by the shell aggregate varied more significantly in the cell population, depending on its location, when compared to a homogeneous NP distribution. These combined simulation and experimental data provide first evidence for optimising MRT through the incorporation of newly observed Ta2O5 NP distributions within 9L cancer cells. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  18. [Optimization of postoperative medical therapy of infective endocarditis in patients with congenital valvular heart disease].

    Science.gov (United States)

    Chistyakov, I S; Medvedev, A P; Pichugin, V V

    2016-01-01

    The purpose of this study was to evaluate the effectiveness of combined surgical and medical treatment of infective endocarditis in patients with congenital valvular heart disease when included in a regimen of the drug Reamberin. In this regard, the analysis of the effectiveness of a combination regimen of 74 patients with valvular congenital heart diseases complicated with infective endocarditis. Given the indications for surgical correction operative technique features and possible technical difficulties in carrying out such operations, due to the inflammatory changes and tissue destruction, and ways to overcome them. For the correction of metabolic disorders in the postoperative period, 47 patients (main group) was appointed Reamberin: once, intravenous drip 400 ml/day during the first 5 days after surgery. 27 patients (control group) was conducted infusion therapy depending on the severity of the condition according to the classical scheme. In addition to standard clinical and laboratory examination, to assess the effectiveness of Reamberin was investigated catalase activity of CPK in blood serum in the dynamics of observation (1, 3 and 5 days after surgery). It is revealed that surgical approach, used in complex treatment of patients with valvular congenital heart diseases, including reorganization of the cavities of the heart, increasing the frequency of joints and the use of reinforcing strips of synthetic material that prevents the cutting of sutures through the inflamed tissue has achieved good short-and long-term results. Infective endocarditis and destruction of the valvular annulus fibrosus the use of a frame of strips of polytetrafluoroethylene allows you to restore its integrity and to implant a mechanical prosthesis. The inclusion in the regimen of patients with infective endocarditis complicated by cardiac insufficiency in the early postoperative period the drug Reamberin improves the efficiency of treatment by a more rapid restoration of the normal

  19. MO-AB-BRA-08: Rapid Treatment Field Uniformity Optimization for Total Skin Electron Beam Therapy Using Cherenkov Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Andreozzi, J; Zhang, R; Glaser, A; Pogue, B [Dartmouth College, Hanover, NH (United States); Jarvis, L [Dartmouth-Hitchcock Medical Center, City Of Lebanon, New Hampshire (United States); Williams, B [Dartmouth Hitchcock Medical Center, Lebanon, NH (Lebanon); Gladstone, D [Dartmouth Hitchcock-Medical Center, Hanover, NH (United States)

    2015-06-15

    Purpose: To evaluate treatment field heterogeneity resulting from gantry angle choice in total skin electron beam therapy (TSEBT) following a modified Stanford dual-field technique, and determine a relationship between source to surface distance (SSD) and optimized gantry angle spread. Methods: Cherenkov imaging was used to image 62 treatment fields on a sheet of 1.2m x 2.2m x 1.2cm polyethylene following standard TSEBT setup at our institution (6 MeV, 888 MU/min, no spoiler, SSD=441cm), where gantry angles spanned from 239.5° to 300.5° at 1° increments. Average Cherenkov intensity and coefficient of variation in the region of interest were compared for the set of composite Cherenkov images created by summing all unique combinations of angle pairs to simulate dual-field treatment. The angle pair which produced the lowest coefficient of variation was further studied using an ionization chamber. The experiment was repeated at SSD=300cm, and SSD=370.5cm. Cherenkov imaging was also implemented during TSEBT of three patients. Results: The most uniform treatment region from a symmetric angle spread was achieved using gantry angles +/−17.5° about the horizontal axis at SSD=441cm, +/−18.5° at SSD=370.5cm, and +/−19.5° at SSD=300cm. Ionization chamber measurements comparing the original treatment spread (+/−14.5°) and the optimized angle pair (+/−17.5°) at SSD=441cm showed no significant deviation (r=0.999) in percent depth dose curves, and chamber measurements from nine locations within the field showed an improvement in dose uniformity from 24.41% to 9.75%. Ionization chamber measurements correlated strongly (r=0.981) with Cherenkov intensity measured concurrently on the flat Plastic Water phantom. Patient images and TLD results also showed modest uniformity improvements. Conclusion: A decreasing linear relationship between optimal angle spread and SSD was observed. Cherenkov imaging offers a new method of rapidly analyzing and optimizing TSEBT setup

  20. Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

    Science.gov (United States)

    Behan, Lucy-Ann; Rogers, Bairbre; Hannon, Mark J; O'Kelly, Patrick; Tormey, William; Smith, Diarmuid; Thompson, Christopher J; Agha, Amar

    2011-10-01

    The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen's equation. All results were compared to those of healthy, matched controls. Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0·05). The lower dose regimen C (10 mg mane/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane/10 mg tarde) and B(10 mg mane/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0·001). The lower dose of hydrocortisone (10 mg/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality. © 2011 Blackwell Publishing Ltd.

  1. Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2012-02-01

    BACKGROUND: The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. OBJECTIVE: Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). DESIGN: Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. RESULTS: Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0.05). The lower dose regimen C (10 mg mane\\/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane\\/10 mg tarde) and B(10 mg mane\\/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0.001). CONCLUSIONS: The lower dose of hydrocortisone (10 mg\\/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  2. Percutaneous Coronary Intervention Is More Beneficial Than Optimal Medical Therapy in Elderly Patients with Angina Pectoris.

    Science.gov (United States)

    Won, Hoyoun; Her, Ae Young; Kim, Byeong Keuk; Kim, Yong Hoon; Shin, Dong Ho; Kim, Jung Sun; Ko, Young Guk; Choi, Donghoon; Kwon, Hyuck Moon; Jang, Yangsoo; Hong, Myeong Ki

    2016-03-01

    Data comparing the clinical benefits of medical treatment with those of percutaneous coronary intervention (PCI) in an elderly population with angina pectoris are limited. Therefore, we evaluated the efficacy of elective PCI versus optimal medical treatment (OMT) in elderly patients (between 75 and 84 years old) with angina pectoris. One hundred seventy-seven patients with significant coronary artery stenosis were randomly assigned to either the PCI group (n=90) or the OMT group (n=87). The primary outcome was a composite of major adverse events in the 1-year follow-up period that included cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and stroke. Major adverse events occurred in 5 patients (5.6%) of the PCI group and in 17 patents (19.5%) of the OMT group (p=0.015). There were no significant differences between the PCI group and the OMT group in cardiac death [hazard ratio (HR) for the PCI group 0.454; 95% confidence interval (CI) 0.041-5.019, p=0.520], myocardial infarction (HR 0.399; 95% CI 0.039-4.050, p=0.437), or stroke (HR 0.919; 95% CI 0.057-14.709, p=0.952). However, the PCI group showed a significant preventive effect of the composite of major adverse events (HR 0.288; 95% CI 0.106-0.785, p=0.015) and against the need for coronary revascularization (HR 0.157; 95% CI 0.035-0.703, p=0.016). Elective PCI reduced major adverse events and was found to be an effective treatment modality in elderly patients with angina pectoris and significant coronary artery stenosis, compared to OMT.

  3. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

    Science.gov (United States)

    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

    2017-04-12

    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol(®)), Glyceryl palmitostearate (Precirol(®)), Glyceryl behenate (Compritol(®)) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (eR) varied with type and concentration of lipids: Geleol(®) (eR = 0.891-0.997), Precirol(®) (eR = 0.611-0.743), Compritol(®) (eR = 0.665-0.729) and Carnauba wax (eR = 0.499-0.551). Highly spherical pellets were obtained with Geleol(®) (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol(®) and Compritol(®), (ii) Geleol(®) and Carnauba wax and (iii) Geleol(®), Compritol(®) and Carnauba wax. Scanning electron microscopy of Compritol(®) pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol(®) and Compritol(®) pellets, explained by Korsmeyer-Peppas (R(2) = 0.978-0.993) indicated

  4. Prioritizing the patient: optimizing therapy in rheumatoid arthritis. Results of a patient questionnaire in northern Germany

    Directory of Open Access Journals (Sweden)

    Wollenhaupt J

    2013-05-01

    . Independence and mobility were strong priorities for respondents. Physical therapy, provided by RL, was felt to help both physical and mental/emotional health.Keywords: rheumatoid arthritis, patient survey, quality of life, patient satisfaction

  5. Optimization of Cyclosporine Therapy with Predicted AUC in Renal Transplant Patients

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Background: Pre-dose concentration measurement is the most practical method to evaluate cyclosporine(CsA) therapy in renal transplant patients. But it gives no information about the total drug exposure,which relate to graft survival. A number of different new concepts of CsA monitoring,including approaches such as single,double,triple time-point and abbreviated area under curve(AUC) determinaiton,have been introduced. The full CsA AUC value is the most sensitive indicator of clinical outcome. However,its higher analytical costs and time-consuming sampling compromise the benefit of full AUC. Alternative method of predicted AUC by using 2 concentration-time points have been established and used for routine practice in our hospital. [Objectives] The purpose of this study is to determine more sensitive and more predictive markers for CsA dosage adjustment in renal transplant patients. [Methods] Total 44 patients completed the 12-hours CsA pharmacokinetic studies. They had stable renal function. None of them had history of gastrectomy,small bowel resection,cholecystectomy,cholestasis,or had use of medications that might cause an interaction with CsA before the study. Pharmacokinetic parameters were evaluated by use of noncompartmental methods. The correlation equations between drug concentration-time points and AUC were determined by simple and multiple linear regression models using one,two,or three concentration time points as independent variable. [Results] Most of Cmax achieved at about 1~2 hours after dosing,but some delayed absorption was observed at abour 3~5 hours after dosing. C0 and C1 are poorly correlated with AUC of CsA,two of three point have better correlation than single point. Depending on clinical outcomes,predicted AUC goes more reliable than single concentration-time point monitoring for consideration of total exposure amount of CsA. If Tmax of CsA concentration-time curve shifted(delayed) out of population range,the AUC prediction error will be

  6. [Process optimization by central control of acute pain therapy: implementation of standardized treatment concepts and central pain management in hospitals].

    Science.gov (United States)

    Erlenwein, J; Stüder, D; Lange, J-P; Bauer, M; Petzke, F; Przemeck, M

    2012-11-01

    The aim of this investigation was to describe the effects of standardization and central control of the processes involved in postoperative pain management from patient and employee perspectives. Patients (n = 282/307) and respective hospital staff (n = 149/119) evaluated the processes, the quality of postoperative pain management and result parameters 3 months before and 12 months after the introduction of standardization of the postoperative pain therapy process using a set of standardized questionnaires. Pain level and the waiting period for an analgesic partially decreased and a higher subjective effectiveness of medication was achieved in patients after the standardization. Patients felt that the pain was taken more seriously and contacted the staff for additional medication more frequently. From an employee viewpoint the quality of care and individual competence and ability to treat pain increased after the introduction of standardization. Pain assessment was improved and employees rated their knowledge and education level as higher than before the intervention. Patients with pre-existing chronic pain and patients with special regional therapy benefited only partially after the introduction and an increase in pain intensity was even observed. The quality of care was improved by standardization of the postoperative pain management. The legal and practical ability of the nursing stuff to administer pain medication within well-defined margins reduced the dependence on the ward doctor and at the same time patient pain levels. Patients received analgesics more quickly and experienced increased effectiveness. These results should be an incentive to reconsider the importance of the organization of postoperative pain management, because the quality of care with all potential medical and economic advantages, can be easily optimized by such simple mechanisms. They also show that the quality assessment of acute pain and the selection of appropriate indicators

  7. Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study.

    Science.gov (United States)

    Myer, Landon; Phillips, Tamsin K; Zerbe, Allison; Ronan, Agnes; Hsiao, Nei-Yuan; Mellins, Claude A; Remien, Robert H; Le Roux, Stanzi M; Brittain, Kirsty; Ciaranello, Andrea; Petro, Greg; McIntyre, James A; Abrams, Elaine J

    2016-08-01

    Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH.

  8. Optimization of a multiple-scattering Compton camera as a photon-tracking imager for 6-MV photon therapy

    Science.gov (United States)

    Lee, Taewoong; Yoon, Changyeon; Lee, Wonho

    2014-06-01

    During radiation therapy, the irradiated position and the energy deposited in a patient must be monitored. In general, calculations before photon exposure or 2D measurements of the transmitted photons have been widely used for making dose estimates. In this paper, we propose a real-time 3D dose measurement using Compton imaging technology. On the basis of the Monte-Carlo method, we designed a multiple-scattering Compton camera system (MSCC) with semiconductor and scintillation detectors. The MSCC was constructed with two semiconductor detectors as scattering detectors and a cadmium-tungstate (CWO) scintillator detector as an absorber detector. The two planar semiconductor arrays, and the CWO array consisted of 40 × 40 pixels, each with a size of 1 × 1 × ɛ mm3, where ɛ is the variable thickness of the detectors. The design parameters, such as the types of semiconductors, detector thicknesses and distances between detectors, were optimized on the basis of the detection efficiency and angular resolution of reconstructed images for a point source. Under the optimized conditions, uncertainty factors in geometry and energy were estimated for various inter-detector distances. We used a source corresponding to photons scattered from a water phantom exposed to 6-MeV peak X-rays. According to our simulation results, the figure of merit, reached its maximum value when the inter-detector distance was 3 cm. In order to achieve a high FOM, we chose 1 cm as the optimum thickness for the scattering and absorbed detectors. A cadmium-zinc-telluride (CZT) detector showed the best performance among the simulated semiconductors. The position uncertainty caused by the pixelization effect was the major factor in degrading the angular resolution of the reconstructed images, and the degradation caused by energy broadening was less than expected. The angular uncertainties caused by Doppler broadening and incorrect sequencing were minimal compared with that of pixelization. Our

  9. A method of surface marker location optimization for tumor motion estimation in lung stereotactic body radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Bo, E-mail: luboufl@gmail.com; Park, Justin C.; Fan, Qiyong; Kahler, Darren; Liu, Chihray [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida 32610 (United States); Chen, Yunmei [Department of Mathematics, University of Florida College of Liberal Arts and Sciences, Gainesville, Florida 32610 (United States)

    2015-01-15

    Purpose: Accurately localizing lung tumor localization is essential for high-precision radiation therapy techniques such as stereotactic body radiation therapy (SBRT). Since direct monitoring of tumor motion is not always achievable due to the limitation of imaging modalities for treatment guidance, placement of fiducial markers on the patient’s body surface to act as a surrogate for tumor position prediction is a practical alternative for tracking lung tumor motion during SBRT treatments. In this work, the authors propose an innovative and robust model to solve the multimarker position optimization problem. The model is able to overcome the major drawbacks of the sparse optimization approach (SOA) model. Methods: The principle-component-analysis (PCA) method was employed as the framework to build the authors’ statistical prediction model. The method can be divided into two stages. The first stage is to build the surrogate tumor matrix and calculate its eigenvalues and associated eigenvectors. The second stage is to determine the “best represented” columns of the eigenvector matrix obtained from stage one and subsequently acquire the optimal marker positions as well as numbers. Using 4-dimensional CT (4DCT) and breath hold CT imaging data, the PCA method was compared to the SOA method with respect to calculation time, average prediction accuracy, prediction stability, noise resistance, marker position consistency, and marker distribution. Results: The PCA and SOA methods which were both tested were on all 11 patients for a total of 130 cases including 4DCT and breath-hold CT scenarios. The maximum calculation time for the PCA method was less than 1 s with 64 752 surface points, whereas the average calculation time for the SOA method was over 12 min with 400 surface points. Overall, the tumor center position prediction errors were comparable between the two methods, and all were less than 1.5 mm. However, for the extreme scenarios (breath hold), the

  10. SU-E-T-539: Fixed Versus Variable Optimization Points in Combined-Mode Modulated Arc Therapy Planning

    Energy Technology Data Exchange (ETDEWEB)

    Kainz, K; Prah, D; Ahunbay, E; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2014-06-01

    Purpose: A novel modulated arc therapy technique, mARC, enables superposition of step-and-shoot IMRT segments upon a subset of the optimization points (OPs) of a continuous-arc delivery. We compare two approaches to mARC planning: one with the number of OPs fixed throughout optimization, and another where the planning system determines the number of OPs in the final plan, subject to an upper limit defined at the outset. Methods: Fixed-OP mARC planning was performed for representative cases using Panther v. 5.01 (Prowess, Inc.), while variable-OP mARC planning used Monaco v. 5.00 (Elekta, Inc.). All Monaco planning used an upper limit of 91 OPs; those OPs with minimal MU were removed during optimization. Plans were delivered, and delivery times recorded, on a Siemens Artiste accelerator using a flat 6MV beam with 300 MU/min rate. Dose distributions measured using ArcCheck (Sun Nuclear Corporation, Inc.) were compared with the plan calculation; the two were deemed consistent if they agreed to within 3.5% in absolute dose and 3.5 mm in distance-to-agreement among > 95% of the diodes within the direct beam. Results: Example cases included a prostate and a head-and-neck planned with a single arc and fraction doses of 1.8 and 2.0 Gy, respectively. Aside from slightly more uniform target dose for the variable-OP plans, the DVHs for the two techniques were similar. For the fixed-OP technique, the number of OPs was 38 and 39, and the delivery time was 228 and 259 seconds, respectively, for the prostate and head-and-neck cases. For the final variable-OP plans, there were 91 and 85 OPs, and the delivery time was 296 and 440 seconds, correspondingly longer than for fixed-OP. Conclusion: For mARC, both the fixed-OP and variable-OP approaches produced comparable-quality plans whose delivery was successfully verified. To keep delivery time per fraction short, a fixed-OP planning approach is preferred.

  11. Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy

    Directory of Open Access Journals (Sweden)

    Ranjan Amalendu P

    2012-08-01

    Full Text Available Abstract Background Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process. Methods In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid nanoparticles (PLGA-CURC. This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM using Central Composite Design (CCD and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, in vitro release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out. Results Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5 ± 9.8 nm and the drug loading was determined to be 10.32 ± 1.4%. The in vitro release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC0-∞ being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation. Conclusions A successful

  12. A set cover approach to fast beam orientation optimization in intensity modulated radiation therapy for total marrow irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chieh-Hsiu Jason; Aleman, Dionne M [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King' s College Road, Toronto, ON M5S 3G8 (Canada); Sharpe, Michael B, E-mail: chjlee@mie.utoronto.ca, E-mail: aleman@mie.utoronto.ca, E-mail: michael.sharpe@rmp.uhn.on.ca [Princess Margaret Hospital, Department of Radiation Oncology, University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9 (Canada)

    2011-09-07

    The beam orientation optimization (BOO) problem in intensity modulated radiation therapy (IMRT) treatment planning is a nonlinear problem, and existing methods to obtain solutions to the BOO problem are time consuming due to the complex nature of the objective function and size of the solution space. These issues become even more difficult in total marrow irradiation (TMI), where many more beams must be used to cover a vastly larger treatment area than typical site-specific treatments (e.g., head-and-neck, prostate, etc). These complications result in excessively long computation times to develop IMRT treatment plans for TMI, so we attempt to develop methods that drastically reduce treatment planning time. We transform the BOO problem into the classical set cover problem (SCP) and use existing methods to solve SCP to obtain beam solutions. Although SCP is NP-Hard, our methods obtain beam solutions that result in quality treatments in minutes. We compare our approach to an integer programming solver for the SCP to illustrate the speed advantage of our approach.

  13. The application of distance transformation on parameter optimization of inverse planning in intensity-modulated radiation therapy.

    Science.gov (United States)

    Yan, Hui; Yin, Fang-Fang

    2008-04-16

    In inverse planning for intensity-modulated radiation therapy (IMRT), the dose specification and related weighting factor of an objective function for involved organs is usually predefined by a single value and then iteratively optimized, subject to a set of dose-volume constraints. Because the actual dose distribution is essentially non-uniform and considerably affected by the geometric shape and distribution of the anatomic structures involved, the spatial information regarding those structures should be incorporated such that the predefined parameter distribution is made to approach the clinically expected distribution. Ideally, these parameter distributions should be predefined on a voxel basis in a manual method. However, such an approach is too time-consuming to be feasible in routine use. In the present study, we developed a computer-aided method to achieve the goal described above, producing a non-uniform parameter distribution based on spatial information about the anatomic structures involved. The method consists of two steps: Use distance transformation technique to calculate the distance distribution of the structures. Based on the distance distribution, produce the parameter distribution via a function guided by prior knowledge. We use two simulated cases to examine the effectiveness of the method. The results indicate that application of a non-uniform parameter distribution produced by distance transformation clearly improves dose-sparing of critical organs without compromising dose coverage of the planning target.

  14. Effect of Optimal Medical Therapy Before Procedures on Outcomes in Coronary Patients Treated With Drug-Eluting Stents.

    Science.gov (United States)

    Iijima, Raisuke; Nakamura, Masato; Matsuyama, Yutaka; Muramatsu, Toshiya; Yokoi, Hiroyoshi; Hara, Hidehiko; Okada, Hisayuki; Ochiai, Masahiko; Suwa, Satoru; Hozawa, Hidenari; Kawai, Kazuya; Awata, Masaki; Mukawa, Hiroaki; Fujita, Hiroshi; Nanto, Shinsuke

    2016-09-15

    It has not been established whether the achievement of optimal medical therapy (OMT) before implantation of a drug-eluting stent has a clinical benefit for patients with stable coronary artery disease (CAD). This study included 3,004 patients with CAD treated with drug-eluting stent from 123 Japanese participating centers. The achievement of OMT was defined as control of blood pressure OMT group), whereas the remaining 2,456 patients failed to achieve one or more criteria (the non-OMT group). At 24 months, the incidence of target vessel failure was 7.0% in the achieved OMT group versus 10.0% in the non-OMT group (hazard ratio 0.68, 95% CI 0.48 to 0.96, p = 0.03). The incidence of non-Q-wave myocardial infarction was also lower in the achieved OMT group than in the non-OMT group (0.5% vs 1.5%, p = 0.08). Multivariate logistic regression analysis identified that hemoglobin A1c OMT before percutaneous coronary intervention significantly reduced subsequent cardiac events. Achievement of OMT is still insufficient in modern clinical practice.

  15. Otimizando o componente farmacológico da terapia integrada da vertigem Optimizing the pharmacological component of integrated balance therapy

    Directory of Open Access Journals (Sweden)

    Maurício Malavasi Ganança

    2007-02-01

    Full Text Available A farmacoterapia é opção importante no tratamento das vestibulopatias periféricas. OBJETIVO: Identificar a medicação que otimiza a terapia integrada da vertigem (TIV na doença de Ménière e em outras vestibulopatias periféricas. MATERIAL E MÉTODO: Estudo de casos em que pacientes com doença de Ménière ou outras vestibulopatias periféricas receberam TIV com betaistina, cinarizina, clonazepam, flunarizina, Ginkgo biloba ou sem medicação durante 120 dias. RESULTADOS: Na doença de Ménière, TIV com qualquer um dos medicamentos foi mais eficaz do que TIV sem medicação, após 60 dias; a betaistina foi mais efetiva que todas as outras drogas, após 60 e 120 dias. Nas outras vestibulopatias periféricas, diferenças significantes foram observadas entre TIV com betaistina, cinarizina, clonazepam ou flunarizina e TIV sem medicação após 60 dias e todas as drogas foram mais efetivas que TIV sem medicação após 120 dias; betaistina, cinarizina ou clonazepam foram igualmente efetivos e betaistina foi mais efetiva que flunarizina e Ginkgo biloba. Os tratamentos foram bem tolerados. CONCLUSÕES: TIV incluindo medicação é mais efetiva que sem medicação na doença de Ménière ou em outras vestibulopatias periféricas. Betaistina foi o medicamento mais efetivo na doença de Ménière e tão eficaz quanto cinarizina ou clonazepam em outras vestibulopatias periféricas.Drug treatment is an important option for the treatment of peripheral vestibular diseases. AIM: To identify the drug component associated with optimal integrated balance therapy (IBT for Ménière’s disease or other peripheral vestibular disorders. MATERIALS AND METHODS: Analysis of a series of patients with Ménière’s disease patients or patients with other peripheral vestibular disorders that received IBT involving either no medication or betahistine, cinnarizine, clonazepam, flunarizine or Ginkgo biloba during 120 days. RESULTS: In Ménière’s disease

  16. Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl [Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands); Kooy, Hanne M. [F. H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Heijmen, Ben J.M.; Hoogeman, Mischa S. [Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands)

    2015-06-01

    Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

  17. Optimization of the geometry and composition of a neutron system for treatment by Boron Neutron Capture Therapy

    Directory of Open Access Journals (Sweden)

    Rohollah Gheisari

    2015-01-01

    Full Text Available Background: In the field of the treatment by Boron Neutron Capture Therapy (BNCT, an optimized neutron system was proposed. This study (simulation was conducted to optimize the geometry and composition of neutron system and increase the epithermal neutron flux for the treatment of deep tumors is performed. Materials and Methods: A neutron system for BNCT was proposed. The system included 252Cf neutron source, neutron moderator/reflector arrangement, filter and concrete. To capture fast neutrons, different neutron filters Fe, Pb, Ni and PbF2 with various thicknesses were simulated and studied. Li (with 1 mm thick was used for filtering of thermal neutrons. Bi with thickness of 1 cm was used to minimize the intensity of gamma rays. Monte Carlo simulation code MCNPX 2.4.0 was used for design of the neutron system and calculation of the neutron components at the output port of the system. Results: For different thicknesses of the filters, the fast neutron flux, the epithermal and thermal flux were calculated at the output port of the system. The spatial distribution of the fast neutron flux, the epithermal flux and gamma flux in human head phantom with the presence of 40 ppm of 10B were obtained. The present calculations showed that Pb filter (about 1 cm at the output port is suitable for fast neutron capture. The thickness of Li filter was determined due to its high absorption cross-section in thermal region. Bi was used as a gamma filter by the reason of it is good for shielding gamma rays, while having high transmission epithermal neutrons. Conclusion: The epithermal neutron flux has enhanced about 38 percent at the output port of the present system, compared with recent system proposed by Ghassoun et al. At 2 cm depth inside the head phantom, the neutron flux reaches a maximum value about . At this depth, the ratio of the thermal neutron flux to the epithermal flux is about three times, that suggests such a neutron system to treat tumors in the

  18. Optimizing HIV drug therapy

    OpenAIRE

    Calmy, Alexandra

    2010-01-01

    The spectrum of drugs used in HIV-infected patients has dramatically changed since triple antiretroviral combinations were introduced, albeit at the expense of some severe adverse events, in 1996. Long term complications of antiretroviral drug exposure, such as HIV lipodystrophy, as well as organ-specific disease of heart and bone are, therefore, a critical issue when designing antiretroviral regimens. Because it is difficult to predict the occurrence of lipodystrophy, and because there is no...

  19. [The possibility of selecting optimal antiplatelet therapy in patients with coronary heart disease in terms of CYP2C19 polymorphism].

    Science.gov (United States)

    Bockeria, O L; Kudzoeva, Z F; Shvarts, V A; Koasari, A K; Donakanyan, S A

    2016-01-01

    To estimate whether optimal antiplatelet therapy can be selected in terms of CYP2C19 polymorphism. The prospective randomized trial included 124 patients (93 men and 31 women) who were to undergo percutaneous coronary intervention. They initially received dual antiplatelet therapy: clopidogrel 75 mg + acetylsalicylic acid (ASA) 300 mg. Genetic testing was performed in all the patients to reveal the carriage of allelic variants of the genes of cytochrome P-450 isoenzymes and the efficiency of antiplatelet therapy was evaluated. The carriers of one allele (CYP2C19*2/*1) were randomized into 3 subgroups according to further antiplatelet therapy. The therapy was not changed in Subgroup 1. The dose of clopidogrel was increased up to 150 mg/day and that of ASA remained unchanged in Subgroup 2. In Subgroup 3, the therapy was completely changed to the regimen: ASA 300 mg + ticagrelor 90 mg twice daily. Three days later, platelet aggregation was reinvestigated in all the three subgroups. In our investigation, the prevalence of carriage of at least one of the CYP2C19*2 alleles was about 35%. Comparison of the baseline platelet aggregation levels during the same platelet therapy showed statistically significant differences between the carriers and non-carriers: 32.7±11.6 and 44.8±12.9 (p=0.0024). Compared with the baseline values, there was a drug therapy switching-induced reduction in platelet aggregation in Subgroups 2 and 3 (p=0.0001 and p=0.0056, respectively). No statistically significant differences were found in Subgroup 1. The determination of CYP2C19 gene polymorphism allows a personalized approach to be applied in antiplatelet therapy for all patients with coronary artery disease.

  20. Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry.

    Directory of Open Access Journals (Sweden)

    Tianhao Zhang

    Full Text Available The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI provides an opportunity to evaluate how menopausal hormone therapy (HT affects the structure of older women's brains. Our earlier work based on region of interest (ROI analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes.We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA. ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods.Women assigned to HT treatments had significant Gray Matter (GM losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes.HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects.

  1. Optimized methods for epilepsy therapy development using an etiologically realistic model of focal epilepsy in the rat.

    Science.gov (United States)

    Eastman, Clifford L; Fender, Jason S; Temkin, Nancy R; D'Ambrosio, Raimondo

    2015-02-01

    Conventionally developed antiseizure drugs fail to control epileptic seizures in about 30% of patients, and no treatment prevents epilepsy. New etiologically realistic, syndrome-specific epilepsy models are expected to identify better treatments by capturing currently unknown ictogenic and epileptogenic mechanisms that operate in the corresponding patient populations. Additionally, the use of electrocorticography permits better monitoring of epileptogenesis and the full spectrum of acquired seizures, including focal nonconvulsive seizures that are typically difficult to treat in humans. Thus, the combined use of etiologically realistic models and electrocorticography may improve our understanding of the genesis and progression of epilepsy, and facilitate discovery and translation of novel treatments. However, this approach is labor intensive and must be optimized. To this end, we used an etiologically realistic rat model of posttraumatic epilepsy, in which the initiating fluid percussion injury closely replicates contusive closed-head injury in humans, and has been adapted to maximize epileptogenesis and focal non-convulsive seizures. We obtained week-long 5-electrode electrocorticography 1 month post-injury, and used a Monte-Carlo-based non-parametric bootstrap strategy to test the impact of electrode montage design, duration-based seizure definitions, group size and duration of recordings on the assessment of posttraumatic epilepsy, and on statistical power to detect antiseizure and antiepileptogenic treatment effects. We found that use of seizure definition based on clinical criteria rather than event duration, and of recording montages closely sampling the activity of epileptic foci, maximize the power to detect treatment effects. Detection of treatment effects was marginally improved by prolonged recording, and 24h recording epochs were sufficient to provide 80% power to detect clinically interesting seizure control or prevention of seizures with small groups

  2. SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W; Schild, S; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Liao, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Park, P [Scottsdale, GA (United States); Li, H [M.D. Anderson Cancer Center, Houston, TX (United States); Li, Y [Varian Medical Systems, Houston, TX (United States); Li, X; Shen, J [Mayo Clinic Arizona, Phoenix, AA (United States); Anand, A [Mayo Clinic Arizona, Phoenix (United States); Dong, L [Scripps Proton Therapy Center, San Diego, CA (United States); Zhu, X; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-01

    Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from the internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly

  3. ANALYSIS OF THE EFFICIENCY OF A THERAPEUTIC PROGRAM USING 10.2-MEV FAST NEUTRONS. OPTIMIZATION AND PROSPECTS OF THE DEVELOPMENT OF A PROCEDURE FOR COMBINED PHOTON-NEUTRON THERAPY. THE EXPERIENCE OF THE URAL CENTER FOR NEUTRON THERAPY

    Directory of Open Access Journals (Sweden)

    E. Yu. Kandakova

    2013-01-01

    Full Text Available The Ural Center for Neutron Therapy performs combined photon-neutron therapy for cancer patients, by applying an ELLIT-80 gamma unit and a NG-12I neutron generator. After modernization of the NG-12I generator, there was a need for redetermination of the relative biological efficiency (RBE to optimize radiotherapy for the patients. An exotest was used to experimentally estimate RBE according to the survival criteria for stem hematopoietic cells in CBA mice after modernization of the equipment generated by the NG-12I unit with respect to the gamma radiation generated by the ELLIT-80 unit. The investigation established that the RBE factor of NG-12I unit-induced radiation determined as the ratio of equally effective doses (our study used D0 was 1.53 for an acute radiation regimen. During fractional radiation, the RBE factor of neutron radiation was 3.05. That is to say, the total neutron radiation dose replacing 20 % gamma radiation (13 Gy in the used photon-neutron therapy regimen is 4.26 Gy. The experimental findings have led us to conclude that the previously described neuron therapy regimen may be optimized, by increasing the contribution of neutrons to the total course of radiotherapy in a definite category of patients with radioresistant tumors of the head and neck.

  4. International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

    Energy Technology Data Exchange (ETDEWEB)

    Dennis, Kristopher; Zhang Liying [Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Lutz, Stephen [Blanchard Valley Health Systems, Findlay, Ohio (United States); Baardwijk, Angela van [Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Linden, Yvette van der [Leiden University Medical Center, Leiden (Netherlands); Holt, Tanya [Radiation Oncology Mater Centre, Princess Alexandra Hospital, Brisbane (Australia); Arnalot, Palmira Foro [Parc de Salut Mar. Universitat Pompeu Fabra Barcelona (Spain); Lagrange, Jean-Leon [AP-HP Hopital Henri-Mondor, Universite Paris Est Creteil, Creteil (France); Maranzano, Ernesto [' S. Maria' Hospital, Terni (Italy); Liu, Rico [Queen Mary Hospital, Hong Kong (China); Wong, Kam-Hung [Queen Elizabeth Hospital, Hong Kong (Hong Kong); Wong, Lea-Choung [National University Cancer Institute (Singapore); Vassiliou, Vassilios [Bank of Cyprus Oncology Centre, Nicosia (Cyprus); Corn, Benjamin W. [Tel Aviv Medical Center, Tel Aviv (Israel); De Angelis, Carlo; Holden, Lori; Wong, C. Shun [Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2012-09-01

    Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT){sub 3} receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk

  5. Long-term pain relief with optimized medical treatment including antioxidants and step-up interventional therapy in patients with chronic pancreatitis.

    Science.gov (United States)

    Shalimar; Midha, Shallu; Hasan, Ajmal; Dhingra, Rajan; Garg, Pramod Kumar

    2017-01-01

    Abdominal pain is difficult to treat in patients with chronic pancreatitis (CP). Medical therapy including antioxidants has been shown to relieve pain of CP in the short-term. Our aim was to study the long-term results of optimized medical and interventional therapy for pain relief in patients with CP with a step-up approach. All consecutive patients with CP were included prospectively in the study. They were treated medically with a well-balanced diet, pancreatic enzymes, and antioxidants (9000 IU beta-carotene, 0.54 g vitamin C, 270 IU vitamin E, 600 µg organic selenium, and 2 g methionine). Endoscopic therapy and/or surgery were offered if medical therapy failed. Pain relief was the primary outcome measure. A total of 313 patients (mean age 26.16 ± 12.17; 244 males) with CP were included; 288 (92%) patients had abdominal pain. The etiology of CP was idiopathic in 224 (71.6%) and alcohol in 82 (26.2%). At 1-year follow-up, significant pain relief was achieved in 84.7% of patients: 52.1% with medical therapy, 16.7% with endoscopic therapy, 7.6% with surgery, and 8.3% spontaneously. The mean pain score decreased from 6.36 ± 1.92 to 1.62 ± 2.10 (P < 0.001). Of the 288 patients, 261, 218, 112, and 51 patients were followed up for 3, 5, 10, and 15 years, respectively; 54.0%, 57.3%, 60.7%, and 68.8% of them became pain free at those follow-up periods. Significant pain relief is achieved in the majority of patients with optimized medical and interventional treatment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

    Science.gov (United States)

    Zaghian, Maryam; Cao, Wenhua; Liu, Wei; Kardar, Laleh; Randeniya, Sharmalee; Mohan, Radhe; Lim, Gino

    2017-03-01

    Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet

  7. SU-C-204-02: Improved Patient-Specific Optimization of the Stopping Power Calibration for Proton Therapy Planning Using a Single Proton Radiography

    Energy Technology Data Exchange (ETDEWEB)

    Rinaldi, I [Lyon 1 University and CNRS/IN2P3, UMR 5822, Villeurbanne (France); Ludwig Maximilian University, Garching, DE (Germany); Heidelberg University Hospital, Heidelberg, DE (Germany); Parodi, K [Ludwig Maximilian University, Garching, DE (Germany); Heidelberg University Hospital, Heidelberg, DE (Germany); Krah, N [Heidelberg Collaboratory for Image Processing, Heidelberg, DE (Germany)

    2015-06-15

    Purpose: We present an improved method to calculate patient-specific calibration curves to convert X-ray computed tomography (CT) Hounsfield Unit (HU) to relative stopping powers (RSP) for proton therapy treatment planning. Methods: By optimizing the HU-RSP calibration curve, the difference between a proton radiographic image and a digitally reconstructed X-ray radiography (DRR) is minimized. The feasibility of this approach has previously been demonstrated. This scenario assumes that all discrepancies between proton radiography and DRR originate from uncertainties in the HU-RSP curve. In reality, external factors cause imperfections in the proton radiography, such as misalignment compared to the DRR and unfaithful representation of geometric structures (“blurring”). We analyze these effects based on synthetic datasets of anthropomorphic phantoms and suggest an extended optimization scheme which explicitly accounts for these effects. Performance of the method is been tested for various simulated irradiation parameters. The ultimate purpose of the optimization is to minimize uncertainties in the HU-RSP calibration curve. We therefore suggest and perform a thorough statistical treatment to quantify the accuracy of the optimized HU-RSP curve. Results: We demonstrate that without extending the optimization scheme, spatial blurring (equivalent to FWHM=3mm convolution) in the proton radiographies can cause up to 10% deviation between the optimized and the ground truth HU-RSP calibration curve. Instead, results obtained with our extended method reach 1% or better correspondence. We have further calculated gamma index maps for different acceptance levels. With DTA=0.5mm and RD=0.5%, a passing ratio of 100% is obtained with the extended method, while an optimization neglecting effects of spatial blurring only reach ∼90%. Conclusion: Our contribution underlines the potential of a single proton radiography to generate a patient-specific calibration curve and to improve

  8. A practical cone-beam CT scatter correction method with optimized Monte Carlo simulations for image-guided radiation therapy.

    Science.gov (United States)

    Xu, Yuan; Bai, Ti; Yan, Hao; Ouyang, Luo; Pompos, Arnold; Wang, Jing; Zhou, Linghong; Jiang, Steve B; Jia, Xun

    2015-05-07

    Cone-beam CT (CBCT) has become the standard image guidance tool for patient setup in image-guided radiation therapy. However, due to its large illumination field, scattered photons severely degrade its image quality. While kernel-based scatter correction methods have been used routinely in the clinic, it is still desirable to develop Monte Carlo (MC) simulation-based methods due to their accuracy. However, the high computational burden of the MC method has prevented routine clinical application. This paper reports our recent development of a practical method of MC-based scatter estimation and removal for CBCT. In contrast with conventional MC approaches that estimate scatter signals using a scatter-contaminated CBCT image, our method used a planning CT image for MC simulation, which has the advantages of accurate image intensity and absence of image truncation. In our method, the planning CT was first rigidly registered with the CBCT. Scatter signals were then estimated via MC simulation. After scatter signals were removed from the raw CBCT projections, a corrected CBCT image was reconstructed. The entire workflow was implemented on a GPU platform for high computational efficiency. Strategies such as projection denoising, CT image downsampling, and interpolation along the angular direction were employed to further enhance the calculation speed. We studied the impact of key parameters in the workflow on the resulting accuracy and efficiency, based on which the optimal parameter values were determined. Our method was evaluated in numerical simulation, phantom, and real patient cases. In the simulation cases, our method reduced mean HU errors from 44 to 3 HU and from 78 to 9 HU in the full-fan and the half-fan cases, respectively. In both the phantom and the patient cases, image artifacts caused by scatter, such as ring artifacts around the bowtie area, were reduced. With all the techniques employed, we achieved computation time of less than 30 s including the

  9. Response surface method optimization of a novel Hypericin formulation in P123 micelles for colorectal cancer and antimicrobial photodynamic therapy.

    Science.gov (United States)

    Montanha, Maiara Camotti; Silva, Larissa Lachi; Pangoni, Fernanda Belincanta Borghi; Cesar, Gabriel Batista; Gonçalves, Renato Sonchini; Caetano, Wilker; Hioka, Noboru; Tominaga, Tania Toyomi; Consolaro, Márcia Edilaine Lopes; Diniz, Andréa; Kimura, Elza

    2017-05-01

    The photodynamic properties of Hypericin (Hyp) may be used as an alternative treatment for malignancies of the lower gastrointestinal tract and for the prevention of surgical-site infection; however, its use in photodynamic therapy has been limited because of its poor hydrosolubility. Therefore, in order to improve its water solubility and its photodynamic effect, Hyp was encapsulated in Pluronic P123 (P123) and the photodynamic effects against intestinal and epidermal bacteria and against two lineages of intestinal colon carcinoma cells were investigated. Two response surface methods (RSM) were used to achieve the best in vitro photodynamic activity against Enterococcus faecalis, Escherichia coli and Staphylococcus aureus: in the first (full 2(3) RSM), Hyp concentration (HC*), incubation time (IT*) and LED-light time (LT*) were considered as the independent variables and E. faecalis inhibition as the dependent variable. In the second (full 3(2) RSM), Hyp concentration (HC*) and P123 concentration (CC*) were considered as independent variables and E. faecalis, E. coli and S. aureus inhibition as dependent variables. The optimized experimental conditions achieved were: Hyp concentration=37.5μmol/L; P123 concentration=21.5 μmol/L and 6.3J/cm(2), which resulted in 2.86±0.12 and 2.30±0.31CFU log-reductions of E. faecalis and S. aureus. No effect was seen against E. coli. The cytotoxic effects of Hyp/P123 were also investigated for Caco-2 and HT-29 intestinal colon carcinoma cells at Hyp/P123 concentrations of 1, 0.5, 0.25 and 0.1μmol/L for Caco-2 cells and 4, 3, 2 and 1μmol/L for HT-29 cells. The cytotoxic concentrations for 50% (CC50) and 90% (CC90) of Hyp/P123 were 0.443 and 0.870μmol/L for Caco-2 cells and 1.4 and 2.84μmol/L for HT-29 cells. The P123 nanocarrier played a significant role in the permeation of Hyp through the cell membrane leading to significant cell death, and showed itself to be a promising photosensitizer for PDT that could be suitable for

  10. TU-EF-304-02: 4D Optimized Treatment Planning for Actively Scanned Proton Therapy Delivered to Moving Target Volume

    Energy Technology Data Exchange (ETDEWEB)

    Bernatowicz, K; Zhang, Y; Weber, D; Lomax, A [Paul Scherrer Institut, Villigen-psi, Aargau (Switzerland)

    2015-06-15

    Purpose: To develop a 4D treatment optimization approach for Pencil Beam Scanned (PBS) proton therapy that includes breathing variability. Method: PBS proton therapy delivers a pattern of proton pencil beams (PBs), distributed to cover the target volume and optimized such as to achieve a homogenous dose distribution across the target. In this work, this optimization step has been enhanced to include advanced 4D dose calculations of liver tumors based on motion extracted from either 4D-CT (representing a single and averaged respiratory cycle) or 4D-CT(MRI) (including breathing variability). The 4D dose calculation is performed per PB on deforming dose grid, and according to the timestamp of each PB, a displacement due to patient’s motion and a change in radiological depth.Three different treatment fields have been optimized in 3D on the end-exhale phase of a 4D-CT liver data set (3D-opt) and then in 4D using the motion extracted from either 4D-CT or 4D-CT(MRI) using deformable image registration. All plans were calculated directly on the PTV without the use of an ITV. The delivery characteristics of the PSI Gantry 2 have been assumed for all calculations. Results: Dose inhomogeneities (D5-D95) in the CTV for the 3D optimized plans recalculated under conditions of variable motion were increased by on average 19.8% compared to the static case. These differences could be reduced by 4D-CT based 4D optimization to 10.5% and by 4D-CT(MRI) based optimization to only 2.3% of the static value. Liver V25 increased by less than 1% using 4D optimization. Conclusion: 4D optimized PBS treatment plans taking into account breathing variability provide for significantly improved robustness against motion and motion variability than those based on 4D-CT alone, and may negate the need of motion specific target expansions. Swiss National Fund Grant (320030-1493942-1)

  11. Comparison of the Direct Costs, Length of Recovery, and Incidence of Post Operative Anti-Emetic use After Anesthesia Induction with Propofol or a 1:1 Mixture of Thiopental and Propofol

    Science.gov (United States)

    1999-10-01

    et al. (1994) found that Chinese pediatric patients had significantly longer recovery with propofol induction and maintenance versus propofol ...Couchman, & Pollock, 1992). Propofol induction followed by propofol maintenance showed the least hemodynamic changes in pediatric patients versus...COMPARISON OF THE DIRECT COSTS, LENGTH OF RECOVERY, AND INCIDENCE OF POST OPERATIVE ANTI-EMETIC USE AFTER ANESTHESIA INDUCTION WITH PROPOFOL OR A 1:1

  12. SU-E-T-21: A Novel Sampling Algorithm to Reduce Intensity-Modulated Radiation Therapy (IMRT) Optimization Time

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, P; Xie, Y; Chen, Y [Washington University in Saint Louis, Saint Louis, Missouri (United States); Deasy, J [Memorial Sloan Kettering Cancer Center, NY, NY (United States)

    2014-06-01

    Purpose: The IMRT optimization problem requires substantial computer time to find optimal dose distributions because of the large number of variables and constraints. Voxel sampling reduces the number of constraints and accelerates the optimization process, but usually deteriorates the quality of the dose distributions to the organs. We propose a novel sampling algorithm that accelerates the IMRT optimization process without significantly deteriorating the quality of the dose distribution. Methods: We included all boundary voxels, as well as a sampled fraction of interior voxels of organs in the optimization. We selected a fraction of interior voxels using a clustering algorithm, that creates clusters of voxels that have similar influence matrix signatures. A few voxels are selected from each cluster based on the pre-set sampling rate. Results: We ran sampling and no-sampling IMRT plans for de-identified head and neck treatment plans. Testing with the different sampling rates, we found that including 10% of inner voxels produced the good dose distributions. For this optimal sampling rate, the algorithm accelerated IMRT optimization by a factor of 2–3 times with a negligible loss of accuracy that was, on average, 0.3% for common dosimetric planning criteria. Conclusion: We demonstrated that a sampling could be developed that reduces optimization time by more than a factor of 2, without significantly degrading the dose quality.

  13. On the role of the optimization algorithm of RapidArc(®) volumetric modulated arc therapy on plan quality and efficiency.

    Science.gov (United States)

    Vanetti, Eugenio; Nicolini, Giorgia; Nord, Janne; Peltola, Jarkko; Clivio, Alessandro; Fogliata, Antonella; Cozzi, Luca

    2011-11-01

    The RapidArc volumetric modulated arc therapy (VMAT) planning process is based on a core engine, the so-called progressive resolution optimizer (PRO). This is the optimization algorithm used to determine the combination of field shapes, segment weights (with dose rate and gantry speed variations), which best approximate the desired dose distribution in the inverse planning problem. A study was performed to assess the behavior of two versions of PRO. These two versions mostly differ in the way continuous variables describing the modulated arc are sampled into discrete control points, in the planning efficiency and in the presence of some new features. The analysis aimed to assess (i) plan quality, (ii) technical delivery aspects, (iii) agreement between delivery and calculations, and (iv) planning efficiency of the two versions. RapidArc plans were generated for four groups of patients (five patients each): anal canal, advanced lung, head and neck, and multiple brain metastases and were designed to test different levels of planning complexity and anatomical features. Plans from optimization with PRO2 (first generation of RapidArc optimizer) were compared against PRO3 (second generation of the algorithm). Additional plans were optimized with PRO3 using new features: the jaw tracking, the intermediate dose and the air cavity correction options. Results showed that (i) plan quality was generally improved with PRO3 and, although not for all parameters, some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3 optimization leads to simpler patterns of the dynamic parameters particularly for dose rate. (iii) No differences were observed between the two algorithms in terms of pretreatment quality assurance measurements and (iv) PRO3 optimization was generally faster, with a time reduction of a factor approximately 3.5 with respect to PRO2. These results indicate that PRO3 is either clinically beneficial or neutral in terms of dosimetric quality while

  14. WE-AB-BRA-09: Sensitivity of Plan Re-Optimization to Errors in Deformable Image Registration in Online Adaptive Image-Guided Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    McClain, B; Olsen, J; Green, O; Yang, D; Santanam, L; Olsen, L; Zhao, T; Rodriguez, V; Wooten, H; Mutic, S; Kashani, R [Washington University School of Medicine, St. Louis, Missouri (United States); Victoria, J; Dempsey, J [ViewRay Incorporated, Oakwood Village, OH (United States)

    2015-06-15

    Purpose: Online adaptive therapy (ART) relies on auto-contouring using deformable image registration (DIR). DIR’s inherent uncertainties require user intervention and manual edits while the patient is on the table. We investigated the dosimetric impact of DIR errors on the quality of re-optimized plans, and used the findings to establish regions for focusing manual edits to where DIR errors can Result in clinically relevant dose differences. Methods: Our clinical implementation of online adaptive MR-IGRT involves using DIR to transfer contours from CT to daily MR, followed by a physicians’ edits. The plan is then re-optimized to meet the organs at risk (OARs) constraints. Re-optimized abdomen and pelvis plans generated based on physician edited OARs were selected as the baseline for evaluation. Plans were then re-optimized on auto-deformed contours with manual edits limited to pre-defined uniform rings (0 to 5cm) around the PTV. A 0cm ring indicates that the auto-deformed OARs were used without editing. The magnitude of the variations caused by the non-deterministic optimizer was quantified by repeat re-optimizations on the same geometry to determine the mean and standard deviation (STD). For each re-optimized plan, various volumetric parameters for the PTV, the OARs were extracted along with DVH and isodose evaluation. A plan was deemed acceptable if the variation from the baseline plan was within one STD. Results: Initial results show that for abdomen and pancreas cases, a minimum of 5cm margin around the PTV is required for contour corrections, while for pelvic and liver cases a 2–3 cm margin is sufficient. Conclusion: Focusing manual contour edits to regions of dosimetric relevance can reduce contouring time in the online ART process while maintaining a clinically comparable plan. Future work will further refine the contouring region by evaluating the path along the beams, dose gradients near the target and OAR dose metrics.

  15. Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies

    NARCIS (Netherlands)

    S. Bison (Sander); J.C. Haeck (Joost); K. Bol (Karin); S. Koelewijn (Stuart); H.C. Groen (Harald); M.L. Melis (Marleen); J.F. Veenland (Jifke); M.R. Bernsen (Monique); M. de Jong (Marion)

    2015-01-01

    textabstractBackground: Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate (177Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozo

  16. Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies

    NARCIS (Netherlands)

    S. Bison (Sander); J.C. Haeck (Joost); K. Bol (Karin); S. Koelewijn (Stuart); H.C. Groen (Harald); M.L. Melis (Marleen); J.F. Veenland (Jifke); M.R. Bernsen (Monique); M. de Jong (Marion)

    2015-01-01

    textabstractBackground: Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate (177Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and

  17. Medication monitoring and optimization : a targeted pharmacist program for effective and cost-effective improvement of chronic therapy adherence

    NARCIS (Netherlands)

    van Boven, Job F.M.; Stuurman-Bieze, Ada G.G.; Hiddink, Eric G.; Postma, Maarten J.; Vegter, Stefan

    2014-01-01

    BACKGROUND: Community pharmacies provide a promising platform for monitoring and improving therapy adherence and providing pharmaceutical care. Structured methods and appropriate software are important tools to increase pharmacist effectiveness and improve health outcomes. In 2006, the Medication Mo

  18. Predicting optimal outcomes in cognitive therapy or interpersonal psychotherapy for depressed individuals using the personalized advantage index approach

    NARCIS (Netherlands)

    M.J.H. Huibers; Z.D. Cohen; L.H.J.M. Lemmens; A. Arntz; F.P.M.L. Peeters; P. Cuijpers; R.J. DeRubeis

    2015-01-01

    Introduction: Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works b

  19. Analysis of risk factors for chronic subdural haematoma recurrence after burr hole surgery: optimal management of patients on antiplatelet therapy.

    Science.gov (United States)

    Okano, Atsushi; Oya, Soichi; Fujisawa, Naoaki; Tsuchiya, Tsukasa; Indo, Masahiro; Nakamura, Takumi; Chang, Han Soo; Matsui, Toru

    2014-04-01

    OBJECTIVE. Not much is known about surgical management of patients with chronic subdural haematoma (CSDH) treated with antiplatelet or anticoagulant therapy. The aims of this study were to review the surgical outcomes of patients with CSDH and assess the risks of antiplatelet in their surgical management. METHODS. We retrospectively analysed 448 consecutive patients with CSDH treated by one burr hole surgery at our institution. Among them, 58 patients had been on antiplatelet therapy. We discontinued the antiplatelet agents before surgery for all 58 patients. For 51 of these 58 patients (87.9%), early surgery was performed within 0-2 days from admission. We analysed the association between recurrence and patient characteristics, including history of antiplatelet or anticoagulant therapy; age (therapy; and previous medical history of head trauma, infarction, hypertension, diabetes mellitus, haemodialysis, seizure, cancer, or liver cirrhosis. RESULTS. Recurrence occurred in 40 patients (8.9%), which was one of the lowest rates in the literature. Univariate analysis showed that only the presence of bilateral haematomas was associated with increased recurrence rate while antiplatelet or anticoagulant therapy did not significantly increase recurrence risk. Also, the recurrence rate from early surgery (0-2 days from drug cessation) for patients on antiplatelet therapy was not significantly higher than that from elective surgery (5 days or more after drug cessation). However, multivariate analysis revealed that previous history of cerebral infarction was an independent risk factor for CSDH recurrence. CONCLUSIOns. Our overall data support the safety of early surgery for patients on the preoperative antiplatelet therapy without drug cessation or platelet infusion. Patients with a previous history of infarction may need to be closely followed regardless of antiplatelet or anticoagulant therapy.

  20. Molecular Profiling to Optimize Treatment in Non-Small Cell Lung Cancer: A Review of Potential Molecular Targets for Radiation Therapy by the Translational Research Program of the Radiation Therapy Oncology Group

    Energy Technology Data Exchange (ETDEWEB)

    Ausborn, Natalie L. [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Le, Quynh Thu [Department of Radiation Oncology, Stanford University, Palo Alto, California (United States); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Saha, Debabrata [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simko, Jeff [Department of Urology, University of California, San Francisco, California (United States); Story, Michael D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Torossian, Artour [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Lu, Bo, E-mail: bo.lu@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2012-07-15

    Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growth factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.

  1. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Fusella, Marco; Giglioli, Francesca Romana [Medical Physics, AOU Città della Salute e della Scienza Hospital, Torino (Italy); Lohr, Frank [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by

  2. Optimized volumetric modulated arc therapy versus 3D-CRT for early stage mediastinal Hodgkin lymphoma without axillary involvement: a comparison of second cancers and heart disease risk.

    Science.gov (United States)

    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (Pdisease extent. In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach. Copyright © 2015 Elsevier

  3. A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery.

    LENUS (Irish Health Repository)

    Szarvas, Szilvia

    2012-02-03

    In a prospective, double-blinded, randomized trial, we evaluated the efficacy of IV (a) dexamethasone 8 mg, (b) ondansetron 8 mg, and (c) dexamethasone 8 mg plus ondansetron 4 mg for the prevention of postoperative nausea, vomiting (PONV), and pruritus in 130 (ASA physical status I to III) patients undergoing elective major orthopedic surgery after spinal anesthesia with hyperbaric 0.5% bupivacaine and intrathecal morphine. After spinal anesthesia, patients were randomized to one of three groups. Failure of PONV prophylaxis in the 24-h postoperative period occurred more frequently in patients who received dexamethasone alone (29 of 40; 73%) compared with those who received either ondansetron alone (23 of 47; 49%) (P = 0.02) or dexamethasone plus ondansetron together (19 of 43; 44%)(P = 0.01). There was no difference in the incidence of failure of prophylaxis of pruritus (70%, 72%, and 70% in dexamethasone 8 mg, ondansetron 8 mg, and dexamethasone 8 mg plus ondansetron 4 mg, respectively) (P > 0.1) in the 24-h postoperative period. We conclude that the administration of dexamethasone 8 mg with ondansetron 4 mg has no added benefit compared with ondansetron 8 mg alone in the prophylaxis of PONV and pruritus. IMPLICATIONS: Postoperative nausea and vomiting (PONV) and pruritus are common side effects after spinal opioid administration. In this study, dexamethasone 8 mg plus ondansetron 4 mg was as effective as ondansetron 8 mg. The administration of dexamethasone alone was associated with a frequent incidence of PONV, demonstrating a lack of efficacy. This has important cost implications.

  4. Double-blind comparative study of droperidol, granisetron and granisetron plus dexamethasone as prophylactic anti-emetic therapy in patients undergoing abdominal, gynaecological, breast or otolaryngological surgery

    NARCIS (Netherlands)

    Janknegt, R; Pinckaers, JWM; Rohof, MHC; Ausems, MEM; Arbouw, MEL; van der Velden, RW; Brouwers, JRBJ

    1999-01-01

    In this double-blind study the clinical efficacy of a single pre-operative intravenous dose of droperidol 1.25 mg (137 patients), granisetron 1 mg (130 patients) and granisetron 1 mg plus dexamethasone 5 mg (130 patients) was investigated for the prevention of postoperative nausea and vomiting after

  5. Treatment resistant hyperemesis gravidarum in a patient with type 1 diabetes mellitus: neonatal withdrawal symptoms after successful antiemetic therapy with mirtazapine.

    Science.gov (United States)

    Schwarzer, V; Heep, A; Gembruch, U; Rohde, A

    2008-01-01

    Here we present the case of a 30-year-old woman with type I diabetes mellitus, preeclampsia and treatment resistant persistent hyperemesis gravidarum in her 25th week of gestation who was successfully treated with the antidepressant mirtazapine (Remergil). Nausea and vomiting resolved within 5 days. After discharge from the hospital in 28 weeks of gestation and discontinuation of the medication on her own initiative a relapse occurred, once again with good response to mirtazapine. The drug was continued until birth. At 34 + 0 weeks a cesarean section was performed due to fetal growth restriction and deteriorating preeclampsia. During the second and fourth day postnatal age the child temporarily developed hyperarousal which could be explained by mirtazapine withdrawal.

  6. [A method of the interactive visual optimization of the therapeutic dose field in contact radiation therapy of malignant tumors (theoretical aspects of the problem)].

    Science.gov (United States)

    Klepper, L Ia

    2003-01-01

    The mathematical and interpretation tasks of a directed shaping of dose fields in the contrast radiation therapy of malignant tumors are defined on the basis of the dose-field homogeneity parameter. A schematic iterative algorithm of how to solve the tasks is described. A method for the visual optimization of such field is elaborated; it is based on preset limits to the dose field in the lesion focus and in the healthy organs and tissues. The dose field is shaped by an applicator with multiple terminal fixed positions of irradiation sources--the effect is achieved due to variability of their exposure duration.

  7. Comparison of different invasive hemodynamic methods for AV delay optimization in patients with cardiac resynchronization therapy: Implications for clinical trial design and clinical practice☆☆☆

    Science.gov (United States)

    Whinnett, Zachary I.; Francis, Darrel P.; Denis, Arnaud; Willson, Keith; Pascale, Patrizio; van Geldorp, Irene; De Guillebon, Maxime; Ploux, Sylvain; Ellenbogen, Kenneth; Haïssaguerre, Michel; Ritter, Philippe; Bordachar, Pierre

    2013-01-01

    Background Reproducibility and hemodynamic efficacy of optimization of AV delay (AVD) of cardiac resynchronization therapy (CRT) using invasive LV dp/dtmax are unknown. Method and results 25 patients underwent AV delay (AVD) optimisation twice, using continuous left ventricular (LV) dp/dtmax, systolic blood pressure (SBP) and pulse pressure (PP). We compared 4 protocols for comparing dp/dtmax between AV delays:Immediate absolute: mean of 10 s recording of dp/dtmax acquired immediately after programming the tested AVD,Delayed absolute: mean of 10 s recording acquired 30 s after programming AVD,Single relative: relative difference between reference AVD and the tested AVD,Multiple relative: averaged difference, from multiple alternations between reference and tested AVD. We assessed for dp/dtmax, LVSBP and LVPP, test–retest reproducibility of the optimum. Optimization using immediate absolute dp/dtmax had poor reproducibility (SDD of replicate optima = 41 ms; R2 = 0.45) as did delayed absolute (SDD 39 ms; R2 = 0.50). Multiple relative had better reproducibility: SDD 23 ms, R2 = 0.76, and (p AV delay was LVSBP 2% and LVdp/dtmax 5%, while CRT with pre-determined optimal AVD gave 6% and 9% respectively. Conclusions Because of inevitable background fluctuations, optimization by absolute dp/dtmax has poor same-day reproducibility, unsuitable for clinical or research purposes. Reproducibility is improved by comparing to a reference AVD and making multiple consecutive measurements. More than 6 measurements would be required for even more precise optimization — and might be advisable for future study designs. With optimal AVD, instead of nominal, the hemodynamic increment of CRT is approximately doubled. PMID:23481908

  8. Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single–Isocenter Volumetric Modulated Arc Therapy

    Science.gov (United States)

    Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J.; Wen, Ning

    2016-01-01

    Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly. PMID:27688047

  9. SU-E-T-266: Development of Evaluation System of Optimal Synchrotron Controlling Parameter for Spot Scanning Proton Therapy with Multiple Gate Irradiations in One Operation Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, T; Fujii, Y [Hokkaido University Hospital, Sapporo, Hokkaido (Japan); Hitachi Ltd., Hitachi-shi, Ibaraki (Japan); Miyamoto, N; Matsuura, T; Takao, S; Matsuzaki, Y [Hokkaido University Hospital, Sapporo, Hokkaido (Japan); Koyano, H; Shirato, H [Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido (Japan); Nihongi, H; Umezawa, M; Matsuda, K [Hitachi Ltd., Hitachi-shi, Ibaraki (Japan); Umegaki, K [Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido (Japan)

    2015-06-15

    Purpose: We have developed a gated spot scanning proton beam therapy system with real-time tumor-tracking. This system has the ability of multiple-gated irradiation in a single synchrotron operation cycle controlling the wait-time for consecutive gate signals during a flat-top phase so that the decrease in irradiation efficiency induced by irregular variation of gate signal is reduced. Our previous studies have shown that a 200 ms wait-time is appropriate to increase the average irradiation efficiency, but the optimal wait-time can vary patient by patient and day by day. In this research, we have developed an evaluation system of the optimal wait-time in each irradiation based on the log data of the real-time-image gated proton beam therapy (RGPT) system. Methods: The developed system consists of logger for operation of RGPT system and software for evaluation of optimal wait-time. The logger records timing of gate on/off, timing and the dose of delivered beam spots, beam energy and timing of X-ray irradiation. The evaluation software calculates irradiation time in the case of different wait-time by simulating the multiple-gated irradiation operation using several timing information. Actual data preserved in the log data are used for gate on and off time, spot irradiation time, and time moving to the next spot. Design values are used for the acceleration and deceleration times. We applied this system to a patient treated with the RGPT system. Results: The evaluation system found the optimal wait-time of 390 ms that reduced the irradiation time by about 10 %. The irradiation time with actual wait-time used in treatment was reproduced with accuracy of 0.2 ms. Conclusion: For spot scanning proton therapy system with multiple-gated irradiation in one synchrotron operation cycle, an evaluation system of the optimal wait-time in each irradiation based on log data has been developed. Funding Support: Japan Society for the Promotion of Science (JSPS) through the FIRST

  10. Optimizing levodopa therapy to treat wearing-off symptoms in Parkinson's disease: focus on levodopa/carbidopa/entacapone.

    Science.gov (United States)

    Reichmann, Heinz; Emre, Murat

    2012-02-01

    Levodopa has been the mainstay of Parkinson's disease (PD) therapy for over 40 years, with its efficacy surpassing that of other antiparkinsonian medications. As such, most PD patients eventually require levodopa-based therapy during the course of the disease. However, despite its proven efficacy, long-term levodopa therapy is associated with motor complications, with wearing-off being the most prevalent. Wearing-off occurs, in part, as a result of the short half-life of levodopa, which leads to fluctuations in plasma levodopa levels. A pharmacokinetic profile characterized by a higher trough value of levodopa can be achieved by combining levodopa/carbidopa with entacapone, which inhibits the peripheral breakdown of levodopa, resulting in higher plasma levodopa levels. Here, we review the limitations of conventional levodopa and the clinical data for levodopa/carbidopa/entacapone in treating patients with wearing-off.

  11. Caracterización del uso de antieméticos en el postoperatorio en pacientes adultos sometidos a cirugía durante el periodo enero-mayo 2009, en el Hospital Clínica Bíblica de Costa Rica Characterization of the Use of Antiemetics in the Postoperative Period in Adult Patients Undergoing Surgery During January to May 2009 in a private hospital Clínica Bíblica in Costa Rica

    Directory of Open Access Journals (Sweden)

    Natalia Apuy-Roldán

    2010-07-01

    poder así unificar y mejorar los criterios de tratamiento de las náuseas y vómitos postoperatorios.Aim: To evaluate and characterize the pharmaco-therapeutic approach with antiemetics during the postoperative, in adult patients undergoing surgery at a private hospital in Costa Rica (Hospital Clinica Biblica Methods:This is an observational, prospective and cohort study. Those patients who had surgery and received antiemetic prophylaxis before the procedure were selected (ages between 18 and 75 years excluding those who had hospitalization shorter than 24 hours. Results: Prophylactic antiemetic therapy in this private hospital utilizes granisetron, metoclopramide, dexamethasone, and dimenhydrinate, Granisetron, either alone or in combination, was the most used antiemetic in 81%. The combination most commonly used was dexamethasone and granisetron (57%. Without considering the surgical procedure, the incidence of postoperative nausea and vomiting (PONV was 12% in patients taking granisetron, 25% with metoclopramide, 9% with dimenhydrinate, 13% with dexamethasone and 14% with other antiemetics. On the other hand, looking at the procedure, the incidence of PONV in patients undergoing orthopedic surgery was by 30%, and 28% in those after laparoscopic surgery Finally, in cases in which fentanyl was used as an anesthetic 18% of the patients presented PONV, whereas in patients cases were fentanyl was not used, the rate of was 9%. Conclusion: Despite the widespread use of prophylactic antiemetics, PONV is still seen in the patients at this private hospital. In spite of the wealth of knowledge in this field, physicians have not yet found an algorithm capable of the total prevention of PONV. Individual risks and patient`s satisfaction should be taken into account. Further research on this matter must continue in order to unify and improve criteria of PONV treatment.

  12. Treatment Adherence as a New Choice Factor for Optimization of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation and Hemostatic Gene Polymorphisms

    Directory of Open Access Journals (Sweden)

    Yu. P. Skirdenko

    2016-01-01

    Full Text Available Aim. To evaluate treatment adherence and prevalence of CYP2C9 and VKORC1 gene mutations in patients with atrial fibrillation (AF and provide rationale of choice for oral anticoagulation therapy.Material and methods. Treatment adherence was evaluated in 137 AF patients (aged 35-85 years with quantitative estimation of drug therapy adherence along with compliance to medical support and lifestyle modifications. Among them 82 patients underwent polymerase chain reaction (PCR analysis of CYP2C9 and VKORC1 gene polymorphisms.Results. Patients receiving anticoagulation therapy are characterized by lower level of adherence compared to patients without anticoagulants (65.2±19.3% vs 68.5±19.1%; Wald-Wolfowitz; p<0.05. Considering all studied parameters men are less adherent than women (54.7±18.6% vs 60.6±16.7%; Kolmogorov-Smirnov; p<0.05. Patients receiving new oral anticoagulants (NOAC have better compliance compared with patients of warfarin group. Mutations in CYP2C9 gene were detected in 32.9%, VKORC1 – in 68.3%, and their combination – in 21.9% of study participants. Warfarin therapy may be potentially dangerous in such patients due to low adherence.Conclusion. Considering high prevalence of CYP2C9 and VKORC1 gene mutations treatment adherence should be estimated to optimize choice of anticoagulation therapy. NOAC treatment should be considered in patients with low adherence for prevention of thromboembolic complications.

  13. [Potentials for the combined therapy of urination disorders in men: the choice of optimal scheme of treatment].

    Science.gov (United States)

    Golubtsova, E N; Tomilov, A A; Veliev, E I

    2013-01-01

    Moderate to severe urination disorders occur in 13-29% of men, and their frequency increases progressively with age. The key for successful use of the capabilities of modern drug therapy is the understanding of the pathophysiological bases of urination disorders. Despite some successes of monotherapy with alpha-adrenoblockers and 5alpha-reductase inhibitors, combined use of drugs is appropriate, because the differences in mechanisms of action allows to simultaneously act on the smooth muscle tissue, causing its relax, and reduce the size of prostate by the induction of apoptosis, which ultimately allows to expect the maximum therapeutic effect. The goal of therapy in patients with BPH is not only a reduction in the severity of urination disorders, but the prevention of disease progression. Obviously, urination disorders in men are not always caused by an benign prostate hyperplasia. Hyperactive symptoms (primary and secondary, due to metabolic disorders in detrusor against the background of prolonged existence of bladder outlet obstruction) are revealed in significant proportion of men. In this cases, the use of M-anticholinergics is indicated. Administration of alpha-adrenoblockers and antimuscarinic drugs is one of potential variant of combined therapy. Thus, it is important to follow the principles of selectivity in patients with urination disorders. Modern pharmacotherapy has an arsenal of drugs, allowing to choose the drug therapy for patients with urination disorders depending on the prevalence of their types.

  14. Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes

    Science.gov (United States)

    Arch, Joanna J.; Craske, Michelle G.

    2011-01-01

    In this paper, we present a client with panic disorder and agoraphobia who relapses following a full course of cognitive behavioral therapy (CBT). To frame the client's treatment, the major components of CBT for panic disorder with or without agoraphobia (PD/A) are reviewed. Likely reasons for the treatment's failure and strategies for improving…

  15. Shortening delivery times of intensity modulated proton therapy by reducing proton energy layers during treatment plan optimization

    NARCIS (Netherlands)

    S. van de Water (Steven); H.M. Kooy; B.J.M. Heijmen (Ben); M.S. Hoogeman (Mischa)

    2015-01-01

    textabstractPurpose To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment

  16. Shortening delivery times of intensity modulated proton therapy by reducing proton energy layers during treatment plan optimization

    NARCIS (Netherlands)

    S. van de Water (Steven); H.M. Kooy; B.J.M. Heijmen (Ben); M.S. Hoogeman (Mischa)

    2015-01-01

    textabstractPurpose To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment plann

  17. SU-F-BRD-01: A Novel 4D Robust Optimization Mitigates Interplay Effect in Intensity-Modulated Proton Therapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W; Shen, J; Stoker, J; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Schild, S; Wong, W [Mayo Clinic, Phoenix, Arizona (United States); Chang, J; Liao, Z; Wen, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Herman, M [Mayo Clinic, Rochester, MN (United States); Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses to achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest

  18. Bone marrow mesenchymal stem cell therapy in ischemic stroke:mechanisms of action and treatment optimization strategies

    Institute of Scientific and Technical Information of China (English)

    Guihong Li; Fengbo Yu; Ting Lei; Haijun Gao; Peiwen Li; Yuxue Sun; Haiyan Huang; Qingchun Mu

    2016-01-01

    Animal and clinical studies have conifrmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  19. Study on the Material Foundation of Ginger Antiemetic Efficacy%生姜止呕功效的物质基础研究

    Institute of Scientific and Technical Information of China (English)

    刘文娟; 崔瑛; 纪彬; 王君明; 冯志毅

    2013-01-01

    目的:研究生姜止呕功效的物质基础.方法:在大鼠异嗜高岭土模型上,观察生姜汁和生姜水煎液对饲料和高岭土进食量的影响.通过高效液相色谱法初步确定姜止呕的物质基础.结果:模型动物饲料进食量下降,而高岭土的进食量增加;给药组较模型组高岭土摄食量明显减少,并在含药血清中发现了生姜的入血成分-6-姜酚.结论:生姜对大鼠异嗜高岭土模型具有显著减少高岭土摄食量的作用,反映生姜的止呕功效的物质可能为6-姜酚.%Objective:To study the material foundation of ginger antitussive effect Methods:In the rat model of kaolin,observe the effect of ginger juice and ginger decoction on feed intake and kaolin. Through the method of HPLC initially determine the material basis of ginger antiemetic. Results:Feed intake decreased in animal models, while the intake of kaolin increased; drug group than in the model group decreased kaolin intake. And found ginger into blood components in the serum of-6-jiangfen. Conclusion: Ginger has significantly reduced the role of kaolin intake on rat kaolin model, reflect the vomiting effect check bom ginger, the effect of material may be-6-jiangfen.

  20. Construction Of An Optimized Lentiviral Vector Containing Pdx-1 Gene For Transduction Of Stem Cells Towards Gene Therapy Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    S Rahmati

    2013-02-01

    Full Text Available Abstract Background & aim: Nowadays, most of gene therapy protocols are performed by lentiviral vectors. One of the most important factors which is involved in pancreas development and transcription of insulin gene is pancreatic & duodenal homeobox 1 (PDX-1 transcription factor. The goal of this study was to optimize a lentiviral construct, containing pdx-1 gene, to transfect stem cells towards gene therapy of type-1 diabetes. Methods: In this experimental study, first, the pdx-1 gene was multiplied by PCR from pcDNA3.1-pdx-1 and cloned into pTG19-T vector. Then, pdx-1 was subcloned on upstream of IRES-EGFP gene into IRES2-EGFP vector. At the next step, the cloned parts of IRES-EGFP and pdx-1 were isolated and cloned into the lentiviral expression vector pSINTREM in upstream of TRE-CMV gene. After sequencing, final construct was transfected into HEK 293 cells and gene expression of pdx-1 was evaluated using flow cytometry analysis and reverse fluorescent microscopy. Results: Flow cytometry results and inverted fluorescent microscopy observing showed that pdx-1 and GFP genes are expressed in cells transfected with final recombinant construct. Conclusion: Regarding the design of this construct, to ensure long time expression with higher in vivo and in vitro expression efficiency for stem cells and also use of Tet on induced optimized system, it seems that the current construct can be among the best ones to transfect stem cells. Key words: Gene therapy, Diabetes, Stem cells

  1. SU-E-J-16: Automatic Image Contrast Enhancement Based On Automatic Parameter Optimization for Radiation Therapy Setup Verification

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, J [Taishan Medical University, Taian, Shandong (China); Washington University in St Louis, St Louis, MO (United States); Li, H. Harlod; Zhang, T; Yang, D [Washington University in St Louis, St Louis, MO (United States); Ma, F [Taishan Medical University, Taian, Shandong (China)

    2015-06-15

    Purpose: In RT patient setup 2D images, tissues often cannot be seen well due to the lack of image contrast. Contrast enhancement features provided by image reviewing software, e.g. Mosaiq and ARIA, require manual selection of the image processing filters and parameters thus inefficient and cannot be automated. In this work, we developed a novel method to automatically enhance the 2D RT image contrast to allow automatic verification of patient daily setups as a prerequisite step of automatic patient safety assurance. Methods: The new method is based on contrast limited adaptive histogram equalization (CLAHE) and high-pass filtering algorithms. The most important innovation is to automatically select the optimal parameters by optimizing the image contrast. The image processing procedure includes the following steps: 1) background and noise removal, 2) hi-pass filtering by subtracting the Gaussian smoothed Result, and 3) histogram equalization using CLAHE algorithm. Three parameters were determined through an iterative optimization which was based on the interior-point constrained optimization algorithm: the Gaussian smoothing weighting factor, the CLAHE algorithm block size and clip limiting parameters. The goal of the optimization is to maximize the entropy of the processed Result. Results: A total 42 RT images were processed. The results were visually evaluated by RT physicians and physicists. About 48% of the images processed by the new method were ranked as excellent. In comparison, only 29% and 18% of the images processed by the basic CLAHE algorithm and by the basic window level adjustment process, were ranked as excellent. Conclusion: This new image contrast enhancement method is robust and automatic, and is able to significantly outperform the basic CLAHE algorithm and the manual window-level adjustment process that are currently used in clinical 2D image review software tools.

  2. Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis.

    Science.gov (United States)

    Jang, Ji-Yong; Kim, Jung-Sun; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2015-10-01

    Serial follow-up optical coherence tomography (OCT) was used to evaluate the effect of optimal lipid-lowering therapy on qualitative changes in neointimal tissue characteristics after drug-eluting stent (DES) implantation. DES-treated patients (n = 218) who received statin therapy were examined with serial follow-up OCT. First and second follow-up OCT evaluations were performed approximately 6 and 18 months after the index procedure, respectively. Patients were divided into two groups, based on the level of low-density lipoprotein-cholesterol (LDL-C), which was measured at the second follow-up. The optimal lipid-lowering group (n = 121) had an LDL-C reduction of ≥50% or an LDL-C level ≤70 mg/dL, and the conventional group (n = 97). Neointimal characteristics were qualitatively categorized as homogeneous or non-homogeneous patterns using OCT. The non-homogeneous group included heterogeneous, layered, or neoatherosclerosis patterns. Qualitative changes in neointimal tissue characteristics between the first and second follow-up OCT examinations were assessed. Between the first and second follow-up OCT procedures, the neointimal cross-sectional area increased more substantially in the conventional group (0.4 mm(2) vs. 0.2 mm(2) in the optimal lipid-lowering group, p = 0.01). The neointimal pattern changed from homogeneous to non-homogeneous less often in the optimal lipid-lowering group (1.3%, 1/77, p < 0.001) than in the conventional group (15.3%, 11/72, p = 0.44). Optimal LDL-C reduction was an independent predictor for the prevention of neointimal pattern change from homogeneous to non-homogeneous (odds ratio: 0.05, 95% confidence interval: 0.01∼0.46, p = 0.008). Our findings suggest that an intensive reduction in LDL-C levels can prevent non-homogeneous changes in the neointima and increases in neointimal cross-sectional area compared with conventional LDL-C controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Clinically applicable Monte Carlo-based biological dose optimization for the treatment of head and neck cancers with spot-scanning proton therapy

    CERN Document Server

    Tseung, H Wan Chan; Kreofsky, C R; Ma, D; Beltran, C

    2016-01-01

    Purpose: 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: 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 IMPT optimizer. Besides dose, the dose-averaged linear energy transfer (LETd) can be simultaneously scored, which makes biological dose (BD) optimization possible. To convert from LETd to BD, a linear relation was assumed. Using this novel optimizer, inverse biological planning was applied to 4 patients: 2 small and 1 large thyroid tumor targets, and 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 IMRT and IMPT plans were created for each case in Eclipse (Varian, Inc). The same critical structure PD constraints were use...

  4. A simple catheter-vessel model for MR assessment of drug distribution in arteries and optimization of catheter design for intraarterial infusion therapy.

    Science.gov (United States)

    Yoshikawa, Takeshi; Uchida, Koji; Ohno, Yoshiharu; Hirota, Shozo; Nakamura, Tomonori; Yoshizako, Takeshi; Ishida, Jun; Kitagaki, Hajime

    2007-05-01

    To investigate the efficacy of a new catheter-vessel model for MRI to evaluate drug distribution and to optimize catheter design for intraarterial infusion therapy The model consisted of a hepatic artery simulant tube through which blood simulant water flowed continuously and a water cistern. Catheters were inserted into the tube and a gadolinium contrast medium was injected at rates suitable for angiographic or computed tomographic evaluation and commensurate with the clinical drug infusion rate. Axial images of the tube were obtained with a 0.2-T scanner and gradient echo technique. Preliminary studies and catheter tests were conducted. The points at which drug and water were completely mixed were defined as the site with uniform enhancement nearest the catheter tip. Flip angle and gadolinium concentrations were optimized at 90 degrees, and at 62.5 and 500 mM for the high and low infusion rates, respectively. Drug distribution near the catheter tips was clearly visualized. The drug was mixed in shorter distances via the slit side-hole than the end- or side-hole catheters, and the smaller diametrical than the larger at either rate. This model appeared to be effective for evaluation of drug distribution and optimization of catheter design. (c) 2007 Wiley-Liss, Inc.

  5. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Tranekjær; Norregaard, Kamilla; Tian, Pengfei;

    2016-01-01

    Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform...... that PET imaging could be reliably used to monitor early treatment response of photothermal treatment. This multidisciplinary approach provides a much needed platform to benchmark the emerging plethora of novel plasmonic nanoparticles for their potential for photothermal cancer therapy....... predicted photo-absorption. In vivo, the heat generation of irradiated nanoparticles was evaluated in human tumor xenografts in mice using 2-deoxy-2-[F-18]fluoro-D-glucose ((18)F-FDG) PET imaging. To validate the use of this platform, we quantified the photothermal efficiency of near infrared resonant...

  6. Stewardship approach for optimizing antimicrobial therapy through use of a rapid microarray assay on blood cultures positive for Enterococcus species.

    Science.gov (United States)

    Sango, Aaron; McCarter, Yvette S; Johnson, Donald; Ferreira, Jason; Guzman, Nilmarie; Jankowski, Christopher A

    2013-12-01

    Enterococci are a major cause of bloodstream infections in hospitalized patients and have limited antimicrobial treatment options due to their many resistance mechanisms. Molecular technologies have significantly shortened the time to enterococcal isolate identification compared with conventional methods. We evaluated the impact of rapid organism identification and resistance detection with the Verigene Gram-positive blood culture microarray assay on clinical and economic outcomes for patients with enterococcal bacteremia. A single-center preintervention/postintervention quasiexperimental study compared inpatients with enterococcal bacteremia from 1 February 2012 to 9 September 2012 (preintervention period) and 10 September 2012 to 28 February 2013 (postintervention period). An infectious disease and/or critical care pharmacist was contacted with the microarray assay results, and effective antibiotics were recommended. The clinical and economic outcomes for 74 patients were assessed. The mean time to appropriate antimicrobial therapy was 23.4 h longer in the preintervention group than in the postintervention group (P = 0.0054). A nonsignificant decrease in the mean time to appropriate antimicrobial therapy was seen for patients infected with vancomycin-susceptible Enterococcus isolates (P = 0.1145). For patients with vancomycin-resistant Enterococcus bacteremia, the mean time to appropriate antimicrobial therapy was 31.1 h longer in the preintervention group than in the postintervention group (P < 0.0001). In the postintervention group, the hospital length of stay was significantly 21.7 days shorter (P = 0.0484) and mean hospital costs were $60,729 lower (P = 0.02) than in the preintervention group. The rates of attributed deaths in the two groups were not statistically different. Microarray technology, supported by pharmacy and microbiology departments, can decrease the time to appropriate antimicrobial therapy, the hospital length of stay, and health care costs.

  7. Optimization of antiaggregant therapy in rheumatoid arthritis and coronary heart disease patients receiving nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Tatyana Vladimirovna Kropotina

    2012-01-01

    Full Text Available Objective: to study coagulative and vascular-thrombocytic hemostases in patients with rheumatoid arthritis (RA and coronary heart disease (CHD depending on therapy with different nonsteroidal anti-inflammatory drugs (NSAIDs alone and in combination with low-dose aspirin. Subjects and methods. The trial enrolled 58 patients (43 women and 15 men with a valid diagnosis of RA. The patients' mean age was 61.2 years; the disease duration averaged 10 years. All the patients received therapy with disease-modifying antirheumatic drugs (DMARDs and NSAIDs. All had CHD; 52 of the 58 patients presented with arterial hypertension; 30 had noncoronary atherosclerosis. Cardiovascular diseases were first identified in 18 patients. All took heart medications. Coagulative and vascular-thrombocytic hemostases were studied in all the patients and the results were compared depending on to the taken NSAID (diclofenac, tenoxicam, nimesulide, meloxicam. Thirty-seven patients who had not previously received antiaggregant therapy were given aspirin in a dose of 100 mg when they were found to have platelet hyperaggregation and aggregation was restudied on aspirin therapy days 7-8. A control group consisted of 26 healthy men (mean age 55 years who received no medications. Results. In patients with RA and CHD, activated coagulative hemostasis was identified in 65.5% of cases. The signs of hypercoagulation were observed in 35 of the 58 patients. When different NSAIDs were used, the coagulative hemostatic changes were unidirectional and no statistically significant differences were found between the groups. The patients taking diclofenac, nimesulide, or meloxicam were found to have activated vascular-thrombocytic hemostasis. Those receiving tenoxicam showed a tendency towards decreased adrenaline-induced platelet aggregation (the drug's aspirin-like effect; however, no statistical processing was made because of few cases. The use of aspirin in the patients taking diclofenac

  8. TH-A-9A-02: BEST IN PHYSICS (THERAPY) - 4D IMRT Planning Using Highly- Parallelizable Particle Swarm Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Modiri, A; Gu, X; Sawant, A [UT Southwestern Medical Center, Dallas, TX (United States)

    2014-06-15

    Purpose: We present a particle swarm optimization (PSO)-based 4D IMRT planning technique designed for dynamic MLC tracking delivery to lung tumors. The key idea is to utilize the temporal dimension as an additional degree of freedom rather than a constraint in order to achieve improved sparing of organs at risk (OARs). Methods: The target and normal structures were manually contoured on each of the ten phases of a 4DCT scan acquired from a lung SBRT patient who exhibited 1.5cm tumor motion despite the use of abdominal compression. Corresponding ten IMRT plans were generated using the Eclipse treatment planning system. These plans served as initial guess solutions for the PSO algorithm. Fluence weights were optimized over the entire solution space i.e., 10 phases × 12 beams × 166 control points. The size of the solution space motivated our choice of PSO, which is a highly parallelizable stochastic global optimization technique that is well-suited for such large problems. A summed fluence map was created using an in-house B-spline deformable image registration. Each plan was compared with a corresponding, internal target volume (ITV)-based IMRT plan. Results: The PSO 4D IMRT plan yielded comparable PTV coverage and significantly higher dose—sparing for parallel and serial OARs compared to the ITV-based plan. The dose-sparing achieved via PSO-4DIMRT was: lung Dmean = 28%; lung V20 = 90%; spinal cord Dmax = 23%; esophagus Dmax = 31%; heart Dmax = 51%; heart Dmean = 64%. Conclusion: Truly 4D IMRT that uses the temporal dimension as an additional degree of freedom can achieve significant dose sparing of serial and parallel OARs. Given the large solution space, PSO represents an attractive, parallelizable tool to achieve globally optimal solutions for such problems. This work was supported through funding from the National Institutes of Health and Varian Medical Systems. Amit Sawant has research funding from Varian Medical Systems, VisionRT Ltd. and Elekta.

  9. An optimized posterior axillary boost technique in radiation therapy to supraclavicular and axillary lymph nodes: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Victor, E-mail: vhernandezmasgrau@gmail.com [Department of Medical Physics, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain); Arenas, Meritxell [Department of Radiation therapy, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain); Müller, Katrin [Department of Medical Physics, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain); Gomez, David; Bonet, Marta [Department of Radiation therapy, Hospital Sant Joan de Reus, IISPV, Tarragona (Spain)

    2013-01-01

    To assess the advantages of an optimized posterior axillary (AX) boost technique for the irradiation of supraclavicular (SC) and AX lymph nodes. Five techniques for the treatment of SC and levels I, II, and III AX lymph nodes were evaluated for 10 patients selected at random: a direct anterior field (AP); an anterior to posterior parallel pair (AP-PA); an anterior field with a posterior axillary boost (PAB); an anterior field with an anterior axillary boost (AAB); and an optimized PAB technique (OptPAB). The target coverage, hot spots, irradiated volume, and dose to organs at risk were evaluated and a statistical analysis comparison was performed. The AP technique delivered insufficient dose to the deeper AX nodes. The AP-PA technique produced larger irradiated volumes and higher mean lung doses than the other techniques. The PAB and AAB techniques originated excessive hot spots in most of the cases. The OptPAB technique produced moderate hot spots while maintaining a similar planning target volume (PTV) coverage, irradiated volume, and dose to organs at risk. This optimized technique combines the advantages of the PAB and AP-PA techniques, with moderate hot spots, sufficient target coverage, and adequate sparing of normal tissues. The presented technique is simple, fast, and easy to implement in routine clinical practice and is superior to the techniques historically used for the treatment of SC and AX lymph nodes.

  10. An optimized posterior axillary boost technique in radiation therapy to supraclavicular and axillary lymph nodes: a comparative study.

    Science.gov (United States)

    Hernandez, Victor; Arenas, Meritxell; Müller, Katrin; Gomez, David; Bonet, Marta

    2013-01-01

    To assess the advantages of an optimized posterior axillary (AX) boost technique for the irradiation of supraclavicular (SC) and AX lymph nodes. Five techniques for the treatment of SC and levels I, II, and III AX lymph nodes were evaluated for 10 patients selected at random: a direct anterior field (AP); an anterior to posterior parallel pair (AP-PA); an anterior field with a posterior axillary boost (PAB); an anterior field with an anterior axillary boost (AAB); and an optimized PAB technique (OptPAB). The target coverage, hot spots, irradiated volume, and dose to organs at risk were evaluated and a statistical analysis comparison was performed. The AP technique delivered insufficient dose to the deeper AX nodes. The AP-PA technique produced larger irradiated volumes and higher mean lung doses than the other techniques. The PAB and AAB techniques originated excessive hot spots in most of the cases. The OptPAB technique produced moderate hot spots while maintaining a similar planning target volume (PTV) coverage, irradiated volume, and dose to organs at risk. This optimized technique combines the advantages of the PAB and AP-PA techniques, with moderate hot spots, sufficient target coverage, and adequate sparing of normal tissues. The presented technique is simple, fast, and easy to implement in routine clinical practice and is superior to the techniques historically used for the treatment of SC and AX lymph nodes. © 2013 American Association of Medical Dosimetrists.

  11. Optimal length of triple therapy for H pylori eradication in a population with high prevalence of infection in Chile

    Institute of Scientific and Technical Information of China (English)

    Arnoldo Riquelme; Alejandro Pattillo; Douglas Greig; Marco Arrese; Antonio Rollan; Alejandro Soza; Cesar Pedreros; Andrea Bustamante; Felipe Valenzuela; Francisco Otarola; Eduardo Abbott; Narco Arellano; Brenda Medina

    2007-01-01

    AIM: To compare the efficacy of 7-d versus 14-d triple therapy for the treatment of H pylori infection in Chile,with a prevalence of 73% in general population.METHODS: H pylori-infected patients diagnosed by rapid urease test, with non-ulcer dyspepsia or peptic ulcer disease were randomized to receive omeprazole 20 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg bid for 7 (OAC7) or 14 (OAC14) d. Primary outcome was eradication rate 6 wk after the treatment. Subgroup analysis was carried out considering the eradication rate among patients with or without peptic ulcer disease and eradication rate among smokers or non-smokers.RESULTS: One hundred and thirty-one patients were randomized to OAC7 (n = 69) or OAC14 (n = 62). The overall eradication rate (intention-to-treat) was 78.3% in OAC7 and 85.5% in OAC14 groups, without a significant difference (P =0.37). No significant difference in the eradication rate was found among the patients with peptic ulcer disease (n = 31) between the OAC7 group (85.7%) and OAC14 group (87.5%). However, smokers had an obviously lower eradication rate compared to non-smokers, particularly in the OAC7 group (57.1% in smokers vs 83.6% in non-smokers; P = 0.06). Adverse effects rate were similar between both groups.CONCLUSION: Short-term efficacy of triple therapy with OAC for 7 d is comparable to 14 d in this high-prevalence population. Longer follow-up, and studies focused to some subgroups of patients (smokers and non-ulcer patients) are necessary to support widespread use of 7-d instead of 10-14-d triple therapy in a developing country like Chile.

  12. SU-E-T-574: Novel Chance-Constrained Optimization in Intensity-Modulated Proton Therapy Planning to Account for Range and Patient Setup Uncertainties

    Energy Technology Data Exchange (ETDEWEB)

    An, Y; Liang, J [Arizona State University, Tempe, AZ - Arizona (United States); Liu, W [Mayo Clinic Arizona, Phoenix, AZ (United States)

    2015-06-15

    Purpose: We propose to apply a probabilistic framework, namely chanceconstrained optimization, in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to hedge against the influence of uncertainties and improve robustness of treatment plans. Methods: IMPT plans were generated for a typical prostate patient. Nine dose distributions are computed — the nominal one and one each for ±5mm setup uncertainties along three cardinal axes and for ±3.5% range uncertainty. These nine dose distributions are supplied to the solver CPLEX as chance constraints to explicitly control plan robustness under these representative uncertainty scenarios with certain probability. This probability is determined by the tolerance level. We make the chance-constrained model tractable by converting it to a mixed integer optimization problem. The quality of plans derived from this method is evaluated using dose-volume histogram (DVH) indices such as tumor dose homogeneity (D5% – D95%) and coverage (D95%) and normal tissue sparing like V70 of rectum, V65, and V40 of bladder. We also compare the results from this novel method with the conventional PTV-based method to further demonstrate its effectiveness Results: Our model can yield clinically acceptable plans within 50 seconds. The chance-constrained optimization produces IMPT plans with comparable target coverage, better target dose homogeneity, and better normal tissue sparing compared to the PTV-based optimization [D95% CTV: 67.9 vs 68.7 (Gy), D5% – D95% CTV: 11.9 vs 18 (Gy), V70 rectum: 0.0 % vs 0.33%, V65 bladder: 2.17% vs 9.33%, V40 bladder: 8.83% vs 21.83%]. It also simultaneously makes the plan more robust [Width of DVH band at D50%: 2.0 vs 10.0 (Gy)]. The tolerance level may be varied to control the tradeoff between plan robustness and quality. Conclusion: The chance-constrained optimization generates superior IMPT plan compared to the PTV-based optimization with

  13. Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy

    Science.gov (United States)

    Jørgensen, Jesper Tranekjær; Norregaard, Kamilla; Tian, Pengfei; Bendix, Poul Martin; Kjaer, Andreas; Oddershede, Lene B.

    2016-08-01

    Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform to quantitatively correlate the heat generation of plasmonic nanoparticles with their potential as cancer killing agents. In vitro, the heat generation and absorption cross-section of single irradiated nanoparticles were quantified using a temperature sensitive lipid-based assay and compared to their theoretically predicted photo-absorption. In vivo, the heat generation of irradiated nanoparticles was evaluated in human tumor xenografts in mice using 2-deoxy-2-[F-18]fluoro-D-glucose (18F-FDG) PET imaging. To validate the use of this platform, we quantified the photothermal efficiency of near infrared resonant silica-gold nanoshells (AuNSs) and benchmarked this against the heating of colloidal spherical, solid gold nanoparticles (AuNPs). As expected, both in vitro and in vivo the heat generation of the resonant AuNSs performed superior compared to the non-resonant AuNPs. Furthermore, the results showed that PET imaging could be reliably used to monitor early treatment response of photothermal treatment. This multidisciplinary approach provides a much needed platform to benchmark the emerging plethora of novel plasmonic nanoparticles for their potential for photothermal cancer therapy.

  14. Optimization of Surface Coating on Small Pd Nanosheets for in Vivo near-Infrared Photothermal Therapy of Tumor.

    Science.gov (United States)

    Shi, Saige; Huang, Yizhuan; Chen, Xiaolan; Weng, Jian; Zheng, Nanfeng

    2015-07-08

    Palladium nanosheets with strong near-infrared absorption have been recently demonstrated as promising photothermal agents for photothermal therapy (PTT) of cancers. However, systematic assessments of their potential risks and impacts to biological systems have not been fully explored yet. In this work, we carefully investigate how surface coatings affect the in vivo behaviors of small Pd nanosheets (Pd NSs). Several biocompatible molecules such as carboxymethyl chitosan (CMC), PEG-NH2, PEG-SH, and dihydrolipoic acid-zwitterion (DHLA-ZW) were used to coat Pd NSs. The blood circulation half-lives, biodistribution, potential toxicity, clearance, and photothermal effect of different surface-coated Pd NSs in mice after intravenous injection were compared. PEG-SH-coated Pd NSs (Pd-HS-PEG) were found to have ultralong blood circulation half-life and show high uptake in the tumor. We then carry out the in vivo photothermal therapeutic studies on the Pd-HS-PEG conjugate and revealed its outstanding efficacy in in vivo photothermal therapy of cancers. Our results highlight the importance of surface coatings to the in vivo behaviors of nanomaterials and can provide guidelines to the future design of Pd NSs bioconjugates for other in vivo applications.

  15. Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M [Belarusian State University, Minsk (Belarus)

    2015-04-30

    We have solved the problem of layer-by-layer laser-light dosimetry in biological tissues and of selecting an individual therapeutic dose in laser therapy. A method is proposed for real-time monitoring of the radiation density in tissue layers in vivo, concentrations of its endogenous (natural) and exogenous (specially administered) chromophores, as well as in-depth distributions of the spectrum of light action on these chromophores. As the background information use is made of the spectrum of diffuse light reflected from a patient's tissue, measured by a fibre-optic spectrophotometer. The measured spectrum is quantitatively analysed by the method of approximating functions for fluxes of light multiply scattered in tissue and by a semi-analytical method for calculating the in-depth distribution of the light flux in a multi-layered medium. We have shown the possibility of employing the developed method for monitoring photosensitizer and oxyhaemoglobin concentrations in tissue, light power absorbed by chromophores in tissue layers at different depths and laser-induced changes in the tissue morphology (vascular volume content and ratios of various forms of haemoglobin) during photodynamic therapy. (biophotonics)

  16. Optimizing the current therapy for chronic hepatitis C virus: peginterferon and ribavirin dosing and the utility of growth factors.

    Science.gov (United States)

    Shiffman, Mitchell L

    2008-08-01

    Achieving a sustained virologic response depends on the patient achieving three sequential independent milestones: virologic response, maintaining this response throughout treatment, and not relapsing after treatment has been completed. The ability to achieve these milestones depends on the doses of interferon/peginterferon and ribavirin used and on whether treatment with these medications is adjusted, interrupted, or prematurely discontinued in response to adverse events. This review discusses strategies to optimize peginterferon and ribavirin dosing and the impact that growth factors may have on the ability to achieve a sustained virologic response.

  17. Long-term medical management of primary open-angle glaucoma and ocular hypertension in the UK: optimizing cost-effectiveness and clinic resources by minimizing therapy switches.

    Science.gov (United States)

    Orme, Michelle; Collins, Sarah; Loftus, Jane

    2012-09-01

    hypothesis that the economic and clinical benefits can be optimized by minimizing therapy switches.

  18. The Rationale for Optimal Combination Therapy With Sipuleucel-T for Patients With Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Mouraviev, Vladimir; Mariados, Neil; Albala, David; Concepcion, Raoul S; Shore, Neal D; Sims, Robert B; Emberton, Mark; Pieczonka, Christopher M

    2014-01-01

    Immunotherapy encourages the recipient's own immune response to destroy cancer cells, and current evidence suggests that immunotherapies may be most beneficial in early metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T is the first therapeutic cancer vaccine to be approved by both the US Food and Drug Administration and European Medicines Agency for the treatment of asymptomatic or minimally symptomatic mCRPC. Combining immunotherapy with other treatments may have potent anticancer effects; cytoreductive therapies can release tumor antigens and promote a proinflammatory environment that could augment immunotherapies. However, some cytoreductive agents or coadministered drugs may be immunosuppressive. Understanding these interactions between different mCRPC treatment modalities may offer further potential to improve patient outcomes.

  19. Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning.

    Science.gov (United States)

    Huston, Marshall W; van Til, Niek P; Visser, Trudi P; Arshad, Shazia; Brugman, Martijn H; Cattoglio, Claudia; Nowrouzi, Ali; Li, Yuedan; Schambach, Axel; Schmidt, Manfred; Baum, Christopher; von Kalle, Christof; Mavilio, Fulvio; Zhang, Fang; Blundell, Mike P; Thrasher, Adrian J; Verstegen, Monique M A; Wagemaker, Gerard

    2011-10-01

    Clinical trials have demonstrated the potential of ex vivo hematopoietic stem cell gene therapy to treat X-linked severe combined immunodeficiency (SCID-X1) using γ-retroviral vectors, leading to immune system functionality in the majority of treated patients without pretransplant conditioning. The success was tempered by insertional oncogenesis in a proportion of the patients. To reduce the genotoxicity risk, a self-inactivating (SIN) lentiviral vector (LV) with improved expression of a codon optimized human interleukin-2 receptor γ gene (IL2RG) cDNA (coγc), regulated by its 1.1 kb promoter region (γcPr), was compared in efficacy to the viral spleen focus forming virus (SF) and the cellular phosphoglycerate kinase (PGK) promoters. Pretransplant conditioning of Il2rg(-/-) mice resulted in long-term reconstitution of T and B lymphocytes, normalized natural antibody titers, humoral immune responses, ConA/IL-2 stimulated spleen cell proliferation, and polyclonal T-cell receptor gene rearrangements with a clear integration preference of the SF vector for proto-oncogenes, contrary to the PGK and γcPr vectors. We conclude that SIN lentiviral gene therapy using coγc driven by the γcPr or PGK promoter corrects the SCID phenotype, potentially with an improved safety profile, and that low-dose conditioning proved essential for immune competence, allowing for a reduced threshold of cell numbers required.

  20. Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally☆

    Science.gov (United States)

    Kyriacou, Andreas; Pabari, Punam A.; Mayet, Jamil; Peters, Nicholas S.; Davies, D. Wyn; Lim, P. Boon; Lefroy, David; Hughes, Alun D.; Kanagaratnam, Prapa; Francis, Darrel P.; I.Whinnett, Zachary

    2014-01-01

    Background The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown. Methods Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). Results AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p = 0.001, and aortic VTI by 11(SEM 3)%, p = 0.002, but also increased MVO2 by 11(SEM 5)%, p = 0.04. AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p = 0.035 and aortic VTI by 4(SEM 1)%, p = 0.017. MVO2 trended further up by 7(SEM 5)%, p = 0.22. Mechanoenergetics at AV-40 were no different from LBBB. The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly > 1 (p = 0.02). Conclusions Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~ 80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”. PMID:24332598

  1. Correction of Murine Rag2 Severe Combined Immunodeficiency by Lentiviral Gene Therapy Using a Codon-optimized RAG2 Therapeutic Transgene

    Science.gov (United States)

    van Til, Niek P; de Boer, Helen; Mashamba, Nomusa; Wabik, Agnieszka; Huston, Marshall; Visser, Trudi P; Fontana, Elena; Poliani, Pietro Luigi; Cassani, Barbara; Zhang, Fang; Thrasher, Adrian J; Villa, Anna; Wagemaker, Gerard

    2012-01-01

    Recombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We report the development of lentiviral vectors with the spleen focus forming virus (SF) promoter driving codon-optimized human RAG2 (RAG2co), which improved phenotype amelioration compared to native RAG2 in Rag2−/− mice. With the RAG2co therapeutic transgene, T-cell receptor (TCR) and immunoglobulin repertoire, T-cell mitogen responses, plasma immunoglobulin levels and T-cell dependent and independent specific antibody responses were restored. However, the thymus double positive T-cell population remained subnormal, possibly due to the SF virus derived element being sensitive to methylation/silencing in the thymus, which was prevented by replacing the SF promoter by the previously reported silencing resistant element (ubiquitous chromatin opening element (UCOE)), and also improved B-cell reconstitution to eventually near normal levels. Weak cellular promoters were effective in T-cell reconstitution, but deficient in B-cell reconstitution. We conclude that immune functions are corrected in Rag2−/− mice by genetic modification of stem cells using the UCOE driven codon-optimized RAG2, providing a valid optional vector for clinical implementation. PMID:22692499

  2. An Automated Treatment Plan Quality Control Tool for Intensity-Modulated Radiation Therapy Using a Voxel-Weighting Factor-Based Re-Optimization Algorithm.

    Science.gov (United States)

    Song, Ting; Li, Nan; Zarepisheh, Masoud; Li, Yongbao; Gautier, Quentin; Zhou, Linghong; Mell, Loren; Jiang, Steve; Cerviño, Laura

    2016-01-01

    Intensity-modulated radiation therapy (IMRT) currently plays an important role in radiotherapy, but its treatment plan quality can vary significantly among institutions and planners. Treatment plan quality control (QC) is a necessary component for individual clinics to ensure that patients receive treatments with high therapeutic gain ratios. The voxel-weighting factor-based plan re-optimization mechanism has been proved able to explore a larger Pareto surface (solution domain) and therefore increase the possibility of finding an optimal treatment plan. In this study, we incorporated additional modules into an in-house developed voxel weighting factor-based re-optimization algorithm, which was enhanced as a highly automated and accurate IMRT plan QC tool (TPS-QC tool). After importing an under-assessment plan, the TPS-QC tool was able to generate a QC report within 2 minutes. This QC report contains the plan quality determination as well as information supporting the determination. Finally, the IMRT plan quality can be controlled by approving quality-passed plans and replacing quality-failed plans using the TPS-QC tool. The feasibility and accuracy of the proposed TPS-QC tool were evaluated using 25 clinically approved cervical cancer patient IMRT plans and 5 manually created poor-quality IMRT plans. The results showed high consistency between the QC report quality determinations and the actual plan quality. In the 25 clinically approved cases that the TPS-QC tool identified as passed, a greater difference could be observed for dosimetric endpoints for organs at risk (OAR) than for planning target volume (PTV), implying that better dose sparing could be achieved in OAR than in PTV. In addition, the dose-volume histogram (DVH) curves of the TPS-QC tool re-optimized plans satisfied the dosimetric criteria more frequently than did the under-assessment plans. In addition, the criteria for unsatisfied dosimetric endpoints in the 5 poor-quality plans could typically be

  3. Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

    Science.gov (United States)

    Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

    2017-06-01

    To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

  4. Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival

    DEFF Research Database (Denmark)

    Witt, Christoffer Tobias; Kronborg, Mads Brix; Nohr, Ellen Aagaard

    2015-01-01

    after CRT implantation, long-term adherence to this treatment, and its association with patient survival. METHODS AND RESULTS: This observational study included 826 consecutive patients who received a CRT device at a tertiary centre. Data were obtained from patient files and prescription data from...... the Danish National Prescription Registry. Doses are expressed as percentages of target doses. We used Cox proportional hazard model to compute adjusted hazard ratios (aHRs) for survival with 95% confidence intervals (CIs), adjusted for potential confounders. During the median (quartiles) follow-up of 4.4 (3......HR 0.55 (0.38-0.80); P = 0.002). CONCLUSION: After CRT implantation, optimization of HF treatment is possible, and long-term adherence to HF medication remains high. Higher doses of BB and ACEi/ARB were associated with prolonged survival....

  5. Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.

    Science.gov (United States)

    Johnston, J M; Denning, G; Doering, C B; Spencer, H T

    2013-06-01

    We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

  6. Numerical optimization of sequential cryogen spray cooling and laser irradiation for improved therapy of port wine stain.

    Science.gov (United States)

    Milanič, Matija; Jia, Wangcun; Nelson, J Stuart; Majaron, Boris

    2011-02-01

    Despite application of cryogen spray (CS) precooling, customary treatment of port wine stain (PWS) birthmarks with a single laser pulse does not result in complete lesion blanching for a majority of patients. One obvious reason is nonselective absorption by epidermal melanin, which limits the maximal safe radiant exposure. Another possible reason for treatment failure is screening of laser light within large PWS vessels, which prevents uniform heating of the entire vessel lumen. Our aim is to identify the parameters of sequential CS cooling and laser irradiation that will allow optimal photocoagulation of various PWS blood vessels with minimal risk of epidermal thermal damage. Light and heat transport in laser treatment of PWS are simulated using a custom 3D Monte Carlo model and 2D finite element method, respectively. Protein denaturation in blood and skin are calculated using the Arrhenius kinetic model with tissue-specific coefficients. Simulated PWS vessels with diameters of 30-150 µm are located at depths of 200-600 µm, and shading by nearby vessels is accounted for according to PWS histology data from the literature. For moderately pigmented and dark skin phototypes, PWS blood vessel coagulation and epidermal thermal damage are assessed for various parameters of sequential CS cooling and 532-nm laser irradiation, i.e. the number of pulses in a sequence (1-5), repetition rate (7-30 Hz), and radiant exposure. Simulations of PWS treatment in darker skin phototypes indicate specific cooling/irradiation sequences that provide significantly higher efficacy and safety as compared to the customary single-pulse approach across a wide range of PWS blood vessel diameters and depths. The optimal sequences involve three to five laser pulses at repetition rates of 10-15 Hz. Application of the identified cooling/irradiation sequences may offer improved therapeutic outcome for patients with resistant PWS, especially in darker skin phototypes. Copyright © 2011

  7. Noncoplanar Beam Angle Class Solutions to Replace Time-Consuming Patient-Specific Beam Angle Optimization in Robotic Prostate Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Linda, E-mail: l.rossi@erasmusmc.nl; Breedveld, Sebastiaan; Aluwini, Shafak; Heijmen, Ben

    2015-07-15

    Purpose: To investigate development of a recipe for the creation of a beam angle class solution (CS) for noncoplanar prostate stereotactic body radiation therapy to replace time-consuming individualized beam angle selection (iBAS) without significant loss in plan quality, using the in-house “Erasmus-iCycle” optimizer for fully automated beam profile optimization and iBAS. Methods and Materials: For 30 patients, Erasmus-iCycle was first used to generate 15-, 20-, and 25-beam iBAS plans for a CyberKnife equipped with a multileaf collimator. With these plans, 6 recipes for creation of beam angle CSs were investigated. Plans of 10 patients were used to create CSs based on the recipes, and the other 20 to independently test them. For these tests, Erasmus-iCycle was also used to generate intensity modulated radiation therapy plans for the fixed CS beam setups. Results: Of the tested recipes for CS creation, only 1 resulted in 15-, 20-, and 25-beam noncoplanar CSs without plan deterioration compared with iBAS. For the patient group, mean differences in rectum D{sub 1cc}, V{sub 60GyEq}, V{sub 40GyEq}, and D{sub mean} between 25-beam CS plans and 25-beam plans generated with iBAS were 0.2 ± 0.4 Gy, 0.1% ± 0.2%, 0.2% ± 0.3%, and 0.1 ± 0.2 Gy, respectively. Differences between 15- and 20-beam CS and iBAS plans were also negligible. Plan quality for CS plans relative to iBAS plans was also preserved when narrower planning target volume margins were arranged and when planning target volume dose inhomogeneity was decreased. Using a CS instead of iBAS reduced the computation time by a factor of 14 to 25, mainly depending on beam number, without loss in plan quality. Conclusions: A recipe for creation of robust beam angle CSs for robotic prostate stereotactic body radiation therapy has been developed. Compared with iBAS, computation times decreased by a factor 14 to 25. The use of a CS may avoid long planning times without losses in plan quality.

  8. Novel retinoblastoma treatment avoids chemotherapy: the effect of optimally timed combination therapy with angiogenic and glycolytic inhibitors on LHBETATAG retinoblastoma tumors

    Directory of Open Access Journals (Sweden)

    Samuel K Houston

    2011-01-01

    Full Text Available Samuel K Houston1, Yolanda Piña1, Timothy G Murray1, Hinda Boutrid1, Colleen Cebulla2, Amy C Schefler1, Wei Shi1, Magda Celdran1, William Feuer1, Jaime Merchan3, Ted J Lampidis41Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Ophthalmology, The Ohio State University, Columbus, OH, USA; 3Division of Hematology/Oncology, Department of Medicine, 4Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of optimally timed combination treatment with angiogenic and glycolytic inhibitors on tumor burden, hypoxia, and angiogenesis in advanced retinoblastoma tumors.Methods: LHBETATAG mice (n = 30 were evaluated. Mice were divided into 5 groups (n = 6 and received injections at 16 weeks of age (advanced tumors with a saline, b anecortave acetate (AA, c 2-deoxyglucose (2-DG, d AA + 2-DG (1 day post-AA treatment, or e AA + 2-DG (1 week post-AA treatment. Eyes were enucleated at 21 weeks and tumor sections were analyzed for hypoxia, angiogenesis, and tumor burden.Results: Eyes treated with 2-DG 1 day post-AA injection showed a 23% (P = 0.03 reduction in tumor burden compared with 2-DG alone and a 61% (P < 0.001 reduction compared with saline-treated eyes. Eyes treated with 2-DG 1 week post-AA injection showed no significant decrease in tumor burden compared with 2-DG alone (P = 0.21 and a 56% (P < 0.001 decrease in comparison with saline-treated eyes. 2-DG significantly reduced the total density of new blood vessels in tumors by 44% compared to saline controls (P < 0.001, but did not affect the density of mature vasculature.Conclusions: Combination therapy with angiogenic and glycolytic inhibitors significantly enhanced tumor control. Synergistic effects were shown to be dependent on the temporal course of treatment

  9. Optimization of a nanomedicine-based silicon phthalocyanine 4 photodynamic therapy (Pc 4-PDT) strategy for targeted treatment of EGFR-overexpressing cancers.

    Science.gov (United States)

    Master, Alyssa M; Livingston, Megan; Oleinick, Nancy L; Sen Gupta, Anirban

    2012-08-06

    The current clinical mainstays for cancer treatment, namely, surgical resection, chemotherapy, and radiotherapy, can cause significant trauma, systemic toxicity, and functional/cosmetic debilitation of tissue, especially if repetitive treatment becomes necessary due to tumor recurrence. Hence there is significant clinical interest in alternate treatment strategies like photodynamic therapy (PDT) which can effectively and selectively eradicate tumors and can be safely repeated if needed. We have previously demonstrated that the second-generation photosensitizer Pc 4 (silicon phthalocyanine 4) can be formulated within polymeric micelles, and these micelles can be specifically targeted to EGFR-overexpressing cancer cells using GE11 peptide ligands, to enhance cell-specific Pc 4 delivery and internalization. In the current study, we report on the in vitro optimization of the EGFR-targeting, Pc 4 loading of the micellar nanoformulation, along with optimization of the corresponding photoirradiation conditions to maximize Pc 4 delivery, internalization, and subsequent PDT-induced cytotoxicity in EGFR-overexpressing cells in vitro. In our studies, absorption and fluorescence spectroscopy were used to monitor the cell-specific uptake of the GE11-decorated Pc 4-loaded micelles and the cytotoxic singlet oxygen production from the micelle-encapsulated Pc 4, to determine the optimum ligand density and Pc 4 loading. It was found that the micelle formulations bearing 10 mol % of GE11-modified polymer component resulted in the highest cellular uptake in EGFR-overexpressing A431 cells within the shortest incubation periods. Also, the loading of ∼ 50 μg of Pc 4 per mg of polymer in these micellar formulations resulted in the highest levels of singlet oxygen production. When formulations bearing these optimized parameters were tested in vitro on A431 cells for PDT effect, a formulation dose containing 400 nM Pc 4 and photoirradiation duration of 400 s at a fluence of 200 mJ/cm(2

  10. Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.

    Directory of Open Access Journals (Sweden)

    Manuel Romero-Gómez

    Full Text Available Virological response to peginterferon + ribavirin (P+R at week 4 can predict sustained virological response (SVR. While patients with rapid virological response (RVR do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L should have treatment discontinued due to low SVR rate.To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R.In this prospective and multicenter study, HCV mono-infected (n=538 and HCV/HIV co-infected (n=186 patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model and a validation cohort (to validate the model.D1L was reached in 509 (80.2% and RVR in 148 (22.5% patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86 in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79 in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88 in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88 in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.The combination of genetic (IL28B polymorphism and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.

  11. Optimization of the stopping-power-ratio to Hounsfield-value calibration curve in proton and heavy ion therapy.

    Science.gov (United States)

    Witt, Matthias; Weber, Uli; Kellner, Daniel; Engenhart-Cabillic, Rita; Zink, Klemens

    2015-09-01

    For CT-based dose calculation in ion therapy a link between the attenuation coefficients of photons and the stopping-power of particles has to be provided. There are two commonly known approaches to establish such a calibration curve, the stoichiometric calibration and direct measurements with tissue substitutes or animal samples. Both methods were investigated and compared. As input for the stoichiometric calibration the data from ICRP-report 23 were compared to newly available data from ICRP-report 110. By employing the newer data no relevant difference could be observed. The differences between the two acquisition methods (direct measurement and stoichiometric calibration) were systematically analyzed and quantified. The most relevant change was caused by the exchange of carbon and oxygen content in the substitutes in comparison to the data of the ICRP-reports and results in a general overshoot of the Bragg peak. The consequence of the differences between the calibration curves was investigated with treatment planning studies and iso-range surfaces. Range differences up to 6mm in treatment plans of the head were observed. Additionally two improvements are suggested which increase the accuracy of the calibration curve.

  12. Cooperative Strategies for Enhancing Performance of Photothermal Therapy (PTT) Agent: Optimizing Its Photothermal Conversion and Cell Internalization Ability.

    Science.gov (United States)

    Du, Baoji; Ma, Chongbo; Ding, Guanyu; Han, Xu; Li, Dan; Wang, Erkang; Wang, Jin

    2017-01-23

    Photothermal conversion ability (PCA) and cell internalization ability (CIA) are two key factors for determining the performance of photothermal agents. The previous studies mostly focus on improving the PCA by exploring new photothermal nanomaterials. Herein, the authors take the hybrids of graphene and gold nanostar (GGN) as an example to investigate the gradually enhanced phototherapy effect by changing the PCA and CIA of photothermal therapy (PTT) agent simultaneously. Based on the GGN, the GGN and the reduced GGN protected by bovine serum albumin (BSA) or BSA-FA (folic acid) are prepared, which are named as GGNB, rGGNB, and rGGNB-FA, respectively. The rGGNB showed an enhanced PCA compared to GGNB, leading to strong cell ablation. On the other hand, the 1,2-dioleoyl-3-trimethylammoniumpropan (DOTAP) can activate the endocytosis and promote the CIA of rGGNB, further help rGGNB to be more internalized into the cells. Finally, rGGNB-FA with the target ability can make itself further internalized into the cells with the aid of DOTAP, which can significantly destroy the cancer cells even at the low laser density of 0.3 W cm(-2) . Therefore, a new angle of view is brought out for researching the PTT agents of high performance.

  13. Alternative Therapies for the Prevention of Postoperative Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Nicoleta eStoicea

    2015-12-01

    Full Text Available Post-operative nausea and vomiting (PONV is a complication affecting between 20% and 40% of all surgery patients, with high-risk patients experiencing rates of up to 80%. Recent studies and publications have shed light on the uses of alternative treatment for PONV, through their modulation of endogenous opioid neuropeptides and neurokinin ligands. In addition to reducing PONV, hypnosis was reported to be useful in attenuating postoperative pain, anxiety, and contributing to hemodynamic stability. Music therapy has been utilized to deepen the sedation level and decrease patient anxiety, antiemetic and analgesic requirements, hospital length of stay, and fatigue. Isopropyl alcohol and peppermint oil aromatherapy have both been used to reduce postoperative nausea. With correct training in traditional Chinese healing techniques, acupuncture (APu at the P6 acupoint has also been shown to be useful in preventing early PONV, post-discharge nausea and vomiting, and alleviating of pain. Electro-acupuncture (EAPu, as with APu, provided analgesic and antiemetic effects through release of opioid neuropeptides and modulation. These non-pharmacological modalities of treatment contribute to an overall patient wellbeing, assisting in physical and emotional healing.

  14. Supportive therapy in medical therapy of head and neck tumors [

    Directory of Open Access Journals (Sweden)

    Link, Hartmut

    2012-12-01

    Full Text Available [english] Fever during neutropenia may be a symptom of severe life threatening infection, which must be treated immediately with antibiotics. If signs of infection persist, therapy must be modified. Diagnostic measures should not delay treatment. If the risk of febrile neutropenia after chemotherapy is ≥20%, then prophylactic therapy with G-CSF is standard of care. After protocols with a risk of febrile neutropenia of 10–20%, G-CSF is necessary, in patients older than 65 years or with severe comorbidity, open wounds, reduced general condition. Anemia in cancer patients must be diagnosed carefully, even preoperatively. Transfusions of red blood cells are indicated in Hb levels below 7–8 g/dl. Erythropoies stimulating agents (ESA are recommended after chemotherapy only when hemoglobin levels are below 11 g/dl. The Hb-level must not be increased above 12 g/dl. Anemia with functional iron deficiency (transferrin saturation <20% should be treated with intravenous iron, as oral iron is ineffective being not absorbed. Nausea or emesis following chemotherapy can be classified as minimal, low, moderate and high. The antiemetic prophylaxis should be escalated accordingly. In chemotherapy with low emetogenic potential steroids are sufficient, in the moderate level 5-HT3 receptor antagonists (setrons are added, and in the highest level Aprepitant as third drug.

  15. Dose optimization with first-order total-variation minimization for dense angularly sampled and sparse intensity modulated radiation therapy (DASSIM-RT).

    Science.gov (United States)

    Kim, Hojin; Li, Ruijiang; Lee, Rena; Goldstein, Thomas; Boyd, Stephen; Candes, Emmanuel; Xing, Lei

    2012-07-01

    A new treatment scheme coined as dense angularly sampled and sparse intensity modulated radiation therapy (DASSIM-RT) has recently been proposed to bridge the gap between IMRT and VMAT. By increasing the angular sampling of radiation beams while eliminating dispensable segments of the incident fields, DASSIM-RT is capable of providing improved conformity in dose distributions while maintaining high delivery efficiency. The fact that DASSIM-RT utilizes a large number of incident beams represents a major computational challenge for the clinical applications of this powerful treatment scheme. The purpose of this work is to provide a practical solution to the DASSIM-RT inverse planning problem. The inverse planning problem is formulated as a fluence-map optimization problem with total-variation (TV) minimization. A newly released L1-solver, template for first-order conic solver (TFOCS), was adopted in this work. TFOCS achieves faster convergence with less memory usage as compared with conventional quadratic programming (QP) for the TV form through the effective use of conic forms, dual-variable updates, and optimal first-order approaches. As such, it is tailored to specifically address the computational challenges of large-scale optimization in DASSIM-RT inverse planning. Two clinical cases (a prostate and a head and neck case) are used to evaluate the effectiveness and efficiency of the proposed planning technique. DASSIM-RT plans with 15 and 30 beams are compared with conventional IMRT plans with 7 beams in terms of plan quality and delivery efficiency, which are quantified by conformation number (CN), the total number of segments and modulation index, respectively. For optimization efficiency, the QP-based approach was compared with the proposed algorithm for the DASSIM-RT plans with 15 beams for both cases. Plan quality improves with an increasing number of incident beams, while the total number of segments is maintained to be about the same in both cases. For the

  16. Cost-effectiveness of optimized background therapy plus maraviroc for previously treated patients with R5 HIV-1 infection from the perspective of the Spanish health care system.

    Science.gov (United States)

    Moreno, Santiago; González, Juan; Lekander, Ingrid; Martí, Belén; Oyagüez, Itziar; Sánchez-de la Rosa, Rainel; Casado, Miguel Angel

    2010-12-01

    The aim of this work was to evaluate the cost-effectiveness, from the perspective of the Spanish health care system, of optimized background therapy (OBT) plus maraviroc 300 mg BID versus OBT plus placebo in previously treated patients with R5 HIV-1 infection. A lifetime cohort model was developed, based on 24- and 48-week pooled results from the Maraviroc Versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies 1 and 2, to reflect the Spanish health care system's perspective. Treatment duration was based on clinical trial follow-up from MOTIVATE 1 and 2. Clinical data, cohort characteristics, success probability, CD4 increase rate, CD4 cell status link to disease states, and adverse-event probability were taken from the MOTIVATE trials and other published literature. Other input parameters were taken from published sources. Antiretroviral (ARV) costs were derived from local sources. Non-ARV drug costs were obtained from published literature and a cost database. All costs were calculated as year-2009 euros. The annual discount rate was set at 3.0%. The main outcomes were cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained. Uncertainty was assessed with one-way and probabilistic sensitivity analyses. In the model analysis, adding maraviroc to OBT was associated with an increase of 0.952 LYG and 0.909 QALY. Total costs were €275,970 for maraviroc plus OBT and €254,655 for placebo plus OBT (difference: €21,315). The incremental cost per LYG was €22,398 and the incremental cost per QALY gained was €23,457. The model appeared to be robust for variations in key parameters. Results from the probabilistic sensitivity analyses indicated that the probability of the cost per QALY being below €30,000 was 99%. Despite the limitations of the model, our analysis suggested that OBT plus maraviroc 300 mg BID is a clinically valuable option, and cost-effective from the perspective of the

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

    Science.gov (United States)

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

    2017-01-01

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

  18. MALDI-TOF alone versus MALDI-TOF combined with real-time antimicrobial stewardship interventions on time to optimal antimicrobial therapy in patients with positive blood cultures.

    Science.gov (United States)

    Beganovic, Maya; Costello, Michael; Wieczorkiewicz, Sarah M

    2017-02-22

    Introduction: Matrix-assisted laser desorption ionization time of flight (MALDI-TOF) decreases time to organism identification and improves clinical and financial outcomes. The purpose of this study was to evaluate the impact of MALDI-TOF alone vs MALDI-TOF combined with real-time, pharmacist-driven, antimicrobial stewardship (AMS) intervention on patient outcomes.Methods: This single-center, pre-post quasi-experimental study evaluated hospitalized patients with positive blood cultures identified via MALDI-TOF combined with prospective AMS intervention, compared to a control cohort with MALDI-TOF identification without AMS intervention. AMS intervention included: real-time MALDI-TOF pharmacist notification, and prospective AMS provider feedback. The primary outcome was time to optimal antimicrobial therapy (TTOT).Results: A total of 252 blood cultures were included for final analysis: 126 in each group. MALDI-TOF + AMS intervention significantly reduced overall TTOT (75.17 vs 43.06 h, p <0.001), Gram + contaminant TTOT (48.21 vs 11.75 h, p <0.001), Gram - infection (GNI) TTOT (71.83 vs 35.98 h, p <0.001), and reduced overall hospital LOS (15.03 vs 9.02 days, p 0.021). TTOT for Gram + infection (GPI) was improved (64.04 vs 41.61 h, p 0.082). For GPI: reduced hospital LOS (14.64 vs 10.31 days, p 0.002) and length of antimicrobial therapy 24.30 vs 18.97 days, p 0.018). For GNI: reduced time to microbiologic clearance (51.13 vs 34.51 h, p <0.001), hospital LOS (15.40 vs 7.90 days, p 0.027), and ICU LOS (5.55 vs 1.19 days, p 0.035).Conclusion: In order to achieve optimal outcomes, rapid identification with MALDI-TOF combined with real-time AMS interventions is more impactful than MALDI-TOF alone.

  19. Prediction and compensation of magnetic beam deflection in MR-integrated proton therapy: a method optimized regarding accuracy, versatility and speed

    Science.gov (United States)

    Schellhammer, Sonja M.; Hoffmann, Aswin L.

    2017-02-01

    The integration of magnetic resonance imaging (MRI) and proton therapy for on-line image-guidance is expected to reduce dose delivery uncertainties during treatment. Yet, the proton beam experiences a Lorentz force induced deflection inside the magnetic field of the MRI scanner, and several methods have been proposed to quantify this effect. We analyze their structural differences and compare results of both analytical and Monte Carlo models. We find that existing analytical models are limited in accuracy and applicability due to critical approximations, especially including the assumption of a uniform magnetic field. As Monte Carlo simulations are too time-consuming for routine treatment planning and on-line plan adaption, we introduce a new method to quantify and correct for the beam deflection, which is optimized regarding accuracy, versatility and speed. We use it to predict the trajectory of a mono-energetic proton beam of energy E 0 traversing a water phantom behind an air gap within an omnipresent uniform transverse magnetic flux density B 0. The magnetic field induced dislocation of the Bragg peak is calculated as function of E 0 and B 0 and compared to results obtained with existing analytical and Monte Carlo methods. The deviation from the Bragg peak position predicted by Monte Carlo simulations is smaller for the new model than for the analytical models by up to 2 cm. The model is faster than Monte Carlo methods, less assumptive than the analytical models and applicable to realistic magnetic fields. To compensate for the predicted Bragg peak dislocation, a numerical optimization strategy is introduced and evaluated. It includes an adjustment of both the proton beam entrance angle and energy of up to 25° and 5 MeV, depending on E 0 and B 0. This strategy is shown to effectively reposition the Bragg peak to its intended location in the presence of a magnetic field.

  20. Prediction and compensation of magnetic beam deflection in MR-integrated proton therapy: a method optimized regarding accuracy, versatility and speed.

    Science.gov (United States)

    Schellhammer, Sonja M; Hoffmann, Aswin L

    2017-02-21

    The integration of magnetic resonance imaging (MRI) and proton therapy for on-line image-guidance is expected to reduce dose delivery uncertainties during treatment. Yet, the proton beam experiences a Lorentz force induced deflection inside the magnetic field of the MRI scanner, and several methods have been proposed to quantify this effect. We analyze their structural differences and compare results of both analytical and Monte Carlo models. We find that existing analytical models are limited in accuracy and applicability due to critical approximations, especially including the assumption of a uniform magnetic field. As Monte Carlo simulations are too time-consuming for routine treatment planning and on-line plan adaption, we introduce a new method to quantify and correct for the beam deflection, which is optimized regarding accuracy, versatility and speed. We use it to predict the trajectory of a mono-energetic proton beam of energy E 0 traversing a water phantom behind an air gap within an omnipresent uniform transverse magnetic flux density B 0. The magnetic field induced dislocation of the Bragg peak is calculated as function of E 0 and B 0 and compared to results obtained with existing analytical and Monte Carlo methods. The deviation from the Bragg peak position predicted by Monte Carlo simulations is smaller for the new model than for the analytical models by up to 2 cm. The model is faster than Monte Carlo methods, less assumptive than the analytical models and applicable to realistic magnetic fields. To compensate for the predicted Bragg peak dislocation, a numerical optimization strategy is introduced and evaluated. It includes an adjustment of both the proton beam entrance angle and energy of up to 25° and 5 MeV, depending on E 0 and B 0. This strategy is shown to effectively reposition the Bragg peak to its intended location in the presence of a magnetic field.

  1. Filaria associated clinical manifestations in children in an endemic area and morbidity control by immunomonitoring and optimal DEC therapy: Sevagram experience.

    Science.gov (United States)

    Harinath, B C; Reddy, M V; Bhunia, B; Bhandari, Y P; Mehta, V K; Chaturvedi, P; Prajapati, N C; Gupta, R K

    2000-08-01

    Lymphatic filariasis is a major public health problem in India with 412 million people living in bancroftian endemic areas and is a major cause of clinical morbidity. Twenty million people are reported to suffer from chronic disease manifestations such as lymphoedema, hydrocele or elephantiasis. At least twice the number have been shown to suffer from acute and occult filarial infections in an endemic area without diagnosis. Due to non-availability of suitable diagnostic test for confirming filaria aetiology other than parasitological examination, no significant study on filariasis in children has been reported earlier. Studies in our laboratory for more than a decade showed usefulness of microfilarial excretory-secretory antigen in confirming filarial aetiology in acute and occult infections in adults as well as in children. This study reports acute and atypical manifestations such as lymphadenopathy, asthmatic bronchitis, pulmonary eosinophilia, mono-arthritis, recurrent URI, pneumonia, nutritional anemia, pain in abdomen etc. in children living in filaria endemic area having no microfilaraemia but showing filaria aetiology by immunomonitoring for the presence of antibody or antigen and responding to optimal DEC therapy.

  2. SIFT-based dense pixel tracking on 0.35 T cine-MR images acquired during image-guided radiation therapy with application to gating optimization

    Energy Technology Data Exchange (ETDEWEB)

    Mazur, Thomas R., E-mail: tmazur@radonc.wustl.edu, E-mail: hli@radonc.wustl.edu; Fischer-Valuck, Benjamin W.; Wang, Yuhe; Yang, Deshan; Mutic, Sasa; Li, H. Harold, E-mail: tmazur@radonc.wustl.edu, E-mail: hli@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, Campus Box 8224, St. Louis, Missouri 63110 (United States)

    2016-01-15

    Purpose: To first demonstrate the viability of applying an image processing technique for tracking regions on low-contrast cine-MR images acquired during image-guided radiation therapy, and then outline a scheme that uses tracking data for optimizing gating results in a patient-specific manner. Methods: A first-generation MR-IGRT system—treating patients since January 2014—integrates a 0.35 T MR scanner into an annular gantry consisting of three independent Co-60 sources. Obtaining adequate frame rates for capturing relevant patient motion across large fields-of-view currently requires coarse in-plane spatial resolution. This study initially (1) investigate the feasibility of rapidly tracking dense pixel correspondences across single, sagittal plane images (with both moderate signal-to-noise and spatial resolution) using a matching objective for highly descriptive vectors called scale-invariant feature transform (SIFT) descriptors associated to all pixels that describe intensity gradients in local regions around each pixel. To more accurately track features, (2) harmonic analysis was then applied to all pixel trajectories within a region-of-interest across a short training period. In particular, the procedure adjusts the motion of outlying trajectories whose relative spectral power within a frequency bandwidth consistent with respiration (or another form of periodic motion) does not exceed a threshold value that is manually specified following the training period. To evaluate the tracking reliability after applying this correction, conventional metrics—including Dice similarity coefficients (DSCs), mean tracking errors (MTEs), and Hausdorff distances (HD)—were used to compare target segmentations obtained via tracking to manually delineated segmentations. Upon confirming the viability of this descriptor-based procedure for reliably tracking features, the study (3) outlines a scheme for optimizing gating parameters—including relative target position and a

  3. SIFT-based dense pixel tracking on 0.35 T cine-MR images acquired during image-guided radiation therapy with application to gating optimization.

    Science.gov (United States)

    Mazur, Thomas R; Fischer-Valuck, Benjamin W; Wang, Yuhe; Yang, Deshan; Mutic, Sasa; Li, H Harold

    2016-01-01

    To first demonstrate the viability of applying an image processing technique for tracking regions on low-contrast cine-MR images acquired during image-guided radiation therapy, and then outline a scheme that uses tracking data for optimizing gating results in a patient-specific manner. A first-generation MR-IGRT system-treating patients since January 2014-integrates a 0.35 T MR scanner into an annular gantry consisting of three independent Co-60 sources. Obtaining adequate frame rates for capturing relevant patient motion across large fields-of-view currently requires coarse in-plane spatial resolution. This study initially (1) investigate the feasibility of rapidly tracking dense pixel correspondences across single, sagittal plane images (with both moderate signal-to-noise and spatial resolution) using a matching objective for highly descriptive vectors called scale-invariant feature transform (SIFT) descriptors associated to all pixels that describe intensity gradients in local regions around each pixel. To more accurately track features, (2) harmonic analysis was then applied to all pixel trajectories within a region-of-interest across a short training period. In particular, the procedure adjusts the motion of outlying trajectories whose relative spectral power within a frequency bandwidth consistent with respiration (or another form of periodic motion) does not exceed a threshold value that is manually specified following the training period. To evaluate the tracking reliability after applying this correction, conventional metrics-including Dice similarity coefficients (DSCs), mean tracking errors (MTEs), and Hausdorff distances (HD)-were used to compare target segmentations obtained via tracking to manually delineated segmentations. Upon confirming the viability of this descriptor-based procedure for reliably tracking features, the study (3) outlines a scheme for optimizing gating parameters-including relative target position and a tolerable margin about this

  4. Off-pump coronary artery bypass grafting versus optimal medical therapy alone:effectiveness of incomplete revascularization in high risk patients

    Institute of Scientific and Technical Information of China (English)

    Filippo Prestipino; Cristiano Spadaccio; Antonio Nenna; Fraser WH Sutherland; Gwyn W Beattie; Mario Lusini; Francesco Nappi; Massimo Chello

    2016-01-01

    BackgroundGeriatric patients with multivessel coronary artery disease (CAD) are a challenging group to treat; these cases elicit dis-cussion within heart teams regarding the actual benefit of undertaking major surgery on these patients and often lead to abandon the surgical option. Percutaneous procedures represent an important option, but coronary anatomy may be unfavorable. Off-pump coronary artery bypass (OPCAB) provides good quality graft on left anterior descending (LAD) without exposing the patient to cardiopulmonary bypass, and might be the ideal choice in patients with multiple comorbidities, not eligible to percutaneous or on-pump procedures. The objective of this study was to compare survival during a mid-term follow-up in high-risk patients with no percutaneous alternative, either treated with OPCAB or discharged in medical therapy.MethodsWe retrospectively evaluated from June 2008 to June 2013, 83 high-risk patients with multivessel CAD were included: 42 were treated with incomplete off-pump revascularization using left internal mammary artery (LIMA) on LAD; 41 were discharged in optimal medical therapy (OMT), having refused surgery. Follow-up ended in March 2015, with a telephonic interview. Primary endpoint was survival from all-cause mortality; secondary endpoints were survival from cardiac-related mortality and freedom from non-fatal major adverse cardiac events (MACEs).ResultsDuring follow up, 11 deaths in OPCAB group and 27 deaths in OMT group occurred. Death was due to cardiac factors in 6 and 15 patients, respectively. MACEs were observed in 6 patients in OPCAB group and in 4 patients in OMT group. With regards to survival from all-cause mortality, patients who underwent OPCAB survived more than those dis-charged in OMT (Log Rank < 0.001), and OMT group carries a propensity score-adjusted hazard ratio of 3.862 (P < 0.001). With regards to survival from cardiac-related events, patients who underwent OPCAB survived more than those discharged in

  5. Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent chest pain or dyspnea despite optimal medical and revascularization therapy: randomized, double-blind crossover pilot study

    Directory of Open Access Journals (Sweden)

    Shammas NW

    2015-03-01

    Full Text Available Nicolas W Shammas,1 Gail A Shammas,1 Kathleen Keyes,2 Shawna Duske,1 Ryan Kelly,1 Michael Jerin3 1Midwest Cardiovascular Research Foundation, 2Cardiovascular Medicine, Private Corporation, 3St Ambrose University, Davenport, IA, USA Background: Patients with ischemic cardiomyopathy (ICM may continue to experience persistent chest pain and/or dyspnea despite pharmacologic therapy and revascularization. We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients.Methods: In this randomized, double-blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less or equal 40% were included after providing informed consent. A total of 24 patients completed both placebo and ranolazine treatments and were analyzed. All patients were on treatment with a beta blocker, an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker, and at least one additional antianginal drug. After randomization, patients received up to 1,000 mg ranolazine orally twice a day, as tolerated, versus placebo. The primary end point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ, or in dyspnea as assessed by the Rose Dyspnea Scale (RDS. Change in the RDS and SAQ score from baseline was compared, for ranolazine and placebo, using the Wilcoxon signed rank test or paired t-test.Results: Patients had the following demographic and clinical variables: mean age of 71.5 years; male (82.1%; prior coronary bypass surgery (67.9%; prior coronary percutaneous intervention (85.7%; prior myocardial infarction (82.1%; diabetes (67.9%; and mean ejection fraction of 33.1%. No statistical difference was seen between baseline RDS score and that after placebo or ranolazine (n=20 (P≥0.05. There was however, an improvement in anginal frequency (8/10 patients (P=0.058, quality of life (8/10 patients (P=0.048, and mean score of all components of the SAQ questionnaire (n=10 (P=0.047 with ranolazine

  6. Beam’s-eye-view dosimetrics (BEVD) guided rotational station parameter optimized radiation therapy (SPORT) planning based on reweighted total-variation minimization

    Science.gov (United States)

    Kim, Hojin; Li, Ruijiang; Lee, Rena; Xing, Lei

    2015-03-01

    Conventional VMAT optimizes aperture shapes and weights at uniformly sampled stations, which is a generalization of the concept of a control point. Recently, rotational station parameter optimized radiation therapy (SPORT) has been proposed to improve the plan quality by inserting beams to the regions that demand additional intensity modulations, thus formulating non-uniform beam sampling. This work presents a new rotational SPORT planning strategy based on reweighted total-variation (TV) minimization (min.), using beam’s-eye-view dosimetrics (BEVD) guided beam selection. The convex programming based reweighted TV min. assures the simplified fluence-map, which facilitates single-aperture selection at each station for single-arc delivery. For the rotational arc treatment planning and non-uniform beam angle setting, the mathematical model needs to be modified by additional penalty term describing the fluence-map similarity and by determination of appropriate angular weighting factors. The proposed algorithm with additional penalty term is capable of achieving more efficient and deliverable plans adaptive to the conventional VMAT and SPORT planning schemes by reducing the dose delivery time about 5 to 10 s in three clinical cases (one prostate and two head-and-neck (HN) cases with a single and multiple targets). The BEVD guided beam selection provides effective and yet easy calculating methodology to select angles for denser, non-uniform angular sampling in SPORT planning. Our BEVD guided SPORT treatment schemes improve the dose sparing to femoral heads in the prostate and brainstem, parotid glands and oral cavity in the two HN cases, where the mean dose reduction of those organs ranges from 0.5 to 2.5 Gy. Also, it increases the conformation number assessing the dose conformity to the target from 0.84, 0.75 and 0.74 to 0.86, 0.79 and 0.80 in the prostate and two HN cases, while preserving the delivery efficiency, relative to conventional single-arc VMAT plans.

  7. 输卵管介入再通术后受孕时机的研究%The optimal time for conception after fallopian tube recanalization therapy

    Institute of Scientific and Technical Information of China (English)

    赵玉峰; 孙玉琴; 韩晓静; 张睿; 赵秀红; 崔艳国; 刘仙明

    2012-01-01

    目的 探讨输卵管介入再通术后最佳受孕时机.方法 选择山东淄博市妇婴保健院收治输卵管不通的不孕患者635例950条输卵管行介入再通,对术后不同受孕时机进行比较.结果 成功介入再通后受孕率1 ~ 4个月组与5 ~ 8个月组、9 ~ 12个月组有明显差异(χ2 = 82.629,P < 0.05、χ2 = 170.08,P < 0.05),以后逐渐递减,5 ~ 8个月组与9 ~ 12个月组则无明显差异(χ2 = 24.297,P﹥0.05).前6个月受孕率明显高于后6个月(χ2 = 154.51,P﹤0.05).前4个月输卵管妊娠率较高,以后逐渐递减,半年后明显降低.结论 成功介入再通后4个月内为最佳受孕时机,我们主张前半年积极采取受孕措施创造受孕机会.%Objective To discuss the optimal time for conception after fallopian tube recanalization therapy. Methods Fallopian tube recanalization procedure was carried out on 950 obstructed fallopian tubes in 635 infertile women. All the patients were followed up. The time of getting conception after the procedure was observed and recorded in all patients, and the results were analyzed. Results The pregnancy rate in the first four months was significantly different from the pregnancy rate after the first four months, while no significant difference in the pregnancy rate existed between the second four months and the third four months after the treatment. The pregnancy rate of the first six months after recanalization treatment was significantly higher than that of the second six months. The ectopic pregnancy rate was relatively high after the first four months and it gradually declined to a quite lower level after six months. Conclusion The optimal time for conception after fallopian tube recanalization therapy is within the first four months after the interventional treatment. During the first six months after the treatment, the opportunities of getting pregnant should be actively created, and special measures for getting fertilization should

  8. Longer Left Ventricular Electric Delay Reduces Mitral Regurgitation After Cardiac Resynchronization Therapy: Mechanistic Insights From the SMART-AV Study (SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy).

    Science.gov (United States)

    Chatterjee, Neal A; Gold, Michael R; Waggoner, Alan D; Picard, Michael H; Stein, Kenneth M; Yu, Yinghong; Meyer, Timothy E; Wold, Nicholas; Ellenbogen, Kenneth A; Singh, Jagmeet P

    2016-11-01

    Mitral regurgitation (MR) is associated with worse survival in those undergoing cardiac resynchronization therapy (CRT). Left ventricular (LV) lead position in CRT may ameliorate mechanisms of MR. We examine the association between a longer LV electric delay (QLV) at the LV stimulation site and MR reduction after CRT. QLV was assessed retrospectively in 426 patients enrolled in the SMART-AV study (SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in CRT). QLV was defined as the time from QRS onset to the first large peak of the LV electrogram. Linear regression and logistic regression were used to assess the association between baseline QLV and MR reduction at 6 months (absolute change in vena contracta width and odds of ≥1 grade reduction in MR). At baseline, there was no difference in MR grade, LV dyssynchrony, or LV volumes in those with QLV above versus below the median (95 ms). After multivariable adjustment, increasing QLV was an independent predictor of MR reduction at 6 months as reflected by an increased odds of MR response (odds ratio: 1.13 [1.03-1.25]/10 ms increase QLV; P=0.02) and a decrease in vena contracta width (P<0.001). At 3 months, longer QLV (≥median) was associated with significant decrease in LV end-systolic volume (ΔLV end-systolic volume -28.2±38.9 versus -4.9±33.8 mL, P<0.001). Adjustment for 3-month ΔLV end-systolic volume attenuated the association between QLV and 6-month MR reduction. In patients undergoing CRT, longer QLV was an independent predictor of MR reduction at 6 months and associated with interval 3-month LV reverse remodeling. These findings provide a mechanistic basis for using an electric-targeting LV lead strategy at the time of CRT implant. © 2016 American Heart Association, Inc.

  9. Optimization of post-operative early enteral nutrition with sequential therapy%"序贯疗法"优化手术后早期肠内营养

    Institute of Scientific and Technical Information of China (English)

    于健春

    2011-01-01

    肠内营养较肠外营养更符合生理,具有保护肠屏障功能、肝功能和免疫功能,促进胃肠道功能及蛋白质合成,降低应激反应及胰岛素抵抗,降低感染并发症和医疗费用等重要作用和优势.肠内营养实施的关键是对肠内营养适应证、并发症和禁忌证的认识,以及对肠内营养制剂、置管途径及器械装置配套的合理选择.为增加手术后肠内营养耐受性,降低并发症,提高营养支持治疗效果,提出了肠内营养临床应用新方法.手术后早期肠内营养"序贯疗法".%Compared with parenteral nutrition (PN) , enteral nutrition (EN) is more favorable in maintaining physiological status, protecting intestinal barrier function, liver function, immune function, and gastrointestinal function, promoting protein synthesis, reducing the stress response and insulin resistance, reducing infectious complications, and lowering healthcare costs. Successful implementation of EN depends on the good knowledge of indications, complications, and contraindications and on the proper choice of EN preparations, tube placement route, and equipment In this article, with an attempt to increase the tolerance of EN after surgery, reduce complications , and improve the therapeutic effect of nutritional support, we propose a new method of clinical application-optimization of post-operative early enteral nutrition with sequential therapy.

  10. Contemporary Trends of Optimal Evidence-Based Medical Therapy at Discharge for Patients Surviving Acute Myocardial Infarction From the Korea Acute Myocardial Infarction Registry.

    Science.gov (United States)

    Lee, Jang Hoon; Bae, Myung Hwan; Yang, Dong Heon; Park, Hun Sik; Cho, Yongkeun; Jeong, Myung Ho; Kim, Young Jo; Kim, Kee-Sik; Hur, Seung Ho; Seong, In Whan; Cho, Myeong Chan; Kim, Chong Jin; Chae, Shung Chull

    2015-06-01

    Temporal trends of evidence-based optimal medical therapy (OMT) at discharge after acute myocardial infarction (AMI) have not been investigated in recent years. OMT should have been increased in AMI and gap between guidelines and practices in its use should have been narrowed. We examined discharge medications of 17,578 post-MI patients who had no documented contraindications to antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, or statins across a 6-year period (divided into subperiods of November 2005 to December 2006 [period 1], 2007 [period 2], 2008 [period 3], 2009 [period 4], 2010 [period 5], and January to June 2011 [period 6]) in the Korean AMI Registry. OMT was defined as use of all 4 indicated medications. Marked increases in OMT (48.6% to 63.2%) were seen irrespective of age and sex, mainly attributed to marked increases in the use of β-blockers (70.3% to 83.7%) and statins (76.9% to 82.6%) from period 1 to period 6. The gap in use of OMT between men and women narrowed over time between the first and second 3 periods, but not between the young and the elderly. Advanced age (odds ratio [OR]: 0.88, P = 0.04) was independently associated with underuse of OMT. Adjusted ORs for OMT from period 1 to period 6 were as follows: 1, 1.14 (P = 0.024), 1.21 (P = 0.001), 1.40 (P OMT over time, the gap between guidelines and practices in use of OMT continues to exist. © 2015 Wiley Periodicals, Inc.

  11. Risk of Stroke in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention versus Optimal Medical Therapy: Systematic Review and Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Taglieri, Nevio; Bacchi Reggiani, Maria Letizia; Ghetti, Gabriele; Saia, Francesco; Dall’Ara, Gianni; Gallo, Pamela; Moretti, Carolina; Palmerini, Tullio; Marrozzini, Cinzia; Marzocchi, Antonio; Rapezzi, Claudio

    2016-01-01

    Background Stroke is a rare but serious adverse event associated with percutaneous coronary intervention (PCI). However, the relative risk of stroke between stable patients undergoing a direct PCI strategy and those undergoing an initial optimal medical therapy (OMT) strategy has not been established yet. This study sought to investigate if, in patients with stable coronary artery disease (SCAD), an initial strategy PCI is associated with a higher risk of stroke than a strategy based on OMT alone. Methods We performed a meta-analysis of 6 contemporary randomized control trials in which 5673 patients with SCAD were randomized to initial PCI or OMT. Only trials with stent utilization more than 50% were included. Study endpoint was the rate of stroke during follow up. Results Mean age of patients ranged from 60 to 65 years and stent utilization ranged from 72% to 100%. Rate of stroke was 2.0% at a weighted mean follow up of 55.3 months. On pooled analysis, the risk of stroke was similar between patients undergoing a PCI plus OMT and those receiving only OMT (2.2% vs. 1.8%, OR on fixed effect = 1.24 95%CI: 0.85–1.79). There was no heterogeneity among the studies (I2 = 0.0%, P = 0.15). On sensitivity analysis after removing each individual study the pooled effect estimate remains unchanged. Conclusions In patients with SCAD an initial strategy based on a direct PCI is not associated with an increased risk of stroke during long-term follow up compared to an initial strategy based on OMT alone. PMID:27391212

  12. Risk of Stroke in Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention versus Optimal Medical Therapy: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Nevio Taglieri

    Full Text Available Stroke is a rare but serious adverse event associated with percutaneous coronary intervention (PCI. However, the relative risk of stroke between stable patients undergoing a direct PCI strategy and those undergoing an initial optimal medical therapy (OMT strategy has not been established yet. This study sought to investigate if, in patients with stable coronary artery disease (SCAD, an initial strategy PCI is associated with a higher risk of stroke than a strategy based on OMT alone.We performed a meta-analysis of 6 contemporary randomized control trials in which 5673 patients with SCAD were randomized to initial PCI or OMT. Only trials with stent utilization more than 50% were included. Study endpoint was the rate of stroke during follow up.Mean age of patients ranged from 60 to 65 years and stent utilization ranged from 72% to 100%. Rate of stroke was 2.0% at a weighted mean follow up of 55.3 months. On pooled analysis, the risk of stroke was similar between patients undergoing a PCI plus OMT and those receiving only OMT (2.2% vs. 1.8%, OR on fixed effect = 1.24 95%CI: 0.85-1.79. There was no heterogeneity among the studies (I2 = 0.0%, P = 0.15. On sensitivity analysis after removing each individual study the pooled effect estimate remains unchanged.In patients with SCAD an initial strategy based on a direct PCI is not associated with an increased risk of stroke during long-term follow up compared to an initial strategy based on OMT alone.

  13. Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol.

    Science.gov (United States)

    Pinto, Camila Bonin; Saleh Velez, Faddi Ghassan; Bolognini, Nadia; Crandell, David; Merabet, Lotfi B; Fregni, Felipe

    2016-07-06

    intervention. This clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years. This factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention. Clinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf).

  14. Preliminary evaluation of multifield and single-field optimization for the treatment planning of spot-scanning proton therapy of head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Enzhuo M.; Liu, Wei; Wu, Richard; Zhang, Xiaodong; Zhu, X. Ronald; Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Li, Yupeng [Varian Medical Systems, Inc., Palo Alto, California 94304 (United States); Frank, Steven J. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2013-08-15

    Purpose: Spot-scanning proton therapy (SSPT) using multifield optimization (MFO) can generate highly conformal dose distributions, but it is more sensitive to setup and range uncertainties than SSPT using single-field optimization (SFO). The authors compared the two optimization methods for the treatment of head and neck cancer with bilateral targets and determined the superior method on the basis of both the plan quality and the plan robustness in the face of setup and range uncertainties.Methods: Four patients with head and neck cancer with bilateral targets who received SSPT treatment in the authors' institution were studied. The patients had each been treated with a MFO plan using three fields. A three-field SFO plan (3F-SFO) and a two-field SFO plan (2F-SFO) with the use of a range shifter in the beam line were retrospectively generated for each patient. The authors compared the plan quality and robustness to uncertainties of the SFO plans with the MFO plans. Robustness analysis of each plan was performed to generate the two dose distributions consisting of the highest and the lowest possible doses (worst-case doses) from the spatial and range perturbations at every voxel. Dosimetric indices from the nominal and worst-case plans were compared.Results: The 3F-SFO plans generally yielded D95 and D5 values in the targets that were similar to those of the MFO plans. 3F-SFO resulted in a lower dose to the oral cavity than MFO in all four patients by an average of 9.9 Gy, but the dose to the two parotids was on average 6.7 Gy higher for 3F-SFO than for MFO. 3F-SFO plans reduced the variations of dosimetric indices under uncertainties in the targets by 22.8% compared to the MFO plans. Variations of dosimetric indices under uncertainties in the organs at risk (OARs) varied between organs and between patients, although they were on average 9.2% less for the 3F-SFO plans than for the MFO plans. Compared with the MFO plans, the 2F-SFO plans showed a reduced dose to

  15. Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial

    DEFF Research Database (Denmark)

    Zeymer, Uwe; Montalescot, Gilles; Ardissino, Diego;

    2016-01-01

    The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two...... strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations...... for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations....

  16. Sub-optimal adherence to combination anti-retroviral therapy and its associated factors according to self-report, clinician-recorded and pharmacy-refill assessment methods among HIV-infected adults in Addis Ababa.

    Science.gov (United States)

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

    2017-04-01

    Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients' response of less than "all-of the time" to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.

  17. Consistent Reduction in Periprocedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions: Findings From CHAMPION PHOENIX (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition).

    Science.gov (United States)

    Cavender, Matthew A; Bhatt, Deepak L; Stone, Gregg W; White, Harvey D; Steg, Ph Gabriel; Gibson, C Michael; Hamm, Christian W; Price, Matthew J; Leonardi, Sergio; Prats, Jayne; Deliargyris, Efthymios N; Mahaffey, Kenneth W; Harrington, Robert A

    2016-09-06

    Cangrelor is an intravenous P2Y12 inhibitor approved to reduce periprocedural ischemic events in patients undergoing percutaneous coronary intervention not pretreated with a P2Y12 inhibitor. A total of 11 145 patients were randomized to cangrelor or clopidogrel in the CHAMPION PHOENIX trial (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). We explored the effects of cangrelor on myocardial infarction (MI) using different definitions and performed sensitivity analyses on the primary end point of the trial. A total of 462 patients (4.2%) undergoing percutaneous coronary intervention had an MI as defined by the second universal definition. The majority of these MIs (n=433, 93.7%) were type 4a. Treatment with cangrelor reduced the incidence of MI at 48 hours (3.8% versus 4.7%; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67-0.97; P=0.02). When the Society of Coronary Angiography and Intervention definition of periprocedural MI was applied to potential ischemic events, there were fewer total MIs (n=134); however, the effects of cangrelor on MI remained significant (OR, 0.65; 95% CI, 0.46-0.92; P=0.01). Similar effects were seen in the evaluation of the effects of cangrelor on MIs with peak creatinine kinase-MB ≥10 times the upper limit of normal (OR, 0.64; 95% CI, 0.45-0.91) and those with peak creatinine kinase-MB ≥10 times the upper limit of normal, ischemic symptoms, or ECG changes (OR, 0.63; 95% CI, 0.48-0.84). MIs defined by any of these definitions were associated with increased risk of death at 30 days. Treatment with cangrelor reduced the composite end point of death, MI (Society of Coronary Angiography and Intervention definition), ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis (1.4% versus 2.1%; OR, 0.69; 95% CI, 0.51-0.92). MI in patients undergoing percutaneous coronary intervention, regardless of definition, remains associated with increased risk of death

  18. Toward optimal organ at risk sparing in complex volumetric modulated arc therapy: An exponential trade-off with target volume dose homogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Tol, Jim P., E-mail: j.tol@vumc.nl; Dahele, Max; Doornaert, Patricia; Slotman, Ben J.; Verbakel, Wilko F. A. R. [Department of Radiation Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam (Netherlands)

    2014-02-15

    Purpose: Conventional radiotherapy typically aims for homogenous dose in the planning target volume (PTV) while sparing organs at risk (OAR). The authors quantified and characterized the trade-off between PTV dose inhomogeneity (IH) and OAR sparing in complex head and neck volumetric modulated arc therapy plans. Methods: Thirteen simultaneous integrated boost plans were created per patient, for ten patients. PTV boost{sub (B)}/elective{sub (E)} optimization priorities were systematically increased. IH{sub B} and IH{sub E}, defined as (100% − V95%) + V107%, were evaluated against the average of the mean dose to the combined composite swallowing and combined salivary organs (D-OAR{sub comp}). To investigate the influence of OAR size and position with respect to PTV{sub B/E}, OAR dose was evaluated against a modified Euclidean distance (DM{sub B}/DM{sub E}) between OAR and PTV. Results: Although the achievable D-OAR{sub comp} for a given level of PTV IH differed between patients, excellent logarithmic fits described the D-OAR{sub comp}/IH{sub B} and IH{sub E} relationship in all patients (mean R{sup 2} of 0.98 and 0.97, respectively). Allowing an increase in average IH{sub B} and IH{sub E} over a clinically acceptable range, e.g., from 0.4% ± 0.5% to 2.0% ± 2.0% and 6.9% ± 2.8% to 14.8% ± 2.7%, respectively, corresponded to a decrease in average dose to the composite salivary and swallowing structures from 30.3 ± 6.5 to 23.6 ± 4.7 Gy and 32.5 ± 8.3 to 26.8 ± 9.3 Gy. The increase in PTV{sub E} IH was mainly accounted for by an increase in V107, by on average 5.9%, rather than a reduction in V95, which was on average only 2%. A linear correlation was found between the OAR dose to composite swallowing structures and contralateral parotid and submandibular gland, with DM{sub E} (R{sup 2} = 0.83, 0.88, 0.95). Only mean ipsilateral parotid dose correlated with DM{sub B} (R{sup 2} = 0.87). Conclusions: OAR sparing is highly dependent on the permitted PTV{sub B

  19. 心脏再同步治疗快速优化新算法%A new algorithm of quick optimization for cardiac resynchronization therapy

    Institute of Scientific and Technical Information of China (English)

    刘汉雄; 蔡琳; 邓晓奇; 李锦; 童琳; 邓珏琳

    2013-01-01

    目的 提出新的心脏再同步治疗(CRT)优化算法,并验证其合理性.方法 根据心脏电机械偶联原理,将体表心电图和超声心动图指标的数量关系用新公式表述,通过前瞻性随机对照研究比较新算法与现有方法的差异.41例患者随机分为新算法组(21例)及腔内心电图(IEGM)组(20例),每例均分别用新算法、传统超声心动图法及IEGM法优化,即刻比较3种方法的主动脉血流速度时间积分(AVTI)及耗时.然后新算法组采用新算法提供的优化参数,IEGM组采用IEGM法提供的参数并进行远期随访.结果 即刻比较:新算法的AVTI优于IEGM法[(22.32±3.48)cm对(19.22±3.07)cm,P<0.05],新算法耗时较传统超声心动图法减少[(18.80±3.30) min对(203.81±20.12) min,P<0.01].随访18个月,新算法组左心室射血分数较IEGM组高[(0.37±0.03)对(0.32±0.04),P<0.05],血浆脑钠肽水平较IEGM组低[(3245.24±644.56) ng/L对(3636.62±560.98) ng/L,P<0.05],终点事件发生率较IEGM组低(P=0.045).结论 新算法用于CRT优化准确、快速,具有合理性及临床推广价值.%Objective To propose a new algorithm of quick optimization for cardiac resyncaronization therapy (CRT) by verification of the rationality of the new method.Methods The quantitative relationship between electrocardiographic and echocardiographic parameter was presented by a new formula on the basis of the principle of cardiac electrical mechanical coupling.A new algorithm method was compared with previous methods by a prospective control study comprising 41 patients who were allocated into new algorithm group(n =21) and intracardiac electrogram(IEGM) group (n =20) at random.Every case of CRT optimization accepted new algorithm method,traditional echocardiographic method,and intracardiac IEGM method respectively.Aortic time velocity integrals (AVTI) and operating time were measured to assess the acute hemodynamic effects of each optimization method.Atrioventricular (AV

  20. 止吐药物对大鼠实验性晕动病模型产生的胃排空抑制的影响%Effect of antiemetic drugs on decrease in gastric emptying in experimental model of motion sickness in rats

    Institute of Scientific and Technical Information of China (English)

    Gupta YK; Chaudhary G

    2003-01-01

    AIM: To study the effect of pretreatment with different antiemetic drugs on the motion sickness-induced inhibitionin gastric emptying. METHODS: The rats were rotated for a period of 45 min at the rate of 30 rotations per min.RESULTS: Rotating the rats caused a significant decrease in gastric emptying as compared to the non-rotatedgroup. Pretreatment with scopolamine (5 mg/kg, ip) did not reverse the delay in gastric emptying, while it per secaused inhibition of gastric emptying in the non-rotated group. Similarly other drugs mepyramine, cisapride, andgranisetron did not have any effect on delay in gastric emptying caused by rotation. However beta blocker propra-nolol could partially but significantly reverse the decrease in gastric emptying. CONCLUSION: The pr